CA1227139A - Oral product for controlling gingivitis - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

An oral composition for treating gingivitis and periodontitis comprising an oral vechicle and an effective amount of the water insoluble antigingivitis agent, imidazoyl-1-(p-chlorophenoxy)3-3-dimethyl 2-butanone solubilized in a nonionic compound containing a mixture of hydrophobic and hydrophilic groups of sufficient length to effect solubilization in an aqueous vehicle, in the weight ratio of 1:1 to 25:1 and preferably 3:1 to 25:1 solubilizer:imidazolyl compound, said agent being selectively effective against the gram negative anaerobic micro-organisms associated with periodontitis.

Description

1227~39 This invention relates to an antibacterial-containing oral composition which promotes oral hygiene, controls plaque formation gingivitis and periodontitis, by the topical application to the oral cavity, of a mouth rinse or dentifrice containing an effective amount of the anti gingivitis agent, 1-imidazoyl-l- ~p-chlorophenoxy)3-3-dimethyl 2-butanone known under a common name as Climbazole by Bayer).
Periodontitis, or pyorrhea, is a disease affecting the supporting tissues of the teeth including the gingiva, the membrane lining the sockets in which the teeth lie, and the bones surrounding the teeth. The disease may initially be associated with conditions of constant irritation of the gingiva by dental plaque, food impaction, poor dental restorations, traumatic occlusion, or chemical irritants.
The gums may be seriously harmed by deposits of dental plaque, a combination of minerals and bacteria found in the mouth. The bacteria associated with plaque can secrete enzymes and endotoxins which can irritate the gums and cause an inflammatory gingivitis. As the gums become increasingly irritated by this process they have a tendency to bleed, lose their toughness and resiliency, and separate from the teeth, leaving periodontal pockets in which debris, secretions, more bacteria and toxins further accumulate. It is also possible for food to accumulate in these pockets, thereby providing noun-ishment for increased growth of bacteria and production of endotoxins and desk tructive enzymes. The pus that forms in this process is capable of destroying gum and bone tissue. Bacteria are generally found to ye present during the active stages of periodontal disease. Such organisms as anaerobic gram Vega-lives are usually present, and are found in the purulent discharge as well as in the involved tissue, and may be absorbed into the general system through the isles lymphatic or venous blood stream.
The progression of the pyrrhic process usually begins with gingivitis, initiating at the margins of the gums, in which the gingiva become more tender and sensitive, and appear flabby, inflamed and swollen. Periodontal pockets become apparent, and infection takes place in these pockets. Effective control and prevention of gingivitis accordingly constitutes a desideratum for the prevention of further periodontal diseases.
A multitude of materials have been previously proposed and employed for controlling oral diseases and malfunctions such as plaque, calculus, tartar, caries, halitosis, and periodontal diseases such as gingivitis and pyorrhea, but none have been entirely satisfactory. For example, oral compositions containing anti-inflammatory agents which reduce the symptoms of swelling, bleeding and inflammation associated with gingivitis, by preventing tartar formation and/or countering oral calculus, include an imidazole such as vista-dine or histamine as disclosed in United States Patent No. 3,497,591; a dichloro-2-quanidino benzimidazole, as disclosed in United States Patent No.
3,523,154; carragheen:in as disclosed in United States Patent No. 4,029,760; a mixture of tranexamic acid and folio acid, as disclosed in United States Patent No. 4,272,512; and tannin acid, as disclosed in United States Patent No.
4,273,758. All of aforesaid agents are non-antimicrobial.
United States Patent No. 3,577,520 also discloses a dentifrice come position containing 5,5-diaryl-2,4-imidazolidinediones in the treatment of pyorrhea, by repairing the lesions of p~rlodontitis.
United States Patent No. 3,911,133 discloses an antibacterial compost-lion effective against both gram positive and gram negative bacteria, comprising an imidazole derivative, which is a bis(imidazolium qua ternary salt), useful in 1227~9 mouthwashes, toothpastes and dental gels as a method of inhibiting the formation of dental plaque or in the prevention of gingivitis.
United States Patent No. 4,243,670 discloses imidazolium derivatives having strong antimicrobial activity against dermatophytes, yeasts, molds buffs fungi and gram positive cocci; and useful as an additive to oral hygiene products such as toothpastes and mouthwashes, to avoid microbial caused infections of the mucus of the mouth and as a prophylactic against infection.
It is also known in the art, that certain gram negative organisms such as Bacteriodes asaccharolyticus or Bacteriodes gingivalis are associated with adult periodontitis. By eliminating these and other gram negative anaerobes from the plaque accumulated on the gingival tissues, effective control and prevention of periodontal disease can be achieved.
Accordingly, it has been shown by Listgarton et at in the J.
Periodont. Rest 14: 65-75 (1979), that metronidazole, given systemically causes the elimination of said gram negative anaerobes from the plaque. This was substantiated by lleijl and Lund in the J. Clinical Period ontology 6, 197-209 (1979~, wherein is shown that metronidazole is effective in reducing plaque and gingivitis scores in dogs; and by Lucia et at in the J. of Clinical Period ontology, 8: 29-44 (1981), wherein it is shown that metronidazole is effective in reducing the anaerobic B. asaccharolyticus ~7~3~

