CA1200505A - Anticaries composition - Google Patents
Anticaries compositionInfo
- Publication number
- CA1200505A CA1200505A CA000411434A CA411434A CA1200505A CA 1200505 A CA1200505 A CA 1200505A CA 000411434 A CA000411434 A CA 000411434A CA 411434 A CA411434 A CA 411434A CA 1200505 A CA1200505 A CA 1200505A
- Authority
- CA
- Canada
- Prior art keywords
- fluoride
- zinc
- composition
- ion
- concentration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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Classifications
-
- 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
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/20—Halogens; Compounds thereof
- A61K8/21—Fluorides; Derivatives thereof
-
- 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
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/27—Zinc; Compounds thereof
Abstract
ABSTRACT
Improved protection against dental enamel caries is provided by applying to the teeth and gingivae an oral hygiene composition containing, in addition to a pharmaceutically acceptable fluoride compound, a sufficient quantity of a pharmaceutically acceptable zinc compound so that the ratio of zinc ion to fluoride ion is at least about 7:1 by weight.
Improved protection against dental enamel caries is provided by applying to the teeth and gingivae an oral hygiene composition containing, in addition to a pharmaceutically acceptable fluoride compound, a sufficient quantity of a pharmaceutically acceptable zinc compound so that the ratio of zinc ion to fluoride ion is at least about 7:1 by weight.
Description
~Z~?~S05 ANTICARIES COMPOSITION
Technical ~ield The present invention relates to compositions for preventing caries. More particularly, it relates to fluoride containing compositions that have enhanced activity in preventing dental enamel caries.
Background Art The use of soluble flu~ride salts, such as stannous fluoride and sodium fluoride, to reduce the incidence of dental caries in the general population is a well known and ongoing endeavor. The administration of these fluoride compounds takes many forms, including the fluoridation of drinking water, professional treatment by dentists and incorporation in oral hygiene compositions such as dentifrices and mouthrinses.
It is also known that zinc plays a role in dental care.
For example~ in U~ S. Patent No. 4,160,821 issued July 10, 1979, there is disclosed a composition for treating gingivitis comprising a vehicle containing a high concentration of glycerol and a zinc salt, such as zinc chloride, that is soluble in the glycerol. In an article entitled "A Study of Zinc In Human Teeth," Arch, Oral Biol., Vol. 8, pp 135-144. 1963. Pergamon Press Ltd.
(Printed in Gt. Britain), the authors, citing reports of animal studies in earlier publications by McClure (1948, Observations on induced caries in rats. J. dent. Res. 27, 3~-40) and Mansell & Hendershot (1960, The spectro-chemical analysis of metals in rat molar enamel, femur and incisors. Arch. oral Biol. 2, 31-37) note the relatively high level of zinc in teeth, and indicate that while the significance of the presence of zinc in teeth is uncertain and there is no evidence that zinc reduces caries in man or experimental animals, the relationship between zinc 3&J 1053 ~(3~5~)5 concentration in enamel and caries susceptibility should be elucidated before this element can be dismissed as a factor in dental health. ~n abstract of a paper entitled "Fluoride Content in Enamel After Topical Applications of AlCl3, ZnCl2 and NaF" presented at the 25th ORCA Congress, Caries Res. 13(2):99,1979 reports on in vitro experiments conducted on 3 groups of 10 permanent teeth each and concludes that pretreatment with AlCl3 results in an appreciable increase of F- in the enamel surface but that the increase was distinctly lower in teeth treated only with NaF or pretreated with ZnCl2.
In British Patent Specification 1,373,003, published November 6, 1974, there is disclosed a dentifrice composition having activity against plaque and calculus on a tooth surface comprisin~ a sparingly soluble zinc salt -which is defined as a zinc salt of an acid, other than zinc fluoride or its hydrates, having a water solubility greater than that of zinc phosphate and less than 1 gram of zinc per 100 ml of water at 20C - and a mixture of detergents. The dentifrice may also contain a compatible abrasive such as alumina and other conventional toothpaste ingredients.
U.S. Patent No. 4,146,606, issued March 27, 1979, relates to a pharmaceutical composition for dental use that can, inter alia, suppress dental caries, this composition .
comprising a strontium compound, a zinc compound, tannin and, optionally, a fluorine compound in such a weight proportion that the weight ratio of strontium, zinc, tannin and fluorine is 1 to 3-2 to 4:1 to 3:0 to 4.
U.S. Patent No. 4,138,~77, issued February 6, 197~, discloses a composition to prevent and control mouth odor, which is also said to be effective in preventing calculus, ~ plaque, caries and periodontal disease, containing as the J&J 1053 5~5 essential agent a zinc-polymer complex formed by the reaction or chelation of a zinc compound with an anionic polymer containing carboxylic, sulfonic and/or phosphoric acid radicals. The composition may also include, inter alia, a fluorine-containing compound that protects the ~eeth against decay.
The Invention ~t has now been discovered that the rate of development of dental enamel caries, as characterized by proximal, smooth surface, pit and fissure caries, can be prevented or substantially retarded by the daily application to the teeth of a composition comprising a pharmaceutically acceptable oral hygiene vehicle containing an effective concentration to prevent or inhibit dental enamel caries of a pharmaceutically acceptable fluoride salt and a pharmaceutically acceptable zinc salt in sufficient amoun.
to provide a large excess by weight of zinc ion over fluoride ion, i.e., at least about 7:1, preferably about 10:1, by weight. Furthermore, it has been found that gingival inflammation can be successfully treated or the development of gingivitis prevented with the daily application to the gingivae of the above composition.
