CA1088429A - Fatty acid amido betaines in oral preparations - Google Patents
Fatty acid amido betaines in oral preparationsInfo
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- CA1088429A CA1088429A CA262,186A CA262186A CA1088429A CA 1088429 A CA1088429 A CA 1088429A CA 262186 A CA262186 A CA 262186A CA 1088429 A CA1088429 A CA 1088429A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/41—Amines
- A61K8/416—Quaternary ammonium compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- Oral & Maxillofacial Surgery (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
METHOD AND COMPOSITION FOR IMPROVING ORAL HYGIENE
Abstract of the Disclosure Method for retarding pellicle and plaque formation which includes contacting sites of plaque formation and growth with dental preparation containing certain fatty acid amido compounds and/or salts thereof and dental preparations con-taining the fatty acid amido compounds and/or salts thereof.
Abstract of the Disclosure Method for retarding pellicle and plaque formation which includes contacting sites of plaque formation and growth with dental preparation containing certain fatty acid amido compounds and/or salts thereof and dental preparations con-taining the fatty acid amido compounds and/or salts thereof.
Description
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.
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 ~ .
.
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 ~ .
2~ ; ., ~ .
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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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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
:;
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.
:~ ,. ' ',.
.' "' ,' ' ":
~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.
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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.
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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:
R - C ~ - ~C~I2)~ ~ B - C - 09 (2) 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 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 ',':.,".
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* Trademark ** Trademark - 9 -:
:' . .'' ' . ' ',~ .
, ~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: :
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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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 ' ..
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 ~': .
~: 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. -,' ,''-' .
.
.. ' ' , ~~: - 1 9- :
.. , . ~ .
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 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-. ,.. .,. ... , . . ., - . . . . ,,, , . , . , . ;, . ,. , :: ~ . . .; . ..... ,, .: : .:
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 ' .. ' .
:" :. ' .
.:
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 :,:
,:" , ,, .: ' ~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 ~()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 ! ~
-` 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 '` ~" ' , '.''.' ~)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.
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 ,' ' `
; 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
Rl is hydrogen or an alkyl group containing from 1 to about 3, carbon atom~ such as methyl, ethyl, a~d propyl.
' ~ . ..
I ;
~ ` ~
~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.
'"',.
~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:
R - C ~ - ~C~I2)~ ~ B - C - 09 (2) 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 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 -:
:' . .'' ' . ' ',~ .
, ~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: :
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.
, ' ~ ' , ~ .
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 ' ..
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 ~': .
~: 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. -,' ,''-' .
.
.. ' ' , ~~: - 1 9- :
.. , . ~ .
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 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-. ,.. .,. ... , . . ., - . . . . ,,, , . , . , . ;, . ,. , :: ~ . . .; . ..... ,, .: : .:
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 ' .. ' .
:" :. ' .
.:
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 :,:
,:" , ,, .: ' ~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 ~()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 ! ~
-` 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 '` ~" ' , '.''.' ~)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.
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 ,' ' `
; 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
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 :~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 ` :, ~ ~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 ' ' ' ~
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 ,, ,., ;
..
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-I ~ '` ' '~''.
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 :~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 ` :, ~ ~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 ' ' ' ~
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 ,, ,., ;
..
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-I ~ '` ' '~''.
Claims (45)
1. A dental preparation in the form of a tooth-paste, dental cream, dental powder, lozenge, tablet, aerosol spray, chewing gum, roll of dental floss or toothpick containing an amount sufficient to retard pellicle and plaque formation on teeth of a compound of the formula:
(1a) wherein:
R represents a monovalent or divalent hydrocarbyl group containing at least 14 carbon atoms;
n is one when R is monovalent and is 2 when R is divalent;
R1 represents a hydrogen atom or a C1 to C3 alkyl group;
A represents a divalent C1 to C6 hydrocarbon bridge;
and the groups R2, which may be the same of differ-ent each represent a C1 to C5 alkyl group, or the groups R2 together with the nitrogen atom to which they are attached represent a 5- or 6-membered heterocyclic ring;
and/or a nontoxic, physiologically and orally acceptable salt thereof; or mixtures thereof.
