JPH0370684B2 - - Google Patents

Description

[Detailed description of the invention]

BACKGROUND OF THE INVENTION The present invention provides a mouth rinse or toothpaste containing an effective amount of a gingivitis inhibitor, 1-imidazoyl-1-(p-chlorophenoxy)3-3-dimethyl-2-butanone (Climbazole by Bayer). The present invention relates to an antimicrobial agent-containing oral composition that promotes oral hygiene and inhibits plaque, gingivitis and periodontitis when applied topically to the oral cavity. Periodontitis, or alveolar pyrorrhea, is a disease that affects the retaining tissues of the teeth, including the gums, the membranes that connect the alveolus in which the teeth reside, and the bone that surrounds the teeth. The disease may initially be associated with constant irritation from plaque, food impact, slow tooth healing, traumatic bites, or chemical irritants. Gums are severely damaged by plaque, a combination of minerals and bacteria found in the mouth. Bacteria associated with plaque can secrete enzymes and endotoxins that can irritate the gums, causing inflammatory gingivitis. As the gingiva becomes increasingly irritated by this process, it bleeds, loses its strength and elasticity, and has a tendency to separate from the tooth, leaving a periodontal pocket in which dental residue, secretions, More bacteria and toxins accumulate. Food can also accumulate in these pockets, thereby providing nutritional conditions for increased bacterial growth and production of endotoxins and destructive enzymes. The pus that forms during this process can destroy gum and bone tissue. Bacteria are commonly found to be present during the active phase of periodontitis. Microorganisms such as anaerobic Gram-negative bacteria are normally present and found in purulent excreta as well as associated tissues and are absorbed into the system through the lymph or venous bloodstream. The progression of the pyorrhea process usually begins with gingivitis that begins around the gums, where the gums become softer and more sensitive, with loose, inflamed, and swollen flesh. Therefore, effective control and prevention of gingivitis is essential for preventing subsequent periodontitis. A number of substances have been previously proposed to control oral diseases and dysfunctions such as plaque, stones, cavities, tartar, bad breath, and periodontitis such as gingivitis and pyorrhea. Nothing was completely satisfying. For example, swelling associated with gingivitis by preventing tartar formation and/or inhibiting oral calculus;
Oral compositions containing anti-inflammatory agents that reduce bleeding and signs of inflammation include imidazoles such as histadine or histamine as disclosed in U.S. Pat. No. 3,497,591; benzimidazole; carrageenan as disclosed in U.S. Pat. No. 4,029,760; tranexamic acid and folic acid as disclosed in U.S. Pat. No. 4,272,512;
and tannic acid as disclosed in U.S. Pat. No. 4,273,758. All of the above agents are non-antibacterial. U.S. Pat. No. 3,577,520 also discloses that 5,5'-diaryl-2,
A dentifrice composition comprising 4-imidazolidinedione is disclosed. U.S. Pat. No. 3,911,133 discloses an antibacterial composition that is effective against both Gram-positive and Gram-negative bacteria and is composed of an imidazole derivative that is a bis(imidazolium quaternary salt), which inhibits tartar formation and It is useful in mouth rinses, toothpastes, and dental gels as a method of preventing gingivitis. U.S. Patent No. 4,243,670 has strong antibacterial activity against dermatophytes, yeasts, molds, biphase fungi and Gram-positive cocci, and is suitable for use in oral hygiene products such as fungi and mouth rinses. It is useful as an additive to oral products to prevent bacterial infection of the mucous membranes of the mouth, and as a preventive agent against infection. Discloses imidazolium derivatives. It is also known in the art that certain Gram-negative microorganisms, such as Bacteroides azatucarolithecus or Bacteroides gingivalis, are associated with periodontitis in adults. By removing these and other Gram-negative anaerobes from plaque accumulated on gingivitis tissue, effective control and prevention of periodontitis can be achieved. Therefore, J.Periodont by Listgarton et al.
