WO2008025468A1

WO2008025468A1 - Oral care effervescent composition

Info

Publication number: WO2008025468A1
Application number: PCT/EP2007/007372
Authority: WO
Inventors: Xiangwei Gong; Anna Anita Gripp; Kwee Choo Oh; Christine Saecker
Original assignee: Dsm Ip Assets B.V.
Priority date: 2006-08-31
Filing date: 2007-08-22
Publication date: 2008-03-06

Abstract

Oral care effervescent compositions are provided. More particularly, an oral care effervescent composition containing epigallocatechin gallate (EGCG) and ascorbic acid or a derivative thereof is provided. Also provided are methods of making and using such oral care effervescent compositions.

Description

Oral care effervescent composition

The present invention refers to an oral care product, especially an effervescent composition, containing epigallocatechin 3-gallate (EGCG) and ascorbic acid or a derivative thereof, to its manufacture, and its use.

The applicants have discovered that EGCG and ascorbic acid or a derivative thereof may be uniformly and accurately dispensed when completely dissolved and dispersed in water. More specifically, EGCG and ascorbic acid or a derivative thereof have been created in the form of an effervescent composition, especially as effervescent tablet or effervescent powder. The effervescent compositions according to the present invention are stable prior to addition to water and therefore do not need a stabilizer.

In addition, because the oral care effervescent composition is packaged in either tablet or pre-measured powder form, a precise amount of the active ingredients can be administered.

In a preferred embodiment of the present invention EGCG and ascorbic acid or a derivative thereof are combined with a material that produces a gas (such as carbon dioxide) upon dissolution in a liquid, such as water. By dissolving the effervescent according to the present invention a liquid oral care product is generated which may be used as mouthwash by the consumer. The use of a pre-measured effervescent composition assures complete dissolution and dispersal of the oral care product.

Effervescent compositions according to the present invention preferably contain a mixture of acids, bicarbonates, and other agents which release carbon dioxide when dissolved in water. In its preferred embodiment, the invention includes an oral care effervescent composition containing ascorbic acid, EGCG, at least one acid, and at least one (bi)carbonate for releasing carbon dioxide when dissolved in a liquid.

According to the present invention it is preferred to utilize a mixture of acids, including citric acid and tartaric acid. Sodium bicarbonate or potassium bicarbonate may be utilized for the release of carbon dioxide. In addition, starch, flavoring agents, and lubricants for tablet compression may also be utilized in the effervescent tablet. While the effervescent composition is preferably in the form of a tablet, it may also be utilized in the form of an effervescent powder. The effervescent composition is preferably stored in a sealed container or other moisture-proof package, since water or other liquids will activate the effervescent process.

The effervescent compositions are intended not to be swallowed directly, since they release carbon dioxide as they dissolve. Thus, the initial step in the method of the invention is to open the moisture-proof package containing the effervescent composition and dispense it into a container of water or other pH neutral liquid. The amount of water is not critical, but it is preferred to use about 60 to about 120 milliliters of water for an optimal concentration of the active ingredients (ascorbic acid (or derivative) and EGCG). The oral care effervescent composition according to the present invention is preferably used to rinse the mouth for 30 seconds.

The beneficial effects of the oral care effervescent composition of the present invention include, for example, an anti-microbial effect, aiding control of plaque, freshening the breath, preventing decay, preventing the formation of mouth odor, preventing the formation of gingivitis, preventing the formation of dental plaque calculus, controlling bad breath, giving a clean mouth feel, and freshening mouth taste. Moreover, the effects of the oral care effervescent composition of the present invention are long-lasting.

Vitamin C kills germs that contribute to bad breath. EGCG combats bad breath originating from the oral cavity caused by volatile sulphur compounds produced by bacteria on the back of the tongue.

The oral care effervescent composition of the present invention allows the user to make a fresh, single use quantity of an oral mouthwash at the time of use. Since ascorbic acid is not stable in water and decomposes with time, the oral care effervescent composition (as compared to liquid mouthwashes) prevents the decomposition of vitamin C because it is prepared shortly before use. Thus, this non-aqueous delivery system, unlike aqueous mouthwash delivery systems, maintains the stability of vitamin C. As a result, the breath freshening benefits of vitamin C are expected to be maintained until the time of use of the oral care effervescent composition. The oral care effervescent composition of the present invention has a great taste, is alcohol-free, is essentially caffeine-free, freshens the breath, is easy to use, and is useful for on-the-go and/or travel use.

