Note: Descriptions are shown in the official language in which they were submitted.
l~Bfd4Z9 :;
.
Back~round of the Invention
The present invention relates to a method for
retarding pellicle and plaque formation and dental prepara- ~
tions employed ~or such purpose. More specifically, the ~-
present invention relates to a method for retarding pellicle
and plaque formation by contacting sites of plaque formation
and growth (i.e., the oral cavity) with certain fatty acid
amido compounds ana/or salts thereof and dental preparations
containing the fatty acid amido compounds and/or salts thereof.
Dental pellicle is a soft deposit tenac~ously held
on the ~ur~aces o~ the teeth w~ich includes salivary protein.
Dental plaque is a product o~ microbial growth, i~ tenaciously
attached to the surfaces of the teeth and adjacent gingiva,
and exhibits a definite microscopic structure. If not re-
moved, the plaque will become mineralized to form calculus
and eventually lead to dental caries. Dental experts gen-
era]Lly believe that calculus, also known as tartar, is dental
plaque which has become mineralized with calcium phosphate,
magnesium phosphate, calcium carbonate and other trace min-
erals found in the mouth. If calculus is not removed from
around the teeth and under the gum, inflammation can result
which can ultimately lead to periodontal disease and subse-
quent tooth loss.
; Although plaque can be removed from the teeth by
thorough abrasive action, it quickly reforms on the tooth
surface. Accordingly, the incidence of dental ca]Lculus and
subsequent periodontal disease can be reduced by reducing or
~ .
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181~1~29
preventing the deposition of plaque and by means which prevent
mineralization of the plaque.
It is therefore an object of the present invention
to provide a method for retarding pellicle and plaque forma~
tion, and to provide compositions containing active ingred~
ients which retard pellicle and plaque deposition. Another
object of the present invention is to provide nontoxic denti-
frice preparations or retarding pellicle and plaque forma- `
tion. The dentifrice preparations include toothpastes, dental
creams, tooth powders, mouthwashes, lozenges, tablets, aerosol
spray~, chewing gum, toothpicks, dental floss, denture clean-
ser~, and the like.
:~ ,. '
',.
.' "' ,' '
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~0884~
Summary of the Invention
One aspect of the present invention is a method ~-
for retarding pellicle and plaque deposition which comprises
intermittently contacting sites of plaque formation and
growth with a preparation comprising, in an amount sufficient
to retard pellicle and plaque formation, a compound of the
formula~
. . .
R -~ C ~ A - 11~3 - B - X~
R2 n
whereln R ls a monovalent or diyalent hydrocarbyl c;roup con-
taining at lea~t 14 carbon atoms, n is one when R is mono- ; ;
valent and is 2 when R is divalent; Rl is H or an alkyl group
.:
containing from 1 to about 3 carbon atoms; A is a divaLent
hydrocarbon bridge containing from 1 to about 6 carbon atoms;
B is a divalent alkylene or alkylidene bridge containing from
1 or 2 carbon atoms; each R2 individually is an alk~l group
containing ~rom 1 to about 5 carbon atoms; or both R2 groups
are interconnected to form a heterocyclic ring with the
atom to w~ich they are attached and containing 5 to 6 members
; in -the ring; and X is a carboxylate or sulfonate group; and/or
nontoxic, physiologically and orally acceptable salts of said
. compound.
The present inven~ion is also concerned with cer- ;
-tain dentifrice preparations containing an amount sufficient ~ .
to retard pellicle and plaque formation of a compound of for-
mula (1) above and/or nontoxic, physiologically and orally
acceptable salts of said compound O.e ~ormula (l).
.; .
, .
Description of Preferrea Embodiments ~ ;
The objectives of the present invention are accom-
plished by dental preparations which contain a compound of
the formula:
R +C ~ -- X ~
R2 n
wherein R in the above formula is a hydrocarbyl group con-
taining at least 14 carbon atoms. R usually contains no more - ;
than about 21 carbon atoms, and prefexably rom 15 to ~bout
21 carbon atom5; and most prefer~bly rom 15 to a~out 17 car-
bon atoms. Example9 o~ some suitable hydrocarbyl groups in-
.
clude aliphatic hydrocarbon groups; alkaryl groups; aral~yl
~ groups; alXacycloalkyl groups; and cycloalkalkyl groups.
-~ 15 The preferred hydrocarbyl group is an aliphatic hydrocarbon
group. ~he aliphatic hydrocarbon group can be saturated or
can be ethylenically unsaturated and can be straight chain
or branched chain. Examples of some suitable aliphatic
hydrocarbon groUps include pentadecyl, heptadecyl, tetra-
~, ~ 20 decyl, and heptadecenyl. The aryl portion of the alkaryl
and aralkyl groups include phenyl and naphthyl. The cyclo-
I alkyl portion o~ the alkacy~loalkyl an~ cycloalkalkyl groups
3 include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl,
R can be monovalent or dival~nt and is preferably monovalent
W~en R is monovalent, n is 1 and when R is divalen~ n is 2.
Rl is hydrogen or an alkyl group containing from 1
to about 3, carbon atom~ such as methyl, ethyl, a~d propyl.
'
~ . ..
I ;
-5-
~ ` ~
~01~384Z~
Rl is preferably hydrogen or methyl and most preferably is
hydrogen.
A is a divalent hydrocarbon bridge containing from
1 to abou-t 6 carbon atoms. A can be straight chain or
branched chain and includes alkylene groups, alXylidene
groups, cycloal~ylene groups, and arylene groups. Examples
of some suitable alkylene groups include methylene, ethylene,
propylene, butylene, pentylene a~d hexylene Examples of
some suitable alkylidene groups include ethylidene and iso-
propylidene. Examples o~ cycloalkylene groups include cyclo-
propylene, cyclobutylene, cyclopent~lene, and cyclohexylene.
~n ex~mple of an ar~le~e group includes phenylene. Pre~erably A
is an alkylene or al~ylidene group. Most preerably A is an
alkylene or alkylidene group containing l to 3 carbon atoms~
B is a divalent alkylene or alkylidene bridge
containing l or 2 carbon atoms. Examples of some suitable
alkylene groups include methylene and ethylene~ An example
o~ a suitable alkylidene group includes ethylidene~
Il .
X is a carboxylate [C00] or a sulfonate [11-0]
group, and preferably is a carboxylate group. It has been
observed that compounds wherein X is carboxylate provided
greater inhibition against pellicle and-plaque formation as ~ -compared to compounds wherein X is sulfonate~ Moreover,
compounds wherein X is carboxylate are preferred since such
;; 25 compounds can be used with water as the carrier; whereas,
those compounds wherein X is sulfona~e are not readil~y dis-
persible in water and re~uire an organic carrier such as
propylene glycol.
'"',.
-6-
~38~zi~
,~ :,. . .
Each R2 individually is an alkyl group containing
from 1 to about 5 carbon atoms; or both R2 groups are inter- ~ :
connected to form a 'neterocyclic ring w.ith the N atom to
which they are attached and containing 5 to 6 members in the ~ :
ring. Examples of some heterocyclic rings include morpholinyl,
piperidinyl, pyrrolidinyl, and piperazlny:L. Preferably R2 ~ :
is an alkyl group. The alkyl group preferably contains 1 to :. . .
3 carbon atoms and most preferably is methyl.