Res. 14 , 65-75 (1979), metronidazole, has been shown to cause the removal of the Gram-negative anaerobes from dental plaque when given systemically.
This was written by Hage and Lindhe in J.
Clinical Periodontology 6 , 197-209 (1979),
in which metronidazole was shown to be effective in reducing plaque and gingivitis scars in dogs, and by Lacier et al., J. of Clinical Pariodontology, 8 , 29-44.
(1981), in which metronidazole was effective in reducing the number of anaerobic B. asatucaroliticus in plaque removed from periodontal pockets, with a concomitant increase in pocket depth. It has been shown that a reduction in the adhesion and a significant recovery in apparent adhesion occur. However, metronidazole, sold under the brand name Flagyl, is carcinogenic (Physician Reference
Handbook, page 1761) and cannot be used indiscriminately. We now know that another derivative of imidazole is effective against the Gram-negative anaerobic microorganisms mentioned above, that it is non-mutagenic, non-carcinogenic, and that it can be applied topically into the oral cavity for the treatment of gingivitis. It was discovered that 1-imidazoyl-1-
(p-chlorophenyl)3-3-dimethyl-2-butanone. 1-imidazoyl-1-(4-chlorophenol)
Imidazoyl ketones such as -3,3-dimethyl 2-butanone are disclosed in U.S. Pat.
In No. 3903287, pastes, gels, creams,
It is disclosed as an antifungal agent useful in pharmaceutical compositions, including aqueous and non-aqueous suspensions. Its action against pathogenic protozoa, Gram-negative and -negative bacteria such as Staphylococcus aureus and Escherichia coli is also described here. British Patent No. 1502144 and its equivalent German Patent No. 2430039 disclose that Pityrosporum ovale contains an imidazoyl ketone antifungal agent dispersed in a dermatologically acceptable carrier containing a detergent active compound.
Discloses hair and skin treatment compositions that are effective against. These compositions are in cream, aerosol, powder and liquid form. German Patent No. 2600800 covers plaster coatings, disperse dyes, wallpapers, tile surfaces, paints, either in dry form or as a dispersion in water, as a water-in-oil or oil-in-water emulsion, or as a spray.
Glues, bitumina, in fungicidal compositions useful for protecting furniture, leather, shower curtains, textiles, carpets, wood and paper against a long list of pathogenic fungi, molds and bacteria. In, 1-imidazoyl-1-
(4-chlorophenoxy)-3,3-dimethyl 2-
Discloses butanone. However, there is no mention of Bacteroides azatucarolitaecus or gingivitis, the particular anaerobic gram-negative microorganism found in gingivitis. German patent no.
No. 2700806 also discloses mixtures of imidazoyl ketone fungicides and quaternary ammonium fungicides that are useful for protecting materials such as paints, glues, bitumen, cellulose, paper, textiles, leather, and paper. ing. Although the prior art discloses identified imidazoyl ketones as antifungal agents and their use in pharmaceutical formulations, especially in compositions for the treatment of hair and skin, they are associated with gingivitis and periodontitis. There is no disclosure regarding its use in dental formulations or its effectiveness against specific Gram-negative anaerobic microorganisms. DESCRIPTION OF THE INVENTION A water-insoluble imidazoyl ketone, 1-imidazoyl-1-(p-chlorophenoxy) 3-3-dimethyl 2-butanone, is associated with gingivitis when applied topically to diseased gums. selectively effective against anaerobic Gram-negative microorganisms,
It has now been discovered here. The main object of the present invention is therefore to provide an oral formulation containing the water-insoluble imidazoyl ketone described above as a gingivitis inhibitor which is solubilized in an oral vehicle. Another object of the invention is to provide a mouth rinse or toothpaste that is effective in controlling and treating dental plaque, gingivitis and periodontitis. Yet another object of the present invention is to provide an oral composition comprising an anti-gingivitis agent as described above solubilized in an aqueous vehicle comprising a non-ionic compound. Another object of the present invention is to provide oral compositions containing antimicrobial agents that are effective in preventing and treating gingivitis in animals. Yet another object of the present invention is to provide a method