NO823422L - ALKALIMETAL SALTS OF POLY (VINYL BENZOIC ACID) AS AN AGENT FOR PLAQUE ON TENNES. - Google Patents

Description

The present invention relates to oral hygiene preparations and methods for using such preparations to prevent the attachment of bacteria to teeth. More particularly, the invention relates to certain alkali metal salts of poly(vinylbenzoic acid) which have been found useful in inhibiting the agglutination of oral microbes to teeth.

The prevention of the deposition of dental plaque on teeth is one highly desired result. Dental plaque results when cariogenic bacteria aggregate in colonies on the surface of teeth and form an adherent deposit thereon. The presence of plaque on teeth is believed to be the precursor to the development of gingivitis, dental caries and periodontitis.

While many attempts have been made to regulate the effects of cariogenic bacteria and the dental plaque they produce, e.g. fluoride, flossing, brushing, etc., these are typically intended to either counteract the secondary effects of plaque on the teeth and gums, or remove plaque that has already formed on and adheres to the teeth

and surrounding tissue. However, such treatments are not completely successful and must be supplemented with periodic treatment by personnel within the dental treatment profession. Until now, there is no commercially feasible home treatment method for preventing the formation of plaque or its adhesion to teeth.

Certain alkali metal salts of poly(vinylbenzoic acid) have been found

to inhibit the deposition of dental plaque on teeth in

humans when applied from various dental<p>astas, mouth-rinse solutions, or other oral hygiene methods. These hydrophilic polymers are substantially soluble in water or water/organic solvent carriers and have good

■ film-forming properties. While the mechanism of action of the hydrophilic polymer films in retarding plaque deposition is not known with absolute certainty, it is believed that the films of anionically charged polymers deposited on teeth cause a mutual repulsion between the negatively charged poly-

merfilm and the negatively charged microorganisms responsible for plaque development. The polymeric salts according to the invention are particularly effective as components of dental

pastes or other oral hygiene preparations when it comes to reducing dental plaque deposition on teeth.

The hydrophilic, polymeric salts which have been found useful for controlling dental plaque according to the present invention are essentially alkali metal salts of the homopolymers of vinylbenzoic acid, where the repeating unit in the polymer is represented by the structure (A):

where M is selected from the group consisting of sodium, potassium and lithium.

The poly(vinylbenzoic acid) polymers which are necessary as intermediates for the preparation of the salts of structure (A) can be easily prepared by free radical polymerization of vinylbenzoic acid monomers, such as 4-vinylbenzoic acid. Neutralization of the poly(vinylbenzoic acid) polymers with alkali metal hydroxides or addition of at least stoichiometric amounts of an alkali metal oxide, carbonate, chloride, nitrate, acetate or sulfate is sufficient to produce the polymer salts according to the invention. If desired, the aqueous solutions of the polymeric salts can be purified by dialysis and the dialyzed polymer solution freeze-dried, spray-dried or evaporated to obtain the polymeric salts in solid form.

The alkali metal salts of the present poly(vinylbenzoic acid) polymers are very effective in reducing the deposition of plaque in in vitro experiments. Sodium poly(4-vinylbenzoate) prepared from poly(4-vinylbenzoic acid) showed e.g. a reduction of 91% in the deposition of plaque during trials. The in vitro experimental method used begins with the growth of plaque in small containers containing sterilized trypti-case media which has been supplemented with sucrose. Typically 10 containers are individually inoculated with 0.5 ml of unpooled

freshly collected plaque from 10 people. In a control

series, a pre-distilled preparation glass or an expressed human tooth is introduced into each container. In the test series, the tooth or specimen slide is pretreated with a 1% solution of the test compound (dissolved in water or another carrier), allowed to dry to deposit a thin film of the compound on the surface, and the specimen slide or tooth is placed in the growth medium. The containers are incubated under anaerobic conditions for two days at 37°C. The tooth or slide is removed, air-dried and stained with 0.15% "FD&C#3" dye solution to

show the accumulated plaque deposits. The tooth or preparation glass is assessed for plaque density using a scale from 0 to 5. Plaque barrier activity is reported as % average plaque reduction compared to appropriate controls for 10 subjects.

Example 1

Sodium poly(4- vinyl benzoate)

A suspension of 4.0 g (0.027 mol) of 4-vinylbenzoic acid and 0.04 g of azobisisobutyronitrile in 25 ml of benzene was heated under nitrogen at 80°C for approx. 8 hours, during which time a strong polymer precipitation took place. The suspension was cooled to room temperature, diluted with 25 ml of benzene and filtered to give 4.0 g of poly(4-vinylbenzoic acid).

A solution of 1.6638 g of poly(4-vinylbenzoic acid) in 30 ml of methanol was adjusted from pH 2.5 to pH 11.0 with 23.3 ml of 0.4 80 N methanolic sodium hydroxide. The resulting solution was solvent stripped to white solid of sodium poly(4-vinylbenzoate). NMR and IR spectra were consistent with the structure of the polymeric salt.