count in plaque removed from periodontal pockets, concomitantly, with a substantial reduction in pocket depth and considerable gain in apparent attachment. However, metronidazole, sold under the trade mark of Flagella, is carcinogenic (Physician Reference Hand-book p.1761) and connote be used indiscriminately.
It has now been found that another derivative of imidazole is effective against said gram negative anaerobic organisms, which is nonmutagenic, non-carcinogenic and can be topically applied to the oral cavity in the treatment of gingivitis, namely, l-imidazoyl-lo l-(p-chlorophenoxy)3-3-dimethyl 2-butanone.
The imidazoyl kittens such as l-imidazoyl-1-(4 sheller-phenoxy)-3,3-dimethyl 2-butanone, are disclosed in United States Patent Nos. 3,812,142 and 3,903,287 as an anti-mycotic agent, use-fur in pharmaceutical compositions including pastes, gels, creams, aqueous and non aqueous suspensions. Its action against pathogenic protozoa, gram positive and negative bacteria such as Staphylococci and Escherichia golf is also noted therein. British Patent No.
1,502,144 and its German counterpart, Patent No. 2,430,039, disclose hair or skin treating compositions, effective against Pityrosporum ovate, containing the imidazoyl kitten antimycotic agents dispersed in a dermatologically acceptable carrier which contains a detergent-active compound. These compositions are in -the form of creams, aerosols, powders and liquids. German Patent No. 2,600,800 discloses the l-imidazoyl-l-(4-chlorophenoxy)-3,3-dimethyl 2-butanone in a fungicidal composition, either in dry form, as a dispersion in water, water-in-oil or oil-in-water emulsion or a ~2~7139 spray, useful for protecting plaster coatings, dispersion dyes, wallpaper, tiled surfaces, paints, glues, boatmen, furniture, leather, shower curtains, textiles, carpets, wood and paper, against a long list of pathogenic fungi, molds and bacteria.
However, there is pa -3~3 no Malaysian of Bacteroids asaccharolyticus or gingivalis, the particular anaerobic gram negative organisms found in gingivitis. German Patent No.