The preferred compounds employed in the present ~ .
invention have the ollowing structural foxmula:
0 H CH3
R - C ~ - ~C~I2)~ ~ B - C - 09 (2)
CH3 O
wherein R is an aliphatic hydrocarbon group containing at
least 14 carbon atoms; B is the s~me as defined hereinabove,
and m is a whole number integer from 1 to 3; andJor nonto~ic,
i physiologically and orally acceptable salts of the compound
o~ ormula ~2).
E~amples of some specific compounds suitabl~ for
the present invention include compounds of the ollowing
structural formula: .
- C - ~ - (CB2)3 - ~ - B - X~ (3
CH3 ...
wherein
"~
',
:~ ~7~ . . .:
8~Z~9
R B X _ ~ame
pentadecyl CH2 C-O palmitic amido be-taine
O . .:
heptadecyl CH2 ICl-O stearic amido betaine
0
heptadecenyl CH2 C-O oleic amido betaine
~ ' ''
pentadecyl -CH- C-O D~-N-carboxymethyl-
methyl-M,~-dimethyl-
. CH3 ~-~3-palmitamido-propyl)-
. ammonium betaine
pentadecyl (CH2)2 C-O N-car.boxyethyl-N,M-di-
methyl-N-(3-palmitamido-
propyl)-ammonium betaine
heptadecenyl -C~I- C-ODL-N-carboxymethylmethyl-
C~I O N,N-dimeth~l-N~(3-oleyl-
3 ~midopropyl)-ammonium
betaine
i heptadecenyl (C~2)2 C-O N-carboxyethyl-~, -
ll dimethyl-N-(3-oleyl-
amidopropyl)-ammonium
betaine
heptadecyl -CH- C-O DL-N-carboxymethylmethyl-
I 1I N,N-dimethyl-N-(3-stear-
CH3 0 amldopropyl)-ammonium
betaine
heptadec~l -(CH2)2 C-O N-carboxyethyl-~,N-di-
methyl-N-(3-stearamido-
. p~opyl)-ammonium betaine.
pentadecyl (CH2)2 0 2-[N~N-dimethyl-~-(3-
_0 palmitamidoprc?pyl)-amino~ .
11 ethanesul:Eobetaine :.~
O :,
heptadecenyl (CH2)2 0 2-[~,N-dimethyl-~-(3- ~ :
S-O oleylamidopropyl)-amino] ... ~.
ll ethanesulfobetaine ... :.
O , .: . .
heptadecyl (CH2)2 0 2-[N~N-dimethyl-N-(3- . ~.
1 stearamidopropyl)-amino] ...
SI-O ethanesul~obetaine ;,
:-:
. ~:
.; 8 ::-
.. .... . ..
:: ~0~8~g ~ ;
In addition, nontoxic salts suitable for use in
the human oral cavity, which, include both acid and base addition -
salts of the above compounds, can be used in the present
invention. Suitable salts include citrate, acetate, maleate,
lactate, and phosphate salts.
It has been observed that compounds similar to
those employed according to the present invention, except
that R contains less than 1~ carbon atoms, do not retard
plaque and pellicle deposition as achieved by the present
invention. In particular, it has been observed that coconut
amido betaine availahle under the trade designation "Tego-
betaine C"* ~rom T. H. ~,oldschmidt, and lauric myristic amido
betaine available under the trade designation "Schercotaine"**
~MAB from Scher Brothers, Inc., Clifton, New Jersev do not
provide plaque inhibition activity. "Tegobetaine C" is a
coconut amido propyl betaine having the general structure
described above in formula (3) except that RC is from a
coconut fatty acid which presumably includes minor amounts
of fatty acids having 15 carbon atoms or more. However, in
view o the small quantities o~ R groups having at least
1~ carbon atoms in "Tegobetaine C", the concentration oE com-
pounds of the type falling within the scope of this inven-
tion, are apparently not sufficient to retard the formation
of plaque and pellicle.
In addition, as will be shown hereinbelow, ~
Denta Fresh ~ a denture cleanser commercially available from ~ :
Noxell, the assignee of the pre~ent application, which
contains about 15~ by weight of "Tegobetaine C" does not in-
hibit
',':.,".
.. ~: :.
* Trademark
** Trademark - 9 -
:
:' . .'' '
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~08134Z9
the formation o~ plaque. With respect to Denta Fresh~, it
is believed that not only is the amount of compounds within
~he scope of the present invention insufficient to retard -
plaque and pellicle formation but also that the formu1ation
includes materials such as sodium lauryl sulfate which ma~
interact with the betaines in the composition to provide
products of a type that do not exhibit plaque retarding pro-
perties. This is demonstrated by the fact that betaines
within the scope of the present invention were used in place
; 10 of Tegobetaine C in Denta Fresh~ but such composition~ still
did not retard plaque formation as will be shown hereinbelow.
In particular, 9ee Examples 17A-C.
Varlous of the compounds 9uitable ~or the present
invention are available. For instance, a preparation con-
taining isostearic amido betaine is available under the trade
designation 'Schercotaine'IAB, and a preparation containing
-~ palmitic amido betaine is available under the trade designa-
tion "Schercotaine"PAB from Scher Brothers, Inc. A discussion
of various amido compound~ including those suitable for use
in the`pre9ent invention as well as those outside the SCOpQ . .
of the present invention can be found in a publication
. : .
entitled "Tegobetaine Chemistry", Goldschmidt Chemical
Corporation, 153 Waverly Place, ~ew York City, ~ew York,
` ::
and in U.S. patent 3,280,179 to Ernst
.. . . ..
The compounds suitable for the present invention
can be prepared, ~or instance, by reacting a diamine! of the
formula:
. , ' '.
Trademark
~l 3
`~ 89~2~ `
Il lR2
H - N - A - N (4) -
R2 ~. ... .. I
with a mono- or dicarboxylic acid of the formula: :
O ~ '.- .
~5)
R- -COH n
to provide an amido amine of the formula: :
IR2
R T C - N - A - N ~ H2O ~6)
L R2 n
The progress o~ khis reaction can be readily monitored by
mea~uring the amount of water ormed~ ~hen a monocarbo~ylic
acid ia employed, the acid and amine are used in about equi- :
' molar quantities. When a dicarboxylic acid is employed, the .
- ~5 molar ratio of acid to amine is about 1:2~ After the amido- :
amine is isolated from the reaction mixture, it is reacted
with a quaternizing agent such as chloroacetic acid, 2- : .
chloropropionic acid, 3-chloropropionic acid, and sodium salt
o~ 2-chloroethane-~ul~onlc acid, according to the ~ollowing.
reaction which shows chloroacetic acid as an exemplary reac- ..
tant ~or convenience to provide compounds employed according .: -
to the present invention. - -~
. O Rl lR2- .: ~.
:. R - -C - ~ - A - ~ ~ ClCH2COOH ) . -
:: 25 _ R2 :
~ O Rl 12
R- -C - ~ - A - ~ - CEI2C - Oe ~ HCl
_ R2 _
8~Z9
This latter reaction can be carried out under reflux for
convenience when desired. The meanings of R, Rl, R2, ~, and
A are the same as discussed hereinabove.
Examples of some diamines o~ formula (4) include
3-dimethylaminopropylamine; para-aminodiethylaniline; para-
aminodimethylaniline; N-aminoethylpiperazine, N-aminopropyl-
morpholine; 3-diethylaminopropylamine; 3-ethylmethylamino- !
propylamine; and dimethylaminome-thylamine.
Examples of some carboxylic acids o ormula (5)
include stearic acid; behenic acid; isostearic acid; palmitic
acid: oleic acid; linoleic acid; linolenic acid; erucic acid;
and pentadecanoic acid.
The fatty acid amido compounds employed according
to the present invention are intermittently contacted with
sites of plaque formation and growth such as the oral cavity
in the form of a dental preparation. The fatty acid amido ;
compounds can be utilized -to retard pellicle and plaque for-
mation on dentures by soaking dentures in a suitable prepar-
ation. Accordingly, sites o~ plaque ormation and growth as
used herein refer to the oral ca~ity as well as dentures or
alse teeth while located in or out of the oral ca~ity.
The term "dental preparation" which is used herein
, is intended to designate products which in the ordinary courseo~ usage are retained in contact with sites for plaq~le for- ;
-'~ 25 mation and grow-th such as in the human oral cavit~ or a t~mesufficient to contact substantially all of the dental sur-
faces but are not intentionally ingested.
, ' ~ '
,
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4Z!~
When the fatty acid amido compounds are to be
utilized in the oral cavity, such compounds are provided in
a nontoxic carrier suitable for use in the oral cavity.
For example, the fatty acid amido compounds when X is car-
boxylate can be dispersed in water and used as such. Some
preparations to which the present invention are directed
include toothpastes, dental creams, tooth powders, mouth
rinses, lozenges, tablets, aerosol sprays, chewing gum,
dental floss, toothpicks, and denture cleansers. The amount
of the fatty acid amido compound employed according to the
present invention is at least su~icient to provlde a compo-
~ition which retards pellicle and plaque formation and is
generally at least about 1% by weight and preferab~ at least
about 5% by weight o the fatty acid amido compound in the `` ;
dental preparation. The maximum amount of fatty acid amido
compound is dependent primarily upon economical and practical
considerations and is generally about 25% by weight in the
. .' .
' dental preparation~
In addition, the threshold efective amount of any
atty acid amido compound is not only dependent upon the
i absoluts ~uantity o the fatty acid amido compo~md in the ~-
preparation but may also be dependent somewhat upon the amount ~ --
, .
o the fatt~ acid amido compound relative to other constit-
. , .
uents in the particular preparation, and the type of other
2g constituents in the particular preparation~ For instance,
if the preparation contains an ingredient which interacts
with the fatty acid amido compound to render it inactive, it
is apparent that the amount o amido compound must be in
''
; 13
.", ~ .
~(188~Z9
excess of that which is interacted. Furthermore, the degree
of rinsing after a treatment may have some efect upon the
amount necessary. For instance, little or no rinsing may
result in some buildup of the compound on the teeth which
would reduce the amount needed in subse~lent treatments. The
minimum amount of the ~atty acid amido compound required or
any particular preparation is readily ascertainable wi~hout
undue experimentation.
That the minimum effective amount is not dependent
solely upon the absolute quantity o the fatty acid amido
compound i5 emphàsized by the observation that compositions
containing about 2.5% palmitic amido betaine or less, about
10% ethyl alcohol, up to about 5% ~aCl and the remainder
being water; and compositions containing about 2.5% palmitic
amido betaine, about 10% by weight of silica, about 56% by
weight sorbitol, up to 5% ~aCl and the remainder wa-ter, did
not retard plaque formation; whereas, compositions -the same
as the above compositions except that no rinsing was carried
out after treatment therewith, prevented the ormation of
plaque. In addition, it has been observed that compositions
containing about 5% palmitic amido betaine and about 95%
water re-tarded plaque formation; whereas, compositions con-
taining about 5% palmitic amido betaine, about 8% of silica,
.
about 50.5% of sorbitol, and about 36 5% by weight of water
were marginally effective in that sometimes the composition
exhibited retardation of pla~ue while other times the com-
position did not.
:
It was urther observed that various compositions
'
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884Z~ ~
containing about 5% isostearic amido betaine or 5% stearic
amido betaine including one which contained about 5% by weight
of isostearic amido betaine, about 24% by weight of glycerin,
about 1% by weight of propylene glycol, about 0.75% by weight
of carboxyme-thyl cellulose, and cibout 69.25% by weight of water
did no-t exhibit plaque inhibition activity; whereas, a compo-
....
sition containing about 5% by weight of isostearic amido be-
taine and being similar to the above composition except that
.. .
it contained about 0.75% of hydroxyethyl cellulose in place -
of the carboxymethyl cellulose retarded plaque formation and
exhibited moderate plaque inhibition.
When preparing dental preparations according to the
present invention and particularly for application in the
.:
oral cavity, carriers and other additives suitable for the ~
.:
oral cavity and which are compatible with the fatty acid amido
compound and each other such as, for example, sudsing agents,
flavoring agents, abrasive polishing compounds, humectants,
and sweetening agents can be employed. The amount and type
of these additive materials used can be varied greatly. In
addition, the pH of dental preparations employed according
to the present invention and particularly those for use in
the oral cavity is usually between about 3 and about 9, and
preferably between about 5 and about 7.5. The additives and
pH for denture preparations not to be used in the oral cavity
2~ need not be suitable for the oral cavity.
i : ~
Examples of some suitable water-insoluble abrasive
- polishing agents include dicalcium phosphate, hydrated alum-
inum oxide, calcium carbonate, calcium polymetaphosphate,
,,.~, .
, ~:
-15~
1(~88~Z9
dicalcium orthophosphate dihydrate, sodium polymetaphosphatet
and various resinous abrasive materials such as particulate
polyethylene, melamines, phenolics, ureas, melamine-ureas,
melamine-~ormaldeh~des, urea-formaldehydes, melamine-urea-
formaldehydes, and cross-linked polyesters. Mixtures of
abrasive polishing agents can be employed when desired.
A preferred abrasive agent is hydrated aluminum ~;
oxide since it has been observed that preparations of the
present invention containing hydrated aluminum oxide exhibit
greater plaque inhibition as compared to preparations con-
taining certain phosphate abrasives. Although not preEerred,
the phosphate abrasive~ can be employed when desired since
the ~atty acid amldo compounds demonstrate plaque inhibltion
in their presence, the degree o~ which is dependent somewhat
upon their respective concentrations~ The total amount of
abrasive agent, when present, can range from about 0.5% to
about 95% by weight of the dental preparation. Preferably
toothpastes con-tain from about 5 to about 60% by weight of
abras~ve with the abrasive particle size pre~erably ranging
~rom about 2 microns to about 20 microns~
Suitable sudsing agents for use according to the ;
present invention are those which are reasonably stable and
form suds throughout a wide pH range and are acceptable for
use in the oral cavity. Examples of some suitable sudsing
agents include water-soluble salts o~ sulfonated monogly-
cerides o~ fatty acids having from about 10 to about 18
; ;. :
carbon atoms such as sodium coconut monoglyceride sulfonate; -
water-soluble salts of ~atty acid amines o~ taurine suah as
~': .
-16-
~: 10884;Z9 -
sodium N-methyl-N-palmitoyl tauride; water-soluble salts of
fatty acid esters of isethionic acid such as the coconut acid
ester of sodium isethionate; substantially saturated aliphatic
acyl amides of saturated aliphatic monoamino carboxylic acid
having from about 2 to about 6 carbon atoms and in which the
acyl radical contains from ~bout 12 to ahout 16 carbon atoms ; -
such as sodium ~-lauroyl sarcosinate; and the polyoxyalkylene ~;
polyols such as the Pluronics from Wyandotte Corporation.
Likewise, mixtures of the sudsing agents can be employed when
desired. Generally, the sudsing agent, when present, is-em~
ployed in amounts ranging from about 0.5% to about 5.0% by
weight.
Moreover, when de5ired, flavoring agents can be
included in the dental preparations employed according to the
present invention and include such flavoring agents as oil o~
wintergreen, oil of peppermint, oil of anise, citrus flavors,
and vanillin. Likewise, various sweetening agents such as,
or example, saccharin, dextrose, mannitol, levulose, and
sodium cyclamate can be employed when desired.
; 20 In certain of the compositions contemplated b~ the
present invention, such as toothpaste, it is generally desir-
able to employ thickening agents, e~emplary of which are
hydroxyethyl cellulose, water-soluble salts of cellulose -
, .~ . ; ~
ethers, including sodium carboxymethyl cellulose and sodium
,'! . :. -.
` 25 carboxymethylhydroxyethyl cellulose, and natural gums such
as gum karaya, gum arabic and gum tragacanth. In addition,
.,:
colloidal magnesium aluminum silicate or finely divided
silica such as silica aerogels and microfine precipitated
. .
* Trad~mark
_
~, .. , ~' . .
~()88429 ~:
. ` . .
silicas can be used as part of the thickening agent to fur-
ther improve te~ture in such compositions as toothpastes.
The thickening agents are generally employed in amounts from
~ . . . .
. .
about 0.1 to ~bout 15% by weight when utilized.
The preferred thickening agents are the natural
gums and finely divided silica, particularly since it has
been observed that preparations o the present invention
., :. . .
`' containing such thic~ening agents exhibit greater plaque
inhibition as ¢ompared to preparations containing cert:ain
other thickening agents in certain amounts such as hydroxy- -
ethyl cellulose, sodium carboxymethyl cellulose, and magnesium `
'~ aluminum silicate. Although not preferred, the above thic~-
, ening agents aan be used when desired since the ~atty acid
i7 amido compound demonstrate plaque inhibition in their pre-
- .
, 15 sence, the degree o which is dependent somewhat upon their~- ;
, .; , ,.' :
I ~ respective concentrations.
~l In addition, in certaln of the dental preparations ;
~ employed in the present invention, such as toothpastes, it
... . .
~ may be desirable to include a humectant or a viscosity mod-
., . :. . .
' 20 ifying material. Examples Oe some suitable humectants in- ~ ;
.j .... ...
clude nontoxic polyhydric alcohols such as glycerin, sorbitol,
mannitol, propylene~glycol, polyethylene glycol, polypropy
lene glycol, and mixtures thereof. The humectants are gen~
erally present in amounts up to about 40% hy weight o~ the
j , : ~' '::
~25 dental preparation.
A typical toothpaste of the present invention can
:
~contain the amido compound in an amount suficient to retard
plaque and pellicle foxmation, from about 5% -to ~bout 60%
. '; : ~ ~ ' ~ '
! , ' . .: .
.. .
~ 18~
lQ1389L~9
' ~,
by weight of an abrasive polishing agent, from ahout 0.5%
to about 5% by weight of a sudsing ayent, from about 0.1% to ~ ;
about 15% by weight of a thickening agent, and the balance
being substantially water and humectants. A -typical mouth-
wash composition suitable for practicing the present invention
can contain the amido compound in an amount sufficient to
retard pellicle and plaque formation, a sudsing agent, ethyl
alcohol, humectant, sweetener, flavor, and water. A typical
chewing gum composition useful for the present invent~Lon can
contain the amido compound in an amount su~ficient to retard
pellicle and plaque formation, and a gum base. A prophylactic
paste suitable for the presenk invention can include the
amido compound in an amount su~ficient to retard pellicle and
plaque ormation and pumice. ~ -
In addition, the present invention can be practiced
, by coating and impregnating dental floss or toothpicks with ;
a composition containing the amido compound of the present
invention. The coating operation can be carried out by any
means well known for coating and impreynating fibers such as
by passing dental floss or toothpicks through an aqueous bath
of the amido compounds and then permitting the water to
i evaporate, e.g., by heating under vacuum.
;~ The following nonlimiting examples are provide~ to
~ further demonstrate the present invention. -
,' ,''-' .
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.. ' ' , ~~: - 1 9- :
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108~429
.
Example 1 - Part A
A set of three extracted human teeth without the
roots is mounted on a plastic strip of ahout 1 inch x 3 inches~
The teeth are then swabbed with human saliva using a sterile
'~acron"swab and allowed to dry for about 15 minutes. The
.
strip is then placed in a petri dish and covered with about
200 ml of an aqueous solution of about 2% trypticase and
about 4% sucrose. Each dish is then inoculated with an
additional 1 ml of human saliva and then incubated at about
37C for about 24 hours.
~ext, the set of teeth is removed from the media,
dried, and then dipped into a 0~5% agueous solution of FD & C
RED No. 3 to visually disclose the pla~ue. The strip is then ~ ;
rinsed under tap water.
....
The teeth show heavy plaque growth. The teeth are
then brushed with an electric toothbrush fitted with a so~t
nylon brush carrying a composition containing about 25% by ~ -
3 weight of a palmitic amido betaine, a~out 2-5% ~aCl and the
remainder water, available under the trade designation
;l . . ;
"Schero~ne ** PAB, until all of the red disclosed pla~ue is
removed and are then rinsed. ~
The teeth are then again swabbed wi~h human saliva, ; ~ ;
:; . . - - ,
3 placed in a petri dish covered with the trypticase-sucrose ~
.; - . ~ ,- .:
media, which is then inoculated with an additional 1 ml of
~ 25 saliva and incubated for ~bout 24 hours at about 37C. A~ -;~ the end of the 24 hours, the set of teeth is removed from the
media, dried, and dipped into a 0.5% FD ~ C RED ~To. 3 solu-
tion for about 60 seconds to visually disclose ~he presence
* Trademark of Du Pont for polyethylene terephtha~ate polyester.
** Trademark
:
:1 B~ -20-
: . . .
1088~Z9 ` `
of plaque and is then rinsea under tap water. No plaque
growth is observed on the teeth brushed with the ~chercotaine
PAB. The palmitic amido betaine effectively inhibits the
redeposition of dental plaque on the teeth.
. .
Comparison - Part B
The general procedure of Part A of this example is
... . . .
repeated except that the set of teeth employed is brushed
with water until all of the red disclosed plaque is removed.
The results after the second 24-hour incubation show heavy
plaque growth on the teeth brushed ~ith water. ~-
.. , , ..
,'" . .
Comparison - Part C
The general procedure o Part A of this example is `
repeated except that the set of teeth employed is brushed ;
with a stannous fluoride toothpaste commercially available
- lS under the trade designation "Crest" until all of the red
, .
disclosed plaque is removed. The results after the second
24-hour incubation period show heavy plaque growth on the
teeth brushed with said toothpaste.
, A comparison between Part A o this ex~mple and
~-~ 20 ' Parts B and C illus~rates the effectiveness of the amido
alkyl betaines employed according to the present invention ~ -
for inhibiting plaque formation.
` * Trademark
:. . ..
:~ -
.-:~ ~. -. ,,
~; .
~. . . ;
~ 1 -21- -
.. 1 .~
~ , .
I
84~
Example 2 ~:
The general procedure of Example lA is repeated
except that the set of teeth employed is brushed with a com~
position of about 20% by weight of palmitic amido betaine, ~`
about 10% by weight ethyl alcohol, and about 70% by weight
; of wa-ter. The results after the second 24-hour incubation
period indicate that the preparation provides pellicle ~nd ;. ~.
.
plaque inhibition although not as great as the preparation
employed in Example 1A. ~ ~ ~
:' ':
` ;~'
Example 3 ~ :.
The general procedure of Example lA i5 repeated. ~
except that the set of teeth employed is brushed with a com-
. position containing about 35% by weight o isostearic amido
betaine, about 2-5% ~aCl and the remainder water, available . :~
under the trade designation Schercotaine IAB. The results. ...
after the second 24-hour incubation period show that the ;;
: isostearic amido betaine provides good plaque and pellicle .
I inhibition.
,
Example 4 ;
The general procedure of Example lA is repeated . -
except that the set of teeth employed is brushed with a com- .
position containing ~bout 10% by weight of the palmitic . .-
.. ..
.. amido betaine, a~out 8% by weight of silica gel having an :
average particle size of 4JU and surface area o~ 310 m2/gm
and available under the trade designation ~yloid 244 fxom
' Davison Chemical; a~out 36.4% by weight of sorbitol, up to
' ' . * Trademark
iJ . -2~-
~8i 34Z9
about 5% by weight of ~aCl, and the remainder water. The
composition is prepared by adding the silica gel to -the
sorbitol and a portion of the water with mixing until a
homogeneous solution is obtained. After this, an aqueous
dispersion of the palmitic amido betaine (Schercotaine PAB)
is added and admixed until a uniform composi-tion is obtained.
The results after the second 24-hour incubation show com-
plete prevention of pellicle and plaque formation on the teeth.
'' ' '
Example 5
The general procedure of Example lA is repeated
i except that the set of teeth employed is brushed with and
dipped into a composition containing aboNt 2.5% by weight
, palmitic amido betaine, about 10% by weight of ethyl alcohol,
up to about 5% ~aCl and the remainder water. Also, the ;
teeth are not rinsed af-ter the brushing. After the second
incubation period of 24 hours, there is no pellicle or
pla~ue formation on the set of teeth.
,
E~ample 6
The general procedure of Example lA is repeated ;
except that the set of teeth employed is brushed with a com- -
position containing about 5% by weight of isostearic amido
betaine, about 24% by weight of glycerin, about 0.75% by
weight of hydroxyethyl cellulose, about 1% by weight of
propylene glycol, up to about 5% by weight of ~aCl, and the
remainder water. The composition is prepare~ by heating the
.
glycerin to about 70C, and then adding the hydroxyethyl
-23-
1. . . .
!
~88~Z~
cellulose with stirring. Next a portion of the water is
added while heating and stirring for about 15 minutes. The
composition is then coolea and a composition of propylene
:.:
glycol, and a mixture of the betaine, NaCl, and the rest of `'
the water (the mixture being available under the trade desig- ~
nation Schercotaine IAB) is added. The xesults a~ter the ~ ~;
second 24-hour incubation period show that the composition '
exhibits moderate pellicle and plaque inhibition.
.: :. ::
Example 7 ~'
Example lA is repeated except that the set of '-
teeth employed is brushed with a composition containing about
25% by weight of oleic amido betaine, up to about 5% by weight
of NaCl and the remainder water (available under the trade
designation'Schercotaine OAB~. The results of the te~ts after ;"
the second 24-hour'incubation period indicate that'the compo- ' '
' sition provides almost complete inhibition of pellicle and '
plaque growth on the teeth.
.
. .
Example 8
;, .
The general procedure of Example lA is repeated
except that the set of teeth employed is brushed with the
composition containing about 10 parts by weight of palmitic ''
2mido betaine, about 35.7 parts by weight of sorbitol, about '
*
8 parts by weight of a silica available as QUS0 G-30 ~rom
' Philadelphia Quartz Co~, about 1 part by weight of propylene ~ '
glycol, up to about 2 parts by weight of NaCl, and about 45
parts by weight of water are employed. The composition is
* Trademark
~;;` . ! -24-
. ,.. .,. ... , . . ., - . . . . ,,, , . , . , . ;, . ,. , :: ~ . . .; . ..... ,, .: : .:
88429
prepared by adding the silica to the sorbitol and a portion
of the water and mixing until a uniform transparent gel is
obtained. ~ext the propylene glycol is mixed with a combi-
; nation of the remainder of the water, betaine, and ~aCl
(available under the trade designation Schercotaine PAB). ;~
Then this mixture of the propylene glycol., betaine, water,
and ~aCl is added to the silica, sorbito]., and a water mix-
ture and agitated until a uni~orm mixture is obtained~ The
results of the tests after the second 24-hour incubat:ion
period indicate that the composition provides complete pel-
licle and plaque inhibition on the teeth.
.
Exam~le 9
The general procedure of Example 1A is repeated
except that the set of teeth employed is brushed with a com-
position containing about 10 parts by weight of palmitic
amido betaine, about 35.7 parts by weight of sorbitol, about
8 parts by weight of a silica availa~le at QUS0 G-32 from
Philadelphia Quartz Company, about 1 part by weight of
propylene glycol, up to about 1.5 par~s by weight of ~aCl,
and about 45 parts by weight of water. The composition is
prepared along the general procedure for preparation o~ the
- .
composition in Example 8. The test results a~ter the second
24-hour incubation period indicate that the composition pro-
vides complete inhibition of pellicle and plaque gxowth.
* Trademark
' .. ' .
:" :. ' .
.:
-25-
i~81~4~9 -: ~
Example 10
The general procedure of Example lA is repeated
i;... .
except that the set of teeth is brushed with a solution o
about 10% by weight of a purified palmitic amido betaine ~-
and about 9~% by weight of water. The purified palmitic
amido betaine is obtained by placing about 200 parts by
weight of Schercotaine PAB in an evaporating dish, and plac~
ing the dish in a vacuum of about 26" of Hg and heating to
about 65C. The composition is maintained for about 48 -
hours in the oven. After this, the composition is heated ~`
in a vacuum of about 28" of Hg, at about 65C for about
; another 8 hours. Nexk, the residue is placed in a 400 ml
bea~er and 300 ml o~ 95% eth~l alcohol are added cmd the
mixture stirred until a solution o~ the betaine is obtained.
f 15 The mixture is then filtered and a precipitate of sodium
chloride is discarded. The iltrate i5 then concentrated
to about 100 mls on a steam bath, cooled and then 200 mls
of acetone are added. A white precipitate is formed. The
precipitate is ~iltered and rinsed on a Buchner funnel.
The precipitate is transerred to an evaporating dish and
le~t overnight at 65C under 28" oE vacuum. The precipitate
becomes a yellow amorphous sol~d. The solid is then pre-
,~ cipi-tated from the ethyl alcohol-acetone mix-ture and the
resulting precipitate allowed to dry in air until all the
acetone vapors are evaporated. A white solid matexial re-
mains. This material is then dissolved in water to provide
1 ,
the above-mentioned composition. The results oE the tests
after the 2~-hour incu~ation period indicate that the
:,:
,:" , ,, .: '
-26-
~18~2'9
composition provides complete inhibition of plaque and
pellicle growth on the teeth. '~
~. ,' ':
ExamPle 11
The general procedure of Example lA is repeated ~;
except that the set of teeth employed is brushed with a com-
position containing about 5% by weight of a purified pal-
mitic amido betaine obtained along the lines of Example 10,
and about 95% by weight of water. The results of the tests ; '
after the 24-hour incubat,ion period indicate that the com-
position provides partial inhibition of plague and pellicle
~ ~ .
gxowth on the teeth.
Example 12
The general procedure of Example lA is repeatea
except that the set of teeth employed is brushed with a com-
position obtained by the following procedure. ~bout 80
parts by weight of sorbitol, about 34 parts by weight of ',
water, and about 10.2 parts by weight of glycerin are heated
to about 65C~ Next about 0.3 parts by weigh~ of sodium
benzoate are added to the mixture. About 1.5 parts by weight'
of carboxymethyl cellulose are added to the above composition
while continuously stirring until a uniform mixture is ob- -
tained. To this composition is added a mixture of about 24
parts by weight of a silica gel available under the trade
, * , , . :
designation'~yloid 244'ifrom Davison Chemical, and about 30
parts by weight of hydrated alumina having an average particle
~, size of about 12.5 ~u and available under the trade designation
.~ . .
* Trademark
27-
~()88~Z,9 :~
~kleen-Dent TA-6 from Reheis Chemical with stirring at agou~
room temperature. About 30 parts b~ weight of palmitic amido ~ -
betaine, up to about 5 parts by weight of ~aCl, and about 90
. . .
parts by weight of water are added to the mixture. The pH
of the composition is ~bout 6.4. The palmitic amido betaine
portion is from';Schercotaine"PAB. The results of ~he tests - ~ -
after the second 24-hour incubation period indicate that the
composition provides complete inhibition of pellicle and
plaque growth on the teeth.
Example 13
The general procedure of Example lA i9 repeated
except that the set of teeth employed is brushed with a com-
position prepared according to the following proaedure~
About 66.5 parts by weight of sorbitol and about 73.5 parts
by weight of water are heated to about 60C. About 0 25
parts by weight of sodium benzoate are added with mixing,
followed by the addition of about 1.25 parts by weight of
carboxymethyl cellulose gradually while mixing until a uni-
fo~m gel is obtained. The composition is then cooled to
room temperature and deaerated. About 25 parts by weight of
a hydrated alumina available under the trade designation
, i .: .
leen Dent TA-6"from Reheis Chemical Company are added with
agitation. ~he composition is then mixed with about 28 parts
I by weight of a silica gel available under the trade designa- ;
¦ 25 tion Syloid 244 from Davison Chemical with agitation until
¦ a uniform composition is obtained. The composition is then
again deaerated. A mixture o~ about 25 parts by weight of
* Trademark
28-
! ~
-` 10~384;~9 ~ `
:..
palmitic amido betaine as purified according to Example 10,
about 8.5 parts by weight of glycerin, and abou~ 25 parts by
weight of water are added to the composition and the mater-
ials are mixed until a homogeneous deaerated paste is obtained.
~he results of the tests after the second 24-hour incubation
period indicate that the composition provides complete plaque
and pellicle inhibition on the teeth.
.' .
Example 14
The general procedure of Example lA is repeated '
except that the set of teeth employed is brushed with a com-
position prepared according to the followin~ procedure.
~bouk 6 parts by weight of a polyoxyprop~leneoxyethylene
*
available under the trade designation'~luronic F-68 from
Wyandotte Corporation are dissolved in about 60 parts by ;
weight of water. About 0.3 parts of sodium benzoate are
added to about 108 parts of a mixture of about 75.5 parts
by weight of sorbitol and about 22.5 parts by weight of
water, which in turn are added to the a~ueous'Pluronic com~
., .; .:
position. About 0.5 parts o carboxymethyl cellulose àre ;
then added with vigorous agitation until a uniform composi-
tion is obtained. The composition is then deaerated. About
30 parts by weight of a hydrated alumina available under the
trade designation Kleen Dent TA6 from Reheis Chemical are
, ~ , , .
~; added and admixed with agitation until a uniform composition
. , .
- 25 is obtained. This is followed by the addition o~ about 24
. .- , ,
parts by weight of a silica gel available from Davison
- Chemical under the trade designation Syloid 244 with mixing
* Trademark
29-
'` ~" ' , '.''.'
~)815 ~Z~ `` ~ - `
and agitation until a uniform composition is obtained. After
this, a composition containing about 30 parts by weight o~ a
purified palmitic amido betaine as prepared according to Exam-
ple 10, about 10.2 parts by weight of glycerin, and about 21
parts by weight of distilled water are adLded to the above com-
position and mixing is continued until a homogeneous composi-
tion is obtained. The results of the tests after the second
24-hour incubation period indicate that -the composition provides
complete inhibition of plaque and pellicle growth on the teeth.
.' ''' ,'.
Example 15
The general procedure o~ Example lA is repeated
excepk that the set o~ teeth employed is brushed with a com-
position of about 14% by weight isostearic amido betaine and
about 86% by weight of water. After the second 24-hour in-
cubation period, no plaque and pellicle are present on the
teeth~
.', . " . .
Comparison Example 16
:''
The general procedure of Example lA is repeated
except that in place of the set of teeth employed, polymethyl
methacrylate strips (which are sanded perpendicular to their
., ., ~ .
lengths to remove the polished surface) are brushed with a
composition o~ Tegobetaine C (a coconut fatty acid amido
betaine). The results of -the tests after the 24-hour incu-
bation period show that the Tegobetaine C does not prevent
the growth of plaque and/or pellicle.
-30-
z9
Example 17A
- The general procedure of Example 16 is repea-ted
except that the polymethylmethacrylate strips are brushed
with Denta Fresh~, a commercial denture cleanser available
from ~oxell, the assignee o~ the present application, which
contains about 15% by weight of Tegobetaine C. ~he results
of the tests a~ter the second 24-hour incubation period in-
dicate that the Denta Fresh~ does not provide any inhibition
of plaque and/or pellicle growth.
Example 17B
The general procedure oE Part ~ o~ Example 17 i5
repeated except that the polymeth~lmethacrylate strips axe
brushed with a composition containing the same ingredients
as Denta Fresh~ except that the Tegobetaine C is replaced ;~ -
with 15% by weight o~ palmitic amido betaine The resul-ts
of the tests after the second 24-hour incubation pexiod in-
dicate that the composition does not prevent plaque and/or ;
pellicle growth.
Example 17C
The general procedure of Part A of Example 17 is re-
. . .
peated except that the polymethylmethacrylate strips are brush-
ed with a composition containing the same ingredients as Denta
Fresh~ except that the Tegobetaine C is replaced with 15% by
weight o~ isostearic amido betaine. The results of the tests
after the second 24-hour incubation period indicate -that the
composition does not prevent plaque and/or pellicle growth.
'` "
t ,' ' `
-31-
4Z9
; The results of Example 17, Parts A-C, indicate that
the Denta Fresh~ contains a material, apparently sodium lauryl
sulEate, which interacts with the betaine to render it inef-
- fective for the purposes of the present invention.
Example 18
. .
The general procedure o~ Example 16 is repeated ex- -
cept that the methylmethacrylate strips are brushed with
Schercotaine LMAB (an aqueous preparation of lauric myristic
amido betaine). The results of the tests after the second 24;
hour incubation period indicate that the lauric myristic amido
betaine does not prevent plaque and/or pellicle formation.
.', '''' ". .
' All of the above examples employed new sets of
'. :. :
teeth or plastic strips and new brushes for the brushing,
respectively. Any NaCl present in the compositions is due -
1 15 to its presence in the available compositions of the Eatty
acid amido compounds.
' ,.