(1a) wherein:
R represents a monovalent or divalent hydrocarbyl group containing at least 14 carbon atoms;
n is one when R is monovalent and is 2 when R is divalent;
R1 represents a hydrogen atom or a C1 to C3 alkyl group;
A represents a divalent C1 to C6 hydrocarbon bridge;
and the groups R2, which may be the same of differ-ent each represent a C1 to C5 alkyl group, or the groups R2 together with the nitrogen atom to which they are attached represent a 5- or 6-membered heterocyclic ring;
and/or a nontoxic, physiologically and orally acceptable salt thereof; or mixtures thereof.
2. The preparation of claim 1, wherein there is present a compound of the formula (1a) in which R represents a monovalent hydrocarbyl group.
3. The preparation of claim 1, wherein there is present a compound of the formula (1a) in which R represents an aliphatic hydrocarbon group.
4. The preparation of claim 3, wherein there is present a compound of the formula (1a) in which R represents an aliphatic C14-C21 hydrocarbon group.
5. The preparation of claim 4, wherein there is present a compound of the formula (1a) in which R represents a monovalent C15-C17 aliphatic hydrocarbon group.
6. The preparation of claim 1, 2 or 3, wherein there is present a compound of the formula (1a) in which R1 represents a hydrogen atom.
7. The preparation of claim 1, 2 or 3, wherein there is present a compound of the formula (1a) in which R1 represents a methyl group.
8. The preparation of claim 1, wherein there is present a compound of the formula (1a) in which A represents an alkylene or alkylidene group.
9. The preparation of claim 8, wherein there is present a compound of the formula (1a) wherein A represents a C1 to C3 alkylene or alkylidene group.
10. The preparation of claim 1, wherein there is present a compound of the formula (1a) wherein the groups R2 each represent a C1- C5 alkyl group.
11. The preparation of Claim 10, wherein there is present a compound of the formula (1a) wherein the groups R2 each represent a C1 to C3 alkyl group.
12. The preparation of Claim 11, wherein there is present a compound of the formula (1a) wherein the groups R2 each represent methyl groups.
13. The preparation of claim 1 or 3, wherein there is present a compound of the formula (1a) wherein the groups R2 together with the nitrogen atom to which they are attached represent a morpholinyl, piperidinyl, pyrrolid-inyl and piperazinyl ring.
14. A dental preparation in the form of a tooth-paste, dental cream, dental powder, lozenge, tablet, aerosol spray, chewing gum, roll of dental floss or toothpick containing an amount sufficient to retard pellicle and plaque formation of one or more of the compounds (a) to (d) listed herein:
(a) palmitic amido betaine;
(b) stearic amido betaine;
(c) isostearic amido betaine;
(d) oleic amido betaine;
or one or more nontoxic physiologically and orally acceptable salts of one or more of the compounds (a) to (d) listed herein, or a mixture of one or more of the compounds (a) to (d) with one or more of the said salts.
(a) palmitic amido betaine;
(b) stearic amido betaine;
(c) isostearic amido betaine;
(d) oleic amido betaine;
or one or more nontoxic physiologically and orally acceptable salts of one or more of the compounds (a) to (d) listed herein, or a mixture of one or more of the compounds (a) to (d) with one or more of the said salts.
15. The preparation of claim 1, wherein the com-pound of formula (1a) is present in an amount of at least 1% by weight.
16. The preparation of Claim 15, wherein the com-pound of formula (1a) is present in an amount of from 1% to 25% by weight.
17. The preparation of claim 1 or claim 14, wherein the pH is from 5 to 7.5.
18. The preparation of claim 1 or claim 14, where-in the compound of formula (1a) is present in association with from 5 to 60% by weight of an abrasive polishing agent;
from 0.5% to 5% by weight of a sudsing agent; from 0.1 to 15% by weight of a thickening agent; or water and humectants.
from 0.5% to 5% by weight of a sudsing agent; from 0.1 to 15% by weight of a thickening agent; or water and humectants.