Typical pharmaceutically acceptable fluoride compounds that are suitable for use in the compositions of this invention include sodium fluoride, potassium fluoride, lithium fluoride, aluminum fluoride, zinc fluoride, stannous fluoride, sodium monofluorophosphate, acidulated phosphate fluoride, ammonium fluoride, ammonium bifluoride and amine fluoride.
Zinc salts that are suitable for use in the compositions of this invention include 7inc chloride, zinc sulfate, zinc acetate, zinc lactate, zinc salicylate, zinc J&J 1053 ~Z(~Q5~?S
thiocyanate, and, more generally, any pharmaceutically acceptable zinc salts.
As already indicated, the concentration of the zinc ion plays a significant role in the compositions of this invention. Thus, it has been found that, in order to provide anticaries activity that is a significant improve-ment over the activity attributable to the presence of the fluoride compound alone, the zinc ion must be present in at least about a 7-fold higher concentration by weight than that of the fluoride ion, e.g., 0.7% zinc ion and 0.1% fluoride ion. Preferably the zinc to fluoride ion ratio is at least about 8:1 or 9:1, more preferably about lO:l by weight.
Consistent with the above ratios, the zinc ion should be present in an effective amount, while the fluoride ion concentration should be from as as low as 0.0025% up to about 3.0~ by weight. The preferred range of fluoride ion concentration is about 0.005 to about 1.0% by weight, re pre~erably about 0.01 to about 0.5~. Similarly the zinc ion concentration should be from about 0.02 to about 25.0 by weight, preferably about 0.05 to about 8.0% by weight, more preferably about 0.1 to about 4.0% by weight. While 2S higher concentrations of both zinc and fluoride ions could be used, no particular advantage would be afforded thereby, and there are some contraindications in the literature concerning safety of higher concentrations of fluoride and zinc ions.
Sui~able pharmaceutically acceptable oral hygiene vehicles, that may be used alone or in any compatible combination, include ylycerol, water, ethanol~ polyethy-lene glycol, propylene glycol and sorbitol. Alternative-ly, any pharmaceutically acceptable vehicle which iscompatible with the zinc and fluoride salts used may be &~ 1053 employed.
3~)5~3~
The compositions of this invention may be in the form of a mouthwash, dentifrice, gel, powder, solution, varnish, lozenge, chewing gum, slow release device or other form suitable for oral application. Any pharmaceutically acceptable materials, such as those ordinarily used in such oral compositions, that are compatible with the æinc and fluoride ions may be employed in the compositions of this invention.
In accordance with the present invention, the compositions are applied to the teeth and the gingivae with an appliance, e.g., toothbrush, swab, impregnated dental floss or the like, on both the buccal and lingual sides, at least once daily, more preferably twice daily.
lS
Illustrative Examples:
The following examples will serve to illustrate typical compositions of this invention. As indicated earlier, while glycerol appears in all the illustrated compositions, this is a matter of convenience and not essential to the invention.
Example I (Solution) w/w%
Glycerol, ~.S.P. 92 t~ 98.3 Zinc fluoride 0.02 to 0.4 Zinc chloride, U.S.P. 0.3 to 8.0 Flavors 1.0 The zinc salts are dissolved in glycerol with continuous stirring at 60C.
J&J 1053 5~5 Examples II-V (Oral Gel) II III IV V
Glycerol, ~.S.P. 52.0 52.0 52.0 52.0 Zinc chloride, U.S.P. 2.0 0.5 1.0 3.0 Sodium fluoride 0.22 0.22 0.22 0.22 Water 2~.0 26.0 26.0 26.0 Pluronic F-127~ 18.0 18.0 18.0 18.0 (Poloxamer 407) Flavors 0.7 0.7 0 7 0.7 Preservatives 0.33 0.33 0.33 0.33 Sodium saccharine 0.5 0.5 0 5 0.5 Color 0.25 0.25 0.25 0.25 100.0100.0 100.0100.0 pH is adjusted to 5.5 with 0.1 N NaOH or with 0.1 N HCI.
The gel is prepared by dissolving the zinc chloride, sodium fluoride, flavor and the preservatives in glycerol.
The Pluronic F-127, sodium saccharine and color are separately dissolved in water. The two solutions are blended together and left standing overnight to gel.
Example VI (Mouthwash) w/w %
Glycerol, ~.S.P. 10.0 to 50.00 Zinc chloride, ~.S.P. 0.15 to 1.5 Sodium fluoride 0.01 to 0.22 Sorbitol 10.0 30 Flavors 0.5 Pluronic F-108 ~ 2.0 Preservatives 0.3 Color 0.2 Deionized water, q.s. to 100g pH is adjusted to 5.0 with 0.1 N HCl or with 0.1 N NaOH.
J&J-1053 The zinc chloride, sodium fluoride and flavors are dissolved in glycerol. The rest of the formula ingredients are dissolved in water. The two solutions are mixed together and diluted q.s. with water.
