CA2026907C - Oral compositions - Google Patents

Abstract

The invention relates to oral compositions such as toothpastes which contain Vitamin C and a copper compound such as coppersulphate. The tendency of these compositions to discolour, particularly if they also contain a zinc compound such as zinc citrate, can be reduced by the inclusion in the compositions of a stannous compound such as stannouspyrophosphate.

Description

1 J 7005 (R) nO}2A'r. C~MposTTIQNs"

The ~ nt invention relates to oral compositions such as mouthwashes, dentifrices, toothpastes, teeth cl~A~i~q powder~ and tablets, gels for the treatment of teeth etc. More particularly, it relates to oral compositions which contain as essential ingredients Vitamin C or a derivative thereof, such as a salt or an ester, and a copper compound which is capable of releasing copper ions such as water soluble correr (II) salts.

Such oral compositions have been described and claimed in our European patent application 0 321,282, published on 21 June 1989. Although these compositions are relatively ~table, effective products for the control of gingivitis and/or periodontitis, they show a ten~pncy to discolour, mainly at the surface of the product, not ~ - ~~only~wXen~eXposed to air upon extrusion of the toothpaste from the container, but also during storage of the toothpaste in a closed contA i n~r at various temperatures. In our above EP O 321,282 it is recommended to minimize the slight discolouration of an extruded toothpaste ribbon by formulating the toothpaste to give a lower pH of from about 4 to about 5.
We have now surprisingly found, that such discolouration can also be prevented or reduced to a significant degree by inclusion in these oral compositions of a stannous com~ , cA~A~le of releasing s~Annol~ ions in the compositions. Not only is the discolouration of the toothpaste when PYrQ~ to air upon extrusion from the container significantly re~nce~, but also the discolouration of the toothpaste which may occur in the container during storage of the toothpaste in the container.

Conseguently, the ~ e~t invention in its broadest aspect relates to an oral composition comprising vitamin 2 J 7005 (R) C or a salt or an ester thereof, and a correr com~o~.d, capable of releasing ~ ions, said composition having a reduced ten~cy to discolour upon storage and upon ex~&~~re to air, characterised in that it further contains an effective amount of a ~t~nno?~ com~ou~
capable of releasing stAnno~ ions.

We have further found, that the yL--ent invention is of particular benefit when the oral composition also contains a zinc compound. Compositions, which contain Vitamin C, a copper com~.d and a zinc compound have a greater tendency to discolour, and by inclusion of the stannous com~o~,d said discolouration i8 also significantly re~Ge~.
The s~Anno~)~ compound, useful in the ~ nt invention, can be any inorganic and/or organic stAnno--~ compound, capable of releasing st~nno~~iong~.~Typical examples of suitable s~nno~C com~o~n~C are stAnnolC fluoride, stannous chloride, stAnno~c chloride fluoride, 8~AnnO-c acetate, sodium stAnno~ fluoride, potassium stAn~o-~s fluoride, stAnno~ hexafluorozirconate, 8tAnn~c sulfate, stAnno~C tartrate, stAnno~ gluconate, stAnno~
pyrophosphate, stannous metAphosr~Ate, stannous oxalate, stannous phosphate etc.

StAnno~l~ fluoride, and particularly stannous p~ol~o~rh~te are the preferred st~nnQll~ salts. Mix~e~
of various st~nno~ salts may also be used. A preferred mixture is the mixture of stiAnno~- fluoride and stAnnQ~lc oll~o-r~te. The stAnno~ com~o~ is generally used in an amount of 0.01-10% by weight of the composition, usually 0.02-5~ by weight and preferably 0.1-3% by weight.
The oral compositions of the y~~^nt invention cont~n~ng Vitamin C, or a salt or ester thereof, a colp~ compound capable of releasing ~cll~- ions and 3 2026~07 J 7005 (R) other ingredients are substantially of the same type as more fully described in our aforesaid EP O 321,282.

Thus, the Vitamin C, or salt or ester thereof, may be present in the product of the invention in an amount of from about 0.05% to about 5%, preferably about 0.~% to about 5% by weight of the product. A mixture of two or more of ascorbic acid, ascorbic salt and ascorbic acid ester may of course be used.

Any physiologically acceptable salt of ascorbic acid may be used. Various alkali metal and alkaline earth metal salts are suitable. Other suitable salts are the ammonium salt and those derived from monoethanolamine, diethanolamine, and amino acids such as arginine and lysine.