19. A dental preparation formulated as a mouthwash containing a compound of formula (1a) as defined in claim 1 in association with a sudsing agent; ethyl alcohol; a humec-tant; a sweetener; a flavouring agent; and water.
20. The preparation of claim 1, formulated as a prophylactic paste containing the compound of formula (1a) in association with pumice.
21. The preparation of claim 1, wherein the com-pound of formula (1a) is in association with:
(a) water and ethyl alcohol; or (b) silica gel, sorbitol and water; or (c) glycerin, hydroxyethyl cellulose, propylene glycol and water; or (d) sorbitol, silica, propylene glycol and water;
or (e) sorbitol, glycerin, carboxymethyl cellulose, silica gel, water and hydrated alumina; or (f) polyoxypropyleneoxyethylene, carboxymethyl cellulose, sorbital, hydrated alumina, silica gel, glycerin and water.
(a) water and ethyl alcohol; or (b) silica gel, sorbitol and water; or (c) glycerin, hydroxyethyl cellulose, propylene glycol and water; or (d) sorbitol, silica, propylene glycol and water;
or (e) sorbitol, glycerin, carboxymethyl cellulose, silica gel, water and hydrated alumina; or (f) polyoxypropyleneoxyethylene, carboxymethyl cellulose, sorbital, hydrated alumina, silica gel, glycerin and water.
22. A dental preparation in the form of a tooth-paste, dental cream, dental powder, lozenge, tablet, aerosol spray, chewing gum, roll of dental floss or toothpick con-taining an amount sufficient to retard pellicle and plaque formation of a compound of the formula:
1(b) wherein R, n, R1, A and R2 have the same meanings as in formula 1(a) defined in Claim 1, B represents a divalent C1 or C2 alkylene or alkylidene group, and X represents a carboxylate or sulphonate group subject to the proviso that when B represents a methylene group X represents a sulphonate group, and/or a nontoxic, physiologically and orally acceptable salt thereof; or mixtures thereof.
1(b) wherein R, n, R1, A and R2 have the same meanings as in formula 1(a) defined in Claim 1, B represents a divalent C1 or C2 alkylene or alkylidene group, and X represents a carboxylate or sulphonate group subject to the proviso that when B represents a methylene group X represents a sulphonate group, and/or a nontoxic, physiologically and orally acceptable salt thereof; or mixtures thereof.
23. The preparation of Claim 22 wherein there is present a compound of the formula (1b) in which R represents a monovalent hydrocarbyl group.
24. The preparation of Claim 22, wherein there is present a compound of the formula (1b) in which R represents an aliphatic hydrocarbon group.
25. The preparation of Claim 24, wherein there is present a compound of the formula (1b) in which R represents an aliphatic C14 - C21 hydrocarbon group.
26. The preparation of Claim 25, wherein there is present a compound of the formula (1b) in which R represents a monovalent C15 - C17 aliphatic hydrocarbon group.
27. The preparation of Claim 22 wherein there is present a compound of the formula (1b) in which R1 represents a hydrogen atom.
28. The preparation of Claim 22, wherein there is present a compound of the formula (1b) in which R1 represents a methyl group.
29. The preparation of Claim 22, wherein there is present a compound of the formula (1b) in which A represents an alkylene or alkylidene group.
30. The preparation of Claim 29 wherein there is present a compound of the formula (1b) wherein A represents a C1 to C3 alkylene or alkylidene group.
31. The preparation of Claim 22 wherein there is present a compound of the formula (1b) wherein the groups R2 each represent a C1-C5 alkyl group.
32. The preparation of Claim 31, wherein there is present a compound of the formula (1b) wherein the groups R2 each represent a C1 to C3 alkyl group.
