HK1070836B - Solid oral anti-tartar and anti-plaque compositions - Google Patents

Description

Solid oral anticalculus and antiplaque composition

The present invention relates to oral anticalculus and antiplaque compositions useful as adjuncts in dental medical hygiene (odontostological hygene).

Background

The problem of plaque and tartar formation has been long studied and active research is underway for active agents that can be used to combat and retard the formation of the plaque and tartar mentioned above.

The mechanisms leading to tartar deposition are well known; these deposits are made up of calcium phosphate crystals that precipitate in the extracellular matrix of dental plaque. The pathogenic role of tartar in periodontal diseases such as pyorrhea, periodontitis, gingivitis and related diseases is also well known.

A variety of materials have proven effective in reducing or preventing tartar formation and deposition on teeth, including soluble pyrophosphates and polyphosphates, zinc salts, fluorides, diphosphonates, antibacterial agents such as triclosan, and abrasives such as silica or alumina. Most anti-tartar toothpastes currently marketed comprise these substances in various combinations with each other. The clinical efficacy of these toothpastes has been examined in several studies, reviewed in j.clin.dent.iv (3), 71-81, 1993.

Most common toothpastes contain soluble polyphosphates as well as fluoride and silica and may also contain bioadhesive polymers as described in e.g. US 4327977, US 4889713, US5017362, US 5139769, US 4921693 and EP 492997.

Similar compositions with the addition of an antibacterial agent such as triclosan are described, for example, in GB 2200551. In addition to toothpastes, chewing gums and confections having similar compositions have been developed.

The efficacy of these toothpastes has been the subject of several studies (J.Clin.Dent.X. (3), 99-102, 1999; Oral surg.oral Med.oral Pathol., 70 (4), 529, 536, 1990; J.Clin.Dent.IX. (4), 101-104, 1998) due to the inhibition of calcium phosphate precipitation by polyphosphates complexed with calcium ions in saliva, the abrasive action of silica, the strengthening action of enamel by fluoride and the action of bioadhesive polymers which, when used, protect the mucous membranes and cause slow release of other ingredients.

The most commonly used polymers in compositions intended for tartar control are polycarboxylates derived from acrylic or methacrylic acid, in particular copolymers of maleic anhydride and methyl vinyl ether (GANTREX)^). However, these polymers are not approved for use in food products, which means that they can only be used for the preparation of toothpastes and mouthwashes.

On the other hand, candies and chewing gums intended for use as adjuvants in dental and oral hygiene in general, which have properties that can be described as anti-tartar, anti-erosion, whitening and/or cooling, are becoming increasingly popular. Apart from the fact that the release of the active ingredient (functional ingredient) is slower and more regular than in ordinary toothpastes, the main advantage of these application forms is that they can be used freely and conveniently throughout the day, anywhere and anywhere.

Disclosure of Invention

The present invention relates to oral formulations in solid form, preferably in the form of chewing gum, which have superior efficacy to similar known formulations.

The compositions of the present invention contain effective amounts of:

a. polyphosphates, preferably mixtures of alkali metal pyrophosphates and tripolyphosphates;

b. an abrasive (preferably hydrated silica);

c. a fluoride ion source;

d. polymers derived from chitin, or other natural hydrocolloids or mixtures thereof;

e. optionally, an extract or active ingredient of plant origin;

f. optionally, an antibacterial or disinfectant.

In addition to the active ingredients mentioned above, the compositions of the invention also contain excipients suitable for determining the final form of administration.

Thus, for example, chewing gum formulations will require a suitable base consisting of gum base, sweeteners, polyols such as xylitol, sorbitol and mannitol, flavoring agents, dyes, softeners, plasticizers, stabilizers, thickeners and the like.

The fact that the composition of the present invention comprises a system capable of forming a film on the oral mucosa enhances the protection against the deposition of tartar, since the active ingredient is able to contact the teeth and gums of the user for a longer time and the polyphosphate is protected from the hydrolysis of the oral cavity.

In the present invention, the system comprises deacetylated derivatives of chitin, possibly chemically modified, optionally in combination with other polymers, in order to enhance its bioadhesiveness and its ability to protect polyphosphates against hydrolysis agents.

Over the past decade, much scientific attention has been given to controlled release systems for the oral mucosa (j.clin.phar.ther. (2000)25, 21-42). The polymers studied include partially chitosan, highly chitosan or chitosan and hydrolyzed chitosan or oligosaccharides, which have been shown to adhere to tissue due to the positive charge of the ammonium group. Due in part to their bioadhesive properties, these polymers can accelerate wound healing and hemostasis (biom.1999, 20 (22): 2139-45; j.oral.max.surg.57: 49-52). A particular study demonstrated the bioadhesive properties of chitosan on oral mucosa (Biom.16(1995) 617-624; J.control Rel.61: 175-183; int.J.Pharm.73: 43-48).

