FR2535970A1 - ORAL COMPOSITION FOR COMBATING GINGIVITIS CONTAINING CLIMBAZOLE - Google Patents

Abstract

ORAL COMPOSITION FOR THE TREATMENT OF GINGIVITIS AND PERIODONTITIS COMPRISING AN ORAL VEHICLE AND AN EFFECTIVE QUANTITY OF THE WATER-INSOLUBLE ANTI-GINGIVITIS AGENT, IMIDAZOLYL-1- (P-CHLOROPHENOXY) -3,3-DIMETHYL- 2-BUTANONE SOLUBILIZED IN A NON-IONIC COMPOUND CONTAINING A MIXTURE OF HYDROPHOBIC AND HYDROPHILIC GROUPS OF SUFFICIENT LENGTH TO PERFORM SOLUBILIZATION IN AN AQUEOUS VEHICLE, AT A WEIGHT OF 1: 1 TO 25: 1 AND PREFERABLY 3: 1 TO 1: 1 25: 1 OF THE SOLUBILIZER WITH IMIDAZOLYL COMPOUND, SAID AGENT IS SELECTIVELY EFFECTIVE AGAINST GRAM-NEGATIVE ANAEROBIC MICROORGANISMS ASSOCIATED WITH PERIODONTITIS.

Description

The present invention relates to an oral composition containing an agent

  antibacterial promoting oral hygiene, fighting the formation of plaque, gingivitis and periodontitis, by topical application, in the oral cavity, of a solution for rinsing the mouth or a toothpaste

  containing an effective amount of the anti-gingival agent

  fast, i.e. 1-imidazolyl-1- (p-chlorophenoxy) -3,3-dimen-

  thyl-2-butanone (Climbazole from Bayer).

  Periodontitis or pyorrhea is an af-

  fect the supporting tissues of the teeth including the gen-

  cive, the membrane covering the alveoli in which the teeth are housed, and the bones surrounding the teeth The disease can initially be associated with states of constant irritation of the gum by dental plaque, shocks caused by food, bad tooth restorations, traumatic occlusion, or irritating chemicals. The gums can be severely damaged by deposits of dental plaque, a combination of mineral substances and bacteria found in the mouth The bacteria associated with plaque can secrete enzymes and endotoxins which can irritate the gums

  and cause inflammatory gingivitis As the ir-

  Ritual gums increase under the action of this process, they tend to bleed, lose their strength and elasticity, and separate from the teeth, leaving

  periodontal voids in which debris,

  more bacteria and toxins can still

  accumulate It is also possible that food accumulates

  accumulate in these voids, which promotes the development of

  bacteria and the production of endotoxins and enzymes-

  trucors The pus that is formed by this process can destroy the gums and bone tissue Bacteria are found

  usually present during the active stages of mala-

  periodontal die Organisms such as microorganisms

  my anaerobic Gram-negatives are generally present, and are found in purulent secretions as well as in

  the tissues involved 1 and can be absorbed by the system

  general tem via the lymphatic vessels or the blood venous current. The progression of the pyorrheic process usually begins with gingivitis, starting at the edges of the gums, during which the gum becomes softer and tender, and appears flaccid, inflamed and swollen Periodontal voids become apparent, and the infection settles in these gaps Control and prevention

  effective gingivitis is therefore an integrated goal

  used to combat other periodontal diseases.

  We have already proposed and used a multitude of ma-

  to fight disease and malfunction -

  mouth, e.g. plaque, arithmetic,

  tartar, cavities, bad breath and

  periodontics such as gingivitis and pyorrhea 1 but none of them was entirely satisfactory For example,

  oral compositions containing anti-inflammatory agents

  roofs reducing symptoms of swelling 1 bleeding

  and inflammation associated with suppressive gingivitis 1

  Scale formation and / or combating dental calculus 1 include an imidazole such as histadine or histamine, as described in the United States patent

  from America N 3,497,591; a dichloro-2-guanidino-benzimi-

  dazole as described in U.S. Patent No. 3,523,154; carrageenan as described in U.S. Patent No. 4,029,760 and a mixture of tranexamic acid and folic acid, as described in U.S. Patent No. 4,272,512; and tannic acid, as described in the United States patent

No 4 273 758.