~, Example l9 ;
An acute oral LDso study was done on rats for
Schercotaine PA~ in mature albino rats. The post-dose ob-
20 ~ servations were characterized by diarrhea and general weak- -
~ ness within the first 48 hours. The resulting mortality
-~ pattern was wide ranging and the LD50 was calculated to be
6000 mg/kg of body weight with 95% confidence limits of 8040
to 4477 mg/kg for the material tested.
Palmitic amido betaine purified according to
-32-
4~29
: .
Example 10 is also tested accordin~ to the above procedure.
The LD50 was calculated to be 2400 mg/kg (2832-2033 mg/kg)
at 95% confidence limit.
Example 20
A set of three extracted human teeth without the
- roots is mounted on a polymethylmethacrylate plastic strip
: .
of about 1 inch x 3 inches A drop o human saliva is ap-
plied to each tooth and allowed to dry. The set o-f teeth
is then placed in a petri dish and covered with about 200 ml
of an aqueous solution of about 2% trypticase and about 4~O ~ -
sucrose. The dish is then inoculated with an additional 1
ml of human saliva and then incubated at about 37C for
about 24 hours.
~ext, the set of teeth is removed from the media,
rinsed, and then dipped into a 0.5/O aqueous solution of
FD ~ C RED No~ 3 to visually disclose the plaque. L
The teeth show heavy plaque growth. The teeth are
then brushed with water using an electric toothbrush ~itted
with a soft nylon brush until all of the red disclosed p].aque
2Q and/or pellicle is removed.
The teeth are then swabbed with human saliva,
placed in a petri dish covered with about 200 ml o~ the --
,
trypticase-sucrose media and about 0.1 ml of a composition ~
containing 1% by weight DL-N-carboxymethylmethyl-~,~-di- ;
:, ... - . .
25~ methyl-~-(3-palmitamidopropyl) ammonium betaine and the
remainder being distilled water. The contents of the dish
are then inoculated with an additional 1 ml of saliva and
_33~
,1 . .,, ~ . " , . " .. . , ., . ' . ', . ' , , ., ~ , ' ' , , ' ,. , , . ' ,' ,,, , " .'~, ' , ,
;. . , ~ ' . ~ ' ,; ' ' ' ' ' . , ' ;
~L~88~29
incubated for about 24 hours at about 37C. At the end of --
the 24 hours, the set of teeth is removed from the media,
dried, and dipped into a 0.5% FD & C RED No. 3 solution for
about 60 seconds to visually disclose the presence of pel-
licle and plaque and is then rinsed undler tap water. ~o
pellicle and plaque growth are observed~ on the teeth con-
tacted with the composition.
The ammonium betaine employecl in this example is
prepared by adding about 131.55 parts by weight of clistilled ;~
water, about 3.51 parts by weight of NaOH pellets, ibout
9.54 parts by weight of 2-chloropropionic acid, and about 30
, ~
parts by weight of dimethylaminopropyl palmitamide ( Tegamine ~`
.. . ...
P-13 from Inolex Division o~ Wilson Pharmaceutical) to a re-
action vessel with mixing. The reaction mass is mixed at
. ~ . .
about 90~C for about 8 h~urs to provide the ammonium betaine. ~
' , ;:
Example 21
Example 20 is repeated except that 0.1 ml of a
i composition of 1% by weight of N-carboxyethyl-N,N-dLmethyl-
N-(3-palmitamidopropyl) ammonium betaine and the remainder
being distilled water is employed in place of the 0.1 ml
composition used in Example 20. The results after the second ~-
24-hour incubation period show that the composition provides
complete inhibition of plaque and pellicle formation on the
teeth and show very slight plaque and/or pellicle on the
plastic strip.
; The ammonium betaine employed in this example is
prepared by adding about 131.55 parts by weight oiE distilled
* Trademark
-34-
:~n88429
water, about 3.51 parts by weight of ~aOH pellets, about
9.54 parts by weight of 3-chloropropionic acid, and about
30 parts by weight of Tegamine P-13 to a reaction vessel
with mixing. Periodically hot distilled water is added to
the reaction to maintain a solution. The reaction mass is
,. ~ .- .
mixed at about 90C for about 8 hours to provide the ammon-
ium betaine.
. :'' .
:.' . .: -
Example 22 ~
.
Example 20 is repeated except that 0.1 ml of a -
composition o~ 1% by weight of DL-~-carboxymethylmethyl-N,~
dimethyl-N-(3-oleylamidopropyl) ammonium betaine and the -
remainder being d~stilled water is employed in place of the
0.1 ml ~omposition used in Example 20. The results after
the second 24-hour incubation period show that the composi-
. . ..
tion inhibits pla~ue and pellicle formation on the teeth.
, The ammonium betaine used in this example is pre-
,
pared by adding with stirring about 32.3 parts by weight of
dimethylaminopropyloleamide ( Tegamine o-13~from Inolex
Divis~on of Wilson Pharmaceutiaal) and about 9.5 parts by
weight of 2-chloropropionic acid to a solu~ion of about 3.5
parts by weight of sodium hydroxide in about 132 parts by
. ., , , . ~ .
volume of distilled water in a reaction vessel. The reac~
tion mixture is mixed at about 800C for a~out 8 hours during
` which time an additional 50 parts by volume o water are
added~ The reaction mass is then placed in a vacuum oven
~ and heated to about 70C for several hours~to evaporate of
I ; the water. The remaining material is then dissolved in about
.::
. ~. , ,. .. - ~ .
~ * ~rademark
. .
~ ~35~
; 250 parts by volume of 95% ethanol and the insoluble ~aCl is
removed by filtration. The ethanol is then removed by evap-
oration and about 250 parts by vol~ume of acetone are then
added. ~aditional insoluble MaC1 is removed by filtration.
The filtrate is then placed in a freezer whereby
.~
the desired compound separates out. Additional 400 parts
by volume of acetone is added and after placing in a freezer
the desired compound separates out. The product is then re- ;~
crystallized using ethyl acetate and about 39.9 parts by
weight of the product is obtained. An infrared scan of the ;;
product indicates that it is the desired ammonium betaine.
,, ,, ~ , .
a~e~ ,.
Example 20 is repeated except that 0.1 ml of a
composition of 1% by weight of ~-carboxyethyl~ dimethyl-
N-(3-oleylamidoprop~l) ammonium betaine and the remainder ~;
being distilled water is employed in place of the 0.1 ml
composition used in EXample 20. The results after the second
24-hour ~ncubation period show that the composition inhibits
plaque and pellicle formation on the teeth.
The ammonium betaine used in this example is pxe-
, pared by adding with stirring about 32.3 parts by weight of
1~ Tegamine 0-13 and about 9.5 parts by wéight of 3-chloro-
propionic acid to a solution of about 3.5 parts by weight of
sodium hydroxide in about 132 parts by volume of distilled
~' 25 water in a reaction vessel. The reaction mixture is mixed
. .
at about 80C or about 7-1/4 hours. The reaction mass is
then placed in a vacuum oven and heated to ahout 70C for
` :,
-36-
~ ~08~3~2~ :
several hours to evaporate off the water. The remaining
material is then dissolved in about 250 parts by volume of
95% ethanol and the insoluble NaCl is removed by filtration. ; ~-
About 100 parts by volume ethanol is then removed by evap-
; 5 oration, followed by cooling after which additional ~aCl is
removed by filtration. The remaining ethanol is evaporated
off.