Suitable ascorbic acid esters are those in which one or more hydroxy groups in the 2-, 3,-, 5- andlor 6-positions are fatty acid ester, sulphate or phosphate.
Examples are ascorbic acid-2-acetate, ascorbic acid-2-sulphate, ascorbic acid-2-phosphate, ascorbic acid-2-palmitate.

The copper compound is preferably incorporated in theproduct of the invention in the form of a water-soluble copper salt to provide copper ions in the aqueous liquid medium of the toothpaste. Any suitable physiologically acceptable salt may be used. Examples of suitable copper salts are copper sulphate, copper halides and pseudohalides, copper nitrate, copper salts of carboxylic acids in the homologous series formic acid to decanoic acid, copper salts of polybasic acids in the series oxalic acid to suberic acid, and copper salts of hydroxycarboxylic acids including glycolic acid, lactic a.~"~ acid, tartaric acid, malic acid and citric acid.

,. ,_~

4 2026907 J 7005 (R) The coprer co~.d may also be included in the toothpaste of the invention in the form of a copper comy~ precipitated on a solid or colloidal D~olL
such as silica, a clay (e.g. montmorillonite) or upon a biopolymer or synthetic polymer. COPPQr com~ which are substantially insoluble but which nevertheless release sufficient corp^r ions, such as copp^r hy~oLalcite, may also be used.
The amount of co~ compound, calculated as co~
which is included in compositions according to the pL~ nt invention ranges from about 1 ppm to 1000 ppm, preferably lo to 200 ppm, more preferably 30 to 100 ppm.
Examples of zinc salts suitable for use in the oral composition of the invention are disclosed in US-A-4,100,269, US-A-4,022,880, 4,160,821 and US-A-4,656,031.
These include by way of example, zinc citrate, zinc chloride and zinc ~ r~te. Examples of other zinc salts that have been pl~ are zinc carboxymethyloxysuccinate (US-A-4,144,323), zinc glycinate (US-A-4,339,432), and zinc aspartate (US-A-4,622,220). Zinc citrate is the preferred zinc salt.
The amount of the zinc salt used in the oral composition of the invention may be from about 0.05% to about 1.5%, preferably from about 0.1% to about 0.7%, calculated as zinc.
The ha 1 ~nGe of the oral composition consists of an orally acceptable medium, the nature of which ~p~nAC
upon the final application form.

The oral composition of the invention is preferably in the form of a toothpaste, by which term we include products sometimes referred to as dental creams or gels.
Toothpaste usually comprise a ~^pencion of a 2026~07 J 7005 (R) particulate solid abrasive cleAn ~ ng agent in a thirkene~
aqueous humectant liquid.

In the oral compo~ition of this invention various of the known abrasive cleA~ng agents can be used but silica abra~ives are preferred. A number of forms of silica are already known in the art as being suitable for dentifrice use including silica xerogels, precipitated silica~ and crystalline silicas. Such silicas are referred to in US-A-3,538,230 and GB-A-2,167,856. Other compatible abrasives include water-insoluble sodium me~Arhscr~-te, alumina, calcium pyror~ocrh~te and plastics materials. Alumina abrasives include the hydrated aluminas. A conventional level of abrasive ranging from 5 to 75% by weight of the toothpaste may be used. As is well know,- use of various silica abrasives permits the toothpaste to be formulated in the form of a ~ tr~n pArent or translucent gel product.

Humectants which may be used include glycerol, sorbitol syrup, polyethylene glycol, lactitol, xylitol or h~d Gyenated corn syrup. The total amount of humectant present will generally range from 10% to 85% by weight of the toothpaste, more usually 20% to 60%.
The remaining liquid phase of toothpaste according to the invention mainly comprises water which will usually amount from about 5% to about 45% by weight of the toothpaste. The amount of water in the toothpaste, including any present in the humectant, will generally~
be in the range about 5% to about 60%, such as from about 10% to about 55% by weight of the toothpaste.

Numerous b;n~i ng or thickening agents have been ~n~ic~ted for u~e in toothpastes, preferred ones being hy~L~ymethylcellulose, sodium ca~bo~ymethylcellulose and xanthan gum. Others include natural gum binders such as gum tragacanth, gum karaya and gum arabic, Irish moss 6 2026~07 J 7005 (R) alginates and carrageenans. Silica thirkening agents include the silica aerogels and various precipitated silicas. Mi~Lule_ of binders and thicken~ ng agents may be used. The amount of binder and thickenin~ agent included in a toothpaste is generally between 0.1 to 10%
by weight.

Toothpastes generally also comprise a surfactant.!
COD only used is sodium lauryl ~ rh-te but others are also known to be suitable. The amount of surfactant is lly within the range 0.5 to 5% by weight of the composition.