  U.S. Patent No. 3,577,520 also describes a dentifrice composition containing, 5-diaryl-2,4-imidazolidinediones in the treatment of

  pyorrhea, healing the lesions of periodontosis.

  U.S. Patent No. 3,911,133 describes an antibacterial composition effective against Gram-positive and Gram-negative bacteria, comprising a

  imidazole derivative, which is a bis (imidazolium qua-

  ternary), useful in mouthwash solutions,

  toothpaste and dental gels as well as a

  yielded inhibiting the formation of dental plaque or preventing

ning gingivitis.

  U.S. Patent No. 4,243,670

  describes imidazolium derivatives having a strong anti-

  microbial against dermatophytes, yeasts, me-

  sissures, biphasic fungi and Gram-posi-

  tifs; and useful as an additive for hygiene products

  mouth such as toothpaste or toothpaste

  these, avoiding microbial mucosal infections

  of the mouth and as a prophylactic agent against infection

tion.

  We also know in practice that some micro-

  Gram-negative organisms such as Bacteriodes asaccharolyti-

  cus or Bacteriodes gingivalis are associated with periodontitis in adults By eliminating these microorganisms as well as other Gram-negative anaerobes from the plaque accumulated on the gum tissue, we can manage to fight

  and effectively prevent periodontitis.

  Therefore, Listgarton et al.

  shown in J Periodonto Res 14, 65:75 (1979) that the metro-

nidazole, CH 2 CH 20 H t 2 N.

  administered systemically causes elimination of-

  so-called Gram-negative anaerobes of plaque This is confirmed

  mé by Heijl and Lindhe in J Clinical Periodontology 6, 197-209 (1979), where it is indicated that metronidazole is effective in reducing plaque and lesions due to gingivitis in dogs; and by Loesche et al in J of Clinical Periodontology, 8; 29-44 (1981), where it is reported that metronidazole is effective in reducing the number of anaerobic B asaccharolyticus in the plaque removed from periodontal while simultaneously greatly reducing the depth of voids and improving

  considerably the apparent fixation However, the metro-

  nidazole, sold under the trademark "Flagyl", is carcinogenic (Physician Reference Handbook, page 1761) and does not

  can be used without discrimination.

  We have now discovered that another derivative

  imidazole is effective in combating said microorganisms

  anaerobic Gram-negative nisms, which is non-mutagenic, non-carcinogenic and which can be applied topically in the oral cavity in the treatment of gingivitis, namely

  1-imidazolyl-1- (p-chloroph 6 noxy) -3,3-dimethyl-2-butanone.

  Imidazolyl ketones such as 1-imidazo-

  lyl-1- (4-chlorophenoxy) -3,3-dimethyl-2-butanone, are de-

  disclosed in U.S. Patent Nos. 3,812,142 and N 3,903,287 as an anti-fungal agent, useful in pharmaceutical compositions comprising pastes,

  gels, creams, aqueous and non-aqueous suspensions.

  Its action against pathogenic protozoa, Grampositive and negative bacteria such as Staphylococci and

  Escherichia coli is also described. The British patent

  that N 1 502 144 and its German equivalent the patent N 2 430 039 describe compositions for treating the hair and the skin, effective against Pityrosporum ovale, containing the antimycotic imidazolyl ketones, dispersed in a dermatologically acceptable carrier which contains

  a compound with detergent action These compositions are presented

  tent in the form of creams, aerosols, powders and liquids.