About 250 parts by volume of acetone are added
and the composition is then placed in a freezer whereby the
` 10 desired compound separates out. The product is then recry-
stallized using ethyl acetate and about 35.4 parts by weight
of the product i9 obtained. An inrared scan o~ the product
indicates that it is the desired ammonium betaine.
~. , , ' "" .
Example 24
~ i ~
Example 20 is repeated except that 0.1 ml of a
composition of 1% by weight of DL-N-carboxymethylmethyl-~,N-
dimethyl-~-(3-stearamidopropyl) ammonium betaine and the
.. . .
remainder being distilled water is emplo~ed in place of the
0.1 ml composition used in Example 20. The results after
the second 24-hour incubation period show that the composi-
tion exhibits slight activity against plague and pellicle
formation on the teeth. ;
The ammonium betaine used in this example is pre-
pared by adding with stirring about 16.25 parts by weight o~ ;
:, " "* ,;,.::
1 25 dimethylaminopropyl stearamide ~Tegamine S-13 ~rom Inolex ~ -
:
Division of Wilson Pharmaceutical) ~nd about 4.8 parts by ;
, weight of 2-chloropropionic acid to a solution of about 1.78
'i~ ' ": :;',
* Trademark ;
1~ 37
.~ : :.-. .:., .
', , , . ! ' , . ' , . . . . . ' , ~ . , ' ,, " ~' ' ' , . ,~ .. , .,, ' ., ' '
, . , ' . ' ,. ," ' '~ ' , . ' , ', ''. . . ' ' '. ''. ', , ! '' ~ , ! I . ' .' ' .'' "' ' . ' ' .'. . ' 'I
1g~81~4Z~
parts by weight of sodium hydroxide in about 66 parts by
volume of distilled water in a reaction vessel. T~e reaction
mixture is mixed at about 80C for about 7-1/4 hours after
which time an additional 100 parts by volume of water are ;
added. The reaction mass is then mixed for an addltional 7
hours at this temperature. After this the reaction mass is
then placed in a vacuum oven and heated to about 70~C ~or -~
several hours to evaporate off the waterr The remaining
material is then dissolved in about 140 parts by volume of
95% ethanol and the insoluble ~aCl is removed by filtration.
The ethanol i9 then removed by evaporation and about 140
parts by volume o~ acetone are then added.
The material is then placed in a freezer after
which it is ~iltered. The ~iltrate is then treated to evap-
1 15 orate acetone. The product is then recrystallized using
~l ethyl acetate. An infrared scan of khe product indicates
that it is the desired ammonium betaine.
Example 25
Example 20 is repeated except that 0.1 ml of a
composition of 1% by weight of N-carboxyethyl-~,N-dimethyl-
E_(3-stearamidopropyl) ammonium betaine and the remainder
Il being distilled water is employed in place of the 0.1 ml ~ -
! composition used in Example 20. The results after the se-
cond 24-hour incubation period show that the composition
inhibits plaque and pellicle formation on the teeth.
.j . , : .
, The ammonium betaine used in this example is pre-
pared by adding with stirring about 16.25 parts by weight
' ' ' ~
-38-
8~1;29 1 `
of Tegamine S-13 and about 4.8 parts by weight of 3-chloxo-
propionic acid to a solution of about 1.78 parts by weight
of sodium hydroxide in about 66 parts by volume or distilled
water in a reaction vessel. The reaction mixture is mixed
at about 80C for about 7-1/2 hours during which time an
additional 40 parts by volume of water are added. The reac-
tion mass is then placed in a vacuum oven and heated to about ; -
70C for several hours to evaporate off the water. The re-
maining material is then dissolved in about 140 parts by vol~
ume of 95% ethanol and the insoluble NaCl is removed by
; filtration. The ethanol is then removed by evaporation and
abouk 130 parts by volume of acetone are then added.
The composition is then placed in a reezer, after
whiah the composition is filtered to yield about 18.3 parts
by weight oE the desired compound. An infrared scan of the
product indicates that it is the desired ammonium betaine.
:: .
, Example 26
Example 20 is repeaked except that 0.1 ml of a com-
` position of 1% by weighk oE 2-~N,N-dimethyl-N-(3-palmitamido- i'
propyl)-amlno~ ethanesulobetaine and the remainder being
! propylene glycol is employed in place of the 0.1 ml composi-
tion used in Example 20. The results after the second 24-
hour incubatlon period show that the composition exhibits
activity against plaque and pellicle formation on the teeth~
Only slight plaque growth is observed on the teeth and plastic.
The sulfobetaine used in this example is prepared
by adding with stirring about 17 parts by weight of Tegamine
.
- ~39-
~. , . ... . .. , i, I ,, ,., ;
Z9
..
P-13 to a solution of about 9.2 parts by weight of 2-chloro-
ethanesulfonic acid, sodium salt monohydrate in about 80
parts by volume of distilled water in a reaction vessel.
The reaction mixture is mixed at about 80C for about 5 hours.
An additional 25 parts by volume of distilled water are added
and the reaction mass is heated for another 9 hours after
which additional amounts of distilled water are added in
incremental amounts o about 100 parts by volume, about 140
parts by volume, about 100 parts by volume, about 120 parts
by volume, and about 140 parts by volume over a period of
about 40 hours of heating at about 80C. ~he reaction i9 '~
maintained at about 80C for another 16 hours. AEter this,
the reaction mixture i9 dried in a vacuum oven under reduced
pressure. The material recovered from the oven is then added
to about 250 ml of 95% ethanol and the praduct is then ob-
tained by filtration. An inrared scan of the product indi-
cates that it is the desired sulobetaine.
" ~...
Example 27
Example 20 is repeated except that 0.1 ml of a com-
position of 1% by weight of 2-~ -dimethyl-N-(3-oleylamido-
propyl)-amino] ethanesulfobetaine and the remainder being
propylene glycol is employed in place o the 0.1 ml composi-
tion used in Example 20. The results ater the second 24-
hour incubation period show that the composition exhibits
activity against plaque and pellicle formation on the
teeth. Very slight plaque gxowth is observed on teeth and
plastic.
, '
a~ o - :
:~0~8~29 ~
The sulfobetaine used in this example is prepared
by adding with stirring about 18.~ parts by weight of Tegamine ;
0-13 to a solution of about 9.2 parts by weight of 2-chloro-
ethanesulfonic acid, sodium sa~t monohydrate in about 80 parts
~ .
by volume of diskilled water in a reaction vessel. The reac- ' ;
tion mass is mixed at about 80C for abou1 70 hours. After
this, thé reaction mass is placed in a vacuum oven at about ~ ~
70C under reduced pressure. The resulting solid material is ' '' '
then dissolved in about 150 parts by ~olume of 95% ethanol ' ,
and the mixture is filtered after heating slightly. About '
i.9 parts by weight of ~aCl is collected. The filtrate i9 `.;;
then evaporated~ About 300 part~ by volume of acetone are j ~;'
then added to ,the residue. Solid material separated ouk and
then acetone i~ decanted off. The solid material is then ' ~'
placed in a desiccator after which remaining acetone evap~
orates. The solid product is then added to about 150 parts ' ~,
by volume of ethyl acetate and heated. The mixture is then '''-'
cooled in a refrigerator, followed by filtration and then ''~
,~ washlng with ether to provide the desired product. An infra- , ',
red scan of the product indicate~ that it i~ the desired , ',~
sulfobetaine. ," , '~,-
I, !. ' ,
,'', ' ;,', '
: ' '' .
Ii . ."'~'~,, '.
' '; .:
.
! -41-
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