Example VII (Toothgel) Sodium fluoride 0.22 Glycerol 89.5 ~ Carboxymethylcellulose 0.8 Carbopol 934 2.0 Zinc chloride, U.S.P. 1.5 Flavors 1.0 Preservatives 0.7 Deionized water 4.28 100.0 Examples VIII - XI (Dentifrice Compositions) VIII IX X XI
Zinc Chloride, U.S.P. 1.5 1.7 3.0 3.7 Zinc Fluoride ~ZnF2.4H2O) - 0.5 0.5 Sodium Fluoride 0.22 - 0.22 Hydrous Silica Gel C45X 15 15 15 15 Sorbitol 10.14 10.14 10.14 10.14 Glycerin, U.S.P. 10.30 10.30 10.30 10.30 Titanium Dioxide 0.5 0.5 0.5 0.5 Pluronic F-68~ 3.0 - - -Natrosol 250H~ 1.0 1.0 1.0 1.0 Sodium Saccharin 0.5 0.6 0.7 0.8 Sodium Chloride 0.1-1.0 0.1-1.0 0.1-1.0 0.1-1.0 Flavor 1.0 1.0 1.0 1.0 Sodium Benzoate 0.2 0.2 0.2 0.2 Veegum K~ - 1.0 Xanthan Gum - - 0.5-1.5 0.5-l.S
Myrj 52 ~ - 2.0 - -Carbomer 940 - - 0.1-0.4 Aerosil 200 4.0 4.0 4.0 4.0 - Purified Water, q.s. 100.0 100.0 100.0 100.0 ~ ~R rtp ,~ R~
J&J 1053 5~S
The pH of the final composition is adjusted to between 5.5 to 6.5, with 0.1N HCl or 0.1N NaOH.
Example XII
In comparative caries studies on rats, the results of which are summarized in Table I below, the composition described in Example II was superior in reducing the development of caries over conventional fluoride containing dentifrices.
In these studies, each group consisted of thirty male IYistar rats, approximately 40 to 50 grams each, and caged by pairs in raised wire cages. At nineteen days of age the animals were weighed and randomly distributed into groups. The animals were fed diet No. 500 and provided deionized water to drink ad libitum. Approximately 0.159 of the gel was applied with a cotton applicator per rat jaw. Treatments were administered seven days per week, twice per day, for three weeks.
Immediately prior to sacrifice all animals were observed for any visual signs of ill health and individually weighed. At the end of the three weeks, the animals were sacrificed, and the heads were then cleaned, stained, sectioned and scored by the method of Keyes. The data were tabulated and statistically analyzed for significant differences between the individual means, for both number and severity of carious lesions, by repeated-t test.
As can be seen from Table I, in two separate experiments on laboratory rats, the composition of Example II, when applied twice daily to teeth, reduced the number of carious lesions by 43~ and 63% and the severity of the lesions by 45~ and 68%, respectively. By contrast, a J&J~10S3 3~5~
g commercial dentifrice gel, containing 0.4% stannous fluoride, reduced the number of carious lesions by 18%
and the severity of the lesions by 15%, under identical test conditions.
J&J 1053 TABLE I
RAT CARIES STUDIES
The Effect of ZnCl~ Conc. on the Development of Pit & Fissure Caries Formula ~% Conc. ~ Conc. % Conc. % Conc. ~ Red. in ~ Red~ in Severity of 2nCl~ Zn~ of NaF F-Total Lesionsof Lesions ~ (2~ 0.5 .2~ - 24* 23*
C (2~ 1.0 ~48 - 4 0 A (1~ 2.0 .96 - 27* 33*
D (2~ 3.3 1.44 _ 42~ 45*
Example III (2) 0.5 G24 0.22 0.1 10 8 Example IV ~2) 1.0 .48 0.22 0.1 10 7 Example II ~1) 2.0 .96 0.22 0.1 43* 45*
Example II (3) 200 .96 0.22 0.1 63* 68*
Example V (2) 3.0 1.44 0.22 0.1 42* 44*
E (2~ - - 0.22 0.1 21* 20*
E (1) - _ 0.22 0.1 26* 24*
Vehicle (2) - - - O O ~nVehicle ~ - -Commercial denti- - - - 0.1 18 15 ~n frice with 0.4%
stannous fluoride *Significantly different, at the P< 0.05 level, from the vehicle control.
(lj Study I
(2~ Study II
(3) Study III
+ Formulas A-D are controls that correspond to Examples II-V, respectively, but without the NaF;
Formula E is the same basic formula as Example II, but without the ZnCl2;
"Vehicle" is the same basic formula with both the ZnC12 and NaF removed.
?5ig~
Variation can, of course, be made without departing from the spirit and scope of the invention.
J&~ 1053
Technical ~ield The present invention relates to compositions for preventing caries. More particularly, it relates to fluoride containing compositions that have enhanced activity in preventing dental enamel caries.
Background Art The use of soluble flu~ride salts, such as stannous fluoride and sodium fluoride, to reduce the incidence of dental caries in the general population is a well known and ongoing endeavor. The administration of these fluoride compounds takes many forms, including the fluoridation of drinking water, professional treatment by dentists and incorporation in oral hygiene compositions such as dentifrices and mouthrinses.
It is also known that zinc plays a role in dental care.