Among the forms, the preferred form is chitosan oligosaccharide (chitosan oligosaccharide), which is a commercially available compound comprising two to seven monomeric D-glucosamine units bound to each other with β -1, 4 linkages, obtained mainly by enzymatic hydrolysis of chitosan having a higher molecular weight.

Although the method is known, it does not appear to be applied in compositions similar to the one intended for the present invention.

Optionally, naturally occurring polysaccharide hydrocolloids may be used as a substitute with similar bioadhesive properties. Such polysaccharide hydrocolloids are: xanthan gum, locust bean gum, alginates, carrageenan, gellan gum, and the like.

In general, the abovementioned polymer-based systems make up from 0.5 to 5%, preferably from 1 to 3%, by weight of the entire composition.

The polyphosphate used in the composition may be an alkali metal pyrophosphate (diphosphate), hexametaphosphate, tripolyphosphate, or a mixture thereof. Particularly preferred are mixtures of disodium dihydrogen diphosphate (disodiamidinium diphosphate) and sodium or potassium tripolyphosphate. Toothpastes containing this mixture have been shown to reduce tartar more significantly than toothpastes containing pyrophosphate but no tripolyphosphate (j. clin. dent. ix (4), 101-.

In general, polyphosphates will be present in a total amount of 0.5 to 5% by weight of the total composition contemplated by the present invention.

The abrasive agent has the function of enhancing the dental plaque removing effect of common chewing gum. It may be formed from hydrated silica (in suitable form), calcium carbonate (in suitable form) or talc, alone or in combination with each other. These abrasives may also be present in whole or in part, alone or in mixtures thereof, in encapsulated form, in particular encapsulated in calcium alginate. Chewing gum containing hydrated silica particles encapsulated in calcium alginate has been shown to be more effective in removing plaque (doc. os 06.2001779-781) than chewing gum of the same formulation without the particles. According to the present invention, the encapsulated microparticles may contain a dye, a fragrance, a functional ingredient and an herbal extract. The abrasive is typically present in a weight percentage of 0.5 to 7%.

Suitable fluoride ion sources include sodium fluoride, potassium fluoride, ammonium fluoride, sodium monofluorophosphate, and other known non-toxic fluoride-containing salts at concentrations that provide 0.005 to 0.2% fluoride by weight.

The plant extracts that may be present in the composition of the invention will preferably be selected from extracts of: centella asiatica (Centella asiatica), mallow (Malva sylvestris), melaleuca alternifolia (melaleuca alternifolia), myrrh (Commiphora abyssinica), Krameria triandra (Krameriatari), Acacia catechu (Acacia catechu), Medicago sativa (Medicago sativa), resins of the genus Styrax such as Styrax benzoin (Styrax benzone), Matricaria recutita (Matricaria recutita), Echinacea purpurea (Echinacea purpurea), and sanguis Draxonis (Croton leceri). These plant extracts are commercially available and their activity has been known for some time.

The combination of these extracts results in a preparation with anti-inflammatory/decongestant, lubricating, wound healing, antimicrobial preservative and astringent properties. These properties are advantageous in at least two respects within the scope of the invention:

first, aiding and enhancing the reduction of oral mucosal disease caused by tartar reduction, and

second, in humans who are particularly susceptible, contact toxic stomatitis, similar to what occurs with toothpaste, known as "toothpaste stomatitis", is controlled and prevented.

In the formulations of the invention, these extracts may be encapsulated in alginate together with an abrasive.

The extract may be added to the formulation in a weight percentage of 0.01 to 2%.

The formulations of the invention may be prepared by conventional techniques, and in the case of chewing gum the various ingredients are added to the gum base and mixed, and then they may be coated according to likewise conventional techniques.

The formulations of the present invention may contain disinfectants or antibacterials such as triclosan, zinc salts or zinc oxide, alone or in combination with each other, at concentrations of 0.1 to 5% by weight. These agents are intended to combat the formation of plaque which causes the deposition of calculus.

The formulation of the invention may also comprise decorative crystals, preferably consisting of gum arabic and dyes with purely aesthetic effect deposited on the surface of the product.

Daily use of the chewing gum of the present invention can reduce tartar deposition and have other beneficial effects on the oral and gingival mucosal conditions.

The following examples illustrate the invention in more detail.

Example 1

Coated chewing gum weighing 1.4 g.