Present plaque barrier oral formulations may comprise any conventional pharmaceutically acceptable oral hygiene formulation containing (and compatible with) an effective amount of a plaque barrier agent as defined herein. Such formulations include e.g. mouthwashes, rinses, rinsing solutions, non-abrasive gel toothpastes, denture cleaners, coated dental floss and interdental stimulator coatings, chewing gums, lozenges, breath fresheners, foams and sprays.

The plaque barrier agents may be present in these formulations in effective concentrations usually in the range of about 0.05% by weight to as much as 30% by weight or the limit of compatibility with the carrier. However, no benefit will be obtained from concentrations above approx. 20% by weight. A preferred concentration range for the plaque barrier agents in the formulations according to the invention is from approx. 0.5 to approx. 10% by weight.

A more preferred area is from approx. 2 to approx. 8% by weight, with approx. 5% is currently the most preferred concentration in a non-abrasive gel carrier.

The pH value of these plaque barrier preparations should be between pH 5.0 and 10.0, preferably between pH 5.0 and 8.0, more preferably between about pH 6.0 and 7.5. Lower pH values than 5.0 are undesirable due to the possible increase in enamel demineralization.

Suitable conventional pharmaceutically acceptable carriers which can be used with the plaque barrier agents for the preparation of the barrier preparations according to the invention may include water, ethanol; such humectants as propylene glycol, glycerol and sorbitol; such gelling agents as cellulose derivatives, e.g. "Methocel", carboxymethylcellulose ("CMC 7MF") and "Klucel HF", polyoxypropylene/polyoxyethylene block copolymers, e.g. "Pluronic F-127", "Pluronic F-108", "Pluronic P-103", "Pluronic P-104", "Pluronic P-105" and "Pluronic P-123", colloidal magnesium aluminum silicate complexes such as "Veegum ", and mucoprotein thickeners such as "Carbopol 934"; gel stabilizers such as the silicon dioxides, e.g. "Cab-O-Sil M5" and polyvinylpyrrolidone; sweeteners such as sodium saccharin; preservatives such as citric acid, sodium benzoate, cetylpyridinium chloride, potassium sorbate, methyl and ethyl parabens; detergents such as sodium lauryl sulfate, sodium coco monoglyceride sulfonate, sodium lauryl sarcosinate and polyoxyethylene iso-hexadecyl ether ("Arlasolve 200") and approved colors and flavors. Anti-caries fluoride compounds such as sodium fluoride can also be incorporated into the present preparations.

The following specific examples further illustrate the present plaque barrier compositions.

Example A - Mouthwash solution

Example B - Mouthwash solution

Example C - Abrasive toothpaste gel Example D - Chewing gum Example E - Non-abrasive gel toothpaste

Example F

The following formulation illustrates a currently preferred non-abrasive gel preparation containing a barrier agent according to the present invention.

While the details for the preparation of all of the above-mentioned formulations are well known to those skilled in the art, for the sake of completeness, a proposed method for the preparation of the gel preparation shall be described in this example.

In a first container, the water, sodium saccharin, sodium benzoate and dyes are mixed. The container is then placed in an ice bath. When the temperature reaches 6°C, the gelling agent is added and the contents are mixed slowly until the gelling agent is dissolved. The solution is then heated to 70°C.

Add the glycerin to another container. Then add "Cab-O-Sil M5" by sprinkling while mixing. After this, the plaque barrier agent is added and mixing is continued to a smooth paste. The pasta is then heated in a water

bath while mixing to a temperature of 70°C.

The contents of the first container are added to the second container and mixed until the batch is homogeneous while maintaining the temperature at 70°C. Flavoring is then added, all mixing is stopped, and the composition is allowed to settle for about 1 hour. If it is necessary to remove air bubbles, cooling overnight can be used.

These preparations are preferably used from 1 to 3 times a day in a routine oral hygiene program to prevent plaque from attaching to the teeth.

Claims (5)

1. Oral hygiene preparation, characterized in that it comprises an effective amount for preventing dental plaque to the teeth, of an alkali metal salt of a homopolymer of vinylbenzoic acid having repeating units with the structure: wherein M is selected from the group consisting of lithium, sodium and potassium in a pharmaceutically acceptable oral hygiene carrier which is compatible with said polymer. 2. Method for preventing the attachment of dental plaque to teeth, characterized in that one periodically applies the preparation according to claim 1 to the teeth. 3. Method according to claim 2, characterized in that the preparation is applied from approx. 1 to approx. 3 times per day. 4. Preparation according to claim 1, characterized in that it also includes an anti-caries fluoride compound. 5. Preparation according to claim 4, characterized in that said fluoride compound is sodium fluoride.