  German patent N 2,600,800 describes that 1-imidazolyl-

  1- (4-chlorophenoxy) -3,3-dimethyl-2-butanone in a compound

  fungicidal sition, in dry form, or of a dispersion in water, of a water-in-oil or oil-in-water emulsion or of a spray, useful for protecting plaster coatings, dyes in dispersions wallpaper, tile surfaces, paints, glues, bitumens, furniture, leather, shower curtains textiles, carpets, wood and paper, against a large amount of fungi, mold and

  pathogenic bacteria However, it does not mention Bacte-

  roides asaccharolyticus or gingivalis, the particular anaerobic Gram-negative microorganisms found in gingivitis German patent N 2 700 806 also describes a mixture of fungicidal imidazolyl ketone and a bactericide

  of the quaternary ammonium type useful for pro-

  tection such as paints, glues, bitumens, cellulose, paper, textiles, leather and wood Although the prior art describes the particular Uimidas zolyl ketone as an antimycotic agent, and its

  application to pharmaceutical formulations, in particular

  bind in hair or skin treatment compositions, there is no mention of its use in dental preparations or of its effectiveness against

  Specific Gram-negative anaerobic microorganisms associated with

  gesivitis and periodontitis

  We have now discovered that an imidazolyl-ce-

  tone insoluble in water, 1-imidazolyl-l- (p-chloropheno-

  xy) -3,3-dimethyl-2-butanone, was selectively effective

  against specific anaerobic Gram-negative microorganisms

  that associated with gingivitis, when applied topi-

  Consequently, the present invention mainly aims to provide an oral formulation containing the imidazolyl ketone insoluble in the abovementioned water as

  anti-gingivitis agent dissolved in an oral vehicle.

  Another object of the present invention is to provide an effective mouthwash solution or toothpaste to combat and treat plaque, gingivitis

and periodontitis.

  Yet another object of the present invention is to provide an oral composition comprising the above-mentioned anti-gingivitis agent dissolved in an aqueous vehicle

comprising a nonionic compound.

  Another object of the present invention is to

  providing an oral composition containing an antibacterial agent

  Nothing useful for preventing and treating gingivitis in animals. Yet another object of the present invention is to provide a method for improving oral hygiene by topical application, in the oral cavity, of the composition containing the antibacterial agent including the aforementioned solubilized imidazolyl ketone Other purposes, advantages and characteristics

  news of the invention will emerge in part from the

  which will follow and, in part, will be evident to the specialist when considering what follows or what he

  will be able to learn by implementing the invention.

  To achieve the above goals as well as others, and according to the present invention, the latter

  relates to an oral composition intended to combat gin-

  frost including an oral vehicle and an effective amount

  of the water-insoluble anti-gingivitis agent 1-imida-

  zolyl-1- (p-chlorophenoxy) -3,3-dimethyl-2-butanone solubili-

  in a nonionic compound containing about 10 to 80%

  of hydrophilic polyoxyethylene units by hydro- radical

  phobe of sufficient length to dissolve said imidazolyl compound in an aqueous medium, and preferably in

  the 8: 1 ratio of hydrophilic radicals to hy-

  drophobic. More particularly, the present invention relates to oral compositions comprising approximately 0.1 to 5% by weight of said anti-gingivitis agent dissolved in a

  aqueous oral vehicle comprising a nonionic compound

  holding a hydrophobic radical comprising an acid radical

  higher fat having 10 to 20 carbon atoms, the mono-

  polyoxypropylene-hexitol higher fatty acid esters,

  and fatty acid amides; and group polybxyethylene

  hydrophilic weight of sufficient length to effect solubilization The oral vehicle may be liquid, for example a mouth wash or rinse solution; solid, for example chewing gum, or a powder for

  the teeth; pasty or creamy, for example a toothpaste

  frice or dental cream These oral compositions are

  non-toxic and have a p H of about 5 to 7.5 The solution of.

  mouthwash which has a p H of about 5 to 7.5 is an aqueous alcoholic vehicle containing about 1 to 5% in

  weight of a nonionic surfactant chosen from the group comprising

  taking block polymers of ethylene oxide, poly-

  mixed mothers of propylene oxide and ethylene oxide,

  polyoxyethylene-hexi- higher fatty acid monoesters

  tol containing 10 to 80 moles of ethylene oxide per mole and the mono and diethanolamides of higher fatty acids and

their mixtures.

