Note: Descriptions are shown in the official language in which they were submitted.
2026907
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
- 2026907
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