for improving oral hygiene by topically applying an antibacterial agent-containing composition comprising the solubilized imidazoyl ketone to the oral cavity. Other objects, advantages, and novel features of the invention will be set forth in part in the following description, or will be apparent to one skilled in the art upon consideration of the following description, or may be apparent to those skilled in the art from practicing the invention. It will be understood by doing. The objects and advantages of the invention may be realized and obtained by means of the instrumentalities and combinations particularly pointed out in the appended claims. To achieve these and other objects in accordance with the present invention as embodied and broadly described herein, the present invention provides an oral vehicle; and an imidazoyl compound as described above in an aqueous medium. an effective amount of a water-insoluble gingivitis inhibitor comprising about 10-80% by weight polyoxyethylene hydrophilic groups of sufficient length to be solubilized in a non-ionic compound, 1 -imidazoyl-1-(p-
chlorophenoxy) 3-3-dimethyl-2-butanone; and an oral composition for suppressing gingivitis. More specifically, the present invention provides hydrophobic groups including higher fatty acid groups containing 10-20 carbons, polyoxypropylene, hexitane mono-higher fatty acid esters, and fatty acid amides; An oral composition comprising from about 0.1 to 5% by weight of the above gingivitis inhibitor solubilized in an aqueous oral vehicle comprising a nonionic compound containing a hydrophilic group of sufficient length polyoxyethylene; It is. Oral vehicles may be liquids such as mouthwashes or rinses, solids such as chewing gum, or creams such as toothpaste, toothpaste or dental creams. These oral compositions are non-toxic and contain from about 5 to
It has a pH of 7.5. Mouthwashes with a pH of about 5 to 7.5 are hydroalcoholic vehicles containing block polymers of ethylene oxide, mixed polymers of propylene oxide and ethylene oxide, 10-80% per mole.
about 1-5% by weight of a nonionic surfactant selected from the group consisting of polyoxyethylene hexitane mono-higher fatty acid esters containing mol of ethylene oxide, and higher fatty acid mono- and di-ethanolamides and mixtures thereof. include. Typical surfactants include hydrophobic groups such as polyoxypropylene with 10 to 80% by weight polyoxyethylene hydrophilic units and preferably a molecular weight of about 3250, as in mixed polymers of propylene oxide and ethylene oxide. include. The ratio of solubilizer to imidazole compound is about 1:1 to 25:1.
and preferably about 3:1 to 25:1.
At ratios greater than 25:1, gelation occurs. Toothpaste, which also has a pH of about 5-7.5, has a dentally acceptable polish; water and about 20-
a non-ionic humidifier comprising 40% by weight of at least one humectant selected from the group consisting of polyethylene glycol and polypropylene glycol;
It consists of a liquid vehicle containing; Glycerin, sorbitol or mannitol may replace part of the humectant content as long as the anti-gingivitis agents mentioned above are solubilized. The gingivitis inhibitor used in the present invention has the structural formula 1-imidazoyl-(p-chlorophenoxy)3-3-dimethyl 2-butanone with
1-bromo-1-(4-chlorophenoxy)-3,
It is made by reacting 3-dimethyl-2-butanone with imidazole dissolved in acetonitrile. This imidazoyl ketone has a melting point of
It is a 94.5-97.8°C water-insoluble crystalline powder available from Bayer as Climbazole. Since the imidazole compound is water-insoluble, it must be solubilized in a non-ionic compound prior to the addition of the ionic substance in the aqueous medium. Surprisingly, this antimicrobial compound added to oral vehicles is not only effective against certain basophilic microorganisms associated with peribacteritis, but also significantly reduces the disease when applied topically. It was discovered that it also reduced the symptoms of gingivitis associated with periodontitis. Walker et al.'s method (Antimicrobial and Chemo therapy, Vol. 16,
The minimum inhibitory concentration (MIC) required to kill Bacteroides saccharolyteix (Forsyth strain) is between 7.8 and 31.2 micrograms per ml, as determined according to the method (pp. 452-457, 1979). be. The MIC value for B. gingivalis is 25 micrograms/ml. B.