33. The preparation of Claim 32 wherein there is present a compound of the formula (1b) wherein the groups R2 each represent methyl groups.
34. The preparation of Claim 22, wherein there is present a compound of the formula (1b) wherein the groups R2 together with the nitrogen atom to which they are attached represent a morpholinyl, piperidinyl, pyrrolidinyl and piperazinyl ring.
35. The preparation of Claim 22, wherein there is present a compound of the formula 1b in which B represents a methylene group and X represents a sulphonate group.
36. The preparation of Claim 22, wherein there is present a compound of the formula (1b) in which B represents an ethylene or ethylidene group.
37. The preparation of Claim 36, wherein there is present a compound of the formula (1b) in which X represents a carboxylate group.
38. A dental preparation in the form of a tooth-paste, dental cream, dental powder, lozenge, tablet, aerosol spray, chewing gum, roll of dental floss or toothpick con-taining an amount sufficient to retard pellicle and plaque formation of one or more of the compounds (e) to (m) listed herein:
(e) DL-N-carboxymethylmethyl-N,N-dimethyl-N-(3-palmitamidopropyl) ammonium betaine;
(f) N-carboxyethyl-N,N-dimethyl-N-(3-palmitamido-propyl) ammonium betaine;
(g) DL-N-carboxymethylmethyl-N,N-dimethyl-N-(3-oleylamidopropyl) ammonium betaine;
(h) N-carboxyethyl-N,N-dimethyl-N-(3-oleylamido-propyl) ammonium betaine;
(i) DL-N-carboxymethylmethyl-N,N-dimethyl-N-(3-stearamidopropyl) ammonium betaine;
(j) N-carboxyethyl-N,N-dimethyl-N-(3-stearamido-propyl) ammonium betaine;
(k) 2-[N,N-dimethyl-N-(3-palmitamidopropyl)-amino]
ethanesulphobetaine;
(l) 2-[N,N-dimethyl-N-(3-oleylamidopropyl)-amino]
ethanesulphobetaine;
(m) 2-N,N-dimethyl-N-(3-stearamidopropyl)-amino ethanesulphobetaine;
or one or more nontoxic physiologically and orally acceptable salts of one or more of the compounds (e) to (m) listed herein, or a mixture of one or more of the compounds (e) to (m) with one or more of the said salts.
(e) DL-N-carboxymethylmethyl-N,N-dimethyl-N-(3-palmitamidopropyl) ammonium betaine;
(f) N-carboxyethyl-N,N-dimethyl-N-(3-palmitamido-propyl) ammonium betaine;
(g) DL-N-carboxymethylmethyl-N,N-dimethyl-N-(3-oleylamidopropyl) ammonium betaine;
(h) N-carboxyethyl-N,N-dimethyl-N-(3-oleylamido-propyl) ammonium betaine;
(i) DL-N-carboxymethylmethyl-N,N-dimethyl-N-(3-stearamidopropyl) ammonium betaine;
(j) N-carboxyethyl-N,N-dimethyl-N-(3-stearamido-propyl) ammonium betaine;
(k) 2-[N,N-dimethyl-N-(3-palmitamidopropyl)-amino]
ethanesulphobetaine;
(l) 2-[N,N-dimethyl-N-(3-oleylamidopropyl)-amino]
ethanesulphobetaine;
(m) 2-N,N-dimethyl-N-(3-stearamidopropyl)-amino ethanesulphobetaine;
or one or more nontoxic physiologically and orally acceptable salts of one or more of the compounds (e) to (m) listed herein, or a mixture of one or more of the compounds (e) to (m) with one or more of the said salts.
39. The preparation of claim 22, wherein the compound of formula 1(b) is present in an amount of at least 1% by weight.
40. The preparation of claim 39, wherein the compound of formula (1b) is present in an amount of from 1 to 25% by weight.
41. The preparation of claim 22 wherein the pH
is from 5 to 7.5.
is from 5 to 7.5.