Surprisingly, the anti-bacterial effects of ascorbic acid (or derivatives), especially of ascorbic acid itself, and EGCG are synergistically increased when put together in an oral care effervescent composition according to the present invention.

The oral care effervescent composition according to the present invention dissolves well in water and leaves very little ringing or scum on the surface of the container in which the oral care effervescent composition is dissolved.

The ingredients are now discussed in further detail below.

(-)-Epigallocatechin qallate and derivatives thereof:

The term "(-)-epigallocatechin gallate" (EGCG; with the chemical name (2R,3R)-2-(3,4,5- Trihydroxy-phenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol-3-(3,4,5-trihydroxy- benzonate)) encompasses also green tea extracts containing (-)-EGCG as well as (-)- EGCG derivatives, such as pharmaceutically acceptable salts.

In one embodiment of the present invention, the oral care effervescent composition contains a green tea extract containing (-)-epigallocatechin gallate in a range of from about 10 to about 100 weight-%, based on the total weight of the green tea extract.

In another embodiment of the present invention, the oral care effervescent composition contains a green tea extract containing (-)-epigallocatechin gallate in a range of from about 20 to 100 weight-%, preferably in a range of from about 40 to 100 weight-%, more preferably in a range of from about 60 to 100 weight-%, most preferably in a range of from about 80 to 100 weight-%, based on the total weight of the green tea extract.

In a preferred embodiment the EGCG has a purity of at least about 80%, preferably of at least about 85%, more preferably of at least about 90%, even more preferably of at least about 92%, and most preferably of at least about 94%. The term "green tea extract" also encompasses green tea that was brewed and spray- dried afterwards.

EGCG can be obtained by any of the processes described in US 6,383,392, EP 1 103 550, US 10/246,112 and EP 1 077 211 and it is explicitly referred to the disclosure of these documents regarding the production of EGCG.

In a preferred embodiment the EGCG is provided as a component of a mixture of green tea catechins and in such a mixture EGCG is usually present in an amount of up to about 50% of the total green tea catechins, preferable in an amount from about 10 to about 50% and more preferable in an amount of about 20 to about 50% and most preferable in an amount of about 30 to about 50%. Other catechins present in green tea are such as Epigallocatechin (EGC)₁ Epicatechingallate (ECG), Epicatechin (EC) and Gallocatechingallate (GCG). Therefore, in another preferred embodiment of the present invention, the EGCG is provided as a component of a mixture of green tea catechins and in such a mixture of EGCG is usually the main component and the total amount of other polyphenols and/or catechins is low, preferably about 5 weight-% or less, more preferably about 3 weight-% or less based on the total weight of the mixture.

A preferred (-)-EGCG is, e.g., Teavigo (a green tea extract containing > 94% of EGCG), commercially available from DSM Nutritional Products Ltd, Kaiseraugst, Switzerland, as well as Teavigo TG (Tablet Grade) (a green tea extract containing ca. 88% of EGCG admixed with ca. 3% of pectin), the latter having a very good flowability. Both have a good water-solubility. Of these, Teavigo is preferred.

A preferred alternative for (-)-epigallocatechin gallate is a green tea fraction comprising at least about 85.0 % weight-% of (-)-epigallocatechin gallate (EGCG) and at most about 2.0 weight-% of caffeine, especially a green tea fraction comprising at least about 90.0 weight-% of (-)-epigallocatechin gallate (EGCG) and at most about 1.6 weight-% of caffeine, whereas this green tea fraction preferably comprises at most about 4.0 weight- % of epicatechin (EC), and/or at most about 4.0 weight-% of catechin, and/or at most about 2.0 weight-% of gallocatechin gallate (GCG), and/or at most about 5.0 weight-% of epicatechin gallate (ECG). A further preferred alternative for (-)-epigallocatechin gallate is a green tea extract comprising at least 91.7 weight-% of (-)-epigallocatechin gallate (EGCG) and at most 1.43 weight-% of caffeine, especially a green tea extract comprising from 91.7 to 97.13 weight-% of EGCG, from 0 to 3.15 weight-% of epicatechin (EC), from 0 to 3.1 weight-% of catechin, from 0.2 to 1.52 weight-% of gallocatechin gallate (GCG), from 0.38 to 4.62 weight-% of epicatechin gallate (ECG) and from 0 to 1.43 weight-% of caffeine, based on the total weight of the green tea extract.

