Note: Descriptions are shown in the official language in which they were submitted.
~~E~'~~~E~
This invention relates to an antibacterial antiplaque oral composition
dentifrice. More particularly, it relates to an oxal composition dentifrice
containing a substantially water-insoluble noncationic antibacterial agent
effective to inhibit plaque.
Dental plaque is a soft deposit which forms on teeth as opposed to
calculus which is a hard calcified deposit on teeth. Unlike calculus,
plaque may form on any part of the tooth surface, particularly including at
the gingival margin. hence, besides being unsightly, it is implicated in
the occurrence of gingivitis.
Accordingly, it is highly desirable to include antimicrobial agents
which have been known to reduce plaque in oral compositions. Frequently,
cationic antibacterial agents have been suggested. Moreover, in U.S. Patent
4,022,880 to Vinson et al, a compound providing zinc ions as an anticalculus
agent is admixed with an antibacterial agent effective to retard the growth
of plaque bacteria. A wide variety of antibacterial agents are described
with the zinc compounds including cationic materials such as guanides and
quaternary ammonium compounds as well as non-cationic compounds such as
halogenated salicylanilides and halogenated hydroxydiphenyl ethers. The
noncationic antibacterial antiplaque halogenated hydroxydiphenyl ether,
triclosan, has also been described in combination with zinc citrate
trihydrate in European Patent Publication 0161,899 to Saxton et al.
Triclosan is also disclosed in European Patent Publication 0271,332 to Davis
as a toothpaste component in a carrier system containing a solubilizing
agent such as propylene glycol.
The cationic antibacterial materials such as chlorhexidine,
benzathonium chloride and cetyl pyridinium chloride have been the subject of
greatest investigation as antibacterial antiplaque agents. However, they
are generally not effective when used with anionic materials. ldoncationic
antibacterial materials, on the other hand, can be compatible with anionic
components in an oral composition.
2
CA 02006716 1999-09-O1
However, oral compositions typically are mixtures of
numerous components and even such typically neutral materials as
humectants can affect performance of such compositions.
Moreover, even noncationic antibacterial antiplaque agents
may have limited antiplaque effectiveness with commonly used
materials such as polyphosphate anticalculus agents which are
disclosed together in British Patent Publication 22 00551 of
Gaffar et al and in EP 0251591 of Jackson et al. In Canadian
Patent Application No. 2,006,718 it is shown that the antiplaque
effectiveness is greatly enhanced by including an antibacterial-
enhancing agent (AEA) which enhances the delivery of said
antibacterial agent to, and retention thereof on, oral surfaces,
and providing optimized amounts and ratios of polyphosphate and
AEA.
Further, even when polyphosphate anticalculus agent is not
present as in Canadian Patent Application No. 2,006,718
antiplaque effectiveness on soft oral tissue is optimized by
including with the AEA a solubilizing material which dissolves
the noncationic antibacterial agent in saliva when the polishing
agent is a siliceous polishing agent present in amount of about
5-30%. Indeed, when the amount of noncationic antibacterial
agent is optimized, even the special solubilizing material is
not required, as in Canadian Patent Application No. 2,006,707
and Canadian Patent No. 2,006,703.
3
62301-1603
CA 02006716 1999-09-O1
It is an advantage of this invention that an oral
composition dentifrice containing an effective antiplaque amount
of a substantially water-insoluble noncationic antibacterial
antiplaque agent and said AEA to inhibit plaque formation and a
dentally acceptable water-insoluble polishing agent in amount of
about 30-75% is provided, wherein polyphosphate anticalculus
agent is not present.
3a
62301-1603
CA 02006716 1999-11-24
It is an advantage of this invention that the said AEA
enhance the delivery and retention of the antibacterial agent on
teeth and on soft oral tissues but Examples 1 and 3 contain 0.5-
2o propylene glycol without requiring the presence of a material
which dissolves the antibacterial agent in saliva.
It is a further advantage of this invention that an
antiplaque oral composition is provided which is directly or
indirectly effective to reduce the occurrence of gingivitis.
Additional advantages of this invention will be apparent
from consideration of the following specification.
In accordance with an aspect, this invention relates to an
oral composition dentifrice comprising in an orally acceptable
vehicle, about 30-75% of a dentally acceptable water-insoluble
polishing agent, an effective antiplaque active ingredient
amount of a substantially water insoluble noncationic anti-
bacterial agent, at least one of a surface-active agent or a
flavoring oil and about 0.005-4o by weight of the AEA, wherein
the oral composition dentifrice is substantially free of
polyphosphate anticalculus agent.
In accordance with another aspect, the invention relates to
an oral dentifrice composition comprising in an orally
acceptable vehicle, about 30-75% of a dentally acceptable water
insoluble polishing agent, about 0.01-50 of a substantially
water insoluble noncationic antibacterial agent, and about 0.05-
4% of a copolymer of malefic acid or anhydride with methyl vinyl
4
CA 02006716 1999-11-24
ether, the composition containing one or both of a surface
active agent and a flavoring oil.
In accordance with a further aspect, the invention relates
to an oral dentifrice composition comprising in an orally
acceptable vehicle, about 30-75% of a dentally acceptable water
insoluble polishing agent, about 0.01-5% of a substantially
water insoluble noncationic antibacterial agent, and about 0.05-
4% of poly (beta-styrenephosphonic acid), copoly (beta-
styrenephosphonic acid/vinyl phosphonic acid) or poly (alpha-
styrenephosphonic acid), the composition containing one or both
of a surface active agent and a flavoring oil.
In accordance with still another aspect, the invention
relates to an oral dentifrice composition comprising in an
orally acceptable vehicle, about 30-75% by weight of a dentally
acceptable water-insoluble polishing agent, an effective
antiplaque amount of a substantially water insoluble noncationic
antibacterial agent and an antibacterial-enhancing agent which
has an average molecular weight or about 1,000 to about
1,000,000, contains at least one delivery enhancing functional
group and at least one organic retention enhancing group, the
agent containing the groups being free from or substantially
free from water soluble alkali metal or ammonium synthetic
anionic linear polymer polycarboxylate salt having a molecular
weight of about 1,000 to about 1,000,000.
In accordance with a still further aspect, the invention
relates to an oral composition dentifrice comprising about 30-
4a
CA 02006716 1999-11-24
75% by weight of a dentally acceptable water insoluble polishing
agent, an effective antiplaque amount of a substantially water
insoluble noncationic antibacterial agent, about 0.05-4% by
weight of a polyvinyl phosphate having a recurring group of the
formula:
CH2-CH-
HO-P=O
I
OH
and an average molecular weight of about 1,000 to about
1,000,000 and an orally acceptable vehicle effective to enable
the antibacterial agent to dissolve in saliva in effective
antiplaque amount, wherein the oral composition has a pH of
about 4.5 to about 10.
Typical examples of water insoluble noncationic
antibacterial agents which are particularly desirable from
considerations of antiplaque effectiveness, safety and
formulation are:
Halogenated biphenyl Ethers
2',4,4'-trichloro-2'-hydroxy-diphenyl ether (Triclosan)
2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.
Halogenated Salicylanilides
4',5-dibromosalicylanilide
3,4',5-trichlorosalcylanilide
3,4',5-tribromosalicylanilide
2,3,3',5-tetrachlorosalicylanilide
3,3,3',5-tetrachlorosalicylanilide
4b
~~~.i'~~.'~a
3,5-dibromo~3'-trifluoromethyl salicylanilide
5-n-octanoyl-3'-trif:Luoromethyl salicylanilide
3,5-dibromo-4'-trifluoromethyl salicylanilide
3,5-dibromo-3°-trifluora methyl salicylanilide (Flurophene)
Benzoic Esters
Methyl - p-Hydroxybenzoic Ester
Ethyl - p-IIydroxybenzoic Ester
Propyl - p-Hydroxybenzoic Ester
Butyl - p-Hydroxybenzoic Ester
Halo~enated Carbanilides
3,4,4'-trichlorocarbanilide
3-trifluoramethyl-4,4'-dichlorocarbanilide
3,3,4'-trichlorocarbanilide
Phenolic Compounds (including phenol and its homologs, mono- and poly-
alkyl and aromatic halo (e. g. F, C1, Br, I)-phenols, resorcinol and catechol
and their derivatives and bisphenolic compounds). Such compounds include
inter alias
Phenol and its Homolo~s
Phenol
2 Methyl - Phenol
3 Methyl - Phenol
4 Methyl - Phenol
4 Ethyl - Phenol
2,4-Dimethyl - Phenol
2,5-Dimethyl - Phenol
3,4-Dimethyl - Phenol
2,6-Dimethyl - Phenol
4-n Propyl - Phenol
4-n-Butyl - Phenol
4-n-Amyl - Phenol
4-tort-Amyl - Phenol
4-n-Hexyl - Phenol
4-n-Heptyl - Phenol
2-Methoxy-4-(2-Propenyl)-Phenol (Eugenol)
2-Isopropyl-5-Methyl- Phenol (T'hymol)
Mono- and Poly-Alkyl and Aralkyl Halo~phenols
Methyl - p-Chlorophenol
Ethyl - p-Chlorphenol
n-Propyl - p-Chlorophenol
n-Butyl - p-Chlorophenol
n-Amyl - p-Chlorophenol
sec-Amyl p-Chlorophenol
n-Hexyl - p-Chlorophenol
Cyclohexyl - p-Chlorophenol
n-Heptyl - p-Chlorophenol
n-Octyl - p-Chlorophenol
6
~~~i'~~..~
0-Chlorophenol
Methyl - o-Chlorophenol
Ethyl - o-Chlorophenol
n-Propyl - o-Chlorophenol
n-Butyl - o-Chlorophenol
n-Amyl - o-Chlorophenol
tert-Amyl - o-Chlorophenol
n-Hexyl - o-chlorophenol
n-Heptyl - o-Chloropenol
p-Chlorophenol
o-Benzyl - p-Chlorophenol
o-Benzyl-m-methyl - p-Chlorophenol
o-Benzyl-m, m-dimethyl - p-Chlorophenol
o-Phenylethyl - p-Chlorophenol
o-Phenylethyl-m-methyl - p-Chlorophenol
3-Methyl - p-Chloxophenol
3,5-Dimethyl - p-Chlorophenol
6-Ethyl-3-methyl - p-Chlorophenol
b-n-Propyl-3-methyl - p-Chlorophenol
6-iso-propyl-3-methyl - p-Chlorophenol
2-Ethyl-3,5-dimethyl - p-Chlorophenol
6-se~ Butyl-3-methyl ' - p-Chlorophenol
2-iso-Propyl-3,5-dimethyl - p-Chlorophenol
6-Diethylmethyl-3-methyl - p-Chlorophenol
6-iso-Propyl-2-ethyl-3-methyl - p-Chlorophenol
2-sec Amyl-3,5-dimethyl - p-Chlorophenol
2-Diethylmethyl.-3,5-dimethyl - p-Chlorophenol
6-sec Octyl-3-methyl - p-Chlorophenol
p-Bromophenol
Methyl - p-Bromophenol
7
~~.)~~i'~~.~~
Ethyl - p-Bromophenol
n-Propyl - p-Bromophenol
n-Butyl - p-Bromophenol
n-Amyl - p-Bromophenol
sec-Amyl - p-Bromophenol
n-FIexyl - p-Bromophenol
cyclohexyl - p-Bromophenol
o-Bromophenol
tert-Amyl - o-Bromophenol
n-Hexyl - o-Bromophenol
n-Propyl-m,m-Dimethyl o-Bromophenol
-
2-Phenyl Phenol
4-Chlora-2-methyl phenol
4-chloro-3-methyl phenol
4-chloro-3,5-dimethyl
phenol
2,4-dichloro-3,5-dimethyl
phenol
3,4,5,6-tetrabromo-2-methylphenol
5-methyl-2-pentylphenol
4-isopropyl-3-methylphenol
5-chloro-2-hydroxydiphenyl
methane
Resorcinol and Its Derivat3~es
Resorcinol
Methyl - Resorcinol
Ethyl - Resorc inol
n-Propyl - Resorcinol
n-Butyl - Resorcinol
n_~yl - Resorcinol
n-Hexyl - Resorcinol
n-Heptyl - Resorcinol
n-Octyl - Resorcinol
8
~'~a~'.~.~
n-Nonyi - Resorcinol
Phenyl - Resorcinol
Benzyl - Resorcinol
Phenylethy:L- Resorcinol
Phenylpropyl- Resorcinol
p-ChlorobenzylResorcinol
5-Chloro -2,4-DihydroxydiphenylMethane
4'-Chloro -2,4-DihydroxydiphenylMethane
5-Bromo -2,4-DihydroxydiphenylMethane
4-Bromo -2,4-DihydroxydiphenylMethane
Bisphenolic Compounds
Bisphenol A
2,2'-methylene bis (4-chlorophenol)
2,2'-methylene bis (3,4,6-trichiorophenol) (hexachlorophene)
2,2'-methylene bis (4-chloro-6-bromophenol)
bis (2-hydroxy-3,5-dichlorophenyl) sulfide
bis (2-hydroxy-5-chlorobenzyl) sulfide
The noncationic antibacterial agent is present in the oral composition
in an effective antiplaque amount, typically about 0.01-5% by weight,
preferably about 0.03-1% and more preferably about 0.3-0.5%. The
antibacterial agent is substantially water-insoluble, meaning that its
solubility is less than about 1% by weight in water at 25°C and may be
even
less than about 0.1%.
The preferred halogenated diphenyl ether is triclosan. The preferred
phenolic compounds are phenol, thymol, eugenol, hexyl resorcinol and
2,2'methylene bis (4-chioro-6-bromophenol). The most preferred
antibacterial antiplaque compound is triclosan. Txiclosan is disclosed in
aforementioned U.S. Patent 4,022,880 as an antibacterial agent in
combination with an anticalculus agent which provides zinc ions and in
9
~~~'~~~..f~
German Patent Disclosure 3532860 in combination with a copper compound. In
European Patent Disclosure 0278744 it is disclosed in combination with a
tooth desensitizing agent containing a source of potassium ions. Tt is also
disclosed as an antiplaque agent in a dentifrice formulated to contain a
lamellar liquid crystal surfactant phase having a lamellar spacing of less
than 6.0 nm and which may optionally contain a zinc salt in published
European Patent Application 0161898 of Lane et al and in a dentifrice
containing zinc citrate trihydrate in published European Patent Application
0161899 to Saxton et al.
The antibacterial-enhancing agent (AEA) which enhances delivery o.f said
antibacterial agent to, and retention thereof on, oral surfaces, is employed
in amounts effective to achieve such enhancement within the range in the
oral composition of about 0.05 to about 4%, preferably about 0.1% to about
3%, more preferably about 0.5% to about 2.5% by weight.
This AEA may be a simple compound, preferably a polymerizable monomore,
more preferably a polymer, which latter 'term is entirely generic, including
for example oligomers, homopolymers, copolymers of two or more monomers,
block copolymers, graft copolymers, crass-linked polymers and copolymers,
and the like. The AEA may be natural or synthetic, and water insoluble or
preferably water (saliva) soluble or swellable (hydratable, hydrogel
forming). Tt has an (weight) average molecular weight of about 100 to about
1,000,000, preferably about 1,000 to about 1,000,000, more preferably about
2,000 or 2,500 to about 250,000 or 500,000.
The AEA ordinarily contains at least one delivery-enhancing group,
which is preferably acidic such as sulfonic, phosphinic, or more preferably
phosphonic or carboxylic, or salt thereof, e.g. alkali metal or ammonium,
and at least one organic retention-enhancing group, preferably a plurality
of both the delivery-enhancing and retention-enhancing groups, which latter
groups preferably have the formula -(X)"-R wherein X is 0, N, S, S0, SOz, P,
PO or Si or the likes, R is hydrophobic alkyl, alkenyl, acyl, aryl, alkaryl,
aralkyl, heterocycl.ic or their inert-substituted derivatives, and n is zero
or 1 or more. The aforesaid "inert-substituted derivatives", are intended
to include substituents on R which are generally non-hydrophilic and do no
significantly interfere with the desired functions of the AEA as enhancing
the delivery of the antibacterial agent to, and retention thereof on, oral
surfaces such as halo, e.g. Cl, Pr, I, and carbo and the like.
Illustrations of such retention-enhancing groups are tabulated below.
n X -(X)"R
p --- methyl, ethyl, propyl, butyl, isobutyl, t-buryl,
cyclohexyl, allyl, benzyl, phenyl, chlorophenyl, xylyl,
pyridyl, furanyl, acetyl, benzoyl, butyryl, terephthaloyl,
etC.
1 D ethoxy, benzyloxy, thioacetoxy, phenoxy, carboethoxy,
carbobenzyloxy, etc.
N ethylamino, diethylamino, propylamido, benzylamino,
benzoylamido, phenylacetamido, etc.
S thiobutyl, thioisobutyl, thioallyl, thiobenzyl, thiophenyl,
thiopropionyl; phenylth:ioacetyl, thiobenzoyl, etc.
SO butylsulfoxy, allylsulfoxy, benzylsulfoxy, phenylsulfoxy,
etc.
SOZ butylsulfonyl, allylsulfonyl, benzylsulfonyl,
phenylsulfonyl, etc.
p diethylphosphinyl, ethylvinylphosphinyl,
ethylallylphosphinyl, ethylbenzylphosphinyl,
ethylphenylphosphinyl, etc.
PO diethylphosphinoxy, ethylvinylphosphinoxy,
methylallylphosphinoxy; methylbenzylphosphinoxy,
methylphenylphosphinoxy, etc.
Si trimethylsilyl, dimethylbutylsilyl, dimethylbenzylsilyl,
dimethylvinylsilyl, dimethylallylsilyl, etc.
As employed herein, the delivery-enhancing group refers to one which
attaches or substantively, adhesively, cohesively or otherwise bonds the AEA
(carrying the antibacterial agent) to oral (e. g. tooth and gum) surfaces,
11
~~(~E~~"~~_~
thereby "delivering" the antibacterial agent to such surfaces. The organic
retention-enhancing group, generally hydrophobic, attaches or otherwise
bonds the antibacterial agent to the AEA, thereby promoting retention of the
antibacterial agent to the AF.A and indirectly on the oral surfaces. In some
instances, attachment of the antibacterial agent occurs through physical
entrapment thereof by the AEA, especially when the AEA is a cross-linked
polymer, the structure of which inherently provides increased sites for such
entrapment. The presence of a higher molecular weight, ore hydrophobic
cross-linking moiety in the cross-linked polymer still further promotes the
physical entrapment of the antibacterial agent to or by the cross-linked AFA
polymer.
Preferably, the AEf1 is an anionic polymer comprising a chain or
backbone containing repeating units each preferably containing at least one
carbon atom and preferably at least one directly or indirectly pendant,
monovalent delivery-enhancing group and at least one directly or indirectly
pendant monovalent retention-enhancing group geminally, vicinally or less
preferably otherwise bonded to atoms, preferably carbon, in the chain. Less
preferably, the polymer may contain delivery-enhancing groups and/or
retention-enhancing groups and/or other divalent atoms or groups as links in
the polymer chain instead of or in addition to carbon atoms, or as cross-
linking moieties.
It will be understood that any exacoples or illustrations of AF~I~s
disclosed herein which do not contain 'both delivery-enhancing groups and
retention enhancing groups may and preferably should be chemically modified
in known manner to obtain the preferred AEA's containing both such groups
and preferably a plurality of each such groups. In the case of the
preferred polymeric AEA's, it is desirable, for maximizing substantivity and
delivery of the antibacterial agent to oral surfaces, that the repeating
units in the polymer chain or backbone containing the acidic delivery
enhancing groups constitute at least about 10%, preferably at least about
12
507, more preferably at least about 807 up to 957 or 1007 by weight of the
polymer.
According to a preferred embodiment of this invention, the AEA
comprises a polymer containing repeating units in which one or more
phosphoric acid delivery-enhancing groups are bonded to one or more carbon
atoms in the polymer chain. An example of such an AEA is poly (vinyl
phosphoric acid) containing units of the formula:
I -[CHZ - ~H]-
P03H~
which however does not contain a retention-enhancing group. A group of the
latter type would however be present in poly (1-phosphonopropene) with units
of the formula:
II -(CH - CH]-
GH3 ~03Ha
A preferred phosphoric acid-containing AEA for use herein is poly (beta
styrene phosphoric acid) containing units of the formula:
III -(CH - CH]-
Ph ,~03Ha
wherein Ph is phenyl, the phosphoric delivery-enhancing group and the phenyl
retention-enhancing group being bonded on vicinal carbon atoms in the chain,
or a copolymer of beta styrene phosphoric acid with vinyl phosphonyl
chloride having the units of the foregoing formula III alternating or in
random association with units of formula I above, or poly (alpha styrene
phosphoric acid) containing units of the formula:
IV -[CHZ - ~ -]_
Ph~03H2
in which the delivery - and retention - enhancing groups are geminally
bonded to the chain.
These styrene phosphoric acid polymers and their copolymers with other
inert ethylenically unsaturated monomers generally have molecular weights in
13
~
CA 02006716 1999-09-O1
the range of about 2,000 to about 30,000, preferably about 2,500
to about 10,000, and are, with their methods of preparation
disclosed and claimed in Canadian Patent No. 2,006,703. Such
"inert" monomers do not significantly interfere with the
intended function of any copolymer employed as an AEA herein.
Other phosphonic-containing polymers include, for example,
phosphonated ethylene having units of the formula.
V -[CH2]14CHP03H2]n-
where n may for example be an integer or have a value
giving the polymer a molecular weight of about 3,000; and sodium
poly (butene-4,4-diphosphonate) having units of the formula:
VI -[CH2 = CH ----]-
CH2/ - CH < (P03Na2)2 and
poly (allyl bis (phosphonoethyl) amine) having units of the
formula:
VII - [CH2~CH ---] -
CH2 - N < ( P03H2 ) 2
Other phosphonated polymers, for example poly (allyl phosphono
acetate), phosphonated polymethacrylate, etc. and the geminal
disphosphonate polymers disclosed in EP Publication 0321233 may
be employed herein as AEA's, provided of course that they
contain or are modified to contain the above-defined organic
retention-enhancing groups.
In an aspect of the invention, the oral dentifrice
composition comprises an orally acceptable vehicle, about 3-75%
14
62301-1603
CA 02006716 1999-09-O1
by weight of a dentally acceptable water-insoluble polishing
agent, an effective antiplaque amount of a substantially water
insoluble noncationic antibacterial agent and an antibacterial-
enhancing agent which has an average molecular weight of about
1,000 to about 1,000,000, contains at least one delivery
enhancing functional group and at least one organic retention
enhancing group, said
14a
62301-1603
agent containing said groups being free from or substantially free from
water soluble alkali metal or ammonium synthetic anionic linear polymer
polycarboxylate salt having a molecular weight of about 1,000 to about
1,000,000
Although not used in the present invention to coact with polyphosphate
anticalculus agent, synthetic anionic polymeric polycarboxylate having a
molecular weight of about 1,000 to about 1,000,000, preferably about 30,000
to about 500,000, has been used as an inhibitor of alkaline phosphatase
enzyme in optimizing anticalculus effectiveness of linear molecularly
dehydrated polyphosphate salts, as disclosed in U.S. Patent 4,627,977 to
Gaffer et al. Indeed, in published British Patent Publication 22 00551, the
polymeric polycarboxylate is disclosed as an optional ingredient in oral
compositions containing linear molecularly dehydrated polyphosphate salts
and substantially water-insoluble noncationic antibacterial agent. It is
further observed, in the context of the present invention that such
polycarboxylate is markedly effective to enhance delivery and retention of
the noncationic antibacterial, antiplaque agent to dental surfaces when
another ingredient with which the polymeric polycarboxylate would coact
(that is, molecularly dehydrated polyphosphate) is absent; for instance,
when the ingredient with which the polymeric polycarboxylate coacts is
especially the noncationic antibacterial agent.
Synthetic anionic polymeric polycarboxylates and their complexes with
various cationic germicides, zinc and magnesium have been previously
disclosed as anticalculus agents per se in, for example U.S. Patent No.
3,429,963 to Shedlovsky; U.S. Patent No. 4,152,420 to Gaffer; U.S. Patent
No. 3,956,480 to Dichter et al; U.S. Patent No. 4,138,477 to Gaffer; and
U.S. Patent No. 4,183,914 to Gaffer et al. It is to be understood that the
synthetic anionic polymeric polycarboxylates so disclosed in these several
patents when containing or modified to contain the above-defined retention-
enhancing groups are operative as AEA's in the compositions and methods of
~~~.DFS~~~D
this invention and such disclosures are to, that extent incorporated herein
by reference thereto.
These synthetic anionic polymeric polycarboxylates are often employed
in the form of their free acids or preferably partially or more preferably
fully neutralized water soluble or water-swe11ab1e (hydratable, gel-forming)
alkali metal (e. g. potassium and preferably sodium) or ammonium salts.
Preferred are 1:4 to 4:1 copolymers of malefic anhydride or acid with another
polymerizable ethylenically unsaturated monomer, preferably methyl vinyl
ether (malefic anhydride) having a molecular weight (M.W.) of about 30,000 to
about 1,000,000, most preferably about 30,000 to about 500,000. These
copolymers are available for example as Gantrez, e.g. AN 139 (M. W. 500,000),
AN 119 (M. W. 250,000); and preferably S-97 Pharmaceutical Grade (M. W.
70,000), of GAF Corporation.
Other AEA-operative polymeric polycarboxylates containing or modified
to contain retention-enhancing gxoups include those disclosed in U.S. Patent
No. 3,956,480 referred to above, such as the 1:1 copolymers of malefic
anhydride with ethyl acxylate, hydroxyethyl methacrylate, N-vinyl-2-
pyrollidone, or ethylene, the latter being available for example as Monsanto
EMA No. 1103 M.W. 10,000 and EMA Grade 61, and 1:1 copolymers of acrylic
acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate,
isobutyl, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.
Additional operative polymeric polycarboxylates disclosed in above
referred to U.S. Patent No. 4,138,477 and 4,183,914 containing or modified
to contain retention-enhancing groups, include copolymers of malefic
anhydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic,
polyitaconic and polymaleic acids, and sulfoacrylic oligomers of M.W. as low
as 1,000, available as Uniroyal ND-2.
Suitable generally axe retention-enhancing group-containing polymerized
olefinically or ethylenically unsaturated carboxylic acids containing an
activated carbon-to-carbon olefinic double bond which readily functions in
16
~~a'~'_'~...
polymerization because of its presence in the monomer molecule either in the
alpha-beta position with respect to a carboxyl group or a part of a terminal
methylene grouping. Illustrative of such acids are acrylic, methacrylic,
ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxy propionic, sorbic,
alpha-chlorsorbic, cinnamic, beta-styrylacrylic, muconic, itaconic,
citraconic, mesaconic, glutaconic, aconitic, alpha-phenylacrylic, 2-benzyl
acrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric, malefic acids and
anhydrides. Other different olefinic monomer copolymerizable with such
carboxylic monomers includ vinylacetate, vinyl chloride, dimethyl maleate
and the like. Copolymers ordinarily contain sufficient carboxylic salt
groups for water-solubility.
Also useful herein are so-called carboxyvinyl polymers disclosed as
toothpaste components in U.S. 3,980,767 to Chown et al;U.S. 3,935,306 to
Roberts et al; U.S. 3,919,409 to Perla et al; U.S. 3,911,904 to Harrison,
and U.S. 3,711,604 to Colodney et al. 'they axe commercially available for
example under the trademarks Carbopol 934, 940 and 941 of B.F. Goodrich,
these products consisting essentially of a colloidally water-soluble polymer
of polyacrylic acid crosslinked with from about 0.75% to about 2.07 of
polyallyl sucrose or polyallyl pentaerythritol as cross linking agent, the
cross-linked structures and linkages in these and other cross-linked
polymeric AEA~s,providing the desired retention enhancement by
hydrophobicity when adequate, and/or physical entrapment of the
antibacterial agent. Polycarbophil, being polyacrylic cross-linked with
less than 0.1% divinyl glycol, the lowex proportion, molecular weight,
and/or hydrophobicity of this cross-linking agent tending to provide
decreased or no retention enhancement 2,5-dimethyl--1,5-hexadiane,
exemplifies a more effective retention-enhancing cross-linking agent.
The synthetic anionic polymeric polycarboxylate component is most often
a hydrocarbon with option halogen and 0-containing substituents and linkages
as present in for example ester, ether and OH groups, and is employed in the
17
instant compositions in approximate weight amounts of 0.05 to 47, preferably
0.05 to 3%, more preferably 0.1 to 2%.
The AEA may also comprise natural anionic polymeric polycarboxylates
containing retention-enhancing groups. Carboxymethyl cellulose and other
binding agents gums and film-formers devoid of the above-defined delivery-
enhancing and/or retention-enhancing groups are ineffective as AEA's.
As illustrative of AEA's containing phosphinic acid and/or sulfonic
acid delivery enhancing groups, there may be mentioned polymers and
copolymers containing units or moieties derived from the polymerization of
vinyl or allyl phosphinic and/or sulfonic acids substituted as needed on the
1 or 2 (or 3) carbon atom by an organic retention-enhancing group, for
example having the formula -(X)"-li defined above. Mixtures of these
monomers may be employed, and copolymers thereof with one or more inert
polymerizable thylenically unsaturated monomers such as those described
above with respect to the operative synthetic anionic polymeric
polycarboxylates. As will be noted, in these and other polymeric AEA's
operative herein, usually only one acid-.ic delivery-enhancing group is bonded
to any given carbon or other atom in the polymer backbone or branch thereon.
Polysiloxanes containing or modified to contain pendant delivery-enhancing
groups and retention enhancing groups may also be employed as AEA's herein.
Also effective as AEA's herein are ionomers containing or modified to
contain delivery-and retention-enhancing groups. Ionomers are described on
pages 546°573 of the Kirk-Othmer Encyclopedia of Chemical Technology,
third
edition, Supplement Volume, John Wiley & Sons, Inc., copywright 1984, which
description is incorporated herein by reference. Also effective as AEA's
herein, provided they contain or are modified to contain retention-enhancing
groups, are polyesters, polyurethanes and synthetic and natural polyamides
including proteins and proteinaceous materials such as collagen, poly
(argenine) and other polymerized amino acids.
18
~~~~'~.~a
Without being bound to a theory, it is believed that the AFA,
especially polymeric AEA is most often and desirably an anionic film forming
material and is thought to attach to tooth surfaces and form a continuous
film over the surfaces, thereby preventing bacterial attachment to tooth
surfaces. It is possible that the noncationic antibacterial agent forms a
complex or other form of association with the AEA, thus forming a film of a
complex or the like over tooth surfaces. The enhanced delivery and film
forming property of the AEA and the enhanced delivery and retention of the
antibacterial agent on tooth surfaces due to the AEA appears to make tooth
surfaces unfavorable for bacterial accumulation particularly since the
direct bacteriostatic action of the antibacterial agent controls bacterial
growth. Therefore, through the combination of three modes of actions: 1)
enhanced delivery, 2) long retention time on tooth surfaces, and 3)
prevention of bacterial attachment to tooth surfaces, the oral composition
is made efficacious for reducing plaque. Similar effectiveness is attained
on soft oral tissue at or near the gum line.
In aforementioned application U.S.S.N. 398,606 filed August 25, 1989
titled "Antibacterial Antiplaque Oral Composition" wherein the dentifrices
thereof contain about 5-3U% by weight of a siliceous polishing agent, a
material which solubilizes the noncationic antibacterial. agent to render it
effective in delivery to soft oral tissues at the gum line is employed. In
the present invention, wherein about 30-75% by weight of a dentally
acceptable water-insoluble polishing agent is present, it is found that the
solubilizing material is not required; but is rather optional.
In the oral preparation dentifrice, an orally acceptable vehicle
including a water-phase witty humectant is present. The humectant is
preferably glycerine and/or sorbitol. Water is present typically in amount
of about 15-35% or ~SO% by weight and glycerine and/or sorbital typically
total about ZO-75% by weight of the oral preparation dentifrice, more
typically about 25-60%. Reference hereto to sorbitol refers to the material
19
typically as available commercially in 70% aqueous solutions. The optional
ingredients which assist solubilization of the antibacterial agent in saliva
are typically incorporated in the water-humectant phase in amount of about
0.5-20% by weight. These optional solubilizing agents include humectant
polyols such propylene glycol, dipropylene glycol and hexylene glycol,
cellosolves such as methyl cellosolve and ethyl cellosolve, vegetable oils
and waxes containing at least about 12 carbons in a straight chain such as
olive oil, castor oil and petrolatum and esters such as amyl acetate, ethyl
acetate and benzyl benzoate. As used herein, "propylene glycol" includes
1,2-propylene glycol and 1,3-propylene glycol. Significant amounts of
polyethylene glycol particularly of molecular weight of 600 ar more should
be avoided since polythylene glycol effectively inhibits the antibacterial
activity of the noncationic antibacterial agent. For instance, polyethylene
glycol (PEG) 600 when present with tricolosan in a weight ratio of 25
triclosan:l PEG 600 can reduce the antibacterial activity of triclosan by a
factor of about 16 from that prevailing in the absence of the polyethylene
glycol.
The pH of such oral preparation dentifrice of the nvention is generally
in the range of about 4.5 to about 9 or 10 and preferably about 6.5 to
about 7.5. It is noteworthy that the compositions of the invention may be
applied orally at a pH below 5 without substantially decalcifying or
otherwise damaging dental enamel. The pH can be controlled with acid (e. g.
citric acid or benzoic acid) or base (e.g. sodium hydroxide) or buffered (as
with sodium citrate, benzoate, carbonate, or bicarbonate, disodium hydrogen
phosphate, sodium dihydrogen phosphate, etc.).
In this invention, the oral composition dentifrice may be substantially
pasty in character, such as a tooth paste (dental cream), although when
siliceous polishing agent is employed (which is not generally the case,
since such material is typically not employed in amount above about 30% by
weight) it can be gel in character. The vehicle of the oral composition
dentifrice contains dentally acceptable polishing material, examples of
which polishing materials are water-insoluble sodium metaphosphate,
potassium metaphosphate, tricalcium phosphate, dihydrated dicalcium
phosphate, anhydrous dicalcium phosphate,, calcium pyrophosphate, magnesium
orthophosphate, trimagnesitum phosphate, calcium carbonate, aluminum
silicate, hydrated alumina, silica, bentonite, and mixtures thereof with
each other or with hard polishing materials such as calcined alumina and
zirconium silicate, maternal including the particulate thermosetting resins
described in U.S. Pat. Ido. 3,070,510 issued Dec. 15, 1962, such as melamine-
, phenolic, and urea-formaldehydes, and cross-linked polyepoxides and
polyesters. Preferred polishing materials include insoluble sodium
metaphosphates, dicalcium phosphate and hydrated alumina.
Many of the so-called "water-insoluble" polishing materials are anionic
in character and also include small amounts of soluble material. Thus,
insoluble sodium metaphosphate may be formed in any suitable manner as
illustated by Thorpe's Dictionary of Applied Chemistry, Volume 9, 4th
Kdition, pp. 510-511. The forms of insoluble sodium metaphosphate known as
Madrell's salt and Kurrol;s salt are further examples of suitable materials.
These metaphosphate salts exhibit only a minute solubility in water, and
therefore are commonly referred to as insoluble metaphnsphates (IMP). There
is present therein a minor amount of soluble phosphate material as
impurities, usually a few percent such as up to 4~ by weight. The amount of
soluble phosphate material, which is believed to include a soluble sodium
trimetaphosphate in the case of insoluble metaphosphate, may be reduced or
eliminated by washing with water if desired. The insoluble alkali metal
metaphosphate is typically employed in powder form of a particle size such
that no more than 1% of the material is larger than 37 microns.
Hydrated alumina is an example of a polishing material which is
essentially nonionic in nature. Typically, it is small. in particle size,
i.e., at least about 857 of the particles are smaller than 20 microns and
21
C~~~>'~'~..~
is such as that classified as gibbsite (alpha alumina trihydrate) and
normally represented chemically as A120~.3H20 or A1(0H)3. The average
particle size of. gibbsite is generally about 6
to 9 microns. A typical grade has the following size distributions
Micron Percent
<30 94--99
<20 85-93
<10 56-67
~ 5 28-40
The polishing material is generally present in the cream, paste or gel
compositions in weight amounts of about 30% to about 75%.
Toothpastes or dental cream typically contain a natural or synthetic
thickener or gelling agent in proportions of about 0.1 to about 10%,
preferably about 0.5 to about 5%. A suitable thickener is syxzthetic
hectorite, a synthetic colloidal magnesium alkali metal silicate complex
clay available for example as Laponite (e.g. CP, SP 2002, D) marketed by
Laporte Industries Limited. Laponite D analysis shows, approximately by
weight, 58.00% Si02, 25.40% MgO, 3.05% Na20, 0.98% Li20); and some water and
trace metals. lts true specific gravity is 2.53 and it has an apparent
bulk density (g./ml. at 8% moisture) of 1,0.
Other suitable thickeners or gelling agents include Irish moss, iota-
carrageenan, gum tragacanth, starch, polyvinylpyrrolidone,
hydroxyethpropyl-cellulose, hydroxybutyl methyl cellulose, hydroxypropyl
methyl cellulose, hydroxyethyl cellulose (e.g. available as Natrosol) and
sodium carboxymethyl cellulose.
Without being bound to a theory whereby the advantages of this
invention are achieved, it is believed that an aqueous, humectant vehicle is
normally solubilized in the surfactant micelles in the mobile, e.g. liquid,
phase (that is, not including gelling agent and polishing agent) of a
dentrifi.ce formula. The mobile phase solution of dentifrice during use can
22
~~~i'7_'~.~a
become diluted with saliva and a portion of the antibacterial agent, e.g.
triclosan, could precipitate out. However, when the amount of polishing
agent is 30% by weight or more of the oral composition dentifrice, the
amotuit of triclosan soluble in the mobile phase is sufficient to provide
substantial antiplaque effect on soft oral tissues as well as on dental
surfaces. This effect can be increased, if desired, if a solubilizing
material compatible with the antibacteral agent which increases its
solubility in saliva is present. In this regard it is noted that the
solubi.lizing agent propylene glycol is widely used in drug delivery systems,
for instance, in European Patent Publication 0271,332 for its strong
interaction with biological membranes. It is expected that triclosan is
partitioned from aqueous environment into propylene glycol and surfactant
emulsions during use and further that propylene glycol in bulk phase allows
greater probability of triclosan emergence out of surfactant micelles,
thereby rendering triclosan mare completely available for delivery into
bacterial and soft surfaces as well as onto tooth surfaces. Similar remarks
apply to other water insoluble noncationic antibacterial agents herein
described.
The oral composition dentifrice may also contain an anticaries amount
of a fluoride ion source sufficient to supply about 25 ppm to 5000 ppm of
fluoride ions.
The sources of fluoride ions, or fluoride~providing component are well
known in the art as anti-caries agents. These compounds may be slightly
soluble in water or may be fully water-soluble. They are characterized by
their ability to release fluoride ions in water and by substantial freedom
from undesired reaction with other compounds of the oral preparation. Among
these materials are inorganic fluoride salts, such as soluble alkali metal,
alkaline earth metal salts, for example sodium fluoride, potassium fluoride,
ammonium fluoride, calcium fluoride, a copper fluoride such as cuprous
fluoride, zinc fluoride, barium fluoride, sodium fluorosilicate, ammonium
23
~~.~~i'~:~~~
fluorosilicate, sodium fluorozirconate, ammonium fluorozirconate, sodium
monofluorphasphate, aluminum mono-and di-fluorophosphate, and fluorinated
sodium calcium pyrophosphate. Alkali metal and tin fluorides, such as
sodium and stannous fluorides, sodium monafluarophosphate (MFP) and mixtures
thereof, are preferred.
The amount of .fluorine-providing compound is dependent to some extent
upon the type of compound, its solubility, and the type of oral preparation,
but it must be a non-toxic amount, generally about 0.0005 to about 3.0% in
the preparation. In a dentifrice preparation, an amount of such compound
which releases up to about 5,000 ppm of F ion by weight of the preparation
is considered satisfactory. Any suitable minimum amount of such compound
may be used, but it is preferable to employ sufficent compound to release
about X00 to 2,000 ppm, more preferably about 800 to about 1,500 ppm of
fluoride ion.
Typically, in the cases of alkali metal fluorides, this component is
present in an amount up to about 2% by weight, based on the weight of the
preparation, and preferably in the range of about 0.05% to 1%. In the case
of sodium monofluarophosphate, the compownd may be the present in an amount
of about 0.1-3%, more typically about 0.76%.
It will be understood that, as is conventional, the oral preparations
are to be sold or otherwise distributed in suitable labelled packages. Thus
a toothpaste or cream will usually be in a collapsible tube typically
aluminum, lined lead or plastic, or other squeeze, pump or pressurized
dispenser for metering out the contents, having a label describing it, in
substance, as a toothpaste, dental cream or the like.
Organic surface-active agents are used in the compositions of the
present invention to achieve increased prophylactic action. Moreover, they
assist in achieving thorough and complete dispersion of the anticalculus
agent arid antiplaque agent throughout the oral cavity, and render the
instant compositions more cosmetically acceptable. Indeed, at least one of
2G
~~~~f
surface-active agent or flavoring oil is present to effect desired
solubilization of the antibacterial agent. The organic surface-active
material is preferably anionic, nonionic or ampholytic in nature, and it is
preferred to employ as the surface-active agent a detersive material which
imparts to the composition detersive and foaming properties. Suitable
examples of anionic surfactants are water-soluble salts of higher fatty
acid monoglyceride monosulfates, such as the sodium salt of the monosulfated
monoglyceride of hydrogenated coconut oil fatty acids, higher alkyl sulfates
such as sodium lauryl. sulfate, alkyl aryl sulfonates such as sodium dodecyl
benzene sulfonate, higher alkyl sulfoacetates, higher .fatty acid esters of
1,2-dihydroxy propane sulfonate, and the substantially saturated higher
aliphatic acyl amides of lower aliphatic amino carboxylic acid compounds,
such as those having 12 to 16 carbons in the fatty acid, alkyl or acyl
radicals, and the like. Examples of the last mentioned amides are N-lauroyl
sarcosine, and the sodium, potassium, and ethanolamine salts of N-lauroyl,
N-myristoyl, or N-palmitoyl sarcosine which should be substantially free
from soap or similar higher fatty acid material. The use of these
sarcosinate compounds in the oral compositions of the present invention is
particularly advantageous since these materials exhibit a prolonged a marked
effect in the inhibition of acid formation in the oral cavity due to
carbohydrates breakdown in addition to exerting some reduction in the
solubility of tooth enamel in acid solutions. Examples of water-soluble
nonionic surfactants are condensation products of ethylene oxide with
various reactive hydrogen-containing compounds reactive therewith having
long hydrophobic chains (e. g. aliphatic chains of about 12 to 20 carbon
atoms), which condensation products ("ethoxamers") contain hydrophilic
polyoxyethylene moieties, such as condensation products of polyethylene
oxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols
(e. g. sorbitan monostearate) and polypropyleneoxide (e. g. Pluronic
materials).
~~~~o'~~.~a
Surface active agent is typically present in amo~mt of about 0.5-5% by
weight, preferably about 1-Z.5%. As indicated, surface active agent is
believed to assist in the dissolving of the noncationic antibacterial
agents.
Various other materials may be incorporated in the oral preparations of
this invention such as whitening agents, preservatives, silicones,
chlorophyll compounds and/or ammoniated material such as urea, diammonium
phosphate, and mixtures thereof. These adjuvants, where present, are
incorporated in the preparations in amounts which do not substantially
adversely affect the properties and characteristics desired. Significant
amounts of zinc, magnesium and other metal salts and materials, generally
soluble, which would complex with active components of the instant invention
are to be avoided.
Any suitable flavoring or sweetening material may also be employed.
Hxamples of suitable flavoring constituents are flavoring oils, e.g. oil of
spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus,
marjoram, cinnamon, lemon, and orange, and methyl salicylate. Suitable
sweetening agents include sucrose, lactcrse, maltose, sorbitol, xylitol,
sodium cyclamate, perillartine, AMP (aspartyl phenyl alanine, methyl ester),
saccharine and the like. Suitably, flavor and sweetening agents each or
together comprise from about 0.1% to 5% more of the preparation. Moreover,
flavor oil is believed to aid the dissolving of the antibacterial agent
together with or even in the absence of surface-active agent.
In the preferred practice of this invention an oral composition
containing the composition of the present invention is preferably applied
regularly to dental enamel, such as every day or every second or third day
or preferably from 1 to 3 times daily, at a pH of about 4.5 to about 9,
generally about 5.5 to about 8, preferably about 6 to 8, for at least 2
weeks up to 8 weeks or more up to lifetime.
26
~~~~1 6~~~
The compositions of this invention can be incorporated in lozenges, or
in chewing gum or othex products, e.g. by stirring into a warm gum base or
coating the outer surface of a gum base, illustrative of which may be
mentioned jelutong, rubber latex, vinylite resins, etc., desirably with
conventional plasticizers of softeners, sugar or other sweeteners or
carbohydrates such as glucose, sorbitol and the like.
The following examples are further illustrative of the nature of the
present invention, but it is understood that the invention is not limited
thereto. All amounts and proportions referred to herein and in the appended
claims are by weight, unless otherwise indicated.
Example 1
The following dentifrice is prepareds
Parts
A B C
Alpha Alumina Trihydrate48.00 48:00 48.00
Propylene Glycol - 0.50 0.50
Sorbitol (70%) 21.70 21.70 21.70
Gantrez S-97 (13% solution)15.00 15.00 -
Gantrez S-97 (powder) - - 2.00
Sodium Lauryl Sulfate 2.00 2.13 2.13
Sodium Saccharine 0,30 0.30 0.30
Sodium Hyroxide (50%) 1.20 1.20 1.20
Flavor Oil 0.95 0.95 0.95
Irish Moss 1.00 -
Sodium carboxymethyl - 1.00 1.00
celluose
Sodium monofluorophosphate0.76 0.76 0.76
Titanium Dioxide - 0.50 0.50
Triclosan 0.30 0.30 0.30
4later Q.S. to Q.S. to Q.S.
to
100.00100.00 100.00
27
~~~~'~~.~
The foregoing dentifrices deliver triclosan to the teeth and soft
tissue areas of the gums substantially more effectively than corresponding
dentifrices in which the Gantrez polycarboxylate is absent.
EXAMPLE 2
The following dentifrices are prepared:
Parts
Glycerine 22.00 10.00
Sorbitol (707) - 17:00
Sodium Carboxymethyl cellulose 1.00 1.00
Gantrez S-97 2.00 2.00
Sodium Saccharin 0.20 0.20
Sodium Benzoate 0.50 0.50
Sodium Monofluorophsophate 0.76 0.76
Dicalcium Phosphate Dihydrate 48.76 48.76
Triclosan 0.30 0.30
Sodium Lauryl Sulfate 1.20 1.20
Flavor Oil 0.89 0.89
Water Q:S. to 100.00 100.00
Q.S. to
The foregoing dentifrices deliver triclosanto saliva coated
hydroxyphate disk more effectively ding dentifrices;in
than correspon which
the Gantrez polycarboxylate is absent.
28
EXAMPLE 3
The following antiplaque dentifrice is prepared:
Parts
Glycerine 15.00
Propylene Glycol 2.00
Sodium Carboxymethyl cellulose J..50
Water 24.93
Vinyl Methyl Ether/Maleic Anhydride copolymer 4.76
(42~ solution)
Sodium Monofluorophosphate 0~76
Sodium Saccharin 0.30
Insoluble Sodium Metaphosphate 47.00
Titanium Dioxide 0.50
Sodium Lauryl Sulfate 2.00
Triclosan 0.30
Flavor Oil 0.95
In the foregoing Examples improved results are also achievable when
triclosan is replaced with each of phenol, 2,2'-methylene bis (4-chloro-6-
Bromophenol), eugenoi and thymol, and/or when Gantrez is replaced by other
AEA's such as Carbopols (e. g. 934), or styrene phosphoric acid polkymers
having molecular weights within the range of about 3,000 to 10,000 such as
poly (beta-styrenephosphonic acid), copolymers of vinyl phosphoric acid with
beta-styrenephosphonic acid, and poly (alpha-styrenephosphonic acid), or
sulfoacrylic oligoraers, or a 1:1 copolymer of malefic anhydridge with ethyl
acrylate.
29
CA 02006716 1999-09-O1
EXAMPLE 4
Dentifrice Mobile Phases Containing
Triclosan
Components ----- --------Composition,%w/w--------------
A B
Sorbitol (70%) 53.33 40.00
Water 40.48 39.15
Gantrez S (15%) ---- 13.33
NaOH (50%) 1.33
Saccharin 0.40 0.40
Sodium Fluoride 0.32 0.32
Flavor Oil 1.47 1.47
Sodium Lauryl Sulfate 3.33 3.33
Triclosan 0.67 0.67
The Concentration of the above components are 1.33%
dentifrice level to reflect 25% level of abrasive which may be
needed to make a complete dentifrice.
The above mobile phases of the indicated dentifrice
formulations are tested for triclosan uptake on saliva coated HA
disks following the standard procedure described in assignee's
Canadian Patent No. 2,006,703. Results are shown in Table I
below.
62301-1603
CA 02006716 1999-09-O1
TABLE I
Uptake of triclosan by Saliva Coated Hydroxyapatite (HA) Disks
from Diluted and Undiluted Dentifrice Mobile Phases.
A B
Trinlnc~n 0.67 0.67
Ionic Strength (M/L) 0.375 ----
(calculated)
PH 8.7 7.6
Triclosan Uptake (ug/disk)
Undiluted 55 122
30a
62301-1603
Gantr
~E~~Ei'°~'E.E~
The above results show a greater then two fold increase in triclosan
uptake achieved with the B formulation containing Gantrez relative to the A
formulation without the Gantrez.
EXAMPLE 5
Concentration and Uptatke of Triclosan by HA from Supernatant of 1:1
Dentifrice/Water Slurries.
Dentifrice Containing Trilosan (ug/ml) in Trilosan Uptake
0.5% Triclosan, 2.5% Supernatant of 1:1 pg/di.sk
Sodium Laurvl Sulfate Slurry
25% Hydrated Silica 1,650 52
+1.5% Gantrez S-97
50% Alumina, 1.905 74
+1.5% Gantrez S-97
Supernatents of 1:1 Dentifrice/Water slurries of the above dentifrices
are tested for concentraton of the triclosan in the supernatant and for
triclosan uptake on saliva coated 13A disks. The results indicate that using ,
50% alumina abrasive increases the triclosan substantially under low 1:1
dilution conditions (from 1,650 to 1,905), resulting in a substantial
increase in the triclosan uptake (fxom 52 to 74).
This invention has been described with respect to certain preferred
embodiments and it will be understood that modifications and variations
thereof obvious to those skilled in the art are to be included within the
purview of this application and the scope of the appended claims.
31