2,700,806 also discloses a mixture of the imidazoyl kitten fungicide and a qua ternary ammonium bactericide useful for protecting materials such as paints, glues, bitumen, cellulose paper, textiles, leather and wood.
Although the prior art discloses the specified imidazoyl kitten as an antimycotic agent, and its use in pharmaceutical formulations, particularly in hair and skin treating compositions, there is no disclosure of its use in dental preparations nor its effectiveness against the specific gram negative anaerobic organisms associated with gingivitis and periodontitis.
It has now been found that the water insoluble imidazoyl kitten, 1-imidazoyl-l-(p-chlorophenoxy)3-3-dimethyl 2-butanone, is selectively effect live against the specific anaerobic gram negative organisms associated with gingivitis, when topically applied to the affected gingiva.
The present invention provides an oral formulation containing the aforesaid water insoluble imidazoyl kitten as the anti gingivitis agent soul-bilized in an oral vehicle.
The formulation may be in the form of a mouth rinse or dentifrice effective in the control and treatment of plague, gingivitis and periodontitis.
Preferably the invention provides an oral composition comprising the aforesaid anti gingivitis agent solubilized in an aqueous vehicle comprising a non ionic compound, the antibacterial-colltaining oral composition being usual in the prevention and treatment of gingivitis in animals.
The oral composition may be used in a method of improving oral hygiene by topically applying to the oral cavity the antibacterial-containing composition comprising aforesaid solubilized imidazoyl kitten.
Objects, advantages and novel features of the invention will be set 1227~39 forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.
According to one aspect of the present invention there is provided an oral composition, which is a mouthwash having a pi of about 5 to 7.5, for treating gingivitis and periodontitis comprising an oral vehicle and an effective amount, which is about 0.1-5% by weight, of the water insoluble anti gingivitis agent, l-imidazoyl-l-(p-chlorophenoxy)3,3-dimethyl 2-butanone, solubilized in a non ionic compound containing a hydrophobic radical and about 10-80% by weight of hydrofoil units of polyoxyethylene of suffix-tent length to effect solubilization, in the weight ratio of 3:1 to 25:1 non ionic; anti gingivitis agent, said agent being selective elm effective against the gram negative anaerobic microorganisms Butterheads assaceharolyticus, Bacteriodes gingivalis and mixtures thereof. Preferably, 0.1-5.0% by weight of said anti gingivitis agent is solubilized in a non ionic compound containing a hydroph-obic radical and about lo to 80~ by weight of hydrophilic units of polyoxyethylene of sufficient length to syllables said imidazoyl compound in an aqueous medium.
More specifically, such aspect of the present invention relates to oral compositions comprising about 0.1 to 5% by weight of said anti gingivitis agent, solubilized in an aqueous oral vehicle ~2Z~39 comprising a non ionic compound containing a hydrophobic radical including a higher fatty acid radical containing 10-20 carbons, polyoxypropylene, hexitan Monroe fatty acid esters, and fatty acid asides; and the hydrophilic group polyoxyethylene of sufficient length to effect solubilization. The oral vehicle may be liquid such as a mouthwash or rinse, solid such as chewing gum, or tooth powder, pasty or creamy such as a toothpaste or dental cream. These oral compositions are nontoxic and have a pi of about 5 to 7.5.
The mouthwash which has a pi of about 5 to 7.5 is an aqueous-alcohol vehicle containing about 1-5% by weight of a non ionic surfactant selected from the group consisting of block polymers of ethylene oxide, mixed polymers of propylene oxide and ethylene oxide, polyoxyethylene hexitan Monroe fatty acid esters containing 10-80 moles ethylene oxide per molt and higher fatty acid moo- and di-ethanolamides and mixtures thereof.
The typical surfactant contains at least 10-80% by weight of hydrophilic units of polyoxyethylene and the hydrophobic radical such as polyoxypropylenewhich preferably has a molecular weight of about 3250, as in the mixed polymers of propylene oxide and ethylene oxide. The ratio of solubilizer to imidazole come pound is about 1:1 to 25:1 and preferably about 3:1 to 25:1. At ratios above 25:1, gelatin occurs.
The toothpaste, which also has a pi of about 5-7.5 comprises a dentally acceptable polishing material, and a liquid vehicle containing water and about 20-40% by weight of a ~27~39 non ionic humectant including at least one humectant selected from the group consisting of polyethylene glycol and polypropylene glycol. Glycerine, sorbitol or minutely maybe substituted for part of the humectant content provided said anti gingivitis agent has been solubilized.
The anti gingivitis agent utilized in present invention is l-imidazolyl-(p-chlorophenoxy) 3,3-dimethyl 2-butanone having the structural formula:

