Novel composition for treating xerostomia

The present invention comprises a mucosal adhesive for oral use such as toothpaste, spray, mouthwash, gel, oral tablets (lozenge), chewing gum, tablets, troches, instant powders, oral strips, oral patches, etc. With respect to objects and the use of such compositions as oral lubricants and to relieve the discomfort associated with xerostomia.

Xerostomia or dry mouth is a condition in which excessive dryness occurs in the oral cavity. Xerostomia is not a disease in itself, but it is a symptom found in various medical conditions, such as the side effects of radiation therapy on the head and neck, or the side effects of various drugs. Xerostomia is a common symptom in the elderly, but it does not appear to be age-related.

Xerostomia is often the cause of both minor and serious health problems and can affect not only mental health but also nutrition and oral hygiene. Common problems with xerostomia include persistent sore throat, burning sensation, difficulty speaking and swallowing, hoarseness, and / or dry nose. If left untreated, xerostomia lowers the oral pH and significantly increases the incidence of plaque and tooth decay. Oral candidiasis is one of the most common oral infections associated with xerostomia.

Considering the above, it is beneficial to supply a composition for use in the oral cavity as a lubricant for improving the discomfort associated with xerostomia.

U.S. Pat. No. 5,496,558 addresses this issue by providing solid xerostomia products in the form of oral tablets, tablets, chewing gum, and lozenges consisting of lubricating polymers, polyethylene glycol, organic acids and sorbitol. The purpose is to solve it. U.S. Pat. No. 5,612,207 aims to solve this problem by providing oral tablets consisting of a hard candy base, palliatives, wetting agents and organic acidulants.<patcit num="1"><text>U.S. Pat. No. 5,496,558</text></patcit><patcit num="2"><text>U.S. Pat. No. 5,612,207</text></patcit>

<p> However, there is still a need for other formulations that can smooth and moisturize the mouth and have a good mouth feel.</p>

<p> It has been found that the symptoms of dry mouth can be reduced by using an oral care composition comprising a combination of polyvinylpyrrolidone (PVP) or a derivative thereof and an anionic mucosal adhesive polymer.</p><p> The mucosal adhesive polymer of the present invention has an affinity for the biological surface, particularly the oral mucosa. The mucosal adhesive substance used in the present invention may be a natural product or a synthetic product.</p><p> Accordingly, the present invention provides a composition comprising PVP or a derivative thereof, an anionic mucosal adhesive polymer, and an orally acceptable carrier or excipient.</p>

<p> The composition according to the present invention is excellent in coating and smoothing the mouth, and has the property of giving a good feel to the mouth. Compositions containing anionic mucosal adhesive polymers can form good coatings, but can also cause the unpleasant sensation of being too sticky when used. This unpleasant sensation was surprisingly overcome by adding PVP or its derivatives to the anionic mucosal adhesive polymer.</p>

Suitable PVP derivatives include vinylpyrrolidone / vinylacetate (VP / VA) copolymers or vinylpyrrolidone / vinyl alcohol (VP / VOH) copolymers. The composition of the present invention preferably comprises a PVP or VP / VA copolymer.

The composition of the present invention can appropriately contain 0.1 to 20% by weight, preferably 0.5 to 10% by weight, and more preferably 0.6 to 8% by weight of PVP or a derivative thereof.

The anionic mucosal adhesive polymer useful in the present invention may be cellulose gum, saccharide gum, polyacrylic acid polymer, or a mixture thereof.

Suitable cellulose gums include carboxymethyl cellulose (CMC) gums, such as sodium carboxymethyl cellulose.

Suitable saccharide gums used in the present invention include xanthan gum, guar gum, gum arabic, tragacanth, gum karaya, locust bean gum and pectin, or mixtures thereof. Xanthan gum is preferred.

Suitable polyacrylic acid polymers are Carbomer, Acrylate / C, available from Noveon Inc, 9911 Brecksville Road, Cleveland, Ohio 44141-3247._10-30Examples thereof include alkyl acrylate crosspolymers and polycarbophils. Preferred polyacrylic acids are carbomer or acrylate / C_10-30It is an alkyl acrylate cross polymer.