For example~ in U~ S. Patent No. 4,160,821 issued July 10, 1979, there is disclosed a composition for treating gingivitis comprising a vehicle containing a high concentration of glycerol and a zinc salt, such as zinc chloride, that is soluble in the glycerol. In an article entitled "A Study of Zinc In Human Teeth," Arch, Oral Biol., Vol. 8, pp 135-144. 1963. Pergamon Press Ltd.
(Printed in Gt. Britain), the authors, citing reports of animal studies in earlier publications by McClure (1948, Observations on induced caries in rats. J. dent. Res. 27, 3~-40) and Mansell & Hendershot (1960, The spectro-chemical analysis of metals in rat molar enamel, femur and incisors. Arch. oral Biol. 2, 31-37) note the relatively high level of zinc in teeth, and indicate that while the significance of the presence of zinc in teeth is uncertain and there is no evidence that zinc reduces caries in man or experimental animals, the relationship between zinc 3&J 1053 ~(3~5~)5 concentration in enamel and caries susceptibility should be elucidated before this element can be dismissed as a factor in dental health. ~n abstract of a paper entitled "Fluoride Content in Enamel After Topical Applications of AlCl3, ZnCl2 and NaF" presented at the 25th ORCA Congress, Caries Res. 13(2):99,1979 reports on in vitro experiments conducted on 3 groups of 10 permanent teeth each and concludes that pretreatment with AlCl3 results in an appreciable increase of F- in the enamel surface but that the increase was distinctly lower in teeth treated only with NaF or pretreated with ZnCl2.
In British Patent Specification 1,373,003, published November 6, 1974, there is disclosed a dentifrice composition having activity against plaque and calculus on a tooth surface comprisin~ a sparingly soluble zinc salt -which is defined as a zinc salt of an acid, other than zinc fluoride or its hydrates, having a water solubility greater than that of zinc phosphate and less than 1 gram of zinc per 100 ml of water at 20C - and a mixture of detergents. The dentifrice may also contain a compatible abrasive such as alumina and other conventional toothpaste ingredients.
U.S. Patent No. 4,146,606, issued March 27, 1979, relates to a pharmaceutical composition for dental use that can, inter alia, suppress dental caries, this composition .
comprising a strontium compound, a zinc compound, tannin and, optionally, a fluorine compound in such a weight proportion that the weight ratio of strontium, zinc, tannin and fluorine is 1 to 3-2 to 4:1 to 3:0 to 4.
U.S. Patent No. 4,138,~77, issued February 6, 197~, discloses a composition to prevent and control mouth odor, which is also said to be effective in preventing calculus, ~ plaque, caries and periodontal disease, containing as the J&J 1053 5~5 essential agent a zinc-polymer complex formed by the reaction or chelation of a zinc compound with an anionic polymer containing carboxylic, sulfonic and/or phosphoric acid radicals. The composition may also include, inter alia, a fluorine-containing compound that protects the ~eeth against decay.
The Invention ~t has now been discovered that the rate of development of dental enamel caries, as characterized by proximal, smooth surface, pit and fissure caries, can be prevented or substantially retarded by the daily application to the teeth of a composition comprising a pharmaceutically acceptable oral hygiene vehicle containing an effective concentration to prevent or inhibit dental enamel caries of a pharmaceutically acceptable fluoride salt and a pharmaceutically acceptable zinc salt in sufficient amoun.
to provide a large excess by weight of zinc ion over fluoride ion, i.e., at least about 7:1, preferably about 10:1, by weight. Furthermore, it has been found that gingival inflammation can be successfully treated or the development of gingivitis prevented with the daily application to the gingivae of the above composition.
Typical pharmaceutically acceptable fluoride compounds that are suitable for use in the compositions of this invention include sodium fluoride, potassium fluoride, lithium fluoride, aluminum fluoride, zinc fluoride, stannous fluoride, sodium monofluorophosphate, acidulated phosphate fluoride, ammonium fluoride, ammonium bifluoride and amine fluoride.
Zinc salts that are suitable for use in the compositions of this invention include 7inc chloride, zinc sulfate, zinc acetate, zinc lactate, zinc salicylate, zinc J&J 1053 ~Z(~Q5~?S
thiocyanate, and, more generally, any pharmaceutically acceptable zinc salts.
As already indicated, the concentration of the zinc ion plays a significant role in the compositions of this invention. Thus, it has been found that, in order to provide anticaries activity that is a significant improve-ment over the activity attributable to the presence of the fluoride compound alone, the zinc ion must be present in at least about a 7-fold higher concentration by weight than that of the fluoride ion, e.g., 0.7% zinc ion and 0.1% fluoride ion. Preferably the zinc to fluoride ion ratio is at least about 8:1 or 9:1, more preferably about lO:l by weight.
Consistent with the above ratios, the zinc ion should be present in an effective amount, while the fluoride ion concentration should be from as as low as 0.0025% up to about 3.0~ by weight. The preferred range of fluoride ion concentration is about 0.005 to about 1.0% by weight, re pre~erably about 0.01 to about 0.5~. Similarly the zinc ion concentration should be from about 0.02 to about 25.0 by weight, preferably about 0.05 to about 8.0% by weight, more preferably about 0.1 to about 4.0% by weight. While 2S higher concentrations of both zinc and fluoride ions could be used, no particular advantage would be afforded thereby, and there are some contraindications in the literature concerning safety of higher concentrations of fluoride and zinc ions.
