United States Patent:  6,117,415

Assignee:  AlphaRx Inc. (Richmond Hill, CA)

Filed:  June 17, 1999

Toothpaste incorporating chlorhexidine bigluconate for improved adhesive onto the surface of the teeth. A second embodiment discusses the use of triclosan and in combination with sodium monofluorphosphate for use in the toothpaste.

SUMMARY OF INVENTION

One object of one embodiment of the present invention is to provide a toothpaste composition, comprising:

a physiologically acceptable oil, the oil composed of submicron particles;

a bioadhesive polymer coated on the submicron particles; and

at least one antibacterial compound.

A further object of one embodiment of the present invention is to provide a toothpaste composition, comprising:

a physiologically acceptable oil, the oil composed of submicron particles and present in an amount from between 0.1% and 50% by weight of the composition;

a bioadhesive polymer coated on the submicron particles in an amount from between 0.1% and 1.5%;

at least one antibacterial compound in an amount from between 0.1% and 5% by weight; and

filler material in an amount to 100%.

Since the active antiseptic component is entrapped into finely dispersed oil phase, its concentration in water is lower, thus unpleasant taste is significantly decreased. Moreover, chlorhexidine in submicron emulsion demonstrates less staining because reduced interaction of the oil droplets with tooth dentine and enamel. The bioadhesive coating of the tiny oil particles, charged with chlorhexidine or triclosan leads to significant prolongation of the drug presence on the mucous surfaces of the mouth, providing extended release of the antiseptic and flavor components.

The oil component of the emulsion can be chosen from many physiologically acceptable hydrophobic liquids, such as vegetable oils (soya bean, corn, sunflower, coconut, olive, jojoba, etc.), fish or animal oils, synthetic components--alcanes , squalane, paraffines, mineral oil, mono- and diol esters (propylene glycol caprylate, isopropyl myristate, dioctyl sebacate, lauroglycol) and glycerides (medium chain triglycerides), polymers--polysiloxanes, polyfluoralcanes, etc. The lipid component is preferably selected from long chain triglycerides (LCT, soya bean oil), medium chain triglycerides (MCT), alcanes (squalane) and esters (isopropyl palmitate, propyleneglycol dicaprylate). Concentration of the oil phase can vary from 0.1 to 50%, preferably from 1 to 20%, most preferably from 5 to 10%.

Surfactants, suitable for emulsifications, include most of the compounds, known to those skilled, such as sorbitan derivatives (Tween.TM., Span.TM.), mono-, di- and polyglycerides, sugar derivatives (sucrose mono- and distearates), polyethylene glycol esters and ethers, polyethylene and polypropylene glycol block copolymers (Pluronic, Poloxamer), polyethoxylated oils (Cremophor), vitamins (Tocopherol succinate polyethyleneglycol, TPGS) and alkylphenoles (Triton, Tyloxapol), phosphatidylcholines and analogs (egg and soya lecithin), amphoteric (lauryl sarcosinate, cocoamphodiacetate, Miranol) and many others. All these compounds are generally recognized as safe and widely used in the pharmaceutical and food industries. Surfactants can be used either alone or in a mixture to obtain the desired emulsifying properties.

The surfactants may be selected from polyethoxylated sorbitan esters (Tween.TM.), vitamins (ascorbyl palmitate, TPGS), sugar esters (sucrose stearate), polyethylene-polypropylene glycol copolymers (poloxamer), phosphatidylcholines (lecithin) and amphoterics (lauryl sarcosinate). The concentration range of the surfactant can vary from 0.01 to 10%, preferably from 0.1 to 5% more preferably from 0.2 to 2.0%.

Regarding the bioadhesive polymer used for oil droplet coating, this may be selected from wide variety of natural, synthetic or semi-synthetic products. Some illustrative examples include crosslinked polyacrylic acid (Carbopol.TM.), carboxymethyl cellulose sodium salt (Na-CMC), hydroxypropylmethylcellulose (Methocel.TM.), hyaluronic acid, alginic acid, chitosan, pectin, locust bean gum, xantan gum, acacia gum. The most preferable polymers are Carbopol.TM., hydroxypropylmethylcellulose and xantan gum.

Preferable antibacterial compounds include chlorhexidine and chlorhexidine salts, such as bigluconate or diacetate, triclosan, cetylpyridinium chloride, benzalconium chloride and cetyltrimethylammonium bromide.

Preparation of the submicron emulsion with bioadhesive oil droplets is achieved using a high pressure homogenizer. Different types of such equipment can be used such as Microfluidizer, Gaulin, Avestin, Rainin, etc.

Generally speaking, at a first stage, a lipid phase is prepared by dissolution of the antibacterial component in the oil phase together with surfactant mixture, antioxidant and flavors component. Subsequently, the oil phase undergoes emulsification in a previously prepared water phase comprises diluted water solution of the bioadhesive polymer, using usual propeller or rotor-stator mixer. A coarse emulsion is obtained and treated by the high pressure homogenizer in order to obtain submicron emulsion, followed, if necessary, with pH adjusting.

Particle size in the emulsion depends on oil phase concentration, type and concentration of the surfactant and polymer and treatment intensity. Typically, for 5-10% oil phase, the particle size is between 50 and 200 nm, 10-20% oil phase results in 250-350 nm average diameter (measured by light scattering).

The prepared bioadhesive submicron emulsion including the antibacterial component can be mixed with water-soluble anti-caries compounds (e.g., sodium fluoride).

To prepare a toothpaste based on the bioadhesive emulsion viscosity modifiers, abrasives, sweeteners, humectants, preservatives and other minor components will be added and carefully mixed to obtain the composition with required properties. The paste can be packaged into suitable tubes and can be stored in ambient conditions for long periods of time.

In addition the toothpaste can include an anti-caries agent, selected from fluoride compounds, such as sodium fluoride (for chlorhexidine containing compositions) in concentrations between 0.1 to 0.5%, preferably between 0.20 to 0.23% by weight of the said toothpaste, or sodium monofluorphosphate for triclosan containing compositions, in concentration from between 0.5 to 1.0%, preferably between 0.76 and 0.84% by weight of the said toothpaste.

Viscosity regulating agents can be selected according to prior art from the group of water-soluble polymers (Na-CMC for triclosan formulations, HPMC for chlorhexidine formulations) or colloidal silicon dioxide (fumed silica, Aerosil, Cab-O-Sil).

Precipitated calcium carbonate, silicon dioxide, calcium phosphate, sodium polyphosphate and other compounds can be used as abrasive components.

Peppermint oil, spearmint oil, menthol, clove oil, lemon oil, other essential oils and artificial flavors can be used as flavor agents. Due to the hydrophobic nature of these components most of the flavor substance will be entrapped into the oil particles of submicron emulsion thus providing prolonged presence in the mouth and a feeling of freshness.

Vitamins (vit. A-retinol, vit. E-tocopherol, vit. K-naphtoquinone, vit. C-ascorbyl palmitate) and other biologically active compounds may also be added to the toothpaste.

Claim 1 of 13 Claims

1. A toothpaste composition, comprising:

a physiologically acceptable oil in water emulsion, composed of submicron particles;

a bioadhesive polymer coating on each particle of said submicron particles; and

at least one antibacterial compound of chlorhexidine or chlorhexidine salt.

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