Suitable compositions of the present invention can include a combination of sodium carboxymethyl cellulose and xanthan gum.

Suitable compositions of the invention may comprise 0.02-20% by weight, preferably 0.1-10% by weight, even more preferably 0.15-4% by weight, most preferably 0.2-2% by weight of anionic mucosal adhesive polymers. it can.

Suitable compositions of the present invention may have a weight ratio of PVP or derivative thereof to an anionic mucosal adhesive polymer of 5: 1 to 1: 1, preferably 4: 1 to 2: 1.

The composition of the present invention may further contain up to 8% by weight, for example 1-5% by weight, a silicone-based oil such as dimethicone or simethicone. The hydrophobicity of silicone-based oils enhances the lubricity of the composition in the oral cavity.

The oral compositions of the present invention typically include toothpastes, sprays, mouthwashes, gels, oral tablets (including central filled lozenges), chewing gums, tablets, lozenges, instant powders, etc. It is prescribed in the form of oral strips, oral patches, etc. Preferred compositions of the present invention are mouth spray, mouth wash and oral gel.

Known oral strips or oral patches are adaptable to deliver the polymer combinations of the invention into the oral cavity. For example, the multilayered erodible films disclosed in WO 03/015748 and US 04/0062724 are the adhesive first layer and / or the erosive first layer disclosed therein. Both the PVP of the present invention or a derivative thereof and the anionic mucosa-adhesive polymer can be incorporated into the two layers. If desired, the silicone-based oil can be incorporated or used to cover or incorporate the disclosed erosive layers, either alone or with other hydrophobic polymers.

Suitable oral acceptable carriers and excipients include abrasive polishes (especially for dentifrices), fragrances, moisturizers, binders, sweeteners, surfactants, preservatives, buffers, colorants and water. Can be mentioned.

Suitable moisturizers used in the compositions of the present invention include glycerin, sorbitol, xylitol, propylene glycol or polyethylene glycol, or mixtures thereof, which may be present in the range of 5% to 70%. it can.

Suitable flavors used in the present invention include peppermint, spearmint and fruit flavors. Fragrances have the added benefit of stimulating salivation, which helps alleviate dry mouth symptoms. If desired, edible organic acids such as citric acid can be included as additional salivary gland stimulants.

Suitable preservatives used in the present invention include parabens (methyl and propylparabens), sodium benzoate and potassium sorbate.

Suitable buffers used in the present invention include phosphate buffers such as disodium phosphate and disodium phosphate, or citrate buffers.

Suitable surfactants used in the present invention include polyethylene glycol (PEG), hydrogenated castor oil, sorbitan ester, (Poloxamer).^TMPolyethylene-polypropylene triblock copolymers (such as). Preferred surfactants include PEG-40 or PEG-60 hydrogenated castor oil, and sorbitan ester.

Additional ingredients suitable for use in the present invention include remineralizing agents, antibacterial agents, dental caries preventatives, anti-calculus agents, moisturizers, halitosis deodorants and desensitizers.

Suitable antibacterial agents used in the present invention include chlorhexidine, cetylpyridinium chloride, zinc salts or triclosan. Preferred antibacterial agents are cetylpyridinium chloride, chlorhexidine and zinc salts.

Suitable dental caries preventives used in the present invention include, for example, alkali metal salts such as sodium fluoride, or sodium monofluorophosphate, tin (II) fluoride, or Olaflur or Decaflur. Fluoride ion sources such as fluoride amine salts can be mentioned. Appropriately, this composition contains from 1 to 2500 ppm of fluoride ions.

The compositions according to the invention are formulated by mixing the ingredients in appropriate relative amounts in any convenient order, and then, if necessary, adding a buffer to bring the pH to the final desired value. can do.

The compositions according to the invention generally have an orally acceptable pH in the range of approximately pH 5-10, more preferably pH 5.5-8.

Mouthwash and mouth spray compositions are instant powders in "ready to use" form, as a concentrate for the user to dilute immediately before use, or in tablets or sachets for the user to dissolve immediately before use. Can be provided as. Tablets can be appropriately formulated with xylitol and / or sorbitol as the main ingredients. The sachets and tablets foam to provide a carbonate-free mouthwash by dissolving, or by mixing with a suitable effervescent combination such as sodium carbonate / sodium bicarbonate and citric acid. It can be formulated to provide sex mouthwash.

The compositions of the present invention are useful in reducing the symptoms of xerostomia. In particular, it helps to smooth and moisturize the oral cavity.

The present invention also provides a method of treating xerostomia in humans or animals, which comprises administering a therapeutically effective amount of the aforementioned composition.

The present invention will be described with reference to the following examples, but the present invention is not limited thereto.<tables num="1"><img file="JP2008508338A_D0001.tif" /></tables><tables num="2"><img file="JP2008508338A_D0002.tif" /></tables><tables num="3"><img file="JP2008508338A_D0003.tif" /></tables><tables num="4"><img file="JP2008508338A_D0004.tif" /></tables>

Example 5-Sensory Test A sensory test for optimizing polymers used for xerostomia was performed using a small panel test. The sensory test results include the following.

The use of CMC alone to the extent that it coats the mouth well caused the discomfort of "sticky" and "sticky" sensations.

A sensory test of xanthan gum alone, which coats the mouth well, resulted in a reaction to the unpleasant sensation of "stickiness" and comments on stickiness.

Mixtures of CMC, xanthan gum and PVP have been found to provide a smooth and good mouth feel and a good coating with the ability to smooth and moisturize the mouth. This polymer combination was tested in parallel with the CMC, xanthan, dimethicone combination. Replacing PVP with dimethicone reduced the benefits of the coating and the smoothness of its polymer mixture.

The sensory discomfort associated with using only CMC or xanthan, which provides the benefits of coating and mucosal adhesion, is overcome by incorporating PVP in combination with CMC and xanthan gum, and this effect is further enhanced by PVP in its mixture. It is also suggested that the smoothness was lost when replaced with an alternative polymer in, and all comments on smoothness were lost.

Example 6-Sensory Test A further sensory test for optimizing the polymer used for xerostomia was performed by a small panel test consisting of 6 panelists.

Panelists were tested with 10 ml of polymer solution as shown in the table below.<tables num="5"><img file="JP2008508338A_D0005.tif" /></tables>

The sensory test results include the following.

<u style="single">CMC / CMC + PVP solution</u> Adding PVP to the CMC solution improved the sensory properties of the polymer solution. PVP significantly reduced the stickiness of the CMC solution (p = 0.01) and made the oral texture smoother. The mouth feel and aftertaste of the CMC + PVP solution was more pleasing. The mouth was even more moisturized. Both polymer solutions were perceived to be reasonably sticky. CMC + PVP solutions tended to be perceived as more viscous and gel-like (more sticky) than CMC solutions. This is also explained by the fact that there are more overall polymers that increase the viscosity of the solution.

<u style="single">Xanthan / xanthan + PVP</u> In this small panel test, no significant difference was found between the sensory properties of the xanthan solution and the mixture of xanthan and PVP. Addition of PVP to a xanthan solution tends to slightly reduce the mouth feel and smoothness of the oral texture of the solution due to the increased stickiness, which increases the overall polymer in this system. It can be explained by what you did. However, the addition of PVP increased the ability to coat the mouth. Solutions of both polymers were perceived as moderately moisturizing and smoothing the mouth. Importantly, the addition of PVP reduced the stickiness of the xanthan solution.

<u style="single">Xanthan + CMC / Xanthan + CMC + PVP</u> When PVP was added to the xanthan + CMC solution, the smoothness of the oral texture of the solution was significantly improved (p = 0.03). PVP tended to reduce the stickiness of the xanthan + CMC solution, provide a more pleasing mouth feel, and moisturize and smooth the mouth. The xanthan + CMC + PVP solution was perceived to be more sticky due to the fact that there was more overall polymer that increased the viscosity of the solution.