Sui~able pharmaceutically acceptable oral hygiene vehicles, that may be used alone or in any compatible combination, include ylycerol, water, ethanol~ polyethy-lene glycol, propylene glycol and sorbitol. Alternative-ly, any pharmaceutically acceptable vehicle which iscompatible with the zinc and fluoride salts used may be &~ 1053 employed.
3~)5~3~
The compositions of this invention may be in the form of a mouthwash, dentifrice, gel, powder, solution, varnish, lozenge, chewing gum, slow release device or other form suitable for oral application. Any pharmaceutically acceptable materials, such as those ordinarily used in such oral compositions, that are compatible with the æinc and fluoride ions may be employed in the compositions of this invention.
In accordance with the present invention, the compositions are applied to the teeth and the gingivae with an appliance, e.g., toothbrush, swab, impregnated dental floss or the like, on both the buccal and lingual sides, at least once daily, more preferably twice daily.
lS
Illustrative Examples:
The following examples will serve to illustrate typical compositions of this invention. As indicated earlier, while glycerol appears in all the illustrated compositions, this is a matter of convenience and not essential to the invention.
Example I (Solution) w/w%
Glycerol, ~.S.P. 92 t~ 98.3 Zinc fluoride 0.02 to 0.4 Zinc chloride, U.S.P. 0.3 to 8.0 Flavors 1.0 The zinc salts are dissolved in glycerol with continuous stirring at 60C.
J&J 1053 5~5 Examples II-V (Oral Gel) II III IV V
Glycerol, ~.S.P. 52.0 52.0 52.0 52.0 Zinc chloride, U.S.P. 2.0 0.5 1.0 3.0 Sodium fluoride 0.22 0.22 0.22 0.22 Water 2~.0 26.0 26.0 26.0 Pluronic F-127~ 18.0 18.0 18.0 18.0 (Poloxamer 407) Flavors 0.7 0.7 0 7 0.7 Preservatives 0.33 0.33 0.33 0.33 Sodium saccharine 0.5 0.5 0 5 0.5 Color 0.25 0.25 0.25 0.25 100.0100.0 100.0100.0 pH is adjusted to 5.5 with 0.1 N NaOH or with 0.1 N HCI.
The gel is prepared by dissolving the zinc chloride, sodium fluoride, flavor and the preservatives in glycerol.
The Pluronic F-127, sodium saccharine and color are separately dissolved in water. The two solutions are blended together and left standing overnight to gel.
Example VI (Mouthwash) w/w %
Glycerol, ~.S.P. 10.0 to 50.00 Zinc chloride, ~.S.P. 0.15 to 1.5 Sodium fluoride 0.01 to 0.22 Sorbitol 10.0 30 Flavors 0.5 Pluronic F-108 ~ 2.0 Preservatives 0.3 Color 0.2 Deionized water, q.s. to 100g pH is adjusted to 5.0 with 0.1 N HCl or with 0.1 N NaOH.
J&J-1053 The zinc chloride, sodium fluoride and flavors are dissolved in glycerol. The rest of the formula ingredients are dissolved in water. The two solutions are mixed together and diluted q.s. with water.
Example VII (Toothgel) Sodium fluoride 0.22 Glycerol 89.5 ~ Carboxymethylcellulose 0.8 Carbopol 934 2.0 Zinc chloride, U.S.P. 1.5 Flavors 1.0 Preservatives 0.7 Deionized water 4.28 100.0 Examples VIII - XI (Dentifrice Compositions) VIII IX X XI
Zinc Chloride, U.S.P. 1.5 1.7 3.0 3.7 Zinc Fluoride ~ZnF2.4H2O) - 0.5 0.5 Sodium Fluoride 0.22 - 0.22 Hydrous Silica Gel C45X 15 15 15 15 Sorbitol 10.14 10.14 10.14 10.14 Glycerin, U.S.P. 10.30 10.30 10.30 10.30 Titanium Dioxide 0.5 0.5 0.5 0.5 Pluronic F-68~ 3.0 - - -Natrosol 250H~ 1.0 1.0 1.0 1.0 Sodium Saccharin 0.5 0.6 0.7 0.8 Sodium Chloride 0.1-1.0 0.1-1.0 0.1-1.0 0.1-1.0 Flavor 1.0 1.0 1.0 1.0 Sodium Benzoate 0.2 0.2 0.2 0.2 Veegum K~ - 1.0 Xanthan Gum - - 0.5-1.5 0.5-l.S
Myrj 52 ~ - 2.0 - -Carbomer 940 - - 0.1-0.4 Aerosil 200 4.0 4.0 4.0 4.0 - Purified Water, q.s. 100.0 100.0 100.0 100.0 ~ ~R rtp ,~ R~
J&J 1053 5~S
The pH of the final composition is adjusted to between 5.5 to 6.5, with 0.1N HCl or 0.1N NaOH.
Example XII
In comparative caries studies on rats, the results of which are summarized in Table I below, the composition described in Example II was superior in reducing the development of caries over conventional fluoride containing dentifrices.
In these studies, each group consisted of thirty male IYistar rats, approximately 40 to 50 grams each, and caged by pairs in raised wire cages. At nineteen days of age the animals were weighed and randomly distributed into groups. The animals were fed diet No. 500 and provided deionized water to drink ad libitum. Approximately 0.159 of the gel was applied with a cotton applicator per rat jaw. Treatments were administered seven days per week, twice per day, for three weeks.
Immediately prior to sacrifice all animals were observed for any visual signs of ill health and individually weighed. At the end of the three weeks, the animals were sacrificed, and the heads were then cleaned, stained, sectioned and scored by the method of Keyes. The data were tabulated and statistically analyzed for significant differences between the individual means, for both number and severity of carious lesions, by repeated-t test.
As can be seen from Table I, in two separate experiments on laboratory rats, the composition of Example II, when applied twice daily to teeth, reduced the number of carious lesions by 43~ and 63% and the severity of the lesions by 45~ and 68%, respectively. By contrast, a J&J~10S3 3~5~
g commercial dentifrice gel, containing 0.4% stannous fluoride, reduced the number of carious lesions by 18%
and the severity of the lesions by 15%, under identical test conditions.
J&J 1053 TABLE I
RAT CARIES STUDIES
The Effect of ZnCl~ Conc. on the Development of Pit & Fissure Caries Formula ~% Conc. ~ Conc. % Conc. % Conc. ~ Red. in ~ Red~ in Severity of 2nCl~ Zn~ of NaF F-Total Lesionsof Lesions ~ (2~ 0.5 .2~ - 24* 23*
C (2~ 1.0 ~48 - 4 0 A (1~ 2.0 .96 - 27* 33*
D (2~ 3.3 1.44 _ 42~ 45*
Example III (2) 0.5 G24 0.22 0.1 10 8 Example IV ~2) 1.0 .48 0.22 0.1 10 7 Example II ~1) 2.0 .96 0.22 0.1 43* 45*
Example II (3) 200 .96 0.22 0.1 63* 68*
Example V (2) 3.0 1.44 0.22 0.1 42* 44*
E (2~ - - 0.22 0.1 21* 20*
E (1) - _ 0.22 0.1 26* 24*
Vehicle (2) - - - O O ~nVehicle ~ - -Commercial denti- - - - 0.1 18 15 ~n frice with 0.4%
stannous fluoride *Significantly different, at the P< 0.05 level, from the vehicle control.
(lj Study I
(2~ Study II
(3) Study III
+ Formulas A-D are controls that correspond to Examples II-V, respectively, but without the NaF;
Formula E is the same basic formula as Example II, but without the ZnCl2;
"Vehicle" is the same basic formula with both the ZnC12 and NaF removed.
?5ig~
Variation can, of course, be made without departing from the spirit and scope of the invention.
J&~ 1053
Claims (10)
1. A composition for preventing dental enamel caries consisting essentially of a pharmaceutically acceptable oral hygiene vehicle containing an effective concentration to prevent caries of a pharmaceutically acceptable fluoride salt and a pharmaceutically accept-able zinc salt selected from the group consisting of zinc chloride, zinc sulfate, zinc acetate, zinc lactate, zinc salicylate and zinc thiocyanate, wherein the weight ratio of zinc ion to fluoride ion is at least about 7:1.
2. The composition of claim 1, wherein said ratio is at least about 10:1.
3. The composition of claim 1, wherein the fluoride ion is present in a concentration of from about 0.0025 to about 3.0% by weight.
4. The composition of claim 3, wherein the fluoride ion concentration is in the range of from about 0.005 to about 1.0%.
5. The composition of claim 3, wherein the fluoride ion concentration is in the range of from about 0.01 to about 0.5%.
6. The composition of claim 3, wherein the zinc ion is present in a concentration of from about 0.02 to about 25.0% by weight.
7. The composition of claim 6, wherein the zinc ion concentration is from about 0.05 to about 8.0%.
8. The composition of claim 7, wherein the zinc ion concentration is from about 0.1 to about 4.0%.
9. The composition of claim 1, wherein said fluoride salt is selected from the group consisting of sodium fluoride, potassium fluoride, lithium fluoride, aluminum fluoride, zinc fluoride, stannous fluoride, sodium monofluorophosphate, acidulated phosphate fluoride, ammonium fluoride, ammonium bifluoride and amine fluoride.