~3-o-CH-CoC (SHEA

N

u - pa -~227~39 which is prepared by reacting l-bromo-l-(4-chlorophenoxy)-3,3-dimethyl-2-butanone with imidazole dissolved in acetonitrile as disclosed in United States Patent Nos. 3,812,142 and 3,903,287. This imidazoyl kitten is a water insoluble crystalline powder having a melting point of 94.5-97.8C which may be obtained from the Bayer Company as Climbazole. Due to the water insolubility of this imidazole compound, it must first be solubilized in a non ionic compound prior to the addition of ionic materials in an aqueous medium.
It has been unexpectedly found that this antibacterial compound added to oral vehicles is not only effective against the specific anaerobic organisms involved in periodontal disease, but also reduces the disease significantly when applied topically, as well as reduces the symptoms of gingivitis ask-fated with periodontitis. Ike minimum inhibitory concentration (MIX) needed to kill Bacteroides assaccharolyticus (Forsythe strain), determined according to the procedure of Walker et at (Antimicrobial and Chemotherapy, Vol. 16, p. 452-457, 1979), is between 7.8 to 31.2 micrograms per ml. The MIX value for B. gingivalis is 25 micrograms per ml. The MIX value for B. grizzles and Fuso-bacterium, other gram negative organisms is greater than 50 for each;
and the MIX value for the gram positive organism Actinomyces viscous is 125 for the aerobic strain and 250 for the anaerobic strain. This is clearly indicative of the selectivity of the antibacterial activity of the specific imidazole compound utilized herein as the anti gingivitis agent.
Evaluation of oral compositions against gingivitis, using a 0.3%
Climbazole-containing mouth rinse, median a study on 30 beagle dogs for 10 weeks, clearly shows it superior effectiveness against gingivitis. The prove-dune used includes tune complete removal of hard and soft dental deposits, after which the dogs are kept on a soft diet for six weeks to permit the development ~227~39 of gingivitis. The denotations are then treated with the test solutions twice a day, 5 days a week, for about 15 seconds on each side of the mouth. The animals are examined and the degree of inflammation of the gingiva is scored according to a scale of 0 to 3. 0 = No inflammation. 1 = Mild, localized edema, and redness of gingival margin, no bleeding is elicited upon gentle finger pressure. 2 = Moderate edema, and redness of gingival margin with bleeding upon gentle finger pressure. 3 = Severe edema and ulceration of gingival margin and attached gingiva, and bleeding without gentle finger pressure. A placebo rinse and 0.5% metronidazole rinse were used as the lo negative and the positive controls respectfully. The data is summarized in Table 1.

Initial Treatment gingival units 6 weeks 10 weeks Ratings: 0 1 2 3 0 1 2 3 0 1 2 3 Placebo 9583 8 - - 569 31 - - 528 72 Rinse 0.5% Matron- 13578 9 - - 572 28 - - 576 24 dazzle Rinse 0.3% Climbazole 11589 - - 579 21 - - 578 22 Compared to the placebo, both Metronidazole and Climbazole rinses significantly reduced the development of the gingival units of 2. However, a smaller amount (0.3%) of Claimbazole exhibits the same effectiveness against gingivitis than greater amo~mts (0.5'~) of Metronidazole.
Louvre, although metronidazole is effective against the specific gram negative micro-organisms involved in periodontal disease when used systemically, as fully discussed prior art, it does not work as well when 12Z7~39 topically applied. The reason for said poor results is due to the absence in its structural formula of an appropriate hydrophobic group which is necessary for penetration into the gingival tissues. On the contrary, Climbazole has a bulky hydrophobic group, (p-chlorophenoxy) 3-3-dimethyl 2-butanone, which provides good penetration into the tissues where the destructive process of periodontitis occurs, enabling this antibacterial to maintain an effective con-cent ration to reduce the bacterial count of the gram negative anaerobic micro-organisms associated with this disease. In addition, metronidazole is, due to its vitro group, mutagenic, whereas Climbazole is not mutagenic in mutagenic tests, because it lacks the vitro group as can be seen by the structural formulae below:
Climbazole Metronidazole SHEA SHEA OH
Of -C-C~H-COC(CH3)3 / N \

_ N NO- I¦ SHEA

The oral composition of this invention may be liquid such as a mouthwash or rinse. In such a preparation the vehicle is typically a water-alcohol mixture. Generally, the ratio of water to alcohol is in the range of from about 1:1 to about 20:1 preferably from 3:1 to 20:1, by weight. The alcohol content preferably constitutes about 20-~0% by weight of the vehicle.
The total amount of water-alcohol mixture in this type of preparation is typically in the range of from about 70 to about 98% by weight of the preparation.
The pi of such liquid and ether preparations of the invention is generally in the range of from about 5 to about 7.5.

7~39 An essential component of the liquid oral preparations is about 1-5% by weight of a non ionic surfactant containing 10-80 by weight of hydrophilic units of polyoxyethylene and also hydra-phobic polyoxypropylene or higher fatty acid, fatty ester or fatty aside, in order to syllables the water insoluble Climbazole in the aqueous-alcohol vehicle.
Suitable non ionic surfactants include block polymers of ethylene oxide, mixed propylene oxide-ethylene oxide polymers, polyoxyethylene hexitan Monroe fatty acid esters having from 10-20 carbon atoms in the higher fatty azalea thereof and 4-100, preferably 10-80 mows of ethylene oxide per mol. Preferably, the hexitan is sorbitan, although Montana and other hexitans are also often useful, the higher fatty azalea will be of 10-16 or 20 carbon atoms, more preferably of 12-16 or 18 carbon atoms and most preferably of about 12 carbon atoms, and the number of ethoxies will be from 15-80, often preferably about 20. Especially useful is an ICKY. product sold under the trade mark Tweet 20, also known as Polysorbate 20 which is polyoxyethylene (20) sorbitan monolaurate.
Similarly useful products are sold under similar identifications, such as Tweets 40, 60, 65 and 80, all of which are non ionic surface active agents wherein the higher fatty azalea is palmitoyl, stroll or oilily and the number of the mows of ethyl tone oxide per mow is about 20. However, of these materials the polyoxyethylene sorbitan monolaurate is usually favored. Polyp oxyethylene (80) sorbitan monolaurate may be used in place of said polysorbate 20.

~27~ 39 Other suitable non ionic surfactants include the moo-and di-ethanolamides of higher fatty acid having about 10-18 carbon atoms in the azalea group such as cocomonoethanolamide, cocodiethan-olamide, Laurie myristic diethanolamide, Laurie monoethanolamide or combinations thereof.

- ha -1227~39 Present oral compositions may be substantially pasty in character such as a toothpaste or dental cream. The vehicle of such pasty oral preparations contains polishing material. Examples of polishing materials are water insole ruble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, calcium carbonate, alumina, hydrated alumina, aluminum silicate, zirconium silicates, silica bentonite, crystalline silica having particle sizes of up to 5 microns, silica gel, complex amorphous alkali metal aluminosilicate, hydrated alumina, dicalcium phosphate, and mixtures thereof.
When visually clear gels are employed, a polishing agent of colloidal silica, such as those sold under the trade mark SWILLED as Swilled 72 and Swilled 74 or under the trade mark SANTOCEL as Santocel 100 and alkali metal alumina-silicate complexes are particularly useful, since they have refractive indices close to the refractive indices of golfing agent-liquid (including water and/or humectant) systems commonly used in dentifrices.
The polishing material is generally present in amounts ranging from about 10 to about 99% by weight of the oral preparation. Preferably, it is present in amounts ranging from about 10 to about 75% in toothpaste.
In a toothpaste, the liquid vehicle comprises water and humectant typically in an amount ranging from about 10 to about 90% by weight of the preparation. An essential component of the toothpaste and dental cream is about 20-40% by weight of a non ionic humectant including at least one humectantselected from the group consisting of polyethylene glycol and polypropylene glycol in order to syllables the water insoluble Climbazole in the aqueous vehicle. Glycerine, sorbitol or minutely may be substituted for part of the humectant content, provided said imidazole compound is solubilized in the polyp 1~:27~ 9 oxyethylene or polyoxypropylene glycol.
A golfing agent, such as natural or synthetic gums or gum-like materials, typically Irish moss, sodium carboxymethyl-cellulose, methyl cellulose, hydroxyethyl cellulose, gum tragacanth, polyvinylpyrrolidone, starch and hydroxypropyl methyl cellulose is usually present in toothpaste in an amount up to about 1% by weight, preferably in the range of from about 0.5 to about S%. In a tooth-paste or gel, the liquids and solids are proportioned to form a creamy or golfed mass which is extrudable from a pressurized container or from a collapsible, e.g., aluminum or lead, tube.
The oral compositions of this invention may contain a non-soap synthetic sufficiently water soluble organic anionic or non ionic surfactant in concentrations generally ranging from about l-S weight percent, to promote wetting, detersive and foaming properties. united States Patent No. 4,041,149 discloses such suitable anionic surfactants in got. 4, lines 31-38, and such suitable non ionic surfactants in got. 8, lines 30-68 and got. 9, lines 1-12.
The antibacterial-containing oral compositions of this invention may optionally contain a fluorine-providing compound including inorganic fluoride salts, such as soluble alkali metal, alkaline earth metal and heavy metal salts, for example, sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, a copper fluoride such as cuprous fluoride, zinc fluoride, a tin fluoride such as stunk fluoride or stuns chlorofluoride, barium fluoride, sodium fluorosilicate, ammonium fluorosilicate, 122~7~L3~