  Typical surfactant contains at least 10 to 80%

  of hydrophilic polyoxyethylene units by hydro- radical

  phobe, for example polyoxypropylene The preferred ratio of hydrophilic groups to hydrophobic groups is 8: 1 with a molecular weight of about 3250, as in

  mixed polymers of propylene oxide and ethylene oxide.

  The ratio of the solubilizer to the imidazole compound is about

  about 1: 1 to 25: 1, and preferably about 3: 1 to 25: 1 o

  At ratios greater than 25: 1, gelling occurs

253597? O

cation.

  The toothpaste, which also has a p H of en-

  about 5-7.5, includes a dental acceptable abrasive material and a liquid vehicle containing water and about 20 to 40% by weight of a nonionic impregnating agent comprising at least one agent impregnation agent selected from the group comprising polyethylene glycol and polypropylene glycol Glycerin, sorbitol or mannitol can replace part of the content of impregnating agent provided that this anti-gingivitis agent has been dissolved. The anti-gingivitis agent used in this

  invention is 1-imidazolyl- (p-chlorophenoxy) -3,3-dimethyl-

  2-butanone having the structural formula: Ci Z N, O 1 H-coc c H 3)

X

  which is prepared by reaction of 1-bromo-1- (4-chlorophen-

  noxy) -3,3-dimethyl-2-butanone with imidazole dissolved in acetonitrile, as described in United States patents N 3812 142 and N 3 903 287, which are cited as for reference in this specification This imidazolyl ketone is a water-insoluble crystalline powder with a melting point of 94.5-97.8 C, available from Bayer Company under the designation Climbazole Due to the insolubility in water of this imidazole compound,

  it must first be dissolved in a non-ionic compound

  before adding the ionic materials to an aqueous medium.

  It has surprisingly been discovered that this

  Antibacterial landing added to oral vehicles is not only

  highly effective against anaerobic microorganisms specifically

  involved in periodontitis, but also significantly reduces the disease when applied topically, and also reduces the symptoms.

  mes of the gingivitis associated with the periodontiteo The concentra-

  minimum inhibitory action (MIC) necessary to destroy Bacteroides assaccharolyticus (Forsyth strain), determined according to the method of Walker and collo (antimicrobial and Chemotherapy, Volo 16, p 452-4572 1979) is between 7.8 and 31.2 micrograms per mlo The ICD value for Bo gingivalis is 25 micrograms per mlo The ICD value for Bo gracilis and Fusobacterium, other Gram-negative microorganisms, is greater than 50 for each case; and the ICD value for the Gram-positive microorganism Actinomyces viscosus is 125 for the aerobic strain and 250 for the anaerobic strain. This clearly shows the selectivity of l. antibacterial activity of the specific compound Bimidazole used here as an anti-gingiviteo agent The evaluation of the oral compositions for the

  control gingivitis using a rinse solution

  mouth rash containing O 03% Climbazole, obtained by a study carried out on 30 bigle dogs for 10 weeks,

  clearly shows its superior effectiveness against gingi-

  fast The process used includes the complete removal of hard and soft dental deposits, after which dogs are

  maintained on a sugary diet for six weeks to

  put the development of gingivitis The teeth are in-

  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 gum inflammation is assessed on a scale

  from O to 3 o O = no inflammation 1 = slight local edema

  edging and redness of the edges of the gums; no bleeding is caused by light finger pressure O 2 = edema

253597 O

  moderate, and redness of the edges of the gum with bleeding during slight finger pressure o 3 = severe edema and ulceration of the edges of the gum and the neighboring gum

  and bleeding without finger pressure o Rinse solution

  placebo shaking and 0.5% metronidazole solution are

  used as negative and positive controls respectively.

  The results are summarized in Table 1 o

TABLE 1

  Gingival units 6 weeks O 10 weeks Initial treatment Score: 0 1 2 3 O 1 2 3 O 1 2 3 plicebo rinse solution 9 rinse solution at 0.5% metronidazole 13 0.3% of

583 8 569 31

578 9

572 28

_ 528 72 -

576 24

  1 limbazole 11,589,579 21,578 22 Compared to placebo O rinsing solutions with metronidazole and Climbazole markedly reduce the development of the gingival units by 2 o However, a smaller quantity (0.3%) of climbazole deploys the same efficacy against gingivitis than higher amounts

(0.5%) of metronidazole.

  However, although metronidazole is effective

  cace against specific Gram-negative microorganisms involved in periodontal disease when it is

  used systematically, as described more fully-

  in the prior art, it does not behave as well

  when applied topically o The reason for these

  mediocre conditions is due to the lack in its structural formula

  an appropriate hydrophobic group which is necessary for the pe-

  ingress into the gingival tissue On the other hand, the climba-

s la

  zole has a large hydrophobic group, (p-chloro-

  phenoxy) -3,3-dimethyl-2-butanone, which provides good penetration

  tissue tration when the destructive process of

  periodontitis appears, which allows this antibac agent

  térien to maintain an effective concentration to reduce

  the number of bacteria in Gram- anaerobic microorganisms

  negatives associated with this disease In addition, metronida-

  zole is, due to its nitro group, mutagenic, while climbazole is not mutagenic in mutagenic tests, because it does not have a nitro group as can be seen from the formulas developed below Climbazole Metronidazole Ct 3-Oc uO Cc (CH 3) 3

/ 3 C H 2 CH * OH

X___NO C I 3

  The oral composition of the present invention may be liquid, for example in the form of a solution of

  mouth wash or rinse In such a preparation

  tion, the vehicle is typically a water-alcohol mixture In general, the ratio of water to alcohol is in the range of about 1: 1 to about 20: 1, preferably from -3: 1 to: 1 by weight The alcohol content preferably constitutes about 20 to 40% by weight of the vehicle The total amount

  of the water-alcohol mixture in this type of preparation is typical

  only between about 70 and about 98% by weight

  of the preparation The p H of this liquid and other preparations

  tions of the invention is generally between about and about 7.5. An essential component of liquid oral preparations is about 1-5% by weight of a non-surfactant

  ionic containing 10 to 80% of hydrophilic poly units

  oxyethylene by hydrophobic polyoxypropylene radical or higher fatty acid, fatty ester or fatty amide The preferred ratio of hydrophilic groups to hydrophobic groups is 8: 1, in order to dissolve the water-insoluble climbazole in

the water-alcohol vehicle.

  Suitable nonionic surfactants include

  block polymers of ethylene oxide, poly-

  mixed mothers propylene oxide-ethylene oxide, esters

  polyoxyethylene hexitol fatty acids having 10 to 20 ato-

  carbon mes in their higher fatty acyl group and 4 to

  , preferably 10 to 80 moles of ethylene oxide per mole.

  Preferably, hexitol is sorbitan, although man-

  nitane and other hexitols are also often useful, the higher fatty acyl has from 10 to 16 or 20 carbon atoms,

  better still 12 to 16 or 18 carbon atoms, and preferably

  about 12 carbon atoms, and the number of groups

  ethoxy is 15 to 80, often preferably about 20.

  A particularly useful product is a product of IC I. sold under the trademark "Tween 20", also known by the designation polysorbate 20 which is polyoxyethylene (20) sorbitanneo monolaurate. Also useful products are sold under similar identifications, for example the Tween 40,

  60, 65 and 80 which are all non-io- surfactants

  niques in which the higher fatty acyl group is the palmitoyl, stearoyl or oleoyl group, and the number of

  moles of ethylene oxide per mole is about 20 Cepen-

  Among these subjects, we generally give the preferred

  of polyoxyethylene (80) sorbitan monolaurate

place of polysorbate 20.

  Other suitable nonionic surfactants include

  take the higher fatty acid mono and diethanolamides having 10 to 18 carbon atoms in the acyl group, for example coprahmonoethanolamide, copra-diethanolamide, lauric dieteticamide, monoethanolamide

  lauric, or combinations thereof.

  The oral compositions of the present invention may be of a substantially pasty nature, for example a paste or toothpaste or a dental cream. The vehicle for these

  pasty oral preparations contains a polishing material

  wise Examples of abrasive materials are the metaphos-

  sodium phate, potassium metaphosphate, tricalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, carbonate

  calcium, alumina, hydrated alumina, aluminum silicate

  nium, zirconium silicates, silica-bentonite,

  water-insoluble crystalline silica having a dimension

  particulate sion up to 5 microns, silica gel of complex amorphous alkali metal aluminosilicates, hydrated alumina, dicalcium phosphate, and

their mixtures.

  When using clear looking gels,

  a colloidal silica abrasive agent, for example those sold

  due under the trade mark 'SYLOID "such as" Syloid 72 "and" Syloid 74 "' or under the trade mark" SANTOCEL ", such as" Santocel 100 "and alkali metal valuminosilicate complexes are particularly useful because they have refractive indices close to those of agent systems

  liquid-gelling agent (comprising water and / or an impregnating agent

  gnation) commonly used in toothpaste.

  The abrasive material is generally present in proportions of between approximately 10 and approximately 99% by weight of the oral preparation. Preferably, it is present in proportions of between approximately 10 and approximately

*% in toothpaste.

  In a toothpaste, the liquid vehicle comprises water and an impregnating agent, for example in a proportion of between approximately 10 and approximately 90% by weight of the preparation An essential component of the toothpaste and dental cream consists of 40% by weight of a nonionic impregnating agent comprising at least one impregnating agent chosen from the

  group comprising polyethylene glycol and polypropylene

  lene-glycol in order to dissolve the insoluble climbazole in the aqueous vehicle Glycerin, sorbitol and mannitol can replace part of the content of impregnating agent, provided that said imidazole compound is

  solubilized in polyoxyethylene or polyoxypropylene-

  glycol, which contains at least 10 to 80% and preferably 10% of polyoxyethylene or polyoxypropylene groups

  A gelling agent, such as natural gums

  or synthetic or materials analogous to a gum O, for example Irish moss, sodium carboxymethylcellulose, methyl cellulose, hydroxyethyl cellulose,

  tragacanth, polyvinylpyrrolidone, starch and l Vhy-

  droxypropyl-methylcellulose is generally present in

  toothpaste in a proportion of up to

  about 1% by weight, preferably between about 0.5 and about 5% In a toothpaste or gel, the

  liquids and solids are proportioned so as to form

  sea a creamy or gelled mass which can be extruded from a pressure vessel or a collapsible tube, for example aluminum or lead The oral compositions of the present invention can contain an anionic or nonionic organic surfactant without soap , synthetic, sufficiently water-soluble at concentrations generally between about 1 and 5 percent by weight, in order to promote wetting,

  detergent and foaming properties

  United States of America No. 4,041,149 describes such anionic surfactants

  suitable for column 4, lines 31-38 and such nonionic surfactants suitable for column 8, lines

  -68 and column 9, lines 1-12, these passages being incorporated

res here for reference.

  Oral compositions containing an anti-agent

  bacteria of the present invention may optionally contain a fluorine-providing compound comprising mineral fluorides, such as soluble salts of alkali metals, alkaline earth metals and heavy metals, for example sodium fluoride, potassium fluoride, fluoride ammonium, calcium fluoride, copper fluoride such as cuprous fluoride, zinc fluoride, tin fluoride such as stannic fluoride or

  stannous chlorofluoride, barium fluoride, fluoro-

  sodium silicate, ammonium fluorosilicate, fluoro-

  sodium zirconate, sodium monofluorophosphate, aluminum mono and difluorophosphates, and fluorinated sodium and calcium pyrophosphate The fluorides of alkali metals and tin such as sodium fluorides are preferred

  and stannous, sodium monofluorophosphate and their

swaddling clothes.

  The amount of fluorine-providing compound

  depends to some extent on the type of compound, its

  lubricity, and of the type of oral preparation, but it must be a non-toxic amount. In a solid oral preparation, for example a toothpaste or a chewing gum, an amount of such a compound is considered satisfactory.

  which releases a maximum of about 1% by weight of the preparation

  Any suitable minimum amount of such a compound can be used, but it is preferable to use an amount of compound sufficient to release about 0.005

  at 1%, and preferably about 0.1% of fluoride ion Habi-

  in the case of alkali metal fluorides and

  of stannous fluoride, this component can reach a proportion

  about 2% by weight, based on the weight of the pre-

  paration, and preferably between about 0.05 and 1% In the case of sodium monofluorophosphate, the compound can

  reach a proportion of 7.6% by weight, more usual-

about 0.76%.

16 -

  Various other materials can be incorporated.

  in the oral preparations of the present invention

  as long as they do not adversely affect the owners

  of the composition, for example sweeteners (for example saccharin, sucrose, lactose, maltose, sorbitol, etc.); flavoring essences (for example

  essences of spearmint, peppermint, winter-

  green, sassafras, cloves, sage, euca-

  lyptus, marjoram, cinnamon, lemon, orange, etc.), coloring or bleaching agents (eg titanium dioxide), preservatives (eg sodium benzoate), etc. Minor amounts of these materials, up to about a total of 5%, and preferably 0.01 to 3% by weight, can be added to

oral composition.

  The oral compositions of the present invention are easily prepared by simple mixing methods from readily available components. However, it is essential that the imidazolylated compound is first mixed with the nonionic component before being added.

  to the oral vehicle which includes for example water.

  For example, a solution of

  rinsing or washing the mouth by dissolving everything

  edge the imidazole compound by emulsification in an over-

  nonionic factive before addition to the aqueous vehicle or aqueous alcoholic The other ingredients such as the perfume, the sweetener, etc, can be added to the aqueous vehicle either before or after the addition of the dissolved imidazole

to the aqueous vehicle.

  The toothpaste can be prepared as a mixture

  firstly managing the imidazole compound with the im-

  pregnation which is non-ionic, in which it is solubili-

  then add the thickener such as carboxymethyl-

  cellulose to form a gel, then the polishing agent, water and other ingredients The sequence of addition of

  various ingredients may vary, provided that the compound of Vimi-

  dazole is first dissolved in the impregnating agent

  nonionic tion before addition to the aqueous component.

  In the practice of the present invention, an oral composition according to the present invention as

  than a mouthwash solution or a toothpaste

  frice containing 1-imidazolyl-1- (p-chlorophenoxy) -3.3-

  dimethyl-2-butanone as an anti-gingivitis agent in a quan-

  effective in promoting oral hygiene, is applied

  regularly forking with dental enamel preferably about 1 to about 3 times a day at a p H of about 5 to about 7.5. The following examples illustrate the invention without limiting it. All the quantities and proportions referred to here are expressed by weight unless otherwise specified.

EXAMPLE 1 Rinsing of the mouth.

  Mouth rinse solution Alcohol = 25% Climbazole = 083% Flavoring (K-91-3863) = 0.22 * Pluronic F 108 = 3.0 Glycerine = 25 Sodium salt of saccharin = 0.03% Water, complement to = 100% * Block polymer of polyoxyethylene and polyoxypropylene

  at a ratio of 8 g 1 with a molecular weight of 3250 g commercial

  cialized by BASF Wyandotte Company The climbazole is mixed with "Pluronic" 'until a homogeneous and clear mixture is obtained before

  addition to the aqueous-alcoholic vehicle containing glyc

  rine, the flavoring agent and the sodium salt of saccharin.

  The resulting product is effective in fighting gingivitis and treating periodontitis and provides a simple means of improving oral hygiene, when used in a regular treatment of 1 to 3 applications per day at the

oral cavity.

  The unexpected superior anti-gingival activity of this product is shown in Table 1, in which the mouthwash solution of Example 1 is used as a test solution. This product also exhibits

  antibacterial properties against Bacteroides Assaccha-

rolyticus and B gingivalis.

EXAMPLE 2: Dental paste.

Ingredients Per hundred Grams

H 20 31.3 156.5

  Na benzoate 0.5 2.5 Na salt of saccharin 0.2 1.0 Polyethylene glycol 600 (1) 25.0 125.0 Climbazole 1.0 5.0 Carboxymethylcellulose 1.5 7.5 Syloid-244 ( 2) 3.0 15.0 Zeo-49 (3) 35.0 175.0 Sodium lauryl sulfate 1.5 7.5 Flavoring 1.0 5.0 (l) H (OCH 2 CH 2) n OH o N is an integer between 10

  and 14, preferably between 12.5 and 14 and having a molecular weight

from 570 to 630.

(2) Colloidal silica.

  (3) Sodium aluminosilicate (silica with 1% alumina

  binée) from Huber Co. The climbazole is mixed beforehand with

  polyethylene glycol before addition to carboxymethyl-

  cellulose so as to form a gelo To this gel is added, with stirring, the "Syloid", the "'Zeo", the lauryl sulfate

  sodium, flavoring, water, benzoate and saccharin.

  We can dissolve the benzoate and saccharin in water before mixing with the rest of the ingredients.

  "Zeo", the flavoring agent and sodium lauryl sulfate

  may be premixed before adding to the gel.

  This product also has properties

  antimicrobials and antigingivitis also good.

  Other conventional components can be substituted or added, as described above For example, hydrated alumina or water-insoluble metaphosphate or dicalcium phosphate dihydrate and the like

  polishing agents can be substituted for aluminum-

  alkali metal silicate ("Zeo") or colloidal silica

  ("Syloid") in whole or in part Similarly, other sur-

  nonionic elements can be substituted for the block polymer of ethylene oxide ("Pluronic") for example

  polyoxyethylene-hexi- higher fatty acid monoesters

tanned.

Claims (4)

  1 Oral composition for the treatment of gingivitis and periodontitis, characterized in that it   includes an oral vehicle and an effective amount of the a-   gent water-insoluble anti-gingivitis, 1-imidazolyl- 1- (pchlorophenoxy) -3,3-dimethyl-2-butanone, dissolved in a nonionic compound at a weight ratio of 3: 1 to   : 1 between the nonionic compound and the anti-gingivitis agent.   2 oral composition according to claim 1, characterized in that approximately 0.1 to 5% by weight of said anti-gingivitis agent are dissolved in an aqueous oral vehicle comprising a nonionic compound containing approximately 10 to% hydrophilic polyoxyethylene units by radical   hydrophobic of sufficient length to perform a solubi- reading.   3 oral composition according to claim 1, characterized in that the water-insoluble anti-gingivitis agent is dissolved in a nonionic compound containing a mixture of hydrophilic and hydrophobic radicals of sufficient length to effect dissolution in a vehicle   aqueous, the weight ratio of hydrophilic radicals: hydro-   phobes in the nonionic compound being about 8: 1.   4 Oral composition according to claim 3, characterized in that it is a washing solution for the   mouth having a p H of about 5 to 7.5 and an aqueous vehicle   alcoholic containing approximately 1 to 5% by weight of a nonionic surfactant chosen from the group comprising block polymers of ethylene oxide, mixed polymers of propylene oxide and ethylene oxide, monoesters of polyoxyethylenehexitol higher fatty acids containing 10 to   moles of ethylene oxide per mole, and the mono and dietha-   higher fatty acid nolamides and mixtures thereof.   Oral composition according to claim 1, characterized in that it is a toothpaste having   a p H of about 5-7.5 containing an acceptable abrasive material   table for the teeth, and a liquid vehicle comprising   water and about 20 to 40% by weight of an impregnating agent   nonionic tion comprising at least one impregnating agent chosen from the group comprising polyethylene glycol and polypropylene glycol. 6 Oral composition according to claim 5,   characterized in that glycerin, sorbitol or manni-   tol may be substituted for part of the improver   generation, provided that said anti-gingivitis agent has been resolved stabilized.