Percent composition (by weight)
		Ingredient gum base xylitol sorbitol mannitol aromatic agent silicon dioxide acacia glycerodiglyceride disodium dihydrogen phosphate sodium tripolyphosphate chitosan oligosaccharide maltitol syrup titanium dioxide (E171) Quick Coat aspartame decorative crystal acesulfame carnauba wax potassium fluoride	％24.523.523.2161.83111110.930.70.60.60.050.050.050.02100

Example 2

Coated chewing gum containing plant extract and weighing 1.4 g.

Percent composition (by weight)
		An aromatic agent (a) of xylitol sorbitol mannitol*) Silica gum Arabic Glycerol diphosphate disodium tripolyphosphate sodium Chitosan oligosaccharide maltitol syrup titanium dioxide (E171) Quick Coat aspartame acesulfame carnauba wax Potassium fluoride Malva, Myrrha, centella asiatica, Melaleuca leucadendron, Krameria triandra and Catechu extract Total	％24.523.523.2161.83111110.930.70.60.60.050.050.020.05100

Example 3

And (3) efficacy test: reduction of tartar deposition.

A double-blind crossover clinical trial was conducted to compare the efficacy of the chewing gum of example 1 and placebo gum.

28 adults were enrolled in the trial and treated with both gums 4 times a day for 5 minutes each for 6 weeks. At the end of the above period, a quantitative assessment of tartar deposition was made according to the modified Volpe and threshold indicators (j. period. res. (supplement) 14: 31-60, 1974). Throughout the treatment period, patients all used the same toothpaste (without the anti-tartar agent) and consumed similar foods. The same patients were then treated with another chewing gum (example 1 or placebo) for 6 weeks following the same treatment method as before immediately after the first tartar deposition assessment. At the end of the treatment period a second quantitative assessment of tartar deposition was made according to the same method described above.

The results were statistically analyzed using Student's two-tailed paired sample "t" test.

The evaluation of the patient after chewing the gum described in example 1 shows that: tartar deposition was reduced by 13.9% compared to the results observed after chewing the placebo gum. The reduction was statistically significant. The results of the study are summarized in table 1.

TABLE 1

The "T" test: paired samples for mean calculation

	Placebo	Example 1
			Mean variance observations people pearson's correlation hypothesis mean deviation P (T ≦ T) two-tailed	4.241071410.53926928	3.65178577.9599041280.985801106.884-05

Claims (12)

1. An oral formulation in solid form comprising:

a. a polyphosphate salt;

b. an abrasive agent;

c. a fluoride ion source;

d. polymers derived from chitin, or other natural hydrocolloids or mixtures thereof;

e. an extract or active ingredient of plant origin;

f. optionally, the antimicrobial/disinfectant agent(s),

wherein the extract has anti-inflammatory, wound healing, anti-bleeding, soothing, lubricating, decongestant and anti-bacterial preservative properties and is selected from the group consisting of: centella asiatica, mallow, melaleuca alternifolia, myrrh, Krameria triandra, Catechu, Medicago sativa, Styrax resin, Matricaria chamomilla, Echinacea purpurea, and sanguis Draxonis.

2. The formulation of claim 1, wherein the polyphosphate is selected from the group consisting of tripolyphosphates, pyrophosphates, or mixtures thereof.

3. The formulation of claim 2 comprising a mixture of alkali metal pyrophosphate and tripolyphosphate.

4. The formulation of claim 1, further comprising an excipient selected from the group consisting of gum base, sweeteners, polyols, fragrances, dyes, softeners, plasticizers, stabilizers and thickeners.

5. The formulation of claim 1 wherein the abrasive is hydrated silica, calcium carbonate and talc, alone or in combination.

6. The formulation of claim 1, wherein the polymer derived from chitin is a partially or fully deacetylated derivative of chitin, optionally chemically modified, optionally in combination with other polysaccharide hydrocolloids.

7. The formulation of claim 6 wherein the polymer is chitosan.

8. The formulation of claim 7, wherein the chitosan is a chitosan oligosaccharide.

9. The formulation of claim 1 wherein the natural hydrocolloid is xanthan gum, locust bean gum, alginate, carrageenan, gellan gum or other bioadhesive polysaccharide.

10. A formulation according to claim 1, which comprises 0.5 to 5% by weight of polyphosphate, 0.5 to 7% by weight of abrasive, 0.5 to 5% by weight of a polymer derived from chitin, a source of fluoride ions to ensure fluoride uptake of 0.005 to 0.2% and 0.01 to 2% by weight of plant extract, wherein the abrasive may be wholly or partially encapsulated.

11. The formulation of claim 10 comprising a disinfectant and/or antibacterial agent selected from triclosan, zinc oxide and zinc salts, alone or in combination with each other, at a concentration of 0.1% to 5%.

12. The formulation of any one of claims 1-11, wherein the formulation is a chewing gum or a candy.