Ascorbic acid:

The ascorbic acid and/ or derivatives thereof for use in accordance with the present invention may be ascorbic acid and/ or any non-toxic, non skin-irritating water-soluble or oil-soluble ascorbic acid derivative. The term ascorbic acid and/or derivatives thereof encompasses ascorbic acid as well as esters of ascorbic acid, and ester salts of ascorbic acid such as ascorbyl phosphates as well as ascorbic acid derivatives such as ascorbyl palmitate, ascorbyl tetraisopalmitate (for example available from DSM), ascorbyl dipalmitate (for example, NIKKOL CP available from Nikko Chemical), ascorbyl linoleate, ascorbyl octanoate, 2-O-D-glucopyranosyl-L-ascorbic acid, which is an ester of ascorbic acid and glucose and usually referred to as L-ascorbic acid 2-glucoside or ascorbyl glucoside, and its metal salts.

The term "ascorbyl phosphate" as used herein denotes metal salts of mono- and poly- phosphoric acid esters of ascorbic acid wherein the phosphorylated hydroxy group of the ascorbic acid molecule features one or more phosphoric acid (phosphate) units, and metal cations, e.g., sodium and/or magnesium or calcium ions, are also present. The term "poly" generally denotes 2 - 10, preferably 2 - 4, phosphate units. The ascorbyl phosphates may also be referred to in general as "ascorbyl (poly)phosphates" to embrace both mono- and polyphosphates. Typical ascorbyl phosphates for use in the present invention are L-ascorbic acid phosphate ester salts such as sodium ascorbyl phosphate, potassium ascorbyl phosphate, magnesium ascorbyl phosphate, calcium ascorbyl phosphate and sodium magnesium L-ascorbyl-2-monophosphate. Commercially available ascorbyl phosphates comprise trisodium L-ascorbyl-2-monophosphate which is available as STAY-C^®50 form DSM Nutritional Products AG, (4303 Kaiseraugst, Switzerland) and magnesium L-ascorbyl phosphate available from Showa Denko) and sodium magnesium L-ascorbyl-2-monophosphate. The preferred ascorbyl phosphate for the purposes of the present invention is trisodium L-ascorbyl-2-monophosphate.

Preferably, the ascorbic acid or ascorbic acid derivative is present in the oral care effervescent composition of the present invention in an amount of from about 0.1 to about 10 % by weight, preferably about 0.5 to about 10 % by weight, more preferable about 2 to about 6 % by weight, even more preferable about 4 to about 4.5 % by weight, each based on the based on the total weight of the effervescent composition.

Preferably, an ascorbic acid or an ascorbyl phosphate is used in the each of the embodiments above. Of these, ascorbic acid is preferred.

An oral care effervescent composition of the present invention containing ascorbic acid USP (i.e. an ascorbic acid which meets USP testing specifications) results in less ringing or scum on the surface of a container, compared to an oral care effervescent composition containing ascorbic acid DC grade, when the oral care product is dissolved in water.

Polvethyleneqlvcol:

Preferred binders/excipients/adjuvants/lubricants according to the present invention are polyethylene glycols. Preferred are polyethyleneglycols of the following formula: HO- (CH₂-CH₂-O-)_nH, with an average molecular weight from 1000 to 20000. A more preferred polyethyleneglycol is PEG 8000. The number X in the type name "PEG X" indicates the average molecular weight of the polymer. "PEG X" types, e.g. PEG 6000, are commercially available from Clariant GmbH, 65840 Sulzbach, Germany.

Flavor:

Examples of flavors are flavoring oils including oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, orange, methyl salicylate, and menthol, as well as dry or synthetic forms thereof.

Preferably, the flavor is selected from the group consisting of peppermint (flavor), spearmint (flavor), wintergreen (flavor), menthol, and mixtures thereof. More preferably, the flavor is a mixture of cinnamon, peppermint, and menthol. Sweetener:

Examples of sweeteners are sucrose, lactose, maltose, sorbitol, sodium cyclamate perillartine, dextrose, sucralose, maltodextrin, mannitol, saccharine, palatinose, and combinations thereof.