42. The preparation of claim 22, wherein the compound of formula (1b) is present in association with from 5 to 60% by weight of an abrasive polishing agent;
from 0.5% to 5% by weight of a sudsing agent; from 0.1 to 15% by weight of a thickening agent; water and humectants.
from 0.5% to 5% by weight of a sudsing agent; from 0.1 to 15% by weight of a thickening agent; water and humectants.
43. A dental preparation formulated as a mouth-wash containing the compound of formula (1b) as defined in claim 22 in association with a sudsing agent; ethyl alcohol;
a humectant; a sweetener; a flavouring agent; and water.
a humectant; a sweetener; a flavouring agent; and water.
44. The preparation of claim 22, formulated as a prophylactic paste containing the compound of formula (1b) in association with pumice.
45. The preparation of claim 22, wherein the com-pound of formula (1b) is in association with:
(a) water and ethyl alcohol; or (b) silica gel, sorbitol and water; or (c) glycerin, hydroxyethyl cellulose, propylene glycol and water; or (d) sorbitol, silica, propylene glycol and water;
or (e) sorbitol, glycerin, carboxymethyl cellulose, silica gel, water and hydrated alumina; or (f) polyoxypropyleneoxyethylene, carboxymethyl cellulose, sorbitol, hydrated alumina, silica gel, glycerin and water.
(a) water and ethyl alcohol; or (b) silica gel, sorbitol and water; or (c) glycerin, hydroxyethyl cellulose, propylene glycol and water; or (d) sorbitol, silica, propylene glycol and water;
or (e) sorbitol, glycerin, carboxymethyl cellulose, silica gel, water and hydrated alumina; or (f) polyoxypropyleneoxyethylene, carboxymethyl cellulose, sorbitol, hydrated alumina, silica gel, glycerin and water.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/623,277 US4117107A (en) | 1975-10-17 | 1975-10-17 | Method and composition for improving oral hygiene |
| US623,277 | 1975-10-17 | ||
| US05/721,746 US4117108A (en) | 1975-10-17 | 1976-09-09 | Oral hygiene |
| US721,746 | 1985-04-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1088429A true CA1088429A (en) | 1980-10-28 |
Family
ID=27089416
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA262,186A Expired CA1088429A (en) | 1975-10-17 | 1976-09-28 | Fatty acid amido betaines in oral preparations |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JPS5251030A (en) |
| CA (1) | CA1088429A (en) |
| DE (1) | DE2646199A1 (en) |
| GB (1) | GB1567454A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1987004922A1 (en) * | 1986-02-25 | 1987-08-27 | E.B. Michaels Research Associates, Inc. | Process and composition for oral hygiene |
| EP0408174A1 (en) * | 1989-07-12 | 1991-01-16 | Warner-Lambert Company | Antiseptic composition containing hexahydro-5-pyrimidinamine compounds |
| US5270310A (en) * | 1991-12-13 | 1993-12-14 | Sphinx Pharmaceuticals Corporation | N-aminoalkyl amide inhibitors of protein kinase C |
| SG177474A1 (en) | 2009-07-31 | 2012-02-28 | Colgate Palmolive Co | High cleaning dentifrice compositions |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2442712A1 (en) * | 1973-07-27 | 1976-03-25 | Blendax Werke Schneider Co | Betaine-contg tooth (prosthesis) cleaning/caring compsn - maintains activity of chlorhexidine constituent without affecting taste adversely |
-
1976
- 1976-09-28 CA CA262,186A patent/CA1088429A/en not_active Expired
- 1976-10-13 GB GB42512/76A patent/GB1567454A/en not_active Expired
- 1976-10-13 DE DE19762646199 patent/DE2646199A1/en not_active Ceased
- 1976-10-15 JP JP51124361A patent/JPS5251030A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| GB1567454A (en) | 1980-05-14 |
| DE2646199A1 (en) | 1977-04-28 |
| JPS5251030A (en) | 1977-04-23 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |