CA2154860A1 - Oral care products containing zinc-polyamine complex and pyrophosphate - Google Patents
Oral care products containing zinc-polyamine complex and pyrophosphateInfo
- Publication number
- CA2154860A1 CA2154860A1 CA 2154860 CA2154860A CA2154860A1 CA 2154860 A1 CA2154860 A1 CA 2154860A1 CA 2154860 CA2154860 CA 2154860 CA 2154860 A CA2154860 A CA 2154860A CA 2154860 A1 CA2154860 A1 CA 2154860A1
- Authority
- CA
- Canada
- Prior art keywords
- zinc
- oral care
- care product
- accordance
- ingredient
- 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.)
- Abandoned
Links
Abstract
This invention provides an oral care product which has superior properties for controlling plaque, calculus, oral malodor and gingivitis. An invention oral care product contains alkali metal pyrophosphate, and a water-soluble zinc-polyamine complex which slow-releases bioavailable zinc ions in an oral cavity environment. The complex is formed from a polyamine such as polyethylenimine, and a normally water-insoluble zinc compound such as zinc oxide or zinc citrate.
Description
` - -~2749? ~15 48 6 ~
,~.
ORAL CARE PRODUCTS CONTAINING
ZINC-POLYAMINE COMPLEX AND PYROP~OSPE~ATE
CROSS-REFERENCE TO RELATED APPLICATIONS
The subject matter of the present patent application is related to that disclosed in U.S. patent application S. N- 08/269,155, filed June 30, 199~ and U.S. patent application S.N. 08/26~,15~, - , filed J~ne 30, 1994;
incorporated by reference.
BACKGROUND OF THE INVENTION .
The use of zinc compounds as a source for physiologically active zinc ions in oral care products such as mouthwashes, rinses and toothpastes is a widely accepted practice. Zinc has been used 15 for its ability to neutralize oral malodor, and it is also recognized that zinc ions have antiplaque and anticalculus properties.
It is hypothesized that the mechanism of zinc ions in reducing calculus in dental 20 applications is interference with two stages in the development of calculus, i.e., the structural formation of the plaque stage, and the mineralization of the plaque stage. Both of these stages normally make the plaque more cohesive, and 25 therefore less permeable to penetration by the 21548~
physiologically active chemical species in the oral environment. Zinc interferes with the attachment of the microbial elements to each other and to the mucilaginous matrix, and also can interfere with the calcification stage. In both stages the zinc ions function as an antagonist to calcium ions. It is postulated that a zinc compound, by preventing the plaque from becoming dense and strongly cohesive, causes permeability in the plaque which allows penetration by the physiologically active antiplaque and anticalculus ions in the oral environment.
Both water-soluble and water-insoluble zinc compounds have been utilized as physiologically active ingredients in oral care preparations.
Water-soluble and highly ionized zinc compounds such as zinc chloride provide the best source of bioavailable zinc ions. However, zinc chloride in aqueous solution tends to form oxychlorides and zinc hydroxides of low solubility, which results in a two-phase cloudy solution.
The pH of a conventional zinc chloride solution can be lowered to less than 4.5 through the use of mineral or organic acid buffers to provide a stable and clear solution. However, this method is not acceptable since the resultant oral care product exhibits severe astringency and an undesirable sour taste.
~ f ~
" - -- 2154~60 Zinc salts such as zinc phenolsulfonate as disclosed in U.S. 4,022,880, and zinc carboxymethylsuccinate, as disclosed in U.S. 4,144,323, tend to be stable at a higher pH
than other zinc salts. Sparingly water-soluble salts such as zinc citrate have been used to moderate the release of zinc ions, thereby reducing astringency and providing a sustained level of in-vivo anticalculus activity. The use of various complexing agents such as sodium gluconate (U.S. 4,568,540), glycine (U.S. 4,339,432 and U.S. 4,4Z5,325), sodium citrate, citric acid, and the like, have been employed for production of relatively stable solutions of zinc chloride.
The reaction or interaction of zinc compounds of varying solubility with anionic polymers containing carboxylic, sulfonic and/or phosphonic acid functionalities are described in U.S. 4,138,477.
U.S. 4,664,906 describes oral compositions containing hexedine and a zinc compound which exhibit antimicrobial activity. Opacified gel dentifrices are d~sclosed which contain sodium gluconate and a nonionic binder such as hydroxyethylcellulose.
U.S. 4,992,2S9 describes a clear aqueous composition of a zinc salt, a complexing agent such as succinic acid, and an anionic polymer such as sodium alginate.
2ls4s6a ` -Prior art of particular interest with respect to the present invention subject matter includes United States patent 4,022,880; 4,082,841; and 4,522,806. These references describe oral care products which contain a zinc compound and a polyamine compound as two of the formulation ingredients.
There is continuing interest in the development of new and improved oral care products which retard plaque and calculus formation in oral cavities.
Accordingly, it is an object of this invention to provide an oral care product which has superior properties for controlling plaque, calculus, oral malodor and gingivitis.
It is another object of this invention to provide an oral care product which slow-releases bioavailable zinc ions in an oral cavity environment.
It is a further object of this invention to provide a water-soluble polyamine complex of a normally water-insoluble zinc compound which has utility as an ingredient of improved palatability and reduced astringency in oral care products.
Other objects and advantages of the present invention shall become apparent from the accompanying description and examples.
Figure 1 is a graph which represents the mean salivary zinc concentration vs. time curves for three dentifrices. The graph comparative data have correspondence with the dentifrice formulations and procedures described in Example VII.
- 21548~0 DESCRIPTION OF THE INVENTION
One or more objects of the present invention are accomplished by the provision of an oral care product which contains an effective anticalculus mixture of ingredients comprising (1) about 0.1-15 parts by weight of water-insoluble zinc compound; (2) about 0.1-15 parts by weight of water-soluble zinc-complexing polyamine ingredient;
(3) about 0.1-5 parts by weight of alkali metal pyrophosphate; (4) about 0-5 parts by weight of surfactant; and (5) about 0-95 parts by weight of water.
An invention oral care product can be in the form of a powder essentially free of water, and the zinc compound ingredient can have an average particle size between about 0.1-20 microns, and the alkali pyrophosphate ingredient can have an average particle size between about 5-600 microns.
When an invention oral care product has a water content between about 12-95 parts by weight, the zinc compound is in the form of a water-soluble zinc-polyamine complex. An invention oral care product typically is a toothpaste or mouthwash formulation.
The term "single-phase" as employed herein refers to an invention aqueous solution which has a clear transparency, without any visible evidence of a second phase which is distinct from the aqueous phase. The aqueous solution contains zinc compound and polyamine in the form of a water-soluble zinc-polyamine complex.
The term "water-insoluble" as employed herein refers to a zinc-containing compound which has a solubility in water that is equivalent to less than about 0.5 gram of zinc ions in 100 milliliters S of water at 25C. The slight solubility of the zinc compound in water is sufficient to slow-release bioavailable zinc ions in an oral environment.
The term "water-soluble" as employed herein refers to polyamines which have a solubility of at least about two grams per 100 milliliters of water at 25C.
An invention oral care product has an effective anticalculus content of zinc compound, such as between about 0.05-5 weight percent, based on the oral product weight.
Zinc compounds having a solubility which provides less than about 0.5 gram of bioavailable zinc ions per 100 milliliters of water at 25C, and which are suitable as an ingredient in an invention oral care product, include zinc oxide, zinc silicate, zinc carbonate, zinc tetrafluoroborate, zinc hexafluorosilicate, zinc citrate, zinc benzoate, zinc oxalate, zinc stearate, and the like.
Polyamines which are suitable as an ingredient in an invention oral care product include water-soluble chemical structures which have at least 4 amine groups such as polyalkylenamines - 21~4~6Q
having a weight average molecular weight between about 800-1,000,000. A preferred type of polyalkylenamine is one which corresponds to the formula:
R
[ (CH2) n~N ]
where R is a hydrogen, Cl-C3 alkyl or t (CH2)n-NH-~-substituent, and n is an integer in the range of 2-6.
A polyamine ingredient can contain other heteroatoms such as oxygen and sulfur. The amine groups can be any combination selected from primary, secondary and tertiary amine structures. The polyamine ingredient must have sufficient amine basicity to coordinate with the zinc compound and form a water-soluble zinc-polyamine complex.
Another type of polyamine which can be employed as a zinc-complexing ingredient in an invention aqueous solution is a basic aminoacid polymer having a weight average molecular weight between about 1500-70,000. Illustrative of these aminoacid polymers are polyarginine, polylysine and polyhistidine.
\ - -A present invention oral care product can be prepared conveniently by dissolving the polyamine ingredient in an aqueous medium, and then adding the zinc compound in powder form to the aqueous solution with stirring to form a zinc-polyamine complex.
Solubilizing of the zinc compound in the aqueous polyamine solution also can be facilitated by employing an ultrafine powder form. Zinc oxide having an average particle size less than about five microns is a commercially available product.
After completion of the zinc compound addition, the resultant single-phase clear aqueous solution can have a pH above about 10 because of the polyamine basicity. Preferably, an acid reagent such as hydrochloric acid is added to adjust the aqueous solution pH into the range between about 6-10.
A pH above about 10 can have an irritating effect on sensitive membranes when an oral care product containing the aqueous solution is used in a dental application. A pH below about 6 can cause acid etching of tooth enamel. It is advantageous to maintain the aqueous zinc-polyamine complex solution pH in the 6-10 range.
The aqueous zinc-polyamine complex solution can be incorporated as a component of invention oral care products such as toothpastes and mouthwashes. A typical oral care product will have a zinc ion concentration between about 0.05-2.0 weight percent.
215~86~
A toothpaste formulation can be prepared by blending a present invention aqueous solution of zinc-polyamine complex with the pyrophosphate ingredient, and other conventional ingredients which are employed as adjuvants in oral care products.
Suitable alkali metal pyrophosphates include dialkali metal and tetraalkali metal pyrophosphate and mixtures thereof in a hydrated or unhydrated form. Illustrative of pyrophosphate salts are Na2H2P207, Na4P207 and K4 2 7 Suitable adjuvants include whitening agents such as titanium dioxide; preservatives;
silicones; chlorophyll compounds; peroxygen compounds such as sodium percarbonate; antibacterial agents such as cetyl pyridinium chloride; flavorants such as oils of spearmint and peppermint; sweetening agents such as sucrose and sodium cyclamate;
fluoride compounds such as sodium fluoride and sodium monofluorophosphate; humectants such as glycerin; gelling agents such as sodium carboxymethylcellulose; abrasives such as alpha-alumina, particulate polyvinyl chloride, calcium phosphate, silica xerogel and sodium bicarbonate;
and the like.
Other adjuvants employed in toothpaste formulations include between 0.05-S parts by weight of a surfactant such as cetyltrimethylammonium bromide; sodium lauryl sulfate; sodium dodecylbenzenesulfonate; ammonium lignosulfonate;
condensation products of ethylene oxide with fatty alcohols, amines or alkylphenols; partial esters of fatty acids and hexitol anhydrides; and the like.
A mouthwash formulation can be prepared by blending a present invention aqueous solution of zinc-polyamine complex with other ingredients of the type described above, which include aqueous ethanol, glycerin, sorbitol, surfactant, colorant, flavorant, antibacterial agent, and the like.
By the practice of the present invention, an oral care product can be prepared which has superior properties for retarding plaque and calculus formulation, and controlling bad breath and gingivitis. Important advantages derive from the presence of a present invention zinc-polyamine complex as a component of an oral care product, when the oral care product is applied to an oral cavity following a prescribed regimen.
A present invention zinc-polyamine complex can be adsorbed onto oral surfaces. The zinc-polyamine complex provides a means of attachment in the oral cavity, and functions as a reservoir of zinc ions which are sustained-released over an extended time period and are effective for controlling plaque, calculus, mouth odor and gingivitis.
As a further advantage, the zinc-polyamine complex is in a form that decreases the astringency which is characteristic of zinc ions, and thereby leaves a more pleasant taste in the mouth.
The following examples are further illustrative of the present invention. The components and specific ingredients are presented as being typical, and various modifications can be derived in view of the foregoing disclosure within the scope of the invention.
` -21~48SO
EXAMPLE I
This Example illustrates the preparation of a present invention aqueous solution containing a zinc-polyamine complex.
InqredientsParts By Weiqht Polymin p(1) 12 hydrochloric acid (50% aq. sol.) 21 zinc oxide powder 4 distilled water to lO0 lO The polyamine is dissolved in about 50 parts of distilled water. The zinc oxide powder is added to the aqueous solution, and stirring is continued for about 30 minutes. Hydrochloric acid solution is added to adjust the pH to 7-8.
Distilled water is added to lO0 parts by weight.
The final aqueous solution is a single phase transparent medium with a pH of 7-8.
A similar solution of zinc-polyamine complex is obtained when zinc citrate is employed instead of zinc oxide.
PEI 1500 (CTFA) ; polyethylenimine (M.W. 75,000; BASF) - 215~860 EXAMPLE II
This Example illustrates comparative data which demonstrate that a present invention aqueous zinc-polyamine complex solution exhibits an enhanced anticalculus effect.
Anticalculus evaluation is conducted with an in-vitro method similar to that described in J. Clin. Den., 2, 48 (1990) by Schiff & Volpe. A
higher T1 value represents a greater anticalculus effect.
The comparative data are summarized in the following Table:
2l~4a6~
TABLE
Aqueous Systems Tl, minutes 1. distilled water control 14.25 2. 2% zinc oxide aqueous suspension 15.00 3. 6% PEI(l) 14.25 4. 0.25% PEI + 2.0% zinc oxide 16.00 5. 0.25% PEI + 4.0% zinc oxide 16.00 6. 2.0% PEI + 2.0% zinc oxide 21.00 7. 2.0% PEI + 4.0% zinc oxide 21.50 8. 5.0% TSPP(2) aqueous solution 23.00 9. Colgate TC 20.00 10. 6% PEI + 2% zinc oxide 26.50 11. Crest TC 27.75 12. 5.0% zinc citrate(3) 17.25 13. 5.0% zinc citrate + 2% PEI 25.75 14. 2.0% PEI + 4.0% zinc oxide + 2.0% TSPP 32.00 15. 6.0% PEI + 2.0% zinc oxide + 5.0% TSPP 50.25 (1) Polymin P (M.W. 75,000; BASF); PEI 1500 (CTFA) '2) tetrasodium pyrophosphate (3) 2% zinc oxide and 5% zinc citrate are equivalent in zinc molarity - 2~5~6~
EXAMPLE III
This Example illustrates the preparation of a dentifrice composition which contains tetrasodium pyrophosphate and an aqueous solution of a zinc-polyamine complex in accordance with the present invention.
InqredientsParts By Weiqht glycerin 15.00 PEG-8(1) 1.00 10 sodium carboxymethylcellulose gum0.60 sorbitol (70~ soln.) 27.56 distilled water 10.00 sodium fluoride 0.24 hydrated silica 16.00 zinc-PEI 1500 solution (Example I)25.00 tetrasodium pyrophosphate 2.00 sodium lauryl sulfate 1.20 sodium saccharin 0.50 flavor oil 0.90 (1) polyethylene glycol (M.W. 400) 2~ 6a The sodium carboxymethylcellulose, glycerin and PEG-8 ingredients are admixed with stirring to form a suspension. Sorbitol and sodium fluoride (in aqueous solution) are added to the suspension, and stirring is continued for about 30 minutes. Hydrated silica is added with stirring, followed by the addition of the zinc-PEI solution with stirring for about 10 minutes. Tetrasodium pyrophosphate, sodium lauryl sulfate and flavor oil are blended into the admixture to form a homogeneous toothpaste formulation. The product is deaerated and filled into tubes.
~1~4~6Q
EXAMPLE IV
This Example illustrates the preparation of a mouthwash formulation which contains tetrasodium pyrophosphate and an aqueous solution of a zinc-polyamine complex in accordance with the present invention.
Ingredients Parts By Weiqht distilled water 56.09 glycerin 11.00 SD alcohol 38-B~1) 5.00 zinc-PEI 1500 solution (Example I) 25.00 sodium benzoate . 0.20 sodium saccharin 0.50 tetrasodium pyrophosphate 1.00 Poloxamer 407~2) 0.60 flavor oil 0.60 FD&C Blue #1 0.01 ~1) denatured ethanol '2) polyoxyethylene-polyoxypropylene block polymer 2~86a The distilled water, glycerin and zinc-polyamine complex solution are admixed to form an aqueous solution. The sodium benzoate, sodium saccharin, tetrasodium pyrophosphate and colorant are added to the aqueous solution with stirring.
The alcohol, flavorant and Poloxamer 407 ingredients are preblended, and the blend is added to the aqueous solution with stirring to form a clear blue mouthwash formulation.
`- 2l5~86~
EXAMPLE V
This Example illustrates the preparation of toothpaste formulations containing zinc-polyamine complex, sodium bicarbonate and tetrasodium pyrophosphate ingredients in accordance with the present invention.
Ingredients Parts By Weiqht a b c glycerin 14.070 14.070 14.070 PEG-8 1.000 1.000 1.000 sodium carboxymethylcellulose 0.850 0.850 0.850 distilled water ; 11.687 17.687 21.062 sodium fluoride 0.243 0.243 0.243 sodium saccharin 1.200 1.200 1.200 sodium bicarbonate 57.250 55.000 55.000 PEI 1500 (50% soln.) 4.000 2.000 1.000 hydrochloric acid (50% soln.) 3.500 1.750 0.875 zinc oxide 2.000 2.000 0.500 tetrasodium pyrophosphate2.000 2.000 2.000 sodium lauryl sulfate 0.300 0.300 0.300 sodium lauroyl sarcosinate1.000 1.000 1.000 (30% soln.) flavorant o.goo o.goo o.goo TOTAL 100.000 100.000 100.000 - 21~ ~86~
The glycerin, PEG-8 and sodium carboxymethylcellulose are admixed, followed by the addition of aqueous sodium fluoride solution.
Sodium saccharin and sodium bicarbonate are added to the admixture with stirring. Separately, the tetrasodium pyrophosphate is preblended with the PEI 1500, zinc oxide, 50% HCl and distilled water, and the blend is added to the main admixture. The final product is obtained by adding sodium lauryl sulfate, sodium lauroyl sarcosinate and flavorant to the admixture and stirring to form a homogeneous toothpaste formulation.
- ~15~86~
EXAMPLE VI
This Example illustrates the preparation of gel toothpaste formulations containing zinc-polyamine complex, sodium bicarbonate and tetrasodium pyrophosphate ingredients in accordance with the present invention.
Ingredients Parts By Weight a b c glycerin 10.000 10.000 10.000 sorbitol (70% soln.)23.000 23.000 23.000 PEG-8 1.000 1.000 1.000 sodium carboxymethylcellulose 0.650 0.650 0.650 distilled water 7.337 11.087 14.462 sodium fluoride 0.243 0.243 0.243 sodium saccharin 0.500 0.500 0.500 sodium bicarbonate 30.000 30.000 30.000 hydrated silica 12.500 12.500 12.500 PEI 1500 (50% soln.) 4.000 2.000 1.000 hydrochloric acid (50~ soln.) 3.500 1.750 0.875 zinc oxide 2.000 2.000 0.500 tetrasodium pyrophosphate2.000 2.000 2.000 sodium lauryl sulfate 0.500 0.500 0.500 sodium lauroyl sarcosinate1.670 1.670 1.670 (30% soln.) flavorant 0.900 0.900 0.900 FD&C Blue #1 (1% soln.)0.167 0.167 0.167 D&C Yellow #10 (1% soln.)0.033 0.033 0.033 TOTAL 100.000 100.000 100.000 2154~6~
Following the procedure described in Example V, the above ingredients are blended in the approximate order listed. The final homogeneous gel formulations are deaerated and filled into standard toothpaste tubes.
~15~860 EXAMPLE VII
This Example illustrates the increased oral retention of zinc with a toothpaste dentifrice which contains zinc compound and polyamine ingredients in accordance with the present invention.
Comparative salivary tests are conducted to determine the effect of polyethylenimine on the salivary clearance of zinc oxide delivered from a sodium bicarbonate-containing dentifrice.
Dentifrices containing 59.25% sodium bicarbonate and 2% zinc oxide with and without 2% polyethylenimine are prepared, with complete formulations as shown in Table 1. A commercial dentifrice containing 1% zinc citrate trihydrate (ZnCit) also is tested (Close-Up Tartar Control Gel).
The three zinc-containing dentifrice products are tested in a blind cross-over brushing design. Six human subjects are recruited, and they abstain from all oral hygiene on the morning of each test. Only one product per day is tested, and the subjects are blinded to the identity of the products. On the day of testing, an unstimulated saliva sample is obtained from each subject prior to brushing. The subjects brush with 2 g of a test product for 60 seconds and rinse for 5 seconds with 215~8~0 15 ml of distilled water. Following rinsing, unstimulated saliva samples are collected at 1, 5, 10, 15, 30, 45 and 60 minutes. During this period the subjects refrain from eating, drinking or gum chewing, and minimize talking. After sample collection, 0.4 ml of each saliva sample is diluted with 5 ml 1 N HCl in polypropylene vials. The diluted samples are mixed using a vortex mixer, and analyzed for zinc using ICP spectrophotometry.
The mean salivary zinc concentration vs.
time curves for the three test dentifrices are shown in Figure 1. Prior to brushing, the mean baseline salivary zinc concentrations are 0.56, 0.41 and 0.59 ~g Zn/ml saliva for the ZnO, ZnO/PEI 1500 and commercial zinc citrate dentifrices (ZnCit), respectively. The salivary clearance curves for the test products exhibit a typical biphasic salivary clearance pattern. This is characterized by a rapid initial decline in salivary zinc followed by a slower secondary elimination of zinc from saliva.
The salivary zinc levels for all dentifrice products as expected is highest immediately following the water rinse. At 1 minute post-brushing, the mean salivary zinc concentrations are 111, 129 and 44 ~g Zn/ml for the ZnO, ZnO/PEI
1500 and ZnCit dentifrices, respectively. At 5 minutes, the mean salivary zinc levels are 39, 48 215~0 and 15 ~g Zn/ml, respectively. Differences between products at 1 and 5 minutes post-brushing are due to differences in product zinc concentrations. The ZnCit dentifrice contains 1.0% zinc citrate trihydrate, which is equivalent to about 0.31% Zn or 0.39~ ZnO. In comparison, the ZnO dentifrices contain 2.0% ZnO. While higher initial concentrations of zinc are obtained as a result of increased levels of zinc in the ZnO dentifrices, the effect is transitory and not sustained beyond 5 minutes post-brushing.
The mean salivary zinc levels at 10 minutes post-brushing decreased to 13, 18 and 9 ~g Zn/ml respectively for the ZnO, ZnO/PEI and ZnCit dentifrices. These levels are not significantly different from each other (p>0.05).
At 15 to 60 minutes post-brushing, the ZnO/PEI 1500 dentifrice provides significantly (p<0.05) higher mean salivary zinc levels then either the ZnO or ZnCit dentifrices. The ZnO/PEI lSOO dentifrice provides mean salivary zinc concentrations ranging between 10 to 18 ~g Zn/ml during the 15 to 60 minutes post-brushing. In comparison, the ZnCit dentifrice provides mean salivary zinc concentrations ranging from 4 to 6 ~g Zn/ml.
Similarly, the mean salivary zinc concentration 21~48~0 provided by the ZnO dentifrice drops from 7 ~g Zn/ml at 15 minutes to less than 2 ~g Zn/ml at 60 minutes.
There are no differences between the ZnCit and the ZnO dentifrices during this time period. A
statistical summary of the data is illustrated in Table 2.
The salivary test data indicate that zinc can be delivered at a high level to the oral cavity from a zinc oxide baking soda dentifrice, and that the addition of PEI 1500 significantly increases the oral retention of zinc. This delivery and retention directly relates to the beneficial bioactivity of zinc, since the bioactivity of an oral antimicrobial agent is dependent upon the delivery of an effective concentration, i.e., the dosage, frequency of application, and retention of the agent within the oral cavity.
During the saliva collection periods, five of the six subjects offer comments that the aftertaste of the commercial zinc citrate dentifrice is objectionable. The metallic aftertaste and high degree of astringency are the most prevalent observations. The metallic taste and astringent feeling of soluble and partially soluble zinc salts is well-known. The magnitude of these perceptions is dependent upon zinc concentration. Although the 21~48~Q
ZnO/PEI 1500 dentifrice provides a higher sustained level of salivary zinc, no subject finds this product to possess any objectional metallic or astringent aftertaste as is noted with the ZnCit product. The PEI 1500 appears to moderate the taste perception of zinc.
2l5~86~) TABLE I
Parts By Weiqht INGREDIENT ZnOZnO/PEI 1500 Zinc oxide (Sachtleben Chemie)2.000 2.000 PEI 1500 0.000 4.000 (50% soln., Polymin P;
BASF) 50% HCl (6N HCl) 0.000 3.500 Distilled water 19.173 11.673 Sodium bicarbonate59.250 59.250 Glycerin (99.7%)14.070 14.070 PEG-8 (Carbowax 400;1.000 1.000 Union Carbide) Sodium carboxymethyl-0.850 0.850 cellulose Sodium fluoride 0.243 0.243 Sodium saccharin 1.208 1.208 Sodium lauryl sulfate0.300 0.300 Hamposyl L-30 (Grace)(1) 1.000 1.000 Flavor (H&R 9377)0.906 0.906 Total 100.000 100.000 (1) Sodium lauroyl sarcosinate.
- 21~486~
STATISTICAL SUMMARY OF RESULTS*
TEST PRODUCT1-5 mins. 10 mins. 15-60 mins.
ZnO/PEI dentifrice A B
A B
ZnO dentifrice A B C
B C
Close Up (Zn Citrate) B C
*Products with the same letter are not statistically different (p<0.05) within the specified time period.
,~.
ORAL CARE PRODUCTS CONTAINING
ZINC-POLYAMINE COMPLEX AND PYROP~OSPE~ATE
CROSS-REFERENCE TO RELATED APPLICATIONS
The subject matter of the present patent application is related to that disclosed in U.S. patent application S. N- 08/269,155, filed June 30, 199~ and U.S. patent application S.N. 08/26~,15~, - , filed J~ne 30, 1994;
incorporated by reference.
BACKGROUND OF THE INVENTION .
The use of zinc compounds as a source for physiologically active zinc ions in oral care products such as mouthwashes, rinses and toothpastes is a widely accepted practice. Zinc has been used 15 for its ability to neutralize oral malodor, and it is also recognized that zinc ions have antiplaque and anticalculus properties.
It is hypothesized that the mechanism of zinc ions in reducing calculus in dental 20 applications is interference with two stages in the development of calculus, i.e., the structural formation of the plaque stage, and the mineralization of the plaque stage. Both of these stages normally make the plaque more cohesive, and 25 therefore less permeable to penetration by the 21548~
physiologically active chemical species in the oral environment. Zinc interferes with the attachment of the microbial elements to each other and to the mucilaginous matrix, and also can interfere with the calcification stage. In both stages the zinc ions function as an antagonist to calcium ions. It is postulated that a zinc compound, by preventing the plaque from becoming dense and strongly cohesive, causes permeability in the plaque which allows penetration by the physiologically active antiplaque and anticalculus ions in the oral environment.
Both water-soluble and water-insoluble zinc compounds have been utilized as physiologically active ingredients in oral care preparations.
Water-soluble and highly ionized zinc compounds such as zinc chloride provide the best source of bioavailable zinc ions. However, zinc chloride in aqueous solution tends to form oxychlorides and zinc hydroxides of low solubility, which results in a two-phase cloudy solution.
The pH of a conventional zinc chloride solution can be lowered to less than 4.5 through the use of mineral or organic acid buffers to provide a stable and clear solution. However, this method is not acceptable since the resultant oral care product exhibits severe astringency and an undesirable sour taste.
~ f ~
" - -- 2154~60 Zinc salts such as zinc phenolsulfonate as disclosed in U.S. 4,022,880, and zinc carboxymethylsuccinate, as disclosed in U.S. 4,144,323, tend to be stable at a higher pH
than other zinc salts. Sparingly water-soluble salts such as zinc citrate have been used to moderate the release of zinc ions, thereby reducing astringency and providing a sustained level of in-vivo anticalculus activity. The use of various complexing agents such as sodium gluconate (U.S. 4,568,540), glycine (U.S. 4,339,432 and U.S. 4,4Z5,325), sodium citrate, citric acid, and the like, have been employed for production of relatively stable solutions of zinc chloride.
The reaction or interaction of zinc compounds of varying solubility with anionic polymers containing carboxylic, sulfonic and/or phosphonic acid functionalities are described in U.S. 4,138,477.
U.S. 4,664,906 describes oral compositions containing hexedine and a zinc compound which exhibit antimicrobial activity. Opacified gel dentifrices are d~sclosed which contain sodium gluconate and a nonionic binder such as hydroxyethylcellulose.
U.S. 4,992,2S9 describes a clear aqueous composition of a zinc salt, a complexing agent such as succinic acid, and an anionic polymer such as sodium alginate.
2ls4s6a ` -Prior art of particular interest with respect to the present invention subject matter includes United States patent 4,022,880; 4,082,841; and 4,522,806. These references describe oral care products which contain a zinc compound and a polyamine compound as two of the formulation ingredients.
There is continuing interest in the development of new and improved oral care products which retard plaque and calculus formation in oral cavities.
Accordingly, it is an object of this invention to provide an oral care product which has superior properties for controlling plaque, calculus, oral malodor and gingivitis.
It is another object of this invention to provide an oral care product which slow-releases bioavailable zinc ions in an oral cavity environment.
It is a further object of this invention to provide a water-soluble polyamine complex of a normally water-insoluble zinc compound which has utility as an ingredient of improved palatability and reduced astringency in oral care products.
Other objects and advantages of the present invention shall become apparent from the accompanying description and examples.
Figure 1 is a graph which represents the mean salivary zinc concentration vs. time curves for three dentifrices. The graph comparative data have correspondence with the dentifrice formulations and procedures described in Example VII.
- 21548~0 DESCRIPTION OF THE INVENTION
One or more objects of the present invention are accomplished by the provision of an oral care product which contains an effective anticalculus mixture of ingredients comprising (1) about 0.1-15 parts by weight of water-insoluble zinc compound; (2) about 0.1-15 parts by weight of water-soluble zinc-complexing polyamine ingredient;
(3) about 0.1-5 parts by weight of alkali metal pyrophosphate; (4) about 0-5 parts by weight of surfactant; and (5) about 0-95 parts by weight of water.
An invention oral care product can be in the form of a powder essentially free of water, and the zinc compound ingredient can have an average particle size between about 0.1-20 microns, and the alkali pyrophosphate ingredient can have an average particle size between about 5-600 microns.
When an invention oral care product has a water content between about 12-95 parts by weight, the zinc compound is in the form of a water-soluble zinc-polyamine complex. An invention oral care product typically is a toothpaste or mouthwash formulation.
The term "single-phase" as employed herein refers to an invention aqueous solution which has a clear transparency, without any visible evidence of a second phase which is distinct from the aqueous phase. The aqueous solution contains zinc compound and polyamine in the form of a water-soluble zinc-polyamine complex.
The term "water-insoluble" as employed herein refers to a zinc-containing compound which has a solubility in water that is equivalent to less than about 0.5 gram of zinc ions in 100 milliliters S of water at 25C. The slight solubility of the zinc compound in water is sufficient to slow-release bioavailable zinc ions in an oral environment.
The term "water-soluble" as employed herein refers to polyamines which have a solubility of at least about two grams per 100 milliliters of water at 25C.
An invention oral care product has an effective anticalculus content of zinc compound, such as between about 0.05-5 weight percent, based on the oral product weight.
Zinc compounds having a solubility which provides less than about 0.5 gram of bioavailable zinc ions per 100 milliliters of water at 25C, and which are suitable as an ingredient in an invention oral care product, include zinc oxide, zinc silicate, zinc carbonate, zinc tetrafluoroborate, zinc hexafluorosilicate, zinc citrate, zinc benzoate, zinc oxalate, zinc stearate, and the like.
Polyamines which are suitable as an ingredient in an invention oral care product include water-soluble chemical structures which have at least 4 amine groups such as polyalkylenamines - 21~4~6Q
having a weight average molecular weight between about 800-1,000,000. A preferred type of polyalkylenamine is one which corresponds to the formula:
R
[ (CH2) n~N ]
where R is a hydrogen, Cl-C3 alkyl or t (CH2)n-NH-~-substituent, and n is an integer in the range of 2-6.
A polyamine ingredient can contain other heteroatoms such as oxygen and sulfur. The amine groups can be any combination selected from primary, secondary and tertiary amine structures. The polyamine ingredient must have sufficient amine basicity to coordinate with the zinc compound and form a water-soluble zinc-polyamine complex.
Another type of polyamine which can be employed as a zinc-complexing ingredient in an invention aqueous solution is a basic aminoacid polymer having a weight average molecular weight between about 1500-70,000. Illustrative of these aminoacid polymers are polyarginine, polylysine and polyhistidine.
\ - -A present invention oral care product can be prepared conveniently by dissolving the polyamine ingredient in an aqueous medium, and then adding the zinc compound in powder form to the aqueous solution with stirring to form a zinc-polyamine complex.
Solubilizing of the zinc compound in the aqueous polyamine solution also can be facilitated by employing an ultrafine powder form. Zinc oxide having an average particle size less than about five microns is a commercially available product.
After completion of the zinc compound addition, the resultant single-phase clear aqueous solution can have a pH above about 10 because of the polyamine basicity. Preferably, an acid reagent such as hydrochloric acid is added to adjust the aqueous solution pH into the range between about 6-10.
A pH above about 10 can have an irritating effect on sensitive membranes when an oral care product containing the aqueous solution is used in a dental application. A pH below about 6 can cause acid etching of tooth enamel. It is advantageous to maintain the aqueous zinc-polyamine complex solution pH in the 6-10 range.
The aqueous zinc-polyamine complex solution can be incorporated as a component of invention oral care products such as toothpastes and mouthwashes. A typical oral care product will have a zinc ion concentration between about 0.05-2.0 weight percent.
215~86~
A toothpaste formulation can be prepared by blending a present invention aqueous solution of zinc-polyamine complex with the pyrophosphate ingredient, and other conventional ingredients which are employed as adjuvants in oral care products.
Suitable alkali metal pyrophosphates include dialkali metal and tetraalkali metal pyrophosphate and mixtures thereof in a hydrated or unhydrated form. Illustrative of pyrophosphate salts are Na2H2P207, Na4P207 and K4 2 7 Suitable adjuvants include whitening agents such as titanium dioxide; preservatives;
silicones; chlorophyll compounds; peroxygen compounds such as sodium percarbonate; antibacterial agents such as cetyl pyridinium chloride; flavorants such as oils of spearmint and peppermint; sweetening agents such as sucrose and sodium cyclamate;
fluoride compounds such as sodium fluoride and sodium monofluorophosphate; humectants such as glycerin; gelling agents such as sodium carboxymethylcellulose; abrasives such as alpha-alumina, particulate polyvinyl chloride, calcium phosphate, silica xerogel and sodium bicarbonate;
and the like.
Other adjuvants employed in toothpaste formulations include between 0.05-S parts by weight of a surfactant such as cetyltrimethylammonium bromide; sodium lauryl sulfate; sodium dodecylbenzenesulfonate; ammonium lignosulfonate;
condensation products of ethylene oxide with fatty alcohols, amines or alkylphenols; partial esters of fatty acids and hexitol anhydrides; and the like.
A mouthwash formulation can be prepared by blending a present invention aqueous solution of zinc-polyamine complex with other ingredients of the type described above, which include aqueous ethanol, glycerin, sorbitol, surfactant, colorant, flavorant, antibacterial agent, and the like.
By the practice of the present invention, an oral care product can be prepared which has superior properties for retarding plaque and calculus formulation, and controlling bad breath and gingivitis. Important advantages derive from the presence of a present invention zinc-polyamine complex as a component of an oral care product, when the oral care product is applied to an oral cavity following a prescribed regimen.
A present invention zinc-polyamine complex can be adsorbed onto oral surfaces. The zinc-polyamine complex provides a means of attachment in the oral cavity, and functions as a reservoir of zinc ions which are sustained-released over an extended time period and are effective for controlling plaque, calculus, mouth odor and gingivitis.
As a further advantage, the zinc-polyamine complex is in a form that decreases the astringency which is characteristic of zinc ions, and thereby leaves a more pleasant taste in the mouth.
The following examples are further illustrative of the present invention. The components and specific ingredients are presented as being typical, and various modifications can be derived in view of the foregoing disclosure within the scope of the invention.
` -21~48SO
EXAMPLE I
This Example illustrates the preparation of a present invention aqueous solution containing a zinc-polyamine complex.
InqredientsParts By Weiqht Polymin p(1) 12 hydrochloric acid (50% aq. sol.) 21 zinc oxide powder 4 distilled water to lO0 lO The polyamine is dissolved in about 50 parts of distilled water. The zinc oxide powder is added to the aqueous solution, and stirring is continued for about 30 minutes. Hydrochloric acid solution is added to adjust the pH to 7-8.
Distilled water is added to lO0 parts by weight.
The final aqueous solution is a single phase transparent medium with a pH of 7-8.
A similar solution of zinc-polyamine complex is obtained when zinc citrate is employed instead of zinc oxide.
PEI 1500 (CTFA) ; polyethylenimine (M.W. 75,000; BASF) - 215~860 EXAMPLE II
This Example illustrates comparative data which demonstrate that a present invention aqueous zinc-polyamine complex solution exhibits an enhanced anticalculus effect.
Anticalculus evaluation is conducted with an in-vitro method similar to that described in J. Clin. Den., 2, 48 (1990) by Schiff & Volpe. A
higher T1 value represents a greater anticalculus effect.
The comparative data are summarized in the following Table:
2l~4a6~
TABLE
Aqueous Systems Tl, minutes 1. distilled water control 14.25 2. 2% zinc oxide aqueous suspension 15.00 3. 6% PEI(l) 14.25 4. 0.25% PEI + 2.0% zinc oxide 16.00 5. 0.25% PEI + 4.0% zinc oxide 16.00 6. 2.0% PEI + 2.0% zinc oxide 21.00 7. 2.0% PEI + 4.0% zinc oxide 21.50 8. 5.0% TSPP(2) aqueous solution 23.00 9. Colgate TC 20.00 10. 6% PEI + 2% zinc oxide 26.50 11. Crest TC 27.75 12. 5.0% zinc citrate(3) 17.25 13. 5.0% zinc citrate + 2% PEI 25.75 14. 2.0% PEI + 4.0% zinc oxide + 2.0% TSPP 32.00 15. 6.0% PEI + 2.0% zinc oxide + 5.0% TSPP 50.25 (1) Polymin P (M.W. 75,000; BASF); PEI 1500 (CTFA) '2) tetrasodium pyrophosphate (3) 2% zinc oxide and 5% zinc citrate are equivalent in zinc molarity - 2~5~6~
EXAMPLE III
This Example illustrates the preparation of a dentifrice composition which contains tetrasodium pyrophosphate and an aqueous solution of a zinc-polyamine complex in accordance with the present invention.
InqredientsParts By Weiqht glycerin 15.00 PEG-8(1) 1.00 10 sodium carboxymethylcellulose gum0.60 sorbitol (70~ soln.) 27.56 distilled water 10.00 sodium fluoride 0.24 hydrated silica 16.00 zinc-PEI 1500 solution (Example I)25.00 tetrasodium pyrophosphate 2.00 sodium lauryl sulfate 1.20 sodium saccharin 0.50 flavor oil 0.90 (1) polyethylene glycol (M.W. 400) 2~ 6a The sodium carboxymethylcellulose, glycerin and PEG-8 ingredients are admixed with stirring to form a suspension. Sorbitol and sodium fluoride (in aqueous solution) are added to the suspension, and stirring is continued for about 30 minutes. Hydrated silica is added with stirring, followed by the addition of the zinc-PEI solution with stirring for about 10 minutes. Tetrasodium pyrophosphate, sodium lauryl sulfate and flavor oil are blended into the admixture to form a homogeneous toothpaste formulation. The product is deaerated and filled into tubes.
~1~4~6Q
EXAMPLE IV
This Example illustrates the preparation of a mouthwash formulation which contains tetrasodium pyrophosphate and an aqueous solution of a zinc-polyamine complex in accordance with the present invention.
Ingredients Parts By Weiqht distilled water 56.09 glycerin 11.00 SD alcohol 38-B~1) 5.00 zinc-PEI 1500 solution (Example I) 25.00 sodium benzoate . 0.20 sodium saccharin 0.50 tetrasodium pyrophosphate 1.00 Poloxamer 407~2) 0.60 flavor oil 0.60 FD&C Blue #1 0.01 ~1) denatured ethanol '2) polyoxyethylene-polyoxypropylene block polymer 2~86a The distilled water, glycerin and zinc-polyamine complex solution are admixed to form an aqueous solution. The sodium benzoate, sodium saccharin, tetrasodium pyrophosphate and colorant are added to the aqueous solution with stirring.
The alcohol, flavorant and Poloxamer 407 ingredients are preblended, and the blend is added to the aqueous solution with stirring to form a clear blue mouthwash formulation.
`- 2l5~86~
EXAMPLE V
This Example illustrates the preparation of toothpaste formulations containing zinc-polyamine complex, sodium bicarbonate and tetrasodium pyrophosphate ingredients in accordance with the present invention.
Ingredients Parts By Weiqht a b c glycerin 14.070 14.070 14.070 PEG-8 1.000 1.000 1.000 sodium carboxymethylcellulose 0.850 0.850 0.850 distilled water ; 11.687 17.687 21.062 sodium fluoride 0.243 0.243 0.243 sodium saccharin 1.200 1.200 1.200 sodium bicarbonate 57.250 55.000 55.000 PEI 1500 (50% soln.) 4.000 2.000 1.000 hydrochloric acid (50% soln.) 3.500 1.750 0.875 zinc oxide 2.000 2.000 0.500 tetrasodium pyrophosphate2.000 2.000 2.000 sodium lauryl sulfate 0.300 0.300 0.300 sodium lauroyl sarcosinate1.000 1.000 1.000 (30% soln.) flavorant o.goo o.goo o.goo TOTAL 100.000 100.000 100.000 - 21~ ~86~
The glycerin, PEG-8 and sodium carboxymethylcellulose are admixed, followed by the addition of aqueous sodium fluoride solution.
Sodium saccharin and sodium bicarbonate are added to the admixture with stirring. Separately, the tetrasodium pyrophosphate is preblended with the PEI 1500, zinc oxide, 50% HCl and distilled water, and the blend is added to the main admixture. The final product is obtained by adding sodium lauryl sulfate, sodium lauroyl sarcosinate and flavorant to the admixture and stirring to form a homogeneous toothpaste formulation.
- ~15~86~
EXAMPLE VI
This Example illustrates the preparation of gel toothpaste formulations containing zinc-polyamine complex, sodium bicarbonate and tetrasodium pyrophosphate ingredients in accordance with the present invention.
Ingredients Parts By Weight a b c glycerin 10.000 10.000 10.000 sorbitol (70% soln.)23.000 23.000 23.000 PEG-8 1.000 1.000 1.000 sodium carboxymethylcellulose 0.650 0.650 0.650 distilled water 7.337 11.087 14.462 sodium fluoride 0.243 0.243 0.243 sodium saccharin 0.500 0.500 0.500 sodium bicarbonate 30.000 30.000 30.000 hydrated silica 12.500 12.500 12.500 PEI 1500 (50% soln.) 4.000 2.000 1.000 hydrochloric acid (50~ soln.) 3.500 1.750 0.875 zinc oxide 2.000 2.000 0.500 tetrasodium pyrophosphate2.000 2.000 2.000 sodium lauryl sulfate 0.500 0.500 0.500 sodium lauroyl sarcosinate1.670 1.670 1.670 (30% soln.) flavorant 0.900 0.900 0.900 FD&C Blue #1 (1% soln.)0.167 0.167 0.167 D&C Yellow #10 (1% soln.)0.033 0.033 0.033 TOTAL 100.000 100.000 100.000 2154~6~
Following the procedure described in Example V, the above ingredients are blended in the approximate order listed. The final homogeneous gel formulations are deaerated and filled into standard toothpaste tubes.
~15~860 EXAMPLE VII
This Example illustrates the increased oral retention of zinc with a toothpaste dentifrice which contains zinc compound and polyamine ingredients in accordance with the present invention.
Comparative salivary tests are conducted to determine the effect of polyethylenimine on the salivary clearance of zinc oxide delivered from a sodium bicarbonate-containing dentifrice.
Dentifrices containing 59.25% sodium bicarbonate and 2% zinc oxide with and without 2% polyethylenimine are prepared, with complete formulations as shown in Table 1. A commercial dentifrice containing 1% zinc citrate trihydrate (ZnCit) also is tested (Close-Up Tartar Control Gel).
The three zinc-containing dentifrice products are tested in a blind cross-over brushing design. Six human subjects are recruited, and they abstain from all oral hygiene on the morning of each test. Only one product per day is tested, and the subjects are blinded to the identity of the products. On the day of testing, an unstimulated saliva sample is obtained from each subject prior to brushing. The subjects brush with 2 g of a test product for 60 seconds and rinse for 5 seconds with 215~8~0 15 ml of distilled water. Following rinsing, unstimulated saliva samples are collected at 1, 5, 10, 15, 30, 45 and 60 minutes. During this period the subjects refrain from eating, drinking or gum chewing, and minimize talking. After sample collection, 0.4 ml of each saliva sample is diluted with 5 ml 1 N HCl in polypropylene vials. The diluted samples are mixed using a vortex mixer, and analyzed for zinc using ICP spectrophotometry.
The mean salivary zinc concentration vs.
time curves for the three test dentifrices are shown in Figure 1. Prior to brushing, the mean baseline salivary zinc concentrations are 0.56, 0.41 and 0.59 ~g Zn/ml saliva for the ZnO, ZnO/PEI 1500 and commercial zinc citrate dentifrices (ZnCit), respectively. The salivary clearance curves for the test products exhibit a typical biphasic salivary clearance pattern. This is characterized by a rapid initial decline in salivary zinc followed by a slower secondary elimination of zinc from saliva.
The salivary zinc levels for all dentifrice products as expected is highest immediately following the water rinse. At 1 minute post-brushing, the mean salivary zinc concentrations are 111, 129 and 44 ~g Zn/ml for the ZnO, ZnO/PEI
1500 and ZnCit dentifrices, respectively. At 5 minutes, the mean salivary zinc levels are 39, 48 215~0 and 15 ~g Zn/ml, respectively. Differences between products at 1 and 5 minutes post-brushing are due to differences in product zinc concentrations. The ZnCit dentifrice contains 1.0% zinc citrate trihydrate, which is equivalent to about 0.31% Zn or 0.39~ ZnO. In comparison, the ZnO dentifrices contain 2.0% ZnO. While higher initial concentrations of zinc are obtained as a result of increased levels of zinc in the ZnO dentifrices, the effect is transitory and not sustained beyond 5 minutes post-brushing.
The mean salivary zinc levels at 10 minutes post-brushing decreased to 13, 18 and 9 ~g Zn/ml respectively for the ZnO, ZnO/PEI and ZnCit dentifrices. These levels are not significantly different from each other (p>0.05).
At 15 to 60 minutes post-brushing, the ZnO/PEI 1500 dentifrice provides significantly (p<0.05) higher mean salivary zinc levels then either the ZnO or ZnCit dentifrices. The ZnO/PEI lSOO dentifrice provides mean salivary zinc concentrations ranging between 10 to 18 ~g Zn/ml during the 15 to 60 minutes post-brushing. In comparison, the ZnCit dentifrice provides mean salivary zinc concentrations ranging from 4 to 6 ~g Zn/ml.
Similarly, the mean salivary zinc concentration 21~48~0 provided by the ZnO dentifrice drops from 7 ~g Zn/ml at 15 minutes to less than 2 ~g Zn/ml at 60 minutes.
There are no differences between the ZnCit and the ZnO dentifrices during this time period. A
statistical summary of the data is illustrated in Table 2.
The salivary test data indicate that zinc can be delivered at a high level to the oral cavity from a zinc oxide baking soda dentifrice, and that the addition of PEI 1500 significantly increases the oral retention of zinc. This delivery and retention directly relates to the beneficial bioactivity of zinc, since the bioactivity of an oral antimicrobial agent is dependent upon the delivery of an effective concentration, i.e., the dosage, frequency of application, and retention of the agent within the oral cavity.
During the saliva collection periods, five of the six subjects offer comments that the aftertaste of the commercial zinc citrate dentifrice is objectionable. The metallic aftertaste and high degree of astringency are the most prevalent observations. The metallic taste and astringent feeling of soluble and partially soluble zinc salts is well-known. The magnitude of these perceptions is dependent upon zinc concentration. Although the 21~48~Q
ZnO/PEI 1500 dentifrice provides a higher sustained level of salivary zinc, no subject finds this product to possess any objectional metallic or astringent aftertaste as is noted with the ZnCit product. The PEI 1500 appears to moderate the taste perception of zinc.
2l5~86~) TABLE I
Parts By Weiqht INGREDIENT ZnOZnO/PEI 1500 Zinc oxide (Sachtleben Chemie)2.000 2.000 PEI 1500 0.000 4.000 (50% soln., Polymin P;
BASF) 50% HCl (6N HCl) 0.000 3.500 Distilled water 19.173 11.673 Sodium bicarbonate59.250 59.250 Glycerin (99.7%)14.070 14.070 PEG-8 (Carbowax 400;1.000 1.000 Union Carbide) Sodium carboxymethyl-0.850 0.850 cellulose Sodium fluoride 0.243 0.243 Sodium saccharin 1.208 1.208 Sodium lauryl sulfate0.300 0.300 Hamposyl L-30 (Grace)(1) 1.000 1.000 Flavor (H&R 9377)0.906 0.906 Total 100.000 100.000 (1) Sodium lauroyl sarcosinate.
- 21~486~
STATISTICAL SUMMARY OF RESULTS*
TEST PRODUCT1-5 mins. 10 mins. 15-60 mins.
ZnO/PEI dentifrice A B
A B
ZnO dentifrice A B C
B C
Close Up (Zn Citrate) B C
*Products with the same letter are not statistically different (p<0.05) within the specified time period.
Claims (18)
1. An oral care product which contains an effective anticalculus mixture of ingredients comprising (1) about 0.1-15 parts by weight of water-insoluble zinc compound; (2) about 0.1-15 parts by weight of water-soluble zinc-complexing polyamine ingredient; (3) about 0.1-5 parts by weight of alkali metal pyrophosphate;
(4) about 0-5 parts by weight of surfactant; and (5) about 0-95 parts by weight of water.
(4) about 0-5 parts by weight of surfactant; and (5) about 0-95 parts by weight of water.
2. An oral care product in accordance with claim 1 which has a zero content of water, and the zinc compound ingredient has an average particle size between about 0.1-20 microns, and the alkali metal pyrophosphate ingredient has an average particle size between about 5-600 microns.
3. An oral care product in accordance with claim 1 wherein the content of water is about 12-95 parts by weight, and the zinc compound is in the form of a water-soluble zinc-polyamine complex.
4. An oral care product in accordance with claim 1 wherein the zinc compound ingredient is zinc oxide.
5. An oral care product in accordance with claim 1 wherein the zinc compound ingredient is zinc silicate.
6. An oral care product in accordance with claim 1 wherein the zinc compound ingredient is zinc carbonate.
7. An oral care product in accordance with claim 1 wherein the zinc compound ingredient is zinc stearate.
8. An oral care product in accordance with claim 1 wherein the zinc compound ingredient is zinc tetrafluoroborate.
9. An oral care product in accordance with claim 1 wherein the zinc compound ingredient is zinc citrate.
10. A composition in accordance with claim 1 wherein the zinc compound ingredient is zinc benzoate.
11. An oral care product in accordance with claim 1 wherein the zinc compound ingredient is zinc oxalate.
12. An oral care product in accordance with claim 1 wherein the polyamine ingredient is polyalkylenamine having a molecular weight between about 800-1,000,000.
13. An oral care product in accordance with claim 1 wherein the polyamine ingredient is polyethylenimine.
14. An oral care product in accordance with claim 1 wherein the content of surfactant ingredient is about 0.05-5 parts by weight, and the ingredient is an anionic, cationic or nonionic surfactant or any mixture thereof.
15. A method of controlling dental calculus formation in an oral cavity which comprises applying a claim 1 oral care product to the oral cavity in accordance with a prescribed regimen.
16. A method in accordance with claim 15 wherein the oral care product is a dental powder formulation.
17. A method in accordance with claim 15 wherein the oral care product is a toothpaste formulation.
18. A method in accordance with claim 15 wherein the oral care product is a mouthwash formulation.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28041194A | 1994-07-26 | 1994-07-26 | |
| US08/280,411 | 1994-07-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2154860A1 true CA2154860A1 (en) | 1996-01-27 |
Family
ID=23072965
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2154860 Abandoned CA2154860A1 (en) | 1994-07-26 | 1995-07-24 | Oral care products containing zinc-polyamine complex and pyrophosphate |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2154860A1 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6607711B2 (en) | 1997-10-07 | 2003-08-19 | Ejvind Jersie Pedersen | Mouth hygienic composition for the treatment of halitosis |
| EP1910250A1 (en) * | 2005-07-12 | 2008-04-16 | Adelaide Research & Innovation Pty Ltd. | Chelating agents for micronutrient fertilisers |
| WO2013171164A1 (en) | 2012-05-14 | 2013-11-21 | EJP Pharmaceutical ApS | Compositions and formulations for the treatment of halitosis |
| WO2015041523A1 (en) | 2013-09-18 | 2015-03-26 | Glymur B.V. | Oral hygiene compositions |
| US10179038B2 (en) | 2015-12-30 | 2019-01-15 | Colgate-Palmolive Company | Oral care device with sacrificial electrode |
| US11019918B2 (en) | 2018-06-11 | 2021-06-01 | Colgate-Palmolive Company | Oral care device |
| US11241084B2 (en) | 2018-06-11 | 2022-02-08 | Colgate-Palmolive Company | Oral care device |
-
1995
- 1995-07-24 CA CA 2154860 patent/CA2154860A1/en not_active Abandoned
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6607711B2 (en) | 1997-10-07 | 2003-08-19 | Ejvind Jersie Pedersen | Mouth hygienic composition for the treatment of halitosis |
| EP1910250A1 (en) * | 2005-07-12 | 2008-04-16 | Adelaide Research & Innovation Pty Ltd. | Chelating agents for micronutrient fertilisers |
| EP1910250B1 (en) * | 2005-07-12 | 2016-03-30 | Adelaide Research & Innovation Pty Ltd. | Chelating agents for micronutrient fertilisers |
| WO2013171164A1 (en) | 2012-05-14 | 2013-11-21 | EJP Pharmaceutical ApS | Compositions and formulations for the treatment of halitosis |
| WO2015041523A1 (en) | 2013-09-18 | 2015-03-26 | Glymur B.V. | Oral hygiene compositions |
| US10179038B2 (en) | 2015-12-30 | 2019-01-15 | Colgate-Palmolive Company | Oral care device with sacrificial electrode |
| US10932893B2 (en) | 2015-12-30 | 2021-03-02 | Colgate-Palmolive Company | Oral care device with sacrificial electrode |
| US11019918B2 (en) | 2018-06-11 | 2021-06-01 | Colgate-Palmolive Company | Oral care device |
| US11241084B2 (en) | 2018-06-11 | 2022-02-08 | Colgate-Palmolive Company | Oral care device |
| US11712108B2 (en) | 2018-06-11 | 2023-08-01 | Colgate-Palmolive Company | Oral care process |
| US11786034B2 (en) | 2018-06-11 | 2023-10-17 | Colgate-Palmolive Company | Oral care device |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR890002946B1 (en) | Oral hygine compositions | |
| CA2169460C (en) | Oral compositions containing stannous compounds | |
| AU2012396297B2 (en) | Surfactant systems for zinc containing compositions | |
| US4902497A (en) | Oral compositions | |
| AU3275193A (en) | Oral compositions for suppressing mouth odors | |
| CZ156895A3 (en) | Mouth preparation containing agents against formation of microbial plaque and tartar | |
| EA002367B1 (en) | Oral care composition | |
| US5587147A (en) | Aqueous zinc-polyamide complex solution | |
| EP0626843A1 (en) | Use of polyvinyl pyrrolidone for reducing the adherence of oral bacteria. | |
| JPH02286613A (en) | New composition | |
| CA2154860A1 (en) | Oral care products containing zinc-polyamine complex and pyrophosphate | |
| EP0095871A2 (en) | Improvements in or relating to tooth treatment compositions | |
| JPH03127719A (en) | Dental and oral composition | |
| CA2785578C (en) | Dentifrice compositions comprising carboxypeptidase | |
| US20010031245A1 (en) | Compositions | |
| US20090010859A1 (en) | Oral Composition | |
| CA2754213C (en) | Desensitizing dentifrice exhibiting dental tissue antibacterial agent uptake | |
| CA2152982A1 (en) | Oral care products containing zinc-polyamine complex | |
| RU2743997C2 (en) | Oral care compositions | |
| AU2021232731B2 (en) | Oral composition | |
| JP3877412B2 (en) | Liquid oral composition | |
| EP2167021A1 (en) | Dentrifice composition | |
| WO1997045096A1 (en) | Compositions | |
| KR100416416B1 (en) | Tooth Paste-Composition Reporting A Moderate Gargling Time | |
| JP2015227362A (en) | Dentifrice composition with reduced astringency |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |