WO1999020238A1

WO1999020238A1 - Metal ion-containing oral products with reduced astringency

Info

Publication number: WO1999020238A1
Application number: PCT/US1998/021438
Authority: WO
Inventors: David Scott Harper; Rita M. Parikh; Charles Pozzi; Jing Cao
Original assignee: Warner-Lambert Company
Priority date: 1997-10-23
Filing date: 1998-10-09
Publication date: 1999-04-29
Also published as: ZA989641B; AU1077499A

Abstract

The astringency of an astringent metal salt containing oral composition is reduced by the addition of a non-ionic polymer without the use of glycine, chelators, other complexing agents or buffering agents. The astringent metal can be a zinc salt such as zinc chloride and the non-ionic polymer can be hydroxyethylcellulose.

Description

METAL ION-CONTAINING ORAL PRODUCTS WITH REDUCED ASTRINGENCY

BACKGROUND OF THE INVENTION 1. Field of the Invention

The present invention relates to low astringent oral care products including

mouthwashes, dentifrices, lozenges and the like, comprising a combination of metal ions and gums. 2. Related Art The incorporation of metal compounds such as zinc or copper salts into oral dental care products to provide beneficial effects such as anti-plaque, anticalculus

(that is, antitartar), and deodorant properties is well known in the prior art, as

disclosed in U.S. Pat. Nos. 4,138,477, 4,416,867, 4,425,325 and 4,568,540. However, the extreme astringency of water soluble metal salts such as zinc chloride is a major drawback in their use in oral dental care products. In addition to the

unpleasant astringent taste in the mouth, the efficacy against plaque, calculus and

odor inhibition is short-lived. Usually the complex formation of zinc with anionic counterions such as citrate reduces its astringency but also reduces its solubility and/or biological availability. Accordingly, sparingly soluble zinc salts such as zinc citrate, zinc C14 -alkyl maleate, zinc benzoate, zinc caproate, zinc carbonate, etc.

have been used in dentifrice formulations to prolong the anti-calculus and anti-

plaque effectiveness of the zinc ions due to the slow dissolution of the zinc salts in

the saliva. The sparingly soluble and/or chelant characteristics of these zinc salts

promotes longevity of action against plaque and calculus at the expense of initial or

immediate efficacy.

U.S. Pat. Nos. 4,425,325 and 4,416,867 have addressed the astringency

problem associated with zinc compounds in oral compositions by adding glycine and

adjusting the pH within the range of 4.5 and 9.4 in order to maintain the zinc in

solution which is less astringent than a pH below 4.5.

U.S. Pat. No. 4,138,477 also discloses a non-astringent oral composition

containing a zinc-polymer complex having a pH of 4.5 to 6, formed by the chelation

or reaction of a zinc compound with an anionic polymer containing carboxylic,

sulfonic and/or phosphonic acid radicals.

U.S. Pat. No. 4,568,540 discloses oral compositions effective in controlling

mouth odor, calculus, plaque and caries, containing active zinc ions and fluoride

ions, said zinc ions being provided by zinc salts selected from the group consisting

of zinc chloride, zinc sulfate and zinc thiocyanate, and a specific buffering agent to

maintain a pH of 3.5 to 6.0 in order to permit the fluoride ions and zinc ions to

remain in solution and not precipitate out. This patent also discloses that certain

ingredients minimize the astringency of zinc chloride. These ingredients are

humectants, such as glycerine, sorbitol, xylitol and propylene glycol, the sodium salts of the coconut fatty acid amide of N-methyl-taurine and the Pluronic and

Butronic nonionic surface active agents.

U.S. Pat. No. 4,100,269 discloses an anticalculus dentifrice containing a

substantially insoluble zinc compound. In order to avoid astringency, the solubility

of the zinc should not exceed about 0.5 to 1% by weight (based on the amount of

dissolved zinc ion) at 20 °C. The abrasive with said anticalculus dentifrice

compositions must not interact with the zinc compound. Therefore, the commonly

used phosphate abrasives or polishing agents cannot be used.

In U.S. Pat. No. 4,627,977 an anticalculus oral composition is disclosed

containing a water soluble alkali metal polyphosphate salt, a fluoride ion source, and

a water soluble alkali metal or ammonium anionic linear polymeric polycarboxylate

salt having a molecular weight of 1,000 to 1 ,000,000.

U.S. Patent No. 5,000,944 discloses a zinc-containing antitartar oral product

substantially free of astringency, containing as the essential agent, a

zinc/polyphosphate complex having at least about a 50% water solubility, formed by

the reaction or interaction of a zinc compound with a potassium or sodium

polyphosphate by dissolving a zinc salt in a polyphosphate solution such as

pyrophosphate, tripolyphosphate, hexametaphosphate and combinations thereof.

None of the above cited prior art discloses low astringent oral care products

including mouthwash, dentifrice, lozenge, etc., containing a non-complexed metal

and a gum that is unusually effective in reducing the astringency of the metal and

simultaneously provides anti-plaque, anti-tartar and anti-odor efficacy. SUMMARY OF THE INVENTION

The present invention is directed to oral compositions that contain metal ions

that are known to be astringent but have reduced astringency. Oral compositions

that contain metal ions, such as zinc and copper, have a characteristic astringent

taste. The present invention significantly reduces the astringency of metal

containing oral compositions by the addition of a non-ionic polymer. The present

invention unexpectedly reduces astringency in the absence of previously recognized

astringency reducing ingredients, thus increasing the bioavailability of the metallic

ion.

The compositions according to the present invention do not contain the

buffering agents disclosed in U.S. Patent No. 4,568,540, or the complexing agents

disclosed in U.S. Patent Nos. 4,138,477, 4,992,259 and 5,000,944 or glycine as

disclosed in U.S. Patent No. 4,339,432. The disclosures of U.S. Patent Nos.

4,568,540, 4,992,259, 4,138,477, 5,000,944 and 4339,432 are incorporated by reference herein in their entirety.

The present invention is also directed to a method of reducing the

astringency of a metal containing oral composition. The method of reducing the

astringency of metal containing oral compositions includes formulating the metal

containing oral composition with a non-ionic gum in the absence of metal complexing agents, glycine or buffering agents. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The non-ionic water-soluble polymers used in the oral composition

according to the present invention are compatible with the other ingredients in the

formulation. A preferred non-ionic polymer is hydroxyethylcellulose, available

from Hercules Inc. under the tradename Natrosol®. These non-ionic polymers

should be present in the compositions in an amount from about 0.1% to 2.0%,

preferably from about 0.5% to 0.75%, by weight of the composition.

In addition to the non-ionic polymer, the metal containing oral

compositions according to the present invention may also include xanthan gum,

which improves the ability of the non-ionic polymer to reduce the astringency of

the astringent metal salts. The xanthan gum is used from about 0.1% to about

2.0%), preferably from about 0.5% to about 1.0% by weight of the oral

compositions according to the present invention.

The astringent metal salts used in the oral compositions according to the

present invention are selected from the group consisting of zinc salts, copper salts,

and similar metal ion salts known to have antiodor and/or antitartar efficacy. The

zinc salts useful in the present invention include zinc chloride, zinc sulfate, zinc

citrate, zinc acetate, zinc lactate, zinc salicylate and zinc thiocyanate. The zinc salt

is used from about 0.1 % to about 4.0%, preferably from about 0.25% to about 2.0%,

even more preferably from about 0.5% to about 1.0% by weight of the oral composition according to the present invention. One explanation for the astringency of zinc has been offered by Green in

"Oral astringency: A tactile component of flavor," Acta Psychologica 84 (1993), pp.

119-125. Green theorizes that astringency arises primarily from the precipitation of

salivary mucoproteins, which impairs the natural lubrication of oral surfaces. While

not wishing to be bound by any theory, the non-ionic gums used in the present

invention appear to relubricate the oral cavity.

The compositions according to the present invention can also include

fluoride compounds. Typical pharmaceutically acceptable fluoride compounds that

are suitable for use in the compositions of this invention include sodium fluoride,

potassium fluoride, lithium fluoride, aluminum fluoride, zinc fluoride, stannous

fluoride, sodium monofluorophosphate, acidulated phosphate fluoride, ammonium

fluoride, ammonium bifluoride, titanium tetrafluoride and amine fluoride.

The fluoride ion concentration can be from as low as 0.0025% to about

4.0% by weight. The preferred range of fluoride ion concentration is about

0.005%) to about 1.0% by weight, more preferably about 0.01% to 0.5%.

The fluoride ions are taken up by the dental enamel and render the teeth

less susceptible to caries attack and dental decay by increasing the hardness of the

enamel or reducing the enamel solubility. The metal ions help to prevent the

formation of tartar, oral malodor and gingivitis.

Suitable pharmaceutically acceptable oral hygiene vehicles that may be

used alone or in combination in the compositions of the present invention include glycerol, water, ethanol, polyethylene glycol, propylene glycol, sorbitol and the

like. Other vehicles may be used if compatible with the other ingredients in the

compositions.

If the compositions of the present invention are in the form of a dentifrice,

they should also contain a suitable abrasive. The abrasive should not harm the

enamel or dentin while being capable of cleaning and polishing the teeth as well

as being compatible with the fluoride and metal ions. Preferred abrasives include

the silica abrasives.

Suitable abrasive substances for use in this invention include hydrated silica,

calcium carbonate, calcium pyrophosphate, dicalcium phosphate dihydrate, or alkali

metal meta-phosphates. Silica abrasives in the dentifrice composition according to

this invention may include among others, ZEODENT® (113), manufactured by J.

M. Huber Corp. and SYLOID® or SYLODENT®, manufactured by W.R. Grace Co.

These polishing agents may be used in amounts up to about 75.0% w/w of the

composition, preferably in amounts from about 5.0% w/w to about 40% w/w of the

composition, and most preferably from about 5.0% w/w to about 30.0% w/w of the

composition.

Additionally, when the oral composition according to the present invention is

a dentifiice it has been found that formulating the dentifrice without a gelling or

thickening silica improved the astringency of the composition. In other words,

compositions that contain gelling or thickening silica have higher astringency than those that do not. However, the astringency of compositions that contain gelling or

thickening silicas is improved by the presence of non-ionic gums.

Another component in the oral compositions is a humectant. The humectant

serves to keep the dentifrice compositions from hardening upon exposure to air and

also imparts a desirable sweetness to the formulation. Suitable humectants in this

invention include sorbitol, as 70% sorbitol solution, glycerin, propylene glycol,

polyethylene glycol, mixtures thereof, and the like. Humectants may be present in

amounts from about 1.0% to about 75.0% by weight of the oral composition.

Water is another essential component of oral compositions. Water employed

in the preparation of commercially suitable oral compositions should preferably be

deionized and free of impurities. Water comprises from about 0.05 to 70.0%,

preferably from about 15.0 to 50.0% by weight of the formulations. These amounts

include the added free water plus water introduced with other materials.

Surfactants or surface active agents are organic compounds which reduce

surface tension between liquids and aid in the dispersion of a composition

throughout the oral cavity. The surfactant in the present invention may be anionic,

nonionic, or amphoteric. The oral hygiene or dentifiice compositions of the present

invention may contain surfactants in amounts up to about 5.0% w/w; preferably

from about 0.1% w/w to about 3.0% w/w of the composition; and most preferably from about 0.2% w/w to about 2.0% w/w of the composition. A preferred surfactant in dentifrice compositions is anionic. These anionic

surfactants include but are not limited to sodium lauryl sulfate, sodium lauroyl

sarcosinate, sodium methyl cocoyl taurate, and disodium lauryl sulfosuccinate.

A preferred surfactant in mouthrinse compositions is nonionic. These

nonionic surfactants include but are not limited to pluronic or tetronic surfactants.

Amphoteric surfactants have the capacity to behave as either an acid or a

base and include quaternized imidazole derivatives useful in the present invention.

Preferred amphoteric surfactants include long chain (alkyl) amino-alkylene aklylated

amine derivatives, also known as MIRANOL®, manufactured by Rhone-Poulanc,

Cranberry, New Jersey.

In addition to the above-described components, the oral compositions can

contain a variety of optional conventional ingredients. Such optional ingredients

include preservatives, flavoring agents, sweetening agents, coloring agents and

pigments.

Sweeteners well known in the art, including natural and artificial sweeteners,

may be used. The sweetener may be selected from a wide range of materials

including naturally occurring water-soluble sweeteners, artificial water-soluble

sweeteners and modified water-soluble sweeteners derived from naturally occurring

water-soluble sweeteners. Artificial water-soluble sweeteners include, but are not

limited to, soluble saccharin salts, e.g., sodium or calcium saccharin salts, cyclamate

salts, the sodium, ammonium or calcium salt of 3,4-dihydro-6-methyl-l,2,3-oxathia-

zine-4-one-2,2-dioxide, the potassium salt of 3,4-dihydro-6-methyl-l,2,3-oxathia- zine-4-one-2,2-dioxide (Acesulfame-K), the free acid form of saccharin, and the

like; dipeptide based sweeteners, such as L-aspartic acid derived sweeteners, e.g.,

L-aspartyl-L-phenylalanine methyl ester (Aspartame) and materials described in

U.S. Pat. No. 3,492,131, L-alpha-aspartyl-N-(2,2,4,4-tetramethyl-

3-thietanyl)-D-alaninamide hydrate (Alitame), methyl esters of L-aspartyl-L-

phenylglycerine, and L-aspartyl-L-2,5-dihydrophenylglycine,

L-aspartyl-2,5-dihydro-L-phenylalanine; L-aspartyl-L- (l-cyclohexene)-alanine, and

the like. Naturally occurring water-soluble sweeteners include, but are not limited

to, sugar alcohols, including sorbitol as 70% sorbitol solution, mannitol, xylitol,

maltitol, hydrogenated starch hydrolysates and mixtures thereof.

Water-soluble sweeteners derived from naturally occurring water-soluble

sweeteners include, but are not limited to, chlorinated derivatives of sucrose, known,

for example, under the product designation of Sucralose; and protein-based

sweeteners such as thaumaoccous danielli (Thaumatin I and II).

Sorbitol solution supplies sweetness and body to the composition and gives a

desirable mouth feel. Sorbitol solution also enhances flavor, prevents harsh taste

and provides a fresh and lively sensation in the mouth. It also prevents caking of the

dentifrice.

In general, an effective amount of sweetener is utilized to provide the level of

sweetness desired in any particular embodiment of the oral compositions according

to the present invention. This amount will vary with the sweetener selected and the

final oral hygiene product. The amount of sweetener normally present is from about 0.0025% w/w to about 60% w/w of the oral composition. The exact range of

amounts for each type of sweetener in an oral composition is well known in the art

and is not the subject of the present invention.

The flavors that may be used in the invention include natural and artificial

flavors known in the oral composition art. Suitable flavors include, but are not

limited to, mints, such as peppermint, citrus flavors such as orange and lemon,

essential oils such as thymol, methyl salycilate, menthol and eucalyptol, artificial

vanilla, cinnamon, various fruit flavors, and the like. Anethole (or anise camphor, p-

propenyl anisole) is a flavor constituent of anise and fennel oils which are used

widely as flavoring agent and antiseptic and was found useful in masking the harsh

taste of thymol.

The amount of flavor is normally a matter of preference subject to such

factors as the type of the composition, the individual flavor employed, and the

strength of flavor desired. The flavors are preferably utilized in amounts that may

range in total amounts from about 0.01% w/w to about 6% w/w of the oral composition.

Coloring agents in this invention are used in amounts effective to produce an

oral composition of the desired color. These coloring agents may be incorporated in

amounts up to about 3% by weight of the compositions of the present invention.

The coloring agents may also include natural food colors and dyes suitable for food,

drug and cosmetic applications. These coloring agents are known as FD & C dyes

and lakes. The materials acceptable for the foregoing uses are preferably water-soluble. Illustrative nonlimiting examples include the indigoid dye known as

FD & C Blue No.l, and D & C Yellow No. 10. A full recitation of all FD & C

colorants and their corresponding chemical structures may be found in the

Kirk-Othmer Encyclopedia of Chemical Technology, 3rd Edition, in volume 5 at

pages 857-884. A preferred opacifier, titanium dioxide, may be incorporated in

amounts up to about 2.0% w/w, preferably less than about 1.0% w/w of the

composition, and most preferably less than about 0.4% w/w.

Suitable preservatives in this invention include sodium benzoate, benzoic

acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ascorbic

acid, methyl paraben, propyl paraben, tocopherols and mixtures thereof.

Preservatives when used are generally present in amounts up to about 1.0% w/w, and

preferably from about 0.1% w/w to about 1.0% w/w of the composition.

Sweetening agents that can be used include saccharin, dextrose, levulose,

aspartame, D-tryptophan, dihydrochalcones and sodium cyclamate. Sweetening

agents are generally utilized in dentifrices at levels of from about 0.05% to about 2%

by weight.

In addition to dentifiice compositions, the oral composition according to the

present invention can be mouthwashes, mouthrinses, tooth powders, pressed tablets, lozenges, boiled candies, gums, mints and films. EXAMPLES The following examples are provided to further illustrate the present

invention. These examples are intended to be exemplary and are not exhaustive or

limiting. Unless noted, percentages are percent by weight. Examples 1-3 and

Comparative Example 1 are dentifrice compositions made using processing

techniques known to those skilled in the art.

EXAMPLE 1

Water 20.8703

Sorbitol, 70% solution 35.0000

Sodium Fluoride 0.2430

Sodium Saccharin 0.4000

Acid Saccharin 0.4000

Zinc Chloride 0.5000

Sodium Benzoate 0.2000

Abrasive Silica 23.0000

Titanium dioxide 0.8000

Hydroxyethylcellulose 1.0000

Xanthan Gum 1.0000

Glycerin, 95% Solution 10.4700

Flavor 2.3667

Sodium methyl cocoyl taurate 3.7500 EXAMPLE 2

Water 20.3793

Sorbitol, 70% solution 35.0000

Sodium Fluoride 0.2540

Sodium Saccharin, 85% 0.7000

Acid Saccharin 0.5000

Zinc Chloride 0.5000

Polyethylene Glycol 3.0000

Sodium Benzoate 0.2000

10 Abrasive Silica 25.0000

Titanium dioxide 0.3500

Hydroxyethylcellulose 0.7500

Carboxymethylcellulose 1.5000

Glycerin, 95% Solution 8.0000

15 Flavor 2.3667

Sodium lauryl sulfate 1.5000

EXAMPLE 3

Water 25.8703

Sorbitol, 70% solution 35.0000

Sodium Fluoride 0.2430

Sodium Saccharin 0.4000

Acid Saccharin 0.4000

Zinc Chloride 0.5000

Sodium Benzoate 0.2000

Gelling Silica 7.0000

10 Abrasive Silica 11.0000

Titanium dioxide 0.8000

Hydroxyethylcellulose 1.0000

Xanthan Gum 1.0000

Glycerin, 95% Solution 10.4700

15 Flavor 2.3667

Sodium methyl cocoyl taurate 3.7500

COMPARATIVE EXAMPLE 1

Water 24.8281

Sorbitol, 70% solution 40.0000

Sodium Fluoride 0.2540

Sodium Saccharin, 85% 1.2000

Zinc Chloride 0.5000

NaH₂PO₄ 0.2500

Na₂HPO₄ 0.0300

Polyethylene Glycol 3.0000

Sodium Benzoate 0.2000

Phosphoric Acid 25% 0.0712

Zeosyl 200 7.0000

Sylodent 750 11.0000

Titanium dioxide 0.3500

Xanthan Gum 0.2500

Carboxymethylcellulose 1.2000

Glycerin, 95% Solution 6.0000

Flavor 2.3667

Sodium lauryl sulfate 1.5000

A group of approximately ten panelists used each of Examples 1-3 and

Comparative Example 1 and rated the compositions for astringency on a relative

scale of 0-5. A rating of 0 equals no astringency and a rating of 5 is the most

astringent. Example 1 rates a 0.1. Example 2 rates a 1.0. Example 3 rates a 2.5 and

Comparative Example 1 rates a 5.0. Example 4 is a compressed lozenge and Example 5 is a mouthrinse made

using processing techniques known to those skilled in the art. All the amounts are

percent by wieght.

EXAMPLE 4

Powdered sorbitol 94.1

Partially hydrogenated cottonseed 2.0 oil

Magnesium stearate 1.5

Hydroxyethylcellulose 1.0

Flavor 0.6

Zinc Chloride 0.5

Sodium saccharin 0.3

EXAMPLE 5

Purified water 85.9

Alcohol 7.0

Glycerine, 95% solution 5.0

Sodium acetate 1.0

Hydroxyethylcellulose 0.3

Zinc chloride 0.3

Flavor 0.3

Poloxamer 407 0.1

Sodium Saccharin 0.1

Acetic Acid, Glacial 0.1

Colorant (1% solution) 0.1

Although the invention has been described with reference to specific

preferred embodiments, those skilled in the art will recognize that variations and modifications may be made that are within the spirit of the invention and within the

scope of the claims.

Claims

What is claimed is:

1. An oral composition comprising:

an astringent metal salt; and a non-ionic polymer in an amount effective to reduce the astringency of the

metal salt, wherein the composition does not include glycine, metal complexing

agents or a buffering agent selected from the group consisting of sodium gluconate,

citric acid, maleic acid, aspartic acid, gluconic acid, succinic acid, glucuronic acid,

glucuronic acid lactone, fumaric acid and sodium glutamate.

2. The composition according to claim 1, wherein the astringent metal

salt is a zinc salt.

3. The composition according to claim 1, wherein the astringent metal

salt is a copper salt.

4. The composition according to claim 2ΓÇ₧ wherein the zinc salt is

selected from the group consisting of zinc chloride, zinc sulfate, zinc citrate, zinc

acetate, zinc thiocyanate and mixtures thereof.

5. The composition according to claim 1 , wherein the non-ionic polymer

is hydroxyethylcellulose.

6. The composition according to claim 1 , wherein the non-ionic polymer is in an amount from about 0.1% to about 2.0% by weight of the composition.

7. The composition according to claim 6, wherein the non-ionic polymer

is in an amount from about 0.5% to about 0.75% by weight of the composition.

8. The composition according to claim 5, wherein the

hydroxyethylcellulose is in an amount from about 0.1 % to about 2.0% by weight of

the composition.

9. The composition according to claim 8, wherein the

hydroxyethylcellulose is in an amount from about 0.5% to about 0.75% by weight of

the composition.

10. The composition according to claim 1 further comprising xanthan

gum.

11. The composition according to claim 10, wherein the xanthan gum is

present in an amount from about 0.1% to about 2.0% by weight of the composition.

12. The composition according to claim 11, wherein the xanthan gum is

present in an amount form about 0.5% to about 1.0% by weight of the composition.

13. The composition according to claim 2, wherein the zinc salt is in an

amount from about 0.1% to about 2.0% by weight of the composition.

14. The composition according to claim 13, wherein the zinc salt is in an

amount from about 0.25% to about 1.5% by weight of the composition.

15. The composition according to claim 14, wherein the zinc salt is in an

amount from about 0.5% to about 1.0% by weight of the composition.

16. An oral composition comprising:

a zinc salt in an amount from about 0.1% to about 2.0% by weight of the

composition; and a non-ionic polymer in an amount from about 0.1% to aobut 2.0% by weight

of the composition, wherein the non-ionic polymer reduces the astringency of the

zinc salt and the composition does not include glycine, metal complexing agents or a

buffering agent selected from the group consisting of sodium gluconate, citric acid,

maleic acid, aspartic acid, gluconic acid, succinic acid, glucuronic acid, glucuronic

acid lactone, fumaric acid and sodium glutamate.

17. The oral composition according to claim 16, wherein the non-ionic

polymer is hydroxyethylcellulose.

18. The oral composition according to claim 16, further comprising

xanthan gum.

19. The oral composition according to claim 18, wherein the xanthan

gum is present in an amount from about 0.1% to about 2.0% by weight of the

composition.

20. An oral composition comprising:

a zinc salt in an amount from about 0.1% to about 2.0% by weight of the

composition; and

hydroxyethylcellulose in an amount from about 0.1% to aobut 2.0% by

weight of the composition, wherein the hydroxyethylcellulose reduces the

astringency of the zinc salt and the composition does not include glycine, metal

complexing agents or a buffering agent selected from the group consisting of sodium

gluconate, citric acid, maleic acid, aspartic acid, gluconic acid, succinic acid,

glucuronic acid, glucuronic acid lactone, fumaric acid and sodium glutamate.