A variety of other known toothpaste ingredients may also be included in toothpastes formulated in accordance with the p ~ t invention. Such ingredients include an anti-caries ingredient such as cA~n and cA~n digests, hy~o~yapatites~ trimetaphosphates~sodium fluoride or sodium monofluororhosrhAte or other effective fluorine-contA~n~n~ compound; an additional anti-plaque agent such as an antimicrobial compound for example chlorheY~ne or 2,4,4'-trichloro-2' hyJko~y-~i~henyl ether; sweeten~g agent such as saccharin; an opacifying agent such as titanum dioxide; a preservative such as formalin; a flavouring agent such as reppermint oil or spearmint oil; a colouring agent; or pH ~G,.L~olling agent such as an acid, base or buffer, for example benzoic acid, to give a pH of from about 4 to about 8, preferably about 5 to about 7; anti-calculus agents such as Al~Al~metal ~ lo~p~-tes; polymers such as polyvinylmethylether-maleic a.~dkide copolymers and so on.

Preferred oral compositions of this invention contain 500-5000 ppm F, preferably 1000-2500 ppm F, as ionic fluoride or monofluoroF~Q~r~ate.

7 2~26907 J 7005 tR) For a further A~ ion of the formulation of toothpastes refe~e~,~a is made to Harry's Cosmeticology, Seventh Edition 1982, Edited by J.B. Wilk~n~Qn and R.J.
Moore, pages 609 to 617.

The following Example further illustrates the invention:

.. .. . ... . ..

- ~ 2026907 O O ~ ~
O O O U) N O O O
~a OD ~ ~ ~i ~i o I ~ O I O
O
~ a~ ~ o P: ~1 0 0 N O O O O ~ U') ~1 p, O O O 1~ N OD
O O O N ~1 O I O O O
O O
O
~` 3 O
- 0 a ~ o ~1 0 0 O O ~ O O O O U~ ~
a~ oo . o . o o l~n ~ OD ............... .
11~ O O O N ~1 0 1 1 0 0 3 ~ , o o o o O N O
~ ~ O
._ .... N r-l O ~1 t~ o o In o o It) ~ co o o o o o _I O tOO ~1 ~1 ~1 0 0 0 N ~1 0 1 1 1 ~) o . .
oo J~ ~

~ ~
C .C f ~ ~
O _ a~
~ ~ O

X ~ ~ F. H

-- -- O -- ~ O 1~ 0 j --I _I O
u~ U~ X U.~ U~ ~0 V P ~ U~ UJ ~

-9 2~26~7 J 7005 (R) These pa~tes were made with a green colour, and a ~imilar ~eries was made without the green colour to leave them white. The pastes were tubed on the same day S of manufacture. They were ~h~^quently stored at con~olled temperatures of 6, 20 and 37C. Visual observations for discolouration were made after three and six month's storage. Water-extractable vitamin C was al~o determined, by titration with dichloror~enol ~nA~r~nol~ and with iodine. $he following results were obtained.

A B C D
Discolouration 15 after 3 months at 6C + ++
20C + ++
37C ++ +++ + +

20 After 6 months at 6C + ++
20C + ++ -/+
37C ++ +++ + ++

The number of plus signs corresponds with an increasing degree of brown discolouration ranging from very slight discolouration (+) to very severe darkish discolouration (Illll); a minus sign indicates no substantial brown discolouration.
The residual water-extractable Vitamin C levels (in %) after 8iX months' storage were:
A B C D
at 6C 1.94 1.97 2.0 1.9 35at 20C 1.82 1.79 1.8 1.8 at 37C 1.53 1.40 0.8 <0.1

Claims (5)

1. An oral composition with a reduced tendency to discolour upon storage and upon exposure to air, comprising in an orally acceptable medium, from 0.05% to 5% by weight of vitamin C or a salt or an ester thereof, and from 1 ppm to 1000 ppm, calculated as copper, of a copper-ions releasing copper compound, the composition further comprising from 0.01% to 10% by weight of a stannous-ions releasing stannous compound.

2. An oral composition according to claim 1, comprising from 0.1-3% by weight of the stannous compound.

3. An oral composition according to claim 1, wherein the stannous compound is stannousfluoride or stannouspyrophosphate or a mixture thereof.

4. An oral composition according to claim 1, further containing from 0.05% to 1.5% by weight, calculated as zinc, of a zinc salt.

5. An oral composition according to claim 4, wherein the zinc salt is zinc citrate.