The MIC values for the Gram-positive microorganism Actinomyces viscosus are 125 for aerobic strains and 250 for anaerobic strains. This clearly demonstrates the selectivity of the antimicrobial activity of the specific imidazole compounds utilized herein as mycositis inhibitors. An evaluation of an oral composition against gingivitis using a mouth rinse containing 0.3% climbazol, conducted in a 10-week study on 30 beagle dogs, clearly shows its excellent efficacy against gingivitis. . The method used involved complete removal of hard and soft dental deposits, followed by keeping the dogs on a soft diet for 6 weeks to allow gingivitis to develop. The dentition is then treated with the test solution for approximately 15 seconds on each side of the mouth, twice a day, 5 days a week. The animals are examined and the degree of inflammation of the gums is recorded according to a scale of 0 to 3. 0 = no inflammation. 1 = Mild local edema and redness around the gums; bleeding does not occur with gentle finger pressure. 2 = Moderate edema and redness around the gum line with bleeding during gentle acupressure. 3 =
Severe edema and ulceration of the perigingival margin and attached (attached) gingiva, and bleeding even without gentle acupressure.
A soothing rinse and a 0.5% metronidazole rinse were carefully used as negative and positive controls. The data are summarized in Table 1.

[Table] Rule

* initial gingival units
Compared to placebo medication, both metronidazole and climbazole rinses significantly reduced the development of 2 gingival units. However, a lower dose (0.3%) of climbazole is effective against gingivitis, whereas a higher dose (0.5%)
has shown the same efficacy as metronidazole. However, while metronidazole is effective against certain Gram-negative microorganisms associated with periodontitis when used systemically, it does not work well when applied topically, as is well stated in the prior art. The cause of this poor result is due to the absence of adequate hydrophobic groups in its structural formula, which are necessary for penetration into the gingival tissue. Conversely, climbazole has a bulky hydrophobic group, (p-chlorophenoxy)
3-3-dimethyl-2-butanone, which provides good penetration into the tissues in which the destructive process of periodontitis is taking place, is a Gram-negative anaerobic compound implicated in this disease. The antimicrobial agent can be maintained at a concentration effective to reduce the microbial population. Furthermore, metronidazole is mutagenic due to its nitro group, whereas climbazole is non-mutagenic in mutagenesis tests, and it has the following structural formula This is because it does not have a nitro group as shown by. The oral compositions of the present invention may be liquids such as mouthwashes or mouth rinses. In such formulations, the vehicle is typically a water-alcohol mixture. Generally, the water to alcohol ratio is from about 1:1 to about 20:1 by weight, preferably 3:
It ranges from 1 to 20:1. Preferably, the alcohol content comprises about 20-40% by weight of the vehicle. The total amount of water-alcohol mixture in this type of formulation typically ranges from about 70 to about 98% by weight of the formulation. The pH of such liquid and other formulations of the invention generally ranges from about 5 to about
It's in the 7.5 range. The essential ingredients of the liquid oral preparation are 10-80% by weight of polyoxyethylene hydrophilic units and a nonionic surfactant containing hydrophobic polyoxypropylene or higher fatty acids, fatty acid esters or fatty acid amides, about 1-5% by weight. It is. This surfactant solubilizes the water-insoluble Climbazole in the aqueous-alcoholic vehicle. Suitable nonionic surfactants are block polymers of ethylene oxide, mixed polymers of propylene oxide-ethylene oxide, 10-20 carbon atoms in higher fatty acyls and 4-carbon atoms per mole.
100, preferably 10-80 moles of ethylene oxide. Preferably the hexitane is sorbitan, although mannitane and other hexitanes are also often useful;
Higher fatty acyls have 10-16 or 20 carbon atoms.
