GB2160098A - Dentifrice compositions containing dextranase - Google Patents
Dentifrice compositions containing dextranase Download PDFInfo
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- GB2160098A GB2160098A GB08514601A GB8514601A GB2160098A GB 2160098 A GB2160098 A GB 2160098A GB 08514601 A GB08514601 A GB 08514601A GB 8514601 A GB8514601 A GB 8514601A GB 2160098 A GB2160098 A GB 2160098A
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- 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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/90—Block copolymers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/66—Enzymes
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- 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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/54—Polymers characterized by specific structures/properties
- A61K2800/542—Polymers characterized by specific structures/properties characterized by the charge
- A61K2800/5426—Polymers characterized by specific structures/properties characterized by the charge cationic
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Abstract
Dentifrice compositions contain the enzyme dextranase, an anionic surfactant system, preferably containing an amphoteric or nonionic surfactant, and a polycationic stabilizer, (eg. proteins, quaternised protein hydrolysates polypeptides and polyamines) which stabilizes the dextrancase in the presence of the anionic surfactant without reducing its foaming and cleansing properties.
Description
SPECIFICATION
Oral compositions
The present invention relates to novel oral compositions comprising dextranase enzymes which are enzymatically, physically and cosmetically stabilized in the presence of anionic surfactants by the addition of a polycationic stabilizer selected from e.g. the group consisting of proteins, polypeptides and polyamines which prevents the inactivation of dextranase and the retention of enzyme activity over time. The presence of the amphoteric surfactant assists in providing formula stability.
The prior art is replete with information relating to the effectiveness of dextranase against dental plaque, its dispersion and removal, as shown in an article by Bowen in the British Dental Journal, vol. 24 number 8, pp.347-349, (April 16, 1968); an article by Fitzgerald etal, in JADA, vol.76, pp.301-304, (February 1968); and an article by Duany etal, in Journal of Preventive Dentistry, vol.2, No.2, pp. 23-27, (March-April 1975). The dextranase enzymes also reduce the formation of dental caries and periodontal disease when applied topically. These enzymes degrade or break down the dextrans synthesized in the plaque from sucrose by
Strep. mutans. The dextrans serve as a glue for the cohesion of the plaque.
Accordingly, dextranase has been incorporated in conventional oral hygiene products such as toothpastes, rinses and chewing gum containing surface active cleansing and foaming agents, as shown in
Japanese Patent Public Disclosure No. 56834/1973, and in British Patent No. 1,319,423 containing an anionic surfactant. These surfactants, especially anionic surfactants, tend to deactivate the enzymes such as dextranase, with rapid loss of enzyme activity in the absence of stabilization. Thus, it is difficult to make a stable and foaming dentifrice with dextranase. Accordingly, a number of stabilizers have been incorporated in dentifrice compositions containing dextranase. For example, U.S.Patent No.3,991,177 teaches the use of manganous and calcium ions to stabilize dextranases in the dentifrices in the presence of anionic surfactant such as sodium N-lauroyl sarcosinate. U.S. Patent No.3,981,989 discloses gelatin or peptone as the stabilizing agents for dextranases in the presence of sodium lauryl sulphate. U.S. Patent No.4,140,758 teaches the use of a metal ion selected from the group consisting of manganese, calcium, magnesium and mixtures thereof as a stabilizer/activator for dextranase. Japanese Patent No.013318 by Lion, dated February 6, 1980, utilizes eugenol and 1-menthol as dextranase stabilizers in the presence of anionic surfactants.
Japanese Patent No.010350 by Lion Corp., dated January 1981, utilizes a mixture of dextranase and omega-amino acids in oral compositions to prevent bacterial plaque formation. French Patent Application
No.82/05799 discloses an oral composition comprising a mixture of dextranase and lx-1,3 glucanase. U.K.
Patent Application No. 2,061,727A utilizes aluminas and hydrated aluminas as the abrasive, in order to stabilize the dextranase in the dentifrice composition.
U.S. Patent No. 3,562,385 discloses dental anti-plaque and anticalculus compositions containing a mixture of a bis-biguanido compound, dextranase and sodium hexametaphosphate. U.S. Patent No. 3,622,661 discloses oral preparations containing dextranase and the specific binder Irish moss or gum tragacanth to prevent separation upon standing. Oral antiplaque and/or anticalculus compositions containing dextranase are also disclosed in U.S. Patent Nos. 3,630,924; 3,686,393; and 3,751,561. Oral compositions containing dextranase in combination with other enzymes are disclosed in U.S. Patent No.4,335,101. Dextranase has been modified by molecular alteration by the use of a phosphoprotein carrier and a reacting agent such as ethylchloroformate, in order to provide longer periods of activity in the oral cavity, as disclosed in U.S.
Patent No. 4,138,476.
Toothpastes having cosmetic and enzymatic stability containing a neutral protease of B. Subtilis, stabilized by a partially hydrolyzed protein, are disclosed in U.S. Patent No.4,058,596. The addition of a Group IIA metal ion to the neutral protease and hydrolyzed protein combination provides additional stability as disclosed in U.S. Patent No. 4,058,595.
Although the problem of stabilizing dextranase in the presence of anionic surfactants is well known in the prior art, and has been solved by the addition of a variety of stabilizing agents as aforecited, there is no disclosure of the use of a polycationic stabilizer selected from the group consisting of proteins, polypeptides and polyamines, which more specifically include a quaternized hydrolyzed protein (Crotein Q), polylysine, polyarginine, protamine sulfate, polyacryloxyalkyl ammonium salt, polyvinyl pyridinium ammonium salt, polyoxyethylene (dimethylamino) ethylene dichloride (Busan-77) and poly N-(2-hydroxypropyl methacrylamide).
It has been unexpectedly found that the addition of a polycationic stabilizer, which includes proteins, peptides and polyamines, to a dentifrice comprising a dextranase enzyme, and one or more anionic surfactants, preferably combined with amphoteric or nonionic surfactants, provides better shelf-life stability for the enzyme than gelatin and other prior art enzyme stabilizers, without adversely affecting the foaming power or detergency of the anionic surfactant.
Accordingly, the present invention enables the provision of a stable dentifrice containing an anionic surfactant, a dextranase enzyme and a polycationic stabilizer.
The present invention also enables the provision of a foaming and stable dextranase-containing dentifrice in the presence of anionic and nonionic surfactants.
The present invention further enables the provision of a foaming and stable dextranase-containing dentifrice in the presence of anionic and amphoteric surfactants.
The present invention still further enables the provision of a physically and cosmetically stable dextranase-containing dentifrice with retention of enzyme activity during aging.
The present invention also enables the provision of a stable dextranase-containing dentifrice without adversely affecting the foaming property of the anionic surfactant system.
Accordingly, a stable dentifrice of this invention comprises an anionic surfactant system, a dextranase, and a polycationic stabilizer which may comprise protein, polypeptide and/or polyamine, in, for example, a dental vehicle. Typical stabilizers include a quaternary derivative of hydrolyzed protein, polylysine, polyarginine, protamine sulphate, polyacryloxyalkyl ammonium salt, polyvinyl pyridinium ammonium salt, polyoxyethylene (dimethylamino) ethylene dichloride and poly N-(2-hydroxypropyl methacrylamide).
More specifically, the present invention relates in a preferred embodiment to a stable oral composition, which may be in the form of a powder, paste, cream, liquid or chewing gum, comprising an anionic surfactant system, a dextranase in an amount to provide 1,000 to 55,000 units/g of initial enzyme activity, and a polycationic stabilizer in a weight ratio of 1:1 to 1:2 of anionic surfactant to stabilizer.
Dextranase enzymes are produced from a variety of sources all of which are useful in the present invention. Dextranase enzymes are commonly produced by growing Penicillium funiculosum or otherfungal sources in a dextran-containing medium. The dextran is commonly a commercial grade obtained from
Leuconostoc mesenterioides. This commercial grade of dextran contains about 95 percent a-1,6-glucoside linkages and about 5 percent a-1,3-glucoside linkages. The Penicillium organism produces the dextranase which particularly hydrolyzes the 1,6-linkages.
Dextranase may also be prepared in accordance with procedures which are described in the art. These include the procedure described by Bowen, "British Dental Journal," Vol. 124, No 8, dated April 16, 1968, pages 343-349. Afurther procedure is described in U.S. Patent No. 2,742,399 to Tsuchiya etal. (Note also
Tsuchiya etal, "Journal of Bacteriology," Vol. 64, page 513.)
In the procedure of Bowen, dextran may be prepared from noncariogenic streptococcal strains such as
ATCC 10558, 903-1600, lIA2 + 3, or Leuconostoc mesenterioides and purified according to the method described by Wood et al, "Archives of Oral Biology," Vol. 11, 1066, pages 1039 et seq., except that L.
mesenterioides is grown at 25"C.
Dextranase may be prepared by inoculating Peniclllium funiculosum into flasks containing 250 ml of a medium containing 0.5% yeast extract and 1% dextran. The flasks are incubated at 30 C on a shaking incubator for 4 days. The culture is then centrifuged at 3,000 g for 20 minutes and filtered through Whatman 42 filter paper (the word "Whatman" is a trade mark). Dialysis in 16 mm "Visking" tubing against deionized water and concentrating fifty fold by dialysis against polyethylene glycol (molecular weight 20,000) follows (the word "Visking" is a trade mark). The dextranase produced in accordance with this procedure has a molecular weight of about 200,000 to 275,000. If desired, the dextranase may be further purified by fractionation with ammonium sulphate.
Additional procedures for preparing dextranase include that described in U.S. Patent No. 2,742,399 to
Tsychiya etal.
Dextranases of bacterial origin are also useful in the present compositions. Bacterial-origin dextranase may be prepared in the general manner in which enzymes are derived from bacteria. However, the preferred source of dextranase for the purposes of this invention is a mutant of Bacillus coaguluns, NRRL B-3977 (Beckman dextranase catalogue No. 680000). Bacterial-origin dextranase may be obtained by the addition of a-1,3-dextran or a mixture of a-1,6-, e-1,3- and c-r-1,4-dextrans.
The bacterial stain may be inoculated into a shaker flask orfermentatorfor a period of 1 to 5 days at 25"-40"C. The sterile growth media can consist of the aforementioned dextran or mutan combined with a mixture of carbohydrate (starch, glucose, sucrose, cellulose), nitrogeneous compounds (protein digest, gelatin, casein, ammonium salts), growth stimulators, (yeast extract, corn steep liquor, distiller's solubles), or minerals. Preservatives may be added and the enzyme decanted, filtered, or centrifuged to precipitate the cells (intracellular dextranase). The extracellular dextranase can be precipitated with ammonium sulphate, acetone, sodium sulphate, or a similar salt. The intracellular dextranases are autolyzed and extracted.
Following the salt fractionation step, the enzyme can be further purified by a variety of column (DEAE,
Sephadex, ECTEOLA, hydroxyapatite) chromatography methods and frozen or stabilized by the addition of protein, dextran, salt, etc. (The purification steps are usually conducted at refrigerated temperatures). (The word "Sephadex" is a trademark).
The amount of dextranase employed in the oral compositions of the invention is generally at least such amount as is effective in promoting oral hygiene. This amount is dependent upon the activity of the dextranase which may typically range from 1,000 to 55,000 units/g and therefore upon the mode of its preparation. A typically prepared dextranase enzyme material has an activity of about 5,000 to 10,000 units/g. One Beckman dextranase unit is the amount of enzyme which produces 1 mole of reducing sugar from 1 microgram of maltose monohydrate or native dextran per minute at 35"C and pH 6.0.
While smaller amounts of dextranase may be used, dextranase having an activity of about 1,000-55,000 units/g may be present in amounts of about 0.05-4% by weight of the oral composition.
The dentifrice of this invention preferably contains 5,000-55,000 units/g dentifrice of initial enzyme activity and exhibits physical and cosmetic stability and the retention of enzyme activity over time (at least 75% enzyme activity after 12 weeks of aging at 1 OOoF (38 C)).
An essential ingredient of present dextranase-containing dentifrice is a compatible anionic surfactant to generate a stable foam and assist in achieving thorough and complete dispersion of the composition throughout the oral cavity. The anionic surface active agents contain a sulphonate, sulphate, carboxylate or phosphate as the anionic water solubilizing group. Examples of suitable anionic detergents include the soaps, such as the water soluble salts of higher fatty acids or rosin acids, such as may be derived from fats, oils and waxes of animal, vegetable or marine origin, e.g. the sodium soaps of tallow, grease, coconut, oil, tall oil and mixtures thereof; and the sulphated and sulphonated synthetic detergents, particularly those having from 8 to 26, and preferably from 12 to 22, carbon atoms to the molecule.Examples of suitable synthetic anionic detergents include the higher alkyl mononuclear aromatic sulphonates such as the higher alkylbenzene sulphonates containing from 8 to 16 carbon atoms in the alkyl group in a straight or branched chain, e.g. the sodium salts of decyl, undecyl, dodecyl (lauryl), tridecyl, tetradecyl, pentadecyl, or hexadecyl benzene sulphonate and the C8-C,6 alkyl toluene, xylene and phenol sulphonates: C8-C,6 alkyl naphthalene sulphonate, ammonium diamyl naphthalene sulphonate, and sodium dinonyl naphthalene sulphonate; sulphonated aliphatic alcohols such as sodium lauryl and hexadecyl sulphates, triethanolamine lauryl sulphate, and sodium oleyl sulphate; sulphated alcohol ethers, such as lauryl, tridecyl, ortetradecyl sulphates include 1 to 5 ethylene oxide moieties; ammonium lauryl ether sulphate; sulphonated and sulphonated fatty oils, acids or esters, such as the sodium salts of sulphonated castor oil and sulphated red oil; sulphonated hydroxyamides such as sulphated hydroxyethyl lauramide; sodium salt of lauryl sulphoacetate; sodium salt of dioctyl sulphosuccinate, the sodium salt of oleyl methyl tauride, and sodium N-lauryl sarcosinate.
Also included within the ambit of the invention are the sulphuric acids esters of polyhydric alcohols incompletely esterified with higher fatty acids, e.g. coconut oil monoglyceride monosulphate, tallow diglyceride monosulphate; and the hydroxy sulphonated higher fatty acid esters such as the higher fatty acid esters of low molecular weight alkylol sulphonic acids, e.g. oleic acid ester of isethionic acid.
The anionic surfactants most often used are the ammonium, mono-, di- and triethanolamine, and alkali metal (sodium and potassium) salts of the higher alkyl benzene sulphonates, the higher alkyl sulphonates, the higher fatty acid monoglyceride sulphates and the sulphated ethoxylated alcohols, ammonium lauryl ether sulphate, sodium N-lauroyl sarcosinate, dioctyl sodium sulphosuccinate, and mixtures thereof.
It is preferred to use the anionic surfactant(s) in an amount of about 0.1 to 5% by weight of the carrier or dental vehicle.
Other suitable surface active materials include nonionic agents such as condensates of sorbitan monostearate with approximately 20-60 moles of ethylene oxide, condensates of ethylene oxide with propylene oxide condensates of propylene glycol ("Pluronics"); condensates of higher fatty alcohols or ethers with ethylene oxide; condensates of alkyl thiophenols with 10 to 15 ethylene oxide units, and ethylene oxide addends of monoesters of hexahydric alcohols and inner esters thereof such as sorbitan monolaurate, sorbitol monooleate, mannitan monopalmitate, and sorbitan monoisostearate. Specific examples include polyoxyethylene 20 sorbitan monooleate (Tween 80), polyoxyethylene 20 sorbitan monoisostearate.The weight ratio of anionic to nonionic surfactant of it, 1:2, and 2:1 have been found to afford good dextranase stability in the presence of a polycationic stabilizer such as Crotein Q. (The words "Pluronics", "Tween" and "Crotein" are trade marks).
The amphoteric surfactant, which is a preferred additional surfactant, has both anionic and cationic groups, is ionically balanced, and its isoelectric point is at a pH of about 7 and includes the betaines and sulphobetaines. The betaines are a class of amphoteric surfactants which include alkyl betaines, alkylamido betaines and alkylamano betaines having the general formula:
wherein R1 represents an alkyl group having from 10 to 20 carbon atoms, preferably 12 to 16 carbon atoms or the amido radical:
organ amino radical:
R-NH-(CH2)a wherein R represents an alkyl group having from 10 to 20 carbon atoms and a is an integer from 1 to 3; each of R2 and R3 independently represents an alkyl group having 1 to 3 carbon atoms and preferably 1 carbon atom;R4 represents an alkylene or hydroxyalkylene group having from 1 to 4 carbon atoms and, optionally, one hydroxyl group. Typicat alkyldimethyl betaines include decyl betaine or 2-(N-decyl-N,N-dimethylammonio) acetate, coco betaine or 2-(N-coco-N,N-dimethylammonio) acetate, myristyl betaine, palmityl betaine, lauryl betaine, cetyl betaine and stearyl betaine. The amidobetaines similarly include cocoamidoethyl betaine, cocoamidopropyl betaine, lauramidopropyl betaine and the like.
The sulphobetaines, which are similar in structure to the betaines, have sulphonate groups in place of the carboxylate groups, as represented by the general formula:
wherein R1, R2, R3 and R4 have the same meanings as above, and include alkylsulphobetaines, alkylamidosulphobetaines and alkylaminosulphobetaines.
The molar ratio of anionic to amphoteric surfactant of 1:0.8 to 0.8:2, for example 1:1 to 1 :2, with the optimum being approximately 1.2:1, affords good dextranase stability in the presence of a polycationic stabilizer such as Crotein Q.
It is believed that the desirability of this ratio is due to the optimum establishment of a mixed micelle system helping to moderate the denaturing effect of the sodium lauryl sulphate (SLS). Increasing the betaine to an amount resulting in an SLS to betaine ratio of 1:2 or more produces a stable dentifrice with unsatisfactory taste characteristics. This surfactant system generates a stable foam and assists in achieving thorough and complete dispersion of the composition throughout the oral cavity. J. Garcia Dominguez, International Jo urnal of Cosmetic Science, Volume 3, pp. 57-68 (1981), discloses that amphoteric betaine inhibits sodium lauryl sulphate from denaturing dextranase in an aqueous solution, by the formation of mixed micelles through ionic interaction with SLS.However, its use in a dentifrice together with the cationic protein stabilizer affords unexpected and unusual formula stability and the retention of enzyme activity upon aging.
It is preferred to use the amphoteric surface active agent in an amount of about 2-6% by weight of the carrier or dental vehicle.
The inactivation of the dextranase due to the presence of anionic surfactant in the dentifrice makes it essentially to add (for example in an amount of from 0.5 to 5% by weight of) a cationic stabilizer, having multiple positive charges, to interact with the anionic surfactant sodium lauryl sulphate (SLS), thereby reducing its ability to interact with the enzyme dextranase. Suitable stabilizers are polycationic and include proteins, polypeptides and polyamines. More specifically, the polycationic stabilizer may be a quaternary derivative of hydrolyzed collagen protein, polylysine, polyarginine, protamine sulphate, polyacryloxy alkyl ammonium salt, polyvinyl pyridinium ammonium salt, polyoxyethylene (dimethyl amino) ethylene dichloride (Busan-77) or poly N-(2-hydroxypropyl methacrylamide). (The word "Busan" is a trade mark.)
Cationic surfactants do not function as a stabilizer fo the dextranase. The ratio of stabilizer: anionic surfactant is preferably within the weight range of 1:1 to 2:1 respectively in order to bind the anionic surfactant and prevent its interaction with dextranase.
The quaternary derivative of hydrolyzed collagan product, a preferred polyactionic stabilizer, is a product of Croda Inc. of New York, known as Crotein Q, having a minimum pl of 9.5-10.5, is an off-white free flowing powder and its adopted name is steartrimonium hydrolyzed animal protein. The free amino groups in the protein molecule react with the quaternary ammonium reactant to form the quaternized derivative which has multiple positive charges. At pH's below 5.5, Crotein Q will exhibit a double positive charge, due to protonation of NH groups in the protein chain, as shown diagrammatically in the Crodata circular 7778, page 2.
At pH 9.5, Crotein C)'s quaternary group is still positively charged.
Crotein Q was evaluated as a stabilizer of dextranase activity in a mixed surfactant system. An aqueous system was employed since aging periods are shorter than those required for dentifrices. The effects of temperature, surfactant, and Crotein Q concentrations were evaluated. The time required for 50% loss of activity (t1/2) were calculated and are used for comparison. Representative data from each study are presented.
Effect of SLS concentration on enzyme activity:
SLS Concentration t1/2 - 26"C 0.5% 2.8 hr.
1.0% 0.8 hr.
Enzyme inactivation increases with SLS concentration.
Influence of temperature on enzyme inactivation:
Experimental conditions t112-38 C t112-26 C
1% SLS 0 hr. 0.8 hr.
1% SLS + 1% Crotein 1.5 hr. 22.0 hr.
1%SLS+0.5%Pluronic 1.1 hr. 14.6hr.
(Mixed deterg.)
Mixed deterg. + 1% Crotein 5.3 hr. 31.7 hr.
Enzyme activity is stabilized by lower temperatures.
Stability of Enzyme Activity as a function of Crotein Q concentration:
System Description tl/2 - 38 C 1% SLS, 1% Crotein 1.8 hr.
1% SLS, 2% Crotein 14.8 hr.
In the presence of detergent(s), enzyme stability increases with Crotein Q concentration.
Stability studes conducted on dextranase enzymes have shown that the enzyme inactivating effects of anionic surfactants such as sodium lauryl sulphate (SLS), can be lessened in the presence of a polycationic stabilizer, such as Crotein Q. Although the exact mechanism by which the stabilizer effects this function is not shown, it is hypothesized that the polycationic stabilizer preferentially prevents the reaction of the enzyme with the anionic surfactants without impairing the foaming property of the surfactant. The preferential interaction of the stabilizer with the surfactant prevents the anionic surfactant-inactivation of the dextranase.
The stability of the dextranase-containing dentifrice is measured by the retention of enzyme activity over a protracted period of time as shown in Table I wherein comparative samples of said dentifrice containing anionic and/or nonionic surfactants and stabilizers are evaluated using the following procedure. To 0.05 ml dilute dextranase in distilled water containing 200-300 unitslml, is added 0.95 ml dextran (110,000 av. mol.
wt) dissolved in 0.1 M sodium acetate, and digested for 30 minutes at 37"C. At the end of the digestion period, 1 ml colour reagent is added with mixing, and heated in a boiling water bath for 15 minutes. The samples are cooled, and 10 ml water is added thereto with mixing, and OD readings are made at 540 nm using the maltose standard, 1.0 ml of maltose (100-1000 mcg/ml) and 1 ml colour reagent are boiled for 15 minutes, cooled and read O.D. at 540 nm after addition of 1 Oml H2O. The colour reagent comprises 5 g 3,5-dinitrosalicylic acid, 1 g phenol, 0.25 g sodium sulphite and 100 g potassium sodium tartrate dissolved in 500 ml of 2% NaOH. 1 unit of dextranase activity is defined as the release of 1 mcg maltose monohydrate (Baker) per minute at 370C.
Examples 1-7 inclusive are more fully defined hereinafter.
TABLE IA
%ACTIVITIES LEFT
(Weeks at 38 C)
Dentifrices 1 2 3
Control* 64.6#2.1 48.2#1.2 46.9#2.6 (1) 0.5%SLS 4.8+0.2 3.5+0.3 5.4#1.2 (2) 0.5%Pluronic** 83.9#2.1 76.6#3.1 75.7#3.1 (3) 0.5%SLS + .5% 68.4#1.9 55.3#1.6 43.7#1.0 Pluronic
(4) 0 5% SLS + .5% 93.9#1.9 88.31.1 81.8t5.0 Pluronic + 1%
Polycox***
(5) 0.5% SLS + .5% 94.8#0.8 95.2#1.1 92.6#3.2 Pluronic + 1% Crotein Q
(6) 0.5%SLS + .5% 76.5#1.1 78.2#0.5 71.1#0.9 Pluronic + 1%
Gelatin
(7) 0.5%SLS + .5% 70.7#0.6 55.8#1.8 49.2#1.9 Pluronic + 1% Polyvinyl
Pyrrolidone * Control dentifrice containing enzyme but no SLS or stabilizer.
** Block polymer of about 80% polyoxyethylene and about 20% polyoxypropylene, the latter radical having a molecular weight of 3,250, obtained from BASF Wyandotte Co.
Water soluble resin, a high molecular weight of polyethylene oxide, obtained from Union Carbide Corp.
The word "Polyoxy" is a trade mark.
TABLE IB
% ACTIVITIES LEFT
(Weeks at 38 C)
Dentifrices 4 5 6
Control* 41.6#10.1 33.2#0.6 26.7#0.3 (1) 0.5%SLS 2.8+0.0 2.0t0.4 3.2+0.3 (2) 0.5%Pluronic** 62.1#1.8 56.9#2.1 49.5#2.2 (3) 0.5%SLS + .5% 32.7#1.7 28.7#0.4 21.5#0.6 Pluronic
(4) 0.5%SLS + .5% 75.0#2.4 73.4#1.7 68.9#2.9 Pluronic + 1%
Polyox***
(5) 0.5%SLS + .5% 98.2#1.9 94.7#2.5 80.2#0.3 Pluronic + 1% Crotein Q
(6) 0.5% SLS + .5% 75.2#4.7 74.4#1.9 66.9#2.3 Pluronic + 1%
Gelatin
(7) 0.5% SLS + .5% 48.1#3.5 38.5#0.3 34.9#1.7 Pluronic + 1%
Polyvinyl
Pyrrolidone * Control dentifrice containing enzyme but no SLS or stabilizer.
** Block polymer of about 80% polyoxyethylene and about 20% polyoxypropylene, the latter radical having a molecular weight of 3,250, obtained from BASF Wyandotte Co.
*** Water soluble resin, a high molecular weight of polyethylene oxide, obtained fron Union Carbide Corp.
The word "Polyoxy" is a trade mark.
TABLE IC
% ACTIVITIES LEFT
(Weeks at 38 C)
Dentifrice 7 8 9
Control* 26.2#2.0 26.5#0.1 24.9#1.0 (1) 0.5%SLS 1.6*0.3 2.0i0.0 2.1#0.2 (2) 0.5%Pluronic** 46.5#1.3 51.3#2.8 47.1#0.1 (3) 0.5%SLS + .5% 18.91.0 16.0#0.6 13.6+2.7 Pluronic
(4) 0.5%SLS + .5% 61.3+1.7 63.7t2.0 54.1t1.8
Pluronic + 1%
Polyox***
(5) 0.5%SLS t .5% 84.6#1.2 88.3*2.2 80.2i4.9 Pluronic + 1%
Crotein Q
(6) 0.5%SLS + .5% 64.00.9 70.0*1.4 64.6#0.8 Pluronic+ 1% Gelatin
(7) 0.5%SLS + .5% 32.9#1.0 30.9l1.6 26.4t1.7 Pluronic + 1%
Polyvinyl
Pyrrolidone * Control dentifrice containing enzyme but no SLS or stabilizer.
** Block polymer of about 80% polyoxyethylene and about 20% polyoxypropylene, the latter radical having a molecular weight of 3,250, obtained from BASF Wyandotte Co.
Water soluble resin, a high molecular weight of polyethylene oxide, obtained from Union Carbide Corp.
The word "Polyoxy" is a trade mark.
It is clear from the tables that the enzyme perse in the absence of detergent is unstable in dental cream. An addition of SLS increased deactivation rate (1). The addition of Pluronic to the SLSlenzyme dentifrice (3) does not stabilize the dextranase. The further addition of Polyox provides inadequate stabilization (4), as compared to Crotein Q, (5) gave better stability of the enzyme in the dentifrice than gelatin, (compare 5 vs. 6).
Polyvinyl pyrrolidone (7) is not effective in stabilizing dextranase in the dentifrice.
The stability of the dextranase-containing dentifrice, measured by the retention of enzyme activity over a protracted period of time is also shown in Table II, wherein comparative samples of said dentifrice containing anionic and amphoteric surfactants are evaluated using the manual method of Tsuchiya etal,
Journal of Bacteriology, Vol. 64 (4) pp. 513-514, (1952), which may be modified for the Technicon autoanalyzer, both using the colourimetric reagent dinitro-salicylic acid. (The word "Technicon" is a trade mark.) Aged samples solubilized in water and buffer were incubated for 11.5 minutes with dextran substrate, the reaction stopped by boiling, the solution reacted with colour reagent, and the absorbance read and compared to a glucose standard curve to determine the percent enzyme activity remaining.Despite inconsistencies in the enzyme activities detected for aged dentifrice samples which showed increasing activity with age, trends evidenced a gradual loss in dentifrice enzyme activity by the end of 12 weeks of aging at 100 F (38 C). In the case of some of the better formulations this was spot-checked and verified by manual analysis to be a loss of up to 30% at 12 weeks using the method described above.
Examples 8-10 inclusive are more fully defined hereinafter.
Examples 11-17 inclusive represent other stable dual surfactant dentifrice formulae utilizing conventional humectants, thickening agents, flavours and the like, in conventional amounts as set forth in this specification.
TABLE IIA SLS/Betaine/Dextranase Formulations
and Aging Data
Initial % oflnitial Ingredients Enzyme Activity Enzyme activity
3 wks 6 wks 3.6% Dextranase (0.83 mg 53,130 140 98 protein/ml), 2% Crotein
Q, 1.8% SLS, 5% Betaine,
Silica 3.6% Dextranase (0.83 mg 49,392 100 98 protein/ml), 2% Crotein
Q, 1.8% SLS, 5% Betaine,
Alumina 0.65% Dextranase (0.83 mg 5,340 0 0 protein/ml), 1% Crotein C), 1.2% SLS.Alumina
Alumina, 2% Crotein Q, 1.2% 4,570 110 101
SLS, 4% Betaine, 0.55%
Dextranase
Silica, 2% Crotein Q, 1.2% 18,600 84 71
SLS, 4% Betaine, 1% Amide, 2.1% Dextranase Alumina, 2% Crotein Q, 1.2% 13,800 99 88
SLS, 4% Betaine, 1.8%
Dextranase Alumina, 2% Crotein Q, 0.3% 13,400 91 95
SLS, 0.9% ALES2, 4% Betaine, 1.8% Dextranase Alumina, 2% Crotein Q, 0.3% 27,000 103 99
SLS, 0.9% ALES, 4% Betaine, 3.6% Dextranase Silica, 2% Crotein Q, 0.3% 28,300 102 99
SLS, 0.9% ALES, 4% Betaine, 3.6% Dextranase Alumina, 3% Crotein Q, 1.2% 23,200 104 141
SLS, 5% Betaines, 3.6%
Dextranase 1 Sulphated amido-betaine 2 Ammonium laurylethersulphate.
TABLE IIB
SLS/Betaine/Dextranase Formulations
and Aging Data
Initial % oflnitial Ingredients Enzyme Activity Enzyme activity
9 wks 12 wks
3.6% Dextranase (0.83 mg 53,130 103 99
Protein/ml), 2% Crotein C), 1.8% SLS, 5% Betaine,
Silica - 3.6% Dextranase (0.83 mg 49,392 87 79
protein/ml), 2% Crotein
Q, 1.8% SLS, 5% Betaine,
Alumina
0.65% Dextranase (0.83 mg 5,340 0 0
protein/ml), 1% Crotein
Q, 1.2% SLS, Alumina Alumina, 2% Crotein C), 1.2% 4,570 95 83
SLS, 4% Betaine, 055%
Dextranase Silica, 2% Crotein Q 1.2% 18,600 67 81
SLS, 4% Betaine, 1% Amide,
2.1% Dextranase
Alumina, 2%Crotein Q, 1.2% 13,800 107 107
SLS, 4% Betaine, 1.8%
Dextranase Alumina, 2% Crotein Q, 0.3% 13,400 116 113
SLS, 0.9% ALES2, 4% Betaine,
1.8% Dextranase
Alumina, 2% Crotein Q 0.3% 27,000 123 121
SLS, 0.9% ALES, 4% Betaine,
3.6% Dextranase
Silica, 2% Crotein Q, 0.3% 28,300 102 119
SLS, 0.9% ALES, 4% Betaine,
3.6% Dextranase Alumina, 3% Crotein Q, 1.2% 23,200 139 148
SLS, 5% Betaines, 3.6%
Dextranase 'Sulphated amido-betaine
2 Ammonium laurylether sulphate.
Samples were aged at 1 000F (38 C). Activities determined by colourimetric spectrophotometry using 3,5-dinitrosalicylic acid.
Calculations:
SLS (94% active, F.W. 288.38) 18 grams x 0.94 = 16.9 g = 0.0587 moles.
Betaine (27% active, F.W. 283) 50 grams x 0.27 - 13.5 9 = 0.0477 moles.
Molar ratio SLS: Betaine = 0.06:0.05 = 1.2:1.
The interaction of the stabilizer with the anionic surfactant to prevent its interaction with dextranase does not substantially reduce the foaming ability of the anionic agent. The foaming properties of the surfactants were measured according to standard foam height procedure. This analysis was conducted at 37 C in both distilled and hard water (105 ppm caCI2, and 70 ppm MgCl2). Solutions were prepared to contain singularly or combinations of 0.1% SLS, and 0.2% Crotein Q. Foam volume was measured in ml after 30 inversions of the graduate cylinder.
TABLE Ill
0.1% 0.2% 0.1%SLS+ SLS Crotein Q 0.2% Crotein O distilled water 500 ml 12ml 475 ml
hard water 238 ml 12 ml 425 ml
This data shows that Crotein Q, which is non-foaming, does not readily reduce SLS foaming in distilled water, and increases SLS foaming in hard water. It is also noted that foaming by SLS in hard water is drastically reduced, but is greatly enhanced by the stabilizer Crotein Q.
Figure lisa graph which shows the relative foam volumes in distilled water and hard water. In Figure 1 "SLS" is an abbreviation for sodium lauryl sulphate, "BET" is an abbreviation for betaine and "CRO" is an abbreviation for Crotein Q.
The data graphically represented in Figure 1 show that in distilled water, SLS produces the largest volume of foam. Those combinations containing SLS and Crotein foamed better than the combination of SLS and betaine, Crotein and betaine, and betaine alone. It is also noted that Crotein does not readily reduce SLS foaming although betaine does. In the hard water, foaming of SLS is drastically reduced, whereas foaming by betaine is unchanged. In hard water foaming by SLS is greatly enhanced by the stabilizer Crotein. Overall, these results indicate that the system providing optimal enzyme stabilization, SLS + Crotein t betaine exhibits good foaming characteristics regardless of the water hardness. This point is important since the divalent cation concentration in the oral cavity is quite high.
Accelerated aging studies further show that enzymatically, physically and cosmetically stable dentifrices containing approximately 5,000 units of dextranase per gram of dentifrice exhibit good foaming in the presence of betaine, and anionic surfactants and the cationic stabilizer as shown in Table IV.
TABLE iV
Retention Aged at
of Enzyme 100 F *Height of
Sample Ingredients Activity (38 C) Foam (ml) 1 Alurnina-1.2% 95 9wks 95 54 Betaine, 1.2% SLS, 2% Crotein Q 2 Alumina - 0.9% 96 9 wks 34 Betaine, 0.8% SLS,
1% Crotein Q
3 alumina - 1.2% 98 9 wks 30 Betaine, 0.6% SLS,
1% Crotein Q
4 Silica - 1.2% 104 6wks 32 Betaine, 0.6% SLS,
2% Crotein Q
5 Alumina - 1.2% 83 9 wks 35
Betaine, 0.6% SLS,
6 Alumina - 1.2% 89 9 wks 32
Betaine, 0.5% SLS, * The height of foam was measured after shaking 1 gram of dentifrice in 10 ml of 175 ppm hard water (90"F, 32 C) for 15 sec.
Toothpastes and tooth powders conventionally contain a substantially water insoluble polishing agent or abrasive which is compatible with the formulation. Preferred compatible materials which do not adversely affect the dentifrice composition include dicalcium phosphate dihydrate, silica and hydrated alumina. The polishing agent may be the sole carrier material as in a toothpowder, and is present in an amount up to about 80% of the dental vehicle and generally about 30-75% of the dental vehicle.
In toothpaste formulations the liquids and solids should necessarily be proportioned to form a creamy mass having the desired consistency which is extrudable from a pressurized container or a collapsible tube (for example, aluminium or lead). In general, the liquids in the toothpaste will comprise chiefly water, glycerin, aqueous solutions of sorbitol, propylene glycol, polyethylene glycol 400, etc., and suitable mixtures thereof. It is advantageous usually to use a mixture of both water and a humectant or binder such as glycerin or sorbitol. The total liquid content will generally be about 20-75% of the vehicle. the amount of water is generally about 10-25% of the vehicle.It is preferred to also use a gelling agent in toothpaste such as the natural and synthetic gums and gum-like materials such as Irish moss, gum tragacanth, starch, sodium alginate, carboxymethyl cellulose, Viscarin GMC, iota carrageenan, and the like, usually in an amount up to about 10%, and preferably about 0.2-5%, of the carrier or vehicle. (The word "Viscarin" is a trade mark).
The carrier suitably may contain fluorine-containing compound having a beneficial effect on the care and hygiene of the oral cavity, for example, diminution of enamel solubility in acid and protection of the teeth against decay. Examples thereof include stannous fluoride, potassium stannous fluoride, sodium hexafluorostannate, stannous chlorofluoride, sodium fluorozirconate, and sodium monofluorophosphate.
These materials, which dissociate or release fluorine containing ions in water, suitably may be present in the carrier in an effective but nontoxic amount, usually within the range of about 0.1-5% by weight.
Various other materials may also be incorporated into the carrier. Examples thereof are colouring or whitening agents (for example, titanium dioxide), preservatives (for example, sodium benzoate), silicones, chlorophyll compounds, ammoniated materials such as urea, diammonium phosphate, and mixtures thereof, alcohol, methol, and other constituents. These adjuvants may be incorporated into compositions of the present invention in amounts which do not substantially adversely affect the properties and characteristics and are suitably selected and used in proper amount depending upon the particular type of preparations involved.
Flavouring or sweetening materials of the type commonly employed in dentifrices may be included in the carrier. Such materials, if present, aid in modifying the particular tastes of the flavour in the manner desired.
Examples of such additional materials include the flavouring oils, for example, oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon and orange, as well as methylsalicylate. Suitable sweetening agents include sucrose, lactose, maltose, sorbitol, sodium cyclamate, and saccharin. Suitably, the flavour and sweetening agent may together comprise about 0.01-2% of the carrier.
The dentifrice may be prepared by suitably mixing the ingredients. For instance in making a toothpaste, a gelling agent such as sodium alginate, carboxymethyl cellulose or iota carrageenan and a preservative such as sodium benzoate, if employed, is dispersed in a humectant such as glycerin. Water may also be present.
Additional humectant and water may then be mixed with the dispersion and a homogeneous paste, gel or cream is formed. Dental abrasive agent, surface active agent and flavour are then added. The toothpaste is then thoroughly deaerated (e.g. in vacuo) and tubed. The formulation may be deaerated during mixing or after mixing.
The following examples are merely illustrative of the invention, but it is understood that the invention is not limited thereto. All amounts of various ingredients are by weight unless otherwise specified.
Examples 1 to 7
The stabilization properties of Examples 1 to 7, which are measured by the retention of enzyme activity over a period of time and recorded in Tables IA to IC, clearly shows the superior properties of Example 5 containing a polycationic stabilizer in a dextranase/anionic surfactant dentifrice in accordance with this invention. The other examples are controls containing no polycationic stabilizer (1), and the substitution of nonionic surfactant(s) (3 and 4) or cationic compounds (7) or gelatin (6) for the polycationic stabilizer.
Summary of Examples 1 to 7
% Ingredients Dentifrice (1) (2) (3) (4) (5) (6) (7) Glycerine 15 15 Sodium Alginate 1.0 1.0 Sorbitol 70% 15 15 soln.
Sodium Saccarin 0.1 0.1 SLS 0.5 - 0.5 0.5 0.5 0.5 0.5 Pluronic (F108)1 - 0.5 0.5 0.5 0.5 0.5 0.5 Hydrated Alumina 50 50 Silica Huber 2 2 Flavour 1 1 Dextranase 5000 5000 units/g units/g Crotein - - - - 1.0 - Gelatin - - - - - 1.0 Polyox2 - - - 1.0 - - Polyvinyl - - - - - - 1.0 Pyrrolidone Water C).S 1 Block polymer of about 80% polyoxyethylene and about 20% polyoxypropylene, the latter readical having a molecular weight of 3,250, obtained from BASF Wyandotte Co.
2 Water soluble resin, a high molecular weight polymer of polyethylene oxide, obtained from Union Carbide
Corp.
The word "Huber" is a trade mark.
Example 8
A gel toothpaste was made up from the following ingredients:
Ingredient
Glycerine 25
CMC1 0.35
Na Benzoate 0.5
Na Saccharin 0.2
Monofluorphosphate (MFP) 0.76
Sorbitol 24.09
Carbowax - PEG 6002 3
FDC Blue No. 1 @ 1% 0.1
Deionized water 6.6
Silica containing combined alumina3 18
Colloidal silica aerogel4 8
Sodium lauryl sulphate (SLS) 1.8 Betaine tego-S-10665 5
Crotein Q 2
Flavour 1
Dextranase (20,000 units/g) 3.6
pH 6.5
Foam 84 ml 1 Carboxymethyl cellulose 2 Polyethylene glycol, mol. weight 600 3 Zeo 49B, ex J.M. Huber 4 Syloid 244 5A sulphated amphoteric surfactant manufactured by Goldschmidt Chemical Corp., Actives 27%
The words "Carbowax", "Zeo" and "Syloid" are trade marks.
The toothpaste exhibited good enzyme activity retention.
Example 9
A toothpaste was made up from the following ingredients:
Ingredient % lota carrageenan 0.9
Glycerine 22
Na Benzoate 0.5
Na Saccharin 0.2
MFP (Na monofluorophosphate) 0.76
Deionized water 12.24
Hydrated alumina 50
SLS 1.8
Sulphated amidobetaine (1.5% active) 5
Crotein Q 2
Flavour 1
Dextranase (20,000 units/g) 3.6
pH 7.41
Foam 83 ml
The toothpaste exhibited good enzyme activity retention.
Example 10 (Control)
A toothpaste was made up from the following ingredients:
Ingredient
lota carrageenan 0.9
Glycerin 22
Na Saccharin 0.2
Methyl Paraben 0.1
MFP 0.76
Crotein C) 1
Deionized water 23.19
Hydrated alumina 50
SLS 1.2
Dextranase (20,000 units/g) 0.65
pH 8.08
The omission of the betaine reduces the enzyme stability of this composition to zero.
Example Ii Atoothpaste was made up from the following ingredients:
Ingredient
lota carrageenan 0.9
Glycerin 22.0
MFP (Na monofluorophosphate) 0.76
Na benzoate 0.5
Na saccharin 0.2
Hydrated alumina 50
SLS 1.2
Betaine 4.0
Crotein Q 2
Flavour 1 Dextranase (10,000 units/g) 1.8
Deionized water 15.64
pH 7.44
Foam 58 ml.
The toothpaste exhibited good enzyme activity retention.
Example 12
A toothpaste was made up from the following ingredients: Ingredients lota carrageenan 0.9
Glycerin 22
Na benzoate 0.5
Na saccharin 0.2
MFP (Na monofluorophosphate) 0.76
Hydrated alumina 50
Deionized water 13.64
SLS 1.2
Betainetego-S 1066 5
Crotein Q 3
Flavour 1
Dextranase (10,000 units/g) 1.8
pH 7.17
Foam 71 ml.
The toothpaste exhibited good enzyme activity retention.
Example 13
A toothpaste was made up from the following ingredients:
Ingredient
lota carrageenan 0.9
Glycerin 22
Na benzoate 0.5
Na saccharin 0.2
MFP (Na monofluorophosphate) 0.76
Hydrated alumina 50
Deionized water 11.84
SLS 1.2
Betaine 5
Crotein Q 3
Flavour 1
Dextranase (20,000 units/g) 3.6
pH 7.28
Foam 60 ml.
The toothpaste exhibited satisfactory enzyme activity retention.
Example 14
A mouthwash was made up from the following ingredients:
Ingredient % Ethanol (90%) 5-10
Glycerin 10-20
Sodium saccharin 0-5
Sodium benzoate 0-5
Pluronic F108 1-2
Dextranase (1,000-20,000 units/ml) 0.05-1
Sodium Lauryl Sulphate (SLS) 0.1-0.5
Crotein Q 0.5-3
Flavouring 0.22-0.5
Water C).S.
The mouthwash exhibited good enzyme activity retention.
Example 15
A toothpowder was made up from the following ingredients:
Ingredient
Hydrated alumina 70-80
Glycerin 10
SLS 0.1-0.5
Sodium saccharin 0.1
Flavouring 1.0
Dextranase (1,000-20,000 units/g) 3.6
Crotein Q 0.5-3
Water Q.S.
The tooth powder exhibited good enzyme activity retention.
Example 16
Chewing gum was made up from the following ingredients:
Ingredient
Gum base (Natural or Synthetic elastomer- 20-35
merfiller i.e. gum arabic)
Sorbitol 10-20
Dextranase (5,000-20,000 units/g) 0.1-1.0
Sodium Lauryl Sulphate 0.1-0.5
Crotein Q 0.5-3
Flavouring 0.5-2
Dextrose C).S.
The chewing gum exhibited good enzyme activity retention.
Example 17
A toothpaste was made up from the following ingredients: Ingredient Glycerin 22
Carrageenan 1.3
Dicalcium phosphate dihydrate 50
Sodium benzoate 0.5
Sodium saccharin 0.2
Crotein Q 1.3
SLS 0.75
Pluronic (F108) 0.5
Flavour 1
Dextranase (5,000-20,000 units/g) 3.6
Water C).S.
The toothpaste exhibited good enzyme activity retention.
The following Table defines additional dextranase-containing dentifrice formulations having physical and cosmetic stability and the retention of enzyme activity upon aging.
Examples 18-26 inclusive each comprise an aqueous vehicle containing a suitable flavour material.
Examples 18-21 inclusive each contain 1.8% dextranase Example 22 contains 2.1% dextranase, Example 23 contains 2.5% dextranase and Examples 24-26 inclusive each contain 3.6% dextranase. Conventional humectants or mixtures thereof in suitable amounts as defined in this specification, are utilized. Examples 18, 19,21,24 and 26 each comprise glycerin, whereas Examples 20, 22, 23 and 25 each comprise a mixture of glycerin and sorbitol.
Examples 18 to 26
Toothpastes
Activity after
Intial Enzyme 12 Weeks # 100 F
Ex. Ingredients Foam(ml) Activity (units) (38 C) %of intial 18 lota*/Alumina, 1.2%SLS, 4% 58 13,800 15,200 110
betaine, 2% Crotein Q 19 lota/Alumina, 3% SLS, 0.9% 58 13,400 15,100 113
ALES, 4% Betaine, 2% Crotein Q 20 Silica, 0.3% SLS, 0.9% ALES, 46 14,000 15,800 113
4% Betaine, 2% Crotein Q 21 lota/Alumina, 1,2% SLS, 5% 71 12,500 16,100 129
Betaine, 3% Crotein Q 22 Silica, 1.2% SLS, 4% Betaine, 55 18,600 15,000 81
2% Crotein Q 1% Amide 23 Silica, 0.6% SLS, 4% Betaine, 37 23,800 18,700 79
2% Crotein Q, 1% Amide 24 lota/Alumina, 0.3% SLS, 0.9% 50 27,000 32,700 121
ALES, 4% Betaine, 2% Crotein Q 25 Silica, 0.3% SLS, 0.9% ALES, 51 28,300 33,800 119
4% Betaine, 2% Crotein Q 26 lota/Alumina. 1.2% SLS, 5% 60 23,200 34,300 148
Betaine, 3% Crotein Q * Carageenan.
Variations in the above formulations may be made. For example, other anionic surfactants such as higher alkyl benzene sulphonates, fatty acids soaps such as tallow soap, sulphated alcohol ethers and the like may be substituted for the specific anionic surfactants in the examples. Similarly, other betaines and sulphated betaines may be substituted for the specific betaine surfactants in the examples. Likewise, other nonionic surfactants may be substituted forthe specific nonionic surfactants in the examples.
Other thickening or gelling agents may be substituted for carboxymethyl cellulose, carrageenan or sodium alginate, such as starch, Irish moss, gum tragacanth and the like.
Likewise, other polycationic stabilizers such as polylysine, polyarginine, protamine sulphate, polyvinyl pyridinium ammonium salts, poly N-(2-hydroxypropyl methacrylamide) may be substituted for the Crotein Q used in the examples.
It is understood that the foregoing detailed description is given merely by way of illustration and that variations may be made therein without departing from the spirit of the invention.
Claims (30)
1. An oral composition comprising an anionic surfactant, dextranase and a polycationic stabilizer for the dextranase.
2. An oral composition as claimed in Claim 1, wherein the dextranase is present in an amount of from 1000 to 55000 units/g of initial enzyme activity.
3. An oral composition as claimed in Claim 1 or 2, wherein the polycationic stabilizer comprises protein, polypeptide and/or polyamine.
4. An oral composition as claimed in Claim 1, 2 or 3, wherein the weight ratio of anionic surfactant to polycationic stabilizer is from 1:1 to 1:2.
5. An oral composition as claimed in any one of Claims 1 to 4, the composition including an orally acceptable vehicle.
6. A composition as claimed in Claim 5, wherein the orally acceptable vehicle is a dental vehicle.
7. An oral composition as claimed in Claim 1 or 2, wherein the polycationic stabilizer comprises a quaternary derivative of hydrolyzed collagen protein, polylysine, polyarginine, protamine sulphate, polyacryloxyalkyl ammonium salt, polyvinyl pyridinium ammonium salts, polyoxyethylene (dimethyl amino) ethylene dichloride and/or poly N-(2-hydroxypropyl methacrylamide).
8. An oral composition as claimed in any one of Claims 1 to 7, the composition including a nonionic surfactant.
9. An oral composition as claimed in Claim 8, wherein the weight ratio of nonionicto anionic surfactant is from 2:1 to 1:2.
10. An oral composition as claimed in any one of Claims 1 to 9, the composition including an amphoteric surfactant preferably comprising betaine and/or sulphobetaine, and further preferably in the molar ratio of 1:0.8 to 0.8:2 of anionic to amphoteric surfactant.
11. An oral composition as claimed in Claim 10, wherein the amphoteric surfactant comprises one or more betaines and/or one or more sulphobetaines.
12. An oral composition as claimed in Claim 10 or 11, wherein the ratio of anionic to amphoteric surfactant is from 1:1 to 1:2.
13. An oral composition as claimed in Claim 10, the composition including an amphoteric surfactant of the general formula:
wherein R' represents an alkyl group having from 10 to 20 carbon atoms, an amido radical:
an amino radical: R-NH-(CH2)a wherein R represents an alkyl radical of from 10 to 20 carbon atoms and a is an integer from 1 to 3; each of R2 and R3 represents an alkyl radical having from 1 to 3 carbons; and R4 is an alkylene or hydroxy-alkylene group having from 1 to 4 carbon atoms.
14. An oral composition as claimed in any one of Claims 10 to 13, wherein the amphoteric surfactant constitutes from 2 to 6% by weight of the composition.
15. An oral composition as claimed in any one of Claims 1 to 14, wherein the polycationic stabilizer constitutes from 0.5 to 5% by weight of the composition.
16. An oral composition as claimed in any one of Claims 1 to 15, wherein the dextranase constitutes from 0.05 to 4% by weight of the composition.
17. An oral composition as claimed in any one of Claims 1 to 16, wherein the anionic surfactant comprises sodium lauryl sulphate.
18. An oral composition as claimed in any one of Claims 1 to 16, wherein anionic surfactant comprises sodium lauryl sulphate and ammonium lauryl ether sulphate.
19. An oral composition as claimed in Claim 8 or 9, wherein the nonionic surfactant comprises a block polymer of about 80% polyoxyethylene and about 20% polyoxypropylene having a molecular weight of about 3,250.
20. An oral composition as claimed in any one of Claims 1 to 19, in the form of a toothpaste containing from 30 to 75% by weight of a water insoluble polishing agent.
21. An oral composition as claimed in any one of Claims 1 to 19, in the form of a tooth powder containing from 70 to 80% water insoluble polishing agent.
22. An oral composition as claimed in any one of Claims 1 to 19, in the form of an aqueous mouthwash containing from 5 to 10% ethanol.
23. An oral composition as claimed in any one of Claims 1 to 19, in the form of a chewing gum, comprising from 20 to 35% of a gum base containing a natural or synthetic elastomer filler.
24. An oral composition as claimed in Claim 20 or 21, wherein the polishing agent comprises hydrated alumina.
25. An oral composition as claimed in Claim 20 or 21, wherein the polishing agent comprises dicalcium phosphate dihydrate.
26. An oral composition as claimed in Claim 20 or 21, wherein the polishing agent comprises silica.
27. An oral composition as claimed in Claim 20, the composition having a liquid content of from 20 to 75% by weight of the composiion.
28. An oral composition according to any one of Claims 1 to 27, wherein the polycationic stabilizer is a quaternary derivative of hydrolyzed collagen protein.
29. A foaming, stable oral composition comprising one or more anionic surfactants, a dextranase in an amount to provide 1,000 to 55,000 units/g of initial enzyme activity, and a polycationic stabilizer in an effective amount to stabilize the enzyme activity against loss during aging, and against inactivation due to the presence of the anionic surfactants, selected from the group consisting of proteins, polypeptides and polyamines, in a weight ratio of 1:1 to 1:2 of anionic surfactant to stabilizer, in a dental vehicle.
30. an oral composition substantially as herein described with reference to any one of the Examples other than the comparative examples.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US61987884A | 1984-06-12 | 1984-06-12 | |
US61987984A | 1984-06-12 | 1984-06-12 |
Publications (3)
Publication Number | Publication Date |
---|---|
GB8514601D0 GB8514601D0 (en) | 1985-07-10 |
GB2160098A true GB2160098A (en) | 1985-12-18 |
GB2160098B GB2160098B (en) | 1988-01-06 |
Family
ID=27088612
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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GB08514601A Expired GB2160098B (en) | 1984-06-12 | 1985-06-10 | Dentifrice compositions containing dextranase |
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Country | Link |
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AR (1) | AR241518A1 (en) |
AU (1) | AU577864B2 (en) |
BE (1) | BE902641A (en) |
BR (1) | BR8502769A (en) |
CH (1) | CH668360A5 (en) |
DE (1) | DE3520584A1 (en) |
DK (1) | DK264485A (en) |
ES (1) | ES8700051A1 (en) |
FR (1) | FR2565485B1 (en) |
GB (1) | GB2160098B (en) |
GR (1) | GR851416B (en) |
IT (1) | IT1181681B (en) |
NO (1) | NO852352L (en) |
NZ (1) | NZ212257A (en) |
PT (1) | PT80600B (en) |
SE (1) | SE8502540L (en) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2603800A1 (en) * | 1986-09-15 | 1988-03-18 | Oreal | TOOTHPASTE CONTAINING A POLY NON-IONIC SURFACTANT (HYDROXYPROPYLETHER) AND A SALT OF A SPECIFIC DERIVATIVE OF A PROTEIN DEGRADATION PRODUCT |
US4927625A (en) * | 1987-08-21 | 1990-05-22 | Lever Brothers Company | Toothpastes |
US5073292A (en) * | 1990-06-07 | 1991-12-17 | Lever Brothers Company, Division Of Conopco, Inc. | Heavy duty liquid detergent compositions containing enzymes stabilized by quaternary nitrogen substituted proteins |
EP0518608A1 (en) * | 1991-06-12 | 1992-12-16 | Block Drug Company, Inc. | Taste preserving, mild oral hygiene compositions |
WO2004019899A1 (en) * | 2002-08-28 | 2004-03-11 | Colgate-Palmolive Company | Dual component dental composition containing enzyme |
EP1973986A2 (en) * | 2006-01-03 | 2008-10-01 | The Texas A & M University System | Bioactive complex compositions and methods of