In a preferred embodiment of the present invention, the oral care effervescent composition does not contain silica acid, silicon dioxide, titan dioxide, aluminum dioxide, or strontium or zinc ions.

Preferred embodiments of the oral care effervescent composition according to the present invention are given the following table:

In a further embodiment the oral care effervescent composition according to the present invention is packaged - either in powder or tablet form - in a tea bag which is then either packed in a foil or plastic or any other package type that keeps the composition from absorbing humidity ("outer package").

The term "tea bag" as used herein denotes to a small, porous silk, paper or nylon bag, whereas typical tea bag materials may be preferably used, such as special paper fibers and so on.

The following examples are provided to further illustrate the compositions and methods of the present invention. These examples are illustrative only and are not intended to limit the scope of the invention in any way.

EXAMPLES:

Example 1 : Mouthwash Tablet

A mouthwash tablet having the ingredients listed in Table 2 is produced. Table 2 shows the amounts of each of the ingredients in a 4,300 mg tablet and in a 600 g batch of the mixture, which may then be compressed to form tablets. Table 2 also shows the weight percent of each ingredient in the mouthwash tablet and the mixture.

Example 2:

The mouthwash tablet of Example 1 was produced using the ingredients and amounts listed in Table 2.

Measure out the following ingredients and add to a blending container: Ascorbic Acid, TEAVIGO™, sodium bicarbonate, potassium bicarbonate, sucralose, color, peppermint flavor, menthol flavor, cinnamon flavor, and flavor booster. Mix all above ingredients together and set aside (Blend 1 ). Weight out and set aside the following ingredients: citric acid, canola oil, sorbitol, polyethylene glycol (PEG).

Combine Blend 1 with the citric acid and blend until all material is equally dispersed (about 15 minutes). Add the canola oil and mix thoroughly, making sure that there are no large accumulations within the blend (about 10 minutes). Screen the blend obtain a homologous powder. Add the sorbitol and mix completely until all sorbitol is equally distributed in blend (about 15 minutes). Add PEG and mix thoroughly to obtain a uniform blend of all combined ingredients (about 5 minutes).

Weigh out 4,300 mg of the uniform blend of all combined ingredients and place in an individual plastic container. Pour the uniform blend into a tablet press and compress at 100 tons of pressure. Remove the tablet from the tablet press and place into storage container.

The tablets produced have the following characteristics:

Physical Characteristics: Tablet weight = 4300mg (+/-5%); Tablet thickness = 6.23mm - 6.26mm; Tablet Hardness = 8.0 kp -9.7 kp;

Dissolution time = 2.5 minutes - 3.0 minutes; Tablet Color = opaque white color; and Tablet Smell = peppermint/ menthol/cinnamon. Example 3: Mouthwash Tablet

A mouthwash tablet having the ingredients listed in Table 3 is produced. Table 3 shows the amounts of each of the ingredients in a 1 ,200 mg tablet and a 600 g batch of the mixture, which may then be compressed to form tablets. Table 3 also shows the weight percent of each ingredient in the mouthwash tablet and the mixture.

Table 3. Ingredients of a mouthwash tablet of the present invention. The mouthwash tablets may be prepared according to the following procedure. The ingredients are passed through 1 mm sieve and mixed in an appropriate powder blender for 15 minutes. The mixture is compressed into tablets (tabletting parameters, e.g., tabletting machine Comprex II, punch 25 mm FFBE, compression force 45 kN).

The scope of the present invention is not limited by the description, examples, and suggested uses herein and modifications can be made without departing from the spirit of the invention. Thus, it is intended that the present invention cover modifications and variations of this invention provided that they come within the scope of the appended claims and their equivalents.

Claims

CLAIMS:

1. Oral care effervescent composition comprising: i) a compound selected from the group consisting of ascorbic acid, ascorbic acid salts, and ascorbylphosphates, ii) epigallocatechin gallate, and iii) a compound that produces a gas when dissolved in a solvent.

2. Composition according to claim 1 , wherein compound iii) is a compound that produces carbon dioxide when dissolved in water, preferably in acidic water.

3. Effervescent composition according to claim 1 , wherein compound iii) is selected from the group consisting of (earth) alkaline metal carbonates and (earth) alkaline metal hydrogen carbonate.

4. Effervescent composition according to any of claims 1 to 3, further comprising: iv) an organic or inorganic acid.

5. Effervescent composition according to claim 4, wherein compound iv) is selected from the group consisting of fumaric acid, citric acid, tartaric acid, sulfamic acid, and phosphonic acid.

6. Effervescent composition according to claim 4, wherein compound iv) is citric acid.

7. Effervescent composition according to any one of claims 1 to 6, wherein compound i) is ascorbic acid.

8. Effervescent composition according to claim 7, wherein compound i) is ascorbic acid USP.

9. Effervescent composition according to any of the preceding claims further comprising a colorant, preferably in an amount in the range of from about 0.001 to about 2.0 weight-%, more preferably about 0.001 to about 1.0 weight-%, even more preferably in an amount in the range of from about 0.01 to about 0.2 weight-%, each based on the total weight of the effervescent composition.

10. Effervescent composition according to claim 9, wherein the colorant is Sensient^® Fast Emerald Green Shade.

11. Effervescent composition according to any of the preceding claims further comprising at least a flavor, preferably in an amount in the range of from about 0.01 to about 5.0 weight-%, more preferably in an amount in the range of from about 0.05 to about 2.0 weight-%, each based on the total weight of the effervescent composition.

12. Effervescent composition according to claim 11 , wherein the flavor is selected from the group consisting of peppermint (flavor), spearmint (flavor), wintergreen (flavor), menthol, and any mixture thereof, preferably wherein the flavor is a mixture of cinnamon, peppermint and menthol.

13. Effervescent composition according to any of the preceding claims further comprising an excipient, adjuvant, binder and/or lubricant, preferably in an amount in the range of from about 0.25 to about 75 weight-%, based on the total weight of the effervescent composition.

14. Effervescent composition according to claim 13, wherein the excipient, adjuvant, binder and/or lubricant is polyethyleneglycol.

15. Effervescent composition according to according to any of the preceding claims further comprising a sweetener, preferably in an amount in the range of from about 1 to about 40 weight-%, more preferably in an amount in the range of from about 10 to about 30 weight-%, more preferably in an amount in the range of from about 15 to about 25 weight-%, based on the total weight of the effervescent composition..

16. Effervescent composition according to any of the preceding claims further comprising a whitener and/or a fluorine delivering compound.

17. Effervescent composition according to any of the preceding claims, wherein the amount of component i) is in the range of from about 0.1 to about 10 weight-%, preferably in the range of about 0.5 to about 10 weight-%, and/or the amount of component ii) is in the range of from about 0.01 to about 5 weight-%, preferably in the range of about 0.05 to about 5 weight-%, and/or the amount of component iii) is in the range of about 5 to about 75 weight-%, preferably in the range of from about 10 to about 50 weight-%, each based on the total weight of the effervescent composition.

18. Effervescent composition according to any of the preceding claims wherein the composition is in form of a effervescent powder (sachets) or an effervescent tablet.

19. Use of the oral care effervescent composition as defined in any of claims 1 to 18 as breath refreshing agent.

20. Method for refreshing the breath of mammals including humans comprising the step of administering an effective amount of the oral care effervescent composition as defined in any of the claims 1 to 18 dissolved in a solvent, preferably in water, to the mouth of said mammal, without ingestion of the oral care effervescent composition.

21. An oral care effervescent composition comprising: i) a compound selected from the group consisting of ascorbic acid, ascorbic acid salts, and ascorbylphosphates; preferably ascorbic acid, ii) epigallocatechin gallate, and iii) a compound selected from the group consisting of (earth) alkaline metal carbonate, (earth) alkaline metal hydrogen carbonate, and mixtures thereof, iv) an organic or inorganic acid, preferably selected from the group consisting of fumaric acid, citric acid, tartaric acid, sulfamic acid, phosphonic acid, and mixtures thereof, more preferably citric acid, v) optionally a flavor, vi) optionally a colorant, vii) a sweetener, preferably selected from the group consisting of sucralose, dextrose, maltodextrin, sorbitol, mannitol, and mixtures thereof, and viii) an excipient, adjuvant, binder and/or lubricant, preferably a polyethyleneglycol.

2. A process for the manufacture of an oral care effervescent composition as defined in any of claims 1 to 18 and 21 comprising the steps of i) mixing the ingredients to form a blend and ii) processing the blend to form either a tablet or a powder.