, preferably 12-16 or 18, with about 12 being most preferred, and the number of ethoxides being 15-80, often about 20 being preferred. Particularly preferred is the ICI product sold under the trade name Tween 20, also known as "Polysorbate 20," which is polyoxyethylene (20) sorbitan monolaurate. Products that are also useful are sold under the same name, such as Tween 40, 60, 65 and 80, all of which have a higher fatty acyl of palmitoyl, stearoyl, or oleoyl and a mole of ethylene oxide per mole. It is a nonionic surfactant with a pH of about 20%. However, among these materials polyoxyethylene sorbitan monolaurate is usually preferred.
Polyoxyethylene (80) sorbitan monolaurate may be used in place of polysorbate (20) above. Other suitable nonionic surfactants are cocomonoethanolamide, cocodiethanolamide,
Includes mono- and di-ethanolamides of higher fatty acids having about 10-18 carbon atoms in the acyl group, such as lauryl myristyl diethanolamide, lauryl monoethanolamide, or combinations thereof. The oral compositions of the present invention may be substantially pasty in nature, such as a paste or dental cream. The vehicle for such pasty oral formulations includes a polish. Examples of polishing agents are water-insoluble sodium metaphosphate, potassium metaphosphate, trilime phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, calcium carbonate, alumina, hydrated alumina, aluminum silicate, zirconium silicate, silica, bentonite. , crystalline silica with particle size up to 5 microns,
silica gel, complex amorphous alkali metal aluminosilicate, dicalcium phosphate, and mixtures thereof. When using gels that are transparent to the naked eye, colloidal silicas such as those sold under the trade name Thyroid as Thyroid 72 and Thyroid 74 or those sold under the trade name Santocel, such as Santocel 100, and alkali metal aluminosilicate Salt complexes are particularly useful because they have a refractive index close to that of gelling agent-liquids (including water and/or humectants) commonly used in toothpastes. It is from. Polishing agents generally range from about 10% by weight of the oral preparation.
Present in amounts ranging from 99% by weight. Preferably, it is present in the toothpaste in an amount ranging from about 10% to about 75%. In toothpastes, the liquid vehicle typically consists of water and a humectant in an amount ranging from about 10% to about 90% by weight of the formulation. The essential ingredients of toothpastes and dental creams include the weight of a non-ionic humectant containing at least one humectant selected from the group consisting of polyethylene glycol and polypropylene glycol to solubilize the water-insoluble climbazole in an aqueous vehicle. It is about 20-40%. Glycerin, sorbitol, or mannitol may replace part of the humectant content as long as the imidazole compound is solubilized in the polyoxyethylene or polyoxypropylene glycol. Natural or synthetic rubber or rubber-like substances, typically the red alga Tochiyaka,
Gelling agents such as sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, gum tragacanth, polyvinylpyrrolidone, starch and hydroxypropylmethylcellulose are commonly present in amounts up to about 1% by weight, preferably from about 0.5% to about 5% by weight. Exist in the range of %. In toothpastes or gels, the liquids and solids are in such proportions as to form a creamy or gel-like mass that is extruded from a pressurized container or from a collapsible, e.g., aluminum or lead tube. The oral compositions of the present invention generally include a non-soap, water-soluble synthetic organic anionic or non-ionic surfactant at a concentration in the range of about 1-5% by weight to improve wetting, cleaning properties. may promote firmness and foaming properties. U.S. Pat. No. 4,041,149 lists suitable anionic surfactants of this type in column 4, lines 31-38, and in column 8, lines 30.
Lines -68 and column 9, lines 1-12 disclose suitable nonionic surfactants of this type, each of these sections being cited herein. The antibacterial agent-containing oral composition of the present invention can be prepared using inorganic fluoride salts such as soluble alkali metal salts, alkaline earth metal salts, and heavy metal salts: for example, sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride. , copper fluorides such as cuprous fluoride, zinc fluoride, tin fluorides such as stannic fluoride or stannous chlorofluoride, barium fluoride, sodium silicofluoride, ammonium silicofluoride, Fluorine donating compounds may optionally be included, including: sodium fluorozirconate, sodium monofluorine phosphate, aluminum mono- and di-fluorine phosphates, and sodium calcium fluoride pyrophosphate. Sodium fluoride and stannous fluoride,
Alkali metal and tin fluorides such as sodium monofluorophosphate and mixtures thereof are preferred. The amount of fluorine-providing compound will depend to some extent on the type of compound, its solubility, and the type of oral formulation, but should be a non-toxic amount. In solid oral formulations such as toothpaste or chewing gum, amounts of such compounds releasing up to about 1% by weight of the formulation are considered satisfactory. Although any suitable minimum amount of this type of compound may be used, it is preferred to use an amount sufficient to release about 0.005% to 1%, preferably about 0.1%, of fluoride ions. Typically, in the case of alkali metal fluorides and stannous fluoride, this component is present in an amount up to about 2% by weight based on the weight of the formulation, preferably in the range of about 0.05% to 1%. do. In the case of sodium monofluorophosphate, this compound may contain up to 7.6% by weight, more typically about 0.76%
may be present in amounts of Various other substances which do not impair the properties of the composition, such as sweetening agents (e.g. saccharin, sucrose, lactose,
maltose, sorbitol, etc.), seasoned oils (e.g. Oranda japonica, japonica japonica, Japanese koji, etc.)
Oils such as sassafras, sage, eucalyptus, marjoram, cinnamon, lemon, orange, etc.), colorants or whitening agents (e.g., titanium dioxide), preservatives (e.g., sodium benzoate), etc. for use in the oral cavity of the present invention. May be incorporated into formulations.
Small amounts of these materials, up to a total of about 5% by weight, preferably from 0.01% to 3%, may be added to the oral composition. The oral compositions of the present invention are easily prepared from readily available ingredients by simple mixing techniques.
However, it is important that the imidazoyl compound is first mixed with the nonionic component prior to addition to the oral vehicle, which typically contains water. For example, a mouth rinse or gargle may be made by first solubilizing the imidazole compound by emulsifying it in a nonionic surfactant before adding it to an aqueous or alcoholic vehicle. Other ingredients such as sweeteners, sweeteners, etc. may be added to the aqueous vehicle either before or after adding the solubilized imidazole to the aqueous vehicle. Toothpaste is made by first mixing the imidazole compound with a humectant, which is non-ionic in which the imidazole is solubilized, then adding a thickener such as carboxymethyl cellulose, then adding polish, water, and other ingredients. It can be made by adding. The order of addition of the various ingredients can be varied as long as the imidazole compound is first solubilized in the nonionic humectant before addition to the water component. In the practice of the invention, 1-imidazoyl-
Oral compositions according to the invention, such as mouthwashes or toothpastes, containing 1-(p-chlorophenoxy)3-3-dimethyl-2-butanone, a gingivitis inhibitor, in an amount effective to promote oral hygiene, The composition is applied regularly to the enamel, preferably from about 1 to about 3 times a day, at a pH of from about 5 to about 7.5. DETAILED DESCRIPTION OF THE INVENTION The following specific examples further illustrate the nature of the invention, but the invention is not limited thereto. All amounts and proportions referred to in the claims and herein are by weight unless otherwise specified. Example 1 Mouth Rinse Liquid Alcohol = 25% Climbazol = 0.3% Flavoring agent (K-91-3863) = 0.22 *Pluronik F108 = 3.0 Glycerin = 25 Sodium Saccharin 0.03% Water 100%. *Block polymer consisting of about 80% by weight polyoxyethylene and about 20% by weight polyoxypropylene obtained from BASF Wyandot, molecular weight of polyoxypropylene group: 3250. Crimbazol is mixed with pluronic until homogeneous and clear before addition to the hydroalcoholic vehicle containing glycerin, flavoring and sodium saccharin. The resulting products are effective in controlling gingivitis and treating periodontitis and provide a simple means of improving oral health when used in a regular application regimen of 1 to 3 times daily to the oral cavity. The unexpectedly good anti-gingivitis activity of this product is shown in Table 1, in which the mouth rinse of Example 1 was used as the test solution. The product also has antibacterial properties against Bacteroides azatucaloriticus and B. gingivalis. Example 2 Dental paste

Table: Climbazole is premixed with polyethylene glycol prior to the addition of carboxymethyl cellulose where a gel is formed. Add thyroid, zeo, sodium lauryl sulfate, flavor, water, benzoate, and saccharin to this gel with stirring. The benzoate and saccharin may be dissolved in water before mixing with the remaining ingredients. Similarly, zeo, flavoring agents and sodium lauryl sulfate may be premixed prior to addition to the gel. This product also has good antibacterial and antigingivitis properties. Other conventional ingredients may be substituted or added as described above. For example, hydrated alumina or water-insoluble metaphosphate or dicalcium phosphate dihydrate and other polishing agents can be combined with alkyl metal aluminosilicate (Zeo) or colloidal silica (Syroid).
may be replaced in whole or in part. Similarly, other nonionic surfactants may be substituted, such as polyoxyethylene hexitane mono-higher fatty acid esters, block polymers of ethylene oxide and propylene oxide (Pluronic). It will be understood that the foregoing detailed description is given for purposes of illustration only and that various changes may be made without departing from the spirit of the invention.

Claims (1)

Claims: 1. About 100% by weight dissolved in an oral vehicle and a nonionic compound containing a hydrophobic group of sufficient length to effect solubilization and about 10 to 80% by weight polyoxyethylene hydrophilic units. Contains 0.1 to 5% by weight of 1-imidazoyl-1-(p-chlorophenoxy)3-3-dimethyl 2-butanone, which is a water-insoluble gingivitis inhibitor, and contains the nonionic compound and the water-insoluble gingivitis inhibitor. The water-insoluble gingivitis inhibitor has a weight ratio of 3:1 to 25:1, and the water-insoluble gingivitis inhibitor is selected against Gram-negative anaerobic microorganisms such as Bacteroides azatucarolitichus, Bacteroides gingivitis, and mixtures thereof. An oral composition that is a mouthwash having a pH of about 5 to 7.5, which is effective for the treatment of cancer. 2. The nonionic compound contains a polyoxypropylene hydrophobic group and a polyoxyethylene hydrophilic group of sufficient length to permit subsequent solubilization in an aqueous vehicle; :
2. The oral composition of claim 1, wherein the weight ratio of hydrophilic groups is about 4:1. 3. The gingivitis inhibitor selected from the group consisting of block polymers of propylene oxide and ethylene oxide, polyoxyethylenehexitane mono-higher fatty acid esters containing 10 to 80 moles of ethylene oxide per mole, and mixtures thereof. Oral composition according to claim 1, having an aqueous-alcoholic vehicle comprising a nonionic surfactant as a nonionic solubilizing agent. 4. A tooth-acceptable abrasive; a liquid vehicle comprising water; and about 0.1-5% by weight of a water-insoluble gingivitis inhibitor, 1-imidazoyl-1-(p-chlorophenoxy)3-3-dimethyl 2- butanone, the water-insoluble gingivitis inhibitor is dissolved in about 20-40% by weight of a non-ionic humectant containing at least one humectant selected from the group consisting of polyoxyethylene glycol and polyoxypropylene glycol. and the weight ratio of the nonionic moisturizer and the water-insoluble gingivitis inhibitor is 3:1 to 3:1.
25:1, and the water-insoluble gingivitis inhibitor is selectively effective against Gram-negative anaerobic microorganisms such as Bacteroides atsatsucaroliticus, Bacteroides gingivitis, and mixtures thereof. An oral composition that has a PH of ~7.5 and is a toothpaste for treating gingivitis and periodontitis. 5. The oral composition according to claim 4, wherein glycerin, sorbitol or mannitol may replace part of the humectant content as long as the anti-gingivitis agent is solubilized.