sodium fluorozirconate~ sodium monofluorophosphate, aluminum moo- and di-fluorophosphate, and fluorinated sodium calcium pyrophosphate. Alkali metal and tin fluorides, such as - aye -1~7~39 sodium and stuns fluorides, sodium monofluorophosphate and mixtures thereof, are preferred.
The amount of the fluorine-providing compound is dependent to some extent upon the type of compound, its volubility, and the type of oral prepare-lion, but it must be a nontoxic amount. In solid oral preparation, such as toothpaste or chewing gum, an amount of such compound which releases a maximum of about 1% by weight of the preparation is considered satisfactory. Any suitable minimum amount of such compound may be used, built is preferable to employ sufficient compound to release about 0.005 to 1%, and preferably about 0.1% of fluoride ion. Typically, in the cases of alkali metal fluorides and stuns fluoride, this component is present in an amount up to about 2% by weight, based on the weight of the preparation, and preferably in the range of about 0.05 to 1%. In the case of sodium monofluorophosphate, the compound may be present in an amount up to 7.6% by weight, more typically about 0.76%.
Various other materials may be incorporated in the oral preparations of this invention which do not adversely affect the properties of the composition such as sweetening agents ego., saccharin, sucrose, lactose, maltose, sorbitol, etc.); flavoring oils (e.g., oils of spearmint, peppermint, winter green, sass-fray, clove, sage, eucalyptus, marjoram, cinnamon, lemon, orange, etc.), color-in or whitening agents (e.g., titanium dioxide), preservatives (e.g., sodiumbenzoate) and the like. Minor amounts, up to about 5% in total, and preferably 0.01 to 3% by weight of these materials may be added to the oral composition.
The present oral compositions are readily prepared by simple mixing methods from readily available components. Louvre, it is essential that the imidazoyl compound be first mixed with the non ionic component prior to its addition to the oral vehicle which typically includes water.

1~27139 For instance, a mouth rinse or mouthwash may be prepared by first solubilizing the imidazole compound by emulsifying in a non ionic surfactant prior to addition to the aqueous or alcoholic aqueous vehicle. The other ingredients such as flavor, sweetener, etc. may be added to the aqueous vehicle either prior to or subsequent to the addition of the solubilized imidazole to the aqueous vehicle.
The toothpaste may be prepared by first mixing the imidazole compound with the humectant which is non ionic, wherein it is solubilized, and then add-in the thickener such as carboxymethyl cellulose to form a gel, followed by the addition of polishing agent water and other ingredients. The sequence of the addition of the various ingredients can be varied, provided the imidazole compound is first solubilized in the non ionic humectant prior to addition to the water component.
In the practice of this invention an oral composition according to this invention such as a mouthwash or toothpaste containing l-imidazoyl-l-(p-chlorophenoxy) 3-3-dimethyl 2-butanone anti gingivitis agent in an amount effective to promote oral hygiene, is applied regularly to dental enamel, preferably from about 1 to about 3 times daily at a pi of about 5 to about 7.5.
The following specific examples are further illustrative of the nature of the present invention, but it is understood that the invention is not limited thereto. All amounts and proportions referred to herein and the appended claims are by weight unless outlawries indicated.

Mouth rinse Mouth rinse solution:
Alcohol = 25%
Climbazole = 0.3%
Flavor (K-91-3863) = 0.22 *Pluronic F108 = 3.0 Glycerine = 25 Sodium Saccharin = 0.03%
Water to make 100%
*Trade mark for a block polymer of about 80% by weight of polyoxyethylene and about 20% by weight ofpolyoxypropylene the polyoxypropylene radical having a molecular weight of 3250, obtained from BASS Wyandotte Company.
The Climbazole is mixed with Pluronic until homogeneous and clear, prior to addition to the aqueous-alcoholic vehicle containing glycerin, flavor and sodium saccharin.
The resultant product is effective in controlling gingivitis and treating periodontitis, and provides a simple means of improving oral hygiene, when used on a regular regime of 1 to 3 applications to the oral cavity per day.
The unexpected superior antigingival activity of -this product is shown in Table 1, wherein the mouth rinse of Example 1 was used as the test solution. This product also possesses anti-bacterial properties against Bacteroides assaccharolyticus and B. gingivalis.

1227~39 Dental Paste Ingredients Percent Go H20 31.3 156.5 No - Bonniest 0.5 2.5 No - Saccharin 0.2 1.0 Polyethylene glycol 6001 25.0 125 Climbazole 1.0 5.0 Carboxymethyl cellulose 1.5 7.5 Swilled* - 2442 3.0 15.0 Zoo 35.0 175 Sodium laurel sulfate 1.5 7.5 Flavor 1.0 5.0 HASHISH) OH where n is an integer between 10-14, preferably 12.5 Tao and having a mow weight of 570-630 colloidal silica sodium aluminosilicate (silica with 1% combined alumina) by Huger Co.
* Trade Mark The Climbazole is premixed with the polyethylene glycol prior to the addition of the carboxymethyl cellulose, whereby a gel is formed. To this gel is added, with agitation, the Swilled, Zoo, sodium laurel sulfate, flavor, water, bonniest and saccharin. The bonniest and saccharin may be dissolved in the water prior to mixing with the rest of the ingredients. Similarly, the Zoo, flavor and sodium laurel sulfate may be premixed prior to addition to the gel.
This product also possesses similarly good antimicrobial and anti-gingivitis properties.

~227~

Other conventional components may be substituted or added, as disclosed herein before. For example, hydrated alumina or water insoluble metaphosphate or dicalcium phosphate dehydrate and other polishing agents may be substituted for the alkali metal aluminosilicate (Zoo) or the colloidal silica (Swilled) in total or in part. Similarly, other non ionic surfactants may be substituted for the block polymer of propylene oxide and ethylene oxide (Pluronic) such as the polyoxyethylene hexitan Monroe fatty acid esters.
It is understood that the foregoing detailed description is given merely by way of illustration and that variations may be made therein without departing from the spirit of the invention.
The "Abstract" given above is merely for the convenience of technical searchers and is not to be given any weight with respect to the scope of the invention.

,"~,

Claims (12)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. An oral composition, which is a mouthwash having a pH
of about 5 to 7.5, for treating gingivitis and periodontitis comprising an oral vehicle and an effective amount, which is about 0.1-5% by weight, of the water insoluble antigingivitis agent, 1-imidazoyl-1-(p-chlorophenoxy)3-3-dimethyl 2-butanone, solubilized in a nonionic compound containing a hydrophobic radical and about 10-80% by weight of hydrophilic units of polyoxyethylene of sufficient length to effect solubilization, in the weight ratio of 3:1 to 25:1 nonionic; antigingivitis agent, said agent being selectively effective against the gram negative anaerobic microorganisms Bacteriodes assaccharolyticus, Bacteriodes gingivalis and mixtures thereof.

2. The oral composition according to claim 1, wherein about 0.1-5% by weight of said antigingivitis agent is solubilized in an aqueous oral vehicle comprising a nonionic compound containing about 10-80% hydrophilic units of polyoxyethylene per hydrophobic radical of sufficient length to effect solubilization.

3. An oral composition according to claim 1 or 2, wherein the nonionic compound contains a hydrophobic polyoxypropylene radical and hydrophilic polyoxyethylene radicals of sufficient length to effect subsequent solubilization in an aqueous vehicle, the weight ratio of hydrophilic:hydrophobic radicals in the nonionic compound being about 4:1.

4. The oral composition according to claim 1 or 2 having an aqueous-alcohol vehicle containing a nonionic surfactant, as the nonionic solubilizer for said antigingivitis agent, selected from the group consisting of block polymers of propylene oxide and ethylene oxide, polyoxyethylene hexitan mono-higher fatty acid esters containing 10-80 moles ethylene oxide per mol, and mixtures thereof.

5. An oral composition which is a toothpaste having a pH of about 5 to 7.5, for treating gingivitis and periodontitis contain-ing a dentally acceptable polishing material, a liquid vehicle comprising water and an effective amount, which is about 0.1-5%
by weight, of the water insoluble antigingivitis agent, 1-imidazoyl -1-(p-chlorophenoxy)3,3-dimethyl 2-butanone, solubilized in about 20-40% by weight of the composition of a nonionic humectant including at least one humectant selected from the group consist-ing of polyoxyethylene glycol and polyoxypropylene glycol in the weight ratio of 3:1 to 25:1 nonionic:antigingivitis agent, said agent being selectively effective against the gram negative anaerobic microorganisms Bacteriodes assaccharolyticus, Bacteriodes gingivalis and mixtures thereof.

6. The oral composition according to claim 5, wherein glycerin, sorbitol or mannitol may be substituted for part of the humectant content, provided said antigingivitis agent has been solubilized.

7. A process for preparing an oral composition, which is a mouthwash having a pH of about 5 to 7.5, for treating gingivitis and periodontitis comprising mixing an oral vehicle with an effective amount, which is about 0.1-5% by weight, of the water insoluble antigingivitis agent, 1-imidazoyl-1-(p-chlorophenoxy) 3-3-dimethyl 2-butanone, previously solubilized in a nonionic compound containing a hydrophobic radical and about 10-80% by weight of hydrophilic units of polyoxyethylene of sufficient length to effect solubilization, in the weight ratio of 3:1 to 25:1 nonionic; antigingivitis agent, said agent being selectively effective against the gram negative anaerobic microorganisms Bacteriodes assaccharolyticus, Bacteriodes gingivalis and mixtures thereof.

8. The process according to claim 7,wherein about 0.1-5%
by weight of said antigingivitis agent is solubilized in an aqueous oral vehicle comprising a nonionic compound containing about 10-80%
hydrophilic units of polyoxyethylene per hydrophobic radical of sufficient length to effect solubilization.

9. The process according to claim 7 or 8, wherein the nonionic compound contains a hydrophobic polyoxypropylene radical and hydrophilic polyoxyethylene radicals of sufficient length to effect subsequent solubilization in an aqueous vehicle, the weight ratio of hydrophilic:hydrophobic radicals in the nonionic compound being about 4:1.

10. The process according to claim 7 or 8 wherein said oral composition has, an aqueous-alcohol vehicle containing a nonionic surfactant, as the nonionic solubilizer for said antigingivitis agent, selected from the group consisting of block polymers of propylene oxide and ethylene oxide, polyoxyethylene hexitan mono-higher fatty acid esters containing 10-80 moles ethylene oxide per mol, and mixtures thereof.

11. A process for preparing an oral composition which is a toothpaste having a pH of about 5 to 7.5, for treating gingivitis and periodontitis containing a dentally acceptable polishing material in an aqueous liquid vehicle comprising mixing said vehicle with an effective amount, which is about 0.1-5% by weight, of the water insoluble antigingivitis agent, 1-imidazoyl-1-(p-chlorophenoxy)3,3-dimethyl 2-butanone, previously solubilized in about 20-40% by weight of the composition of a nonionic humectant including at least one humectant selected from the group consist-ing of polyoxyethylene glycol and polyoxypropylene glycol in the weight ratio of 3:1 to 25:1 nonionic:antigingivitis agent, said agent being selectively effective against the gram negative anaerobic microorganisms Bacteriodes assaccharolyticus, Bacter-iodes gingivalis and mixtures thereof.

12. The process according to claim 11, wherein glycerin, sorbitol or mannitol may be substituted for part of the humectant content, provided said antigingivitis agent has been solubilized.