10. The composition of claim 1, wherein said vehicle comprises at least one member selected from the group consisting of glycerol, water, ethanol, polyethylene glycol, propylene glycol and sorbitol.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US303,284 | 1981-09-17 | ||
| US06/303,284 US4396599A (en) | 1981-09-17 | 1981-09-17 | Anticaries composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1200505A true CA1200505A (en) | 1986-02-11 |
Family
ID=23171350
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000411434A Expired CA1200505A (en) | 1981-09-17 | 1982-09-15 | Anticaries composition |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US4396599A (en) |
| EP (1) | EP0075446B1 (en) |
| JP (1) | JPS5862109A (en) |
| KR (1) | KR880001089B1 (en) |
| AT (1) | ATE28978T1 (en) |
| AU (1) | AU556815B2 (en) |
| CA (1) | CA1200505A (en) |
| DE (1) | DE3277001D1 (en) |
| DK (1) | DK414882A (en) |
| ES (1) | ES515738A0 (en) |
| FI (1) | FI823204L (en) |
| GB (1) | GB2105991B (en) |
| GR (1) | GR76434B (en) |
| HK (1) | HK78685A (en) |
| IE (1) | IE53979B1 (en) |
| IN (1) | IN155957B (en) |
| MX (1) | MX164065B (en) |
| MY (1) | MY8600239A (en) |
| NO (1) | NO823144L (en) |
| NZ (1) | NZ201790A (en) |
| PH (1) | PH17133A (en) |
| PT (1) | PT75571B (en) |
| ZA (1) | ZA826818B (en) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU555971B2 (en) * | 1981-09-03 | 1986-10-16 | Richardson-Vicks Inc. | Stable oral compositions containing zinc and fluoride compounds |
| US4568540A (en) * | 1984-04-18 | 1986-02-04 | Johnson & Johnson | Oral hygiene compositions |
| US4562065A (en) * | 1984-12-11 | 1985-12-31 | Colgate-Palmolive Company | Astringent dentifrice |
| US4562063A (en) * | 1984-12-11 | 1985-12-31 | Colgate-Palmolive Company | Astringent gel dentifrice |
| NZ214031A (en) * | 1984-12-11 | 1989-05-29 | Colgate Palmolive Co | Astringent dentifrice containing synthetic, precipitated, amorphous silica gel as polishing agent |
| US4562066A (en) * | 1984-12-11 | 1985-12-31 | Colgate-Palmolive Company | Astringent dentifrice containing monofluorophosphate |
| US4684517A (en) * | 1985-02-04 | 1987-08-04 | Colgate-Palmolive Company | Mouthrinse composition containing hydrogen peroxide and fluoride |
| JPH0747526B2 (en) * | 1986-08-11 | 1995-05-24 | 株式会社コーセー | Makeup cosmetics |
| US5188820A (en) * | 1989-10-05 | 1993-02-23 | Chesebrough-Pond's Usa Co., Dividion Of Conopco, Inc. | Method of inhibiting plaque on teeth by applying an oral composition |
| GB8922434D0 (en) * | 1989-10-05 | 1989-11-22 | Unilever Plc | Oral compositions |
| US5593683A (en) * | 1990-05-01 | 1997-01-14 | Mdv Technologies, Inc. | Method of making thermoreversible polyoxyalkylene gels |
| CA2040460C (en) * | 1990-05-01 | 1997-06-10 | Tacey X. Viegas | Drug delivery with thermoreversible gels |
| GB9107833D0 (en) * | 1991-04-12 | 1991-05-29 | Unilever Plc | Treatment of periodontitis |
| JPH04368333A (en) * | 1991-06-18 | 1992-12-21 | Atsunori Sato | Preventive for dental caries |
| US5385727A (en) * | 1993-05-19 | 1995-01-31 | Church & Dwight Co., Inc. | Dentifrices containing zinc oxide particles and sodium bicarbonate |
| WO1994027565A1 (en) * | 1993-05-28 | 1994-12-08 | Hawe Neos Dental | Tin fluoride preparation for the care of the teeth |
| US5690912A (en) * | 1994-04-25 | 1997-11-25 | Colgate Palmolive Company | SnF2 gel of improved stand-up and efficacy in the treatment of dentine hypersensitivity |
| US5632972A (en) * | 1994-06-30 | 1997-05-27 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Method for treating gingival and periodontal tissues |
| US5587147A (en) * | 1994-06-30 | 1996-12-24 | Church & Dwight Co., Inc. | Aqueous zinc-polyamide complex solution |
| US5871715A (en) * | 1997-02-28 | 1999-02-16 | Gillette Canada Inc. | Stannous fluoride gel with improved stand-up |
| JP3719874B2 (en) * | 1998-04-24 | 2005-11-24 | サンスター株式会社 | Oral composition |
| US20030017219A1 (en) * | 2001-05-25 | 2003-01-23 | Frank Corsini | Carbohydrate modifying agent and drinks containing the modifying agent |
| US20040072123A1 (en) * | 2002-05-08 | 2004-04-15 | Simonton Thomas C. | Capped syringe tip for dispensing and applying liquid or viscous materials |
| US7942669B2 (en) | 2002-12-02 | 2011-05-17 | Centrix, Inc. | Gingival tissue retraction device and method |
| US20070066503A1 (en) | 2005-08-19 | 2007-03-22 | Mores Basaly | Methods and compositions for acid treatment of a metal surface |
| US20080107612A1 (en) * | 2006-09-07 | 2008-05-08 | Simonton Thomas C | Anti-caries dental material |
| US8753613B2 (en) * | 2007-03-30 | 2014-06-17 | Centrix, Inc. | Dental retraction material having enhanced fluid absorption |
| US8143206B2 (en) | 2008-02-21 | 2012-03-27 | S.C. Johnson & Son, Inc. | Cleaning composition having high self-adhesion and providing residual benefits |
| MX2010009161A (en) | 2008-02-21 | 2010-09-14 | Johnson & Son Inc S C | Cleaning composition having high self-adhesion and providing residual benefits. |
| US8980813B2 (en) | 2008-02-21 | 2015-03-17 | S. C. Johnson & Son, Inc. | Cleaning composition having high self-adhesion on a vertical hard surface and providing residual benefits |
| US9410111B2 (en) | 2008-02-21 | 2016-08-09 | S.C. Johnson & Son, Inc. | Cleaning composition that provides residual benefits |
| US9481854B2 (en) | 2008-02-21 | 2016-11-01 | S. C. Johnson & Son, Inc. | Cleaning composition that provides residual benefits |
| US8993502B2 (en) | 2008-02-21 | 2015-03-31 | S. C. Johnson & Son, Inc. | Cleaning composition having high self-adhesion to a vertical hard surface and providing residual benefits |
| US9656102B2 (en) * | 2013-04-23 | 2017-05-23 | Rita Vaccaro | Thin film toothpaste strip |
| US10105296B2 (en) | 2013-04-23 | 2018-10-23 | Rita Vaccaro | Thin film toothpaste strip |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2527686A (en) * | 1945-12-26 | 1950-10-31 | Max H Sandberg | Mouthwash |
| US4100269A (en) * | 1973-06-28 | 1978-07-11 | Lever Brothers Company | Anticalculus dentifrice |
| US4022880A (en) * | 1973-09-26 | 1977-05-10 | Lever Brothers Company | Anticalculus composition |
| US4082841A (en) * | 1975-10-10 | 1978-04-04 | Lever Brothers Company | Dentifrice |
| US4138477A (en) * | 1976-05-28 | 1979-02-06 | Colgate Palmolive Company | Composition to control mouth odor |
| US4144323A (en) * | 1978-06-15 | 1979-03-13 | Lever Brothers Company | Novel anticalculus compositions |
| US4289754A (en) * | 1980-11-03 | 1981-09-15 | Richardson-Vicks Inc. | Zinc derivatives and their use in mouthwash compositions |
| US4289755A (en) * | 1980-11-03 | 1981-09-15 | Richardson-Vicks Inc. | Stable mouthwash compositions containing zinc and fluoride compounds |
-
1981
- 1981-09-17 US US06/303,284 patent/US4396599A/en not_active Expired - Lifetime
-
1982
- 1982-08-19 IN IN967/CAL/82A patent/IN155957B/en unknown
- 1982-09-01 NZ NZ201790A patent/NZ201790A/en unknown
- 1982-09-15 CA CA000411434A patent/CA1200505A/en not_active Expired
- 1982-09-15 MX MX7881A patent/MX164065B/en unknown
- 1982-09-15 ES ES515738A patent/ES515738A0/en active Granted
- 1982-09-16 NO NO823144A patent/NO823144L/en unknown
- 1982-09-16 KR KR8204196A patent/KR880001089B1/en active
- 1982-09-16 AU AU88453/82A patent/AU556815B2/en not_active Ceased
- 1982-09-16 IE IE2259/82A patent/IE53979B1/en not_active IP Right Cessation
- 1982-09-16 EP EP82304883A patent/EP0075446B1/en not_active Expired
- 1982-09-16 DE DE8282304883T patent/DE3277001D1/en not_active Expired
- 1982-09-16 GB GB08226385A patent/GB2105991B/en not_active Expired
- 1982-09-16 AT AT82304883T patent/ATE28978T1/en active
- 1982-09-16 ZA ZA826818A patent/ZA826818B/en unknown
- 1982-09-16 DK DK414882A patent/DK414882A/en not_active Application Discontinuation
- 1982-09-16 PT PT75571A patent/PT75571B/en not_active IP Right Cessation
- 1982-09-16 FI FI823204A patent/FI823204L/en not_active Application Discontinuation
- 1982-09-17 GR GR69297A patent/GR76434B/el unknown
- 1982-09-17 PH PH27886A patent/PH17133A/en unknown
- 1982-09-17 JP JP57161059A patent/JPS5862109A/en active Granted
-
1985
- 1985-10-10 HK HK786/85A patent/HK78685A/en not_active IP Right Cessation
-
1986
- 1986-12-30 MY MY239/86A patent/MY8600239A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HK78685A (en) | 1985-10-18 |
| GR76434B (en) | 1984-08-10 |
| ES8403316A1 (en) | 1984-03-16 |
| FI823204L (en) | 1983-03-18 |
| IE822259L (en) | 1983-03-17 |
| PT75571B (en) | 1985-07-26 |
| KR880001089B1 (en) | 1988-06-23 |
| PT75571A (en) | 1982-10-01 |
| MX164065B (en) | 1992-07-13 |
| EP0075446A2 (en) | 1983-03-30 |
| DK414882A (en) | 1983-03-18 |
| JPS5862109A (en) | 1983-04-13 |
| FI823204A0 (en) | 1982-09-16 |
| US4396599A (en) | 1983-08-02 |
| MY8600239A (en) | 1986-12-31 |
| IN155957B (en) | 1985-04-06 |
| NZ201790A (en) | 1985-05-31 |
| ATE28978T1 (en) | 1987-09-15 |
| ES515738A0 (en) | 1984-03-16 |
| GB2105991B (en) | 1985-05-22 |
| EP0075446A3 (en) | 1984-07-11 |
| GB2105991A (en) | 1983-04-07 |
| AU8845382A (en) | 1983-03-24 |
| IE53979B1 (en) | 1989-05-10 |
| JPH0340006B2 (en) | 1991-06-17 |
| ZA826818B (en) | 1984-04-25 |
| DE3277001D1 (en) | 1987-09-24 |
| AU556815B2 (en) | 1986-11-20 |
| NO823144L (en) | 1983-03-18 |
| PH17133A (en) | 1984-06-01 |
| EP0075446B1 (en) | 1987-08-19 |
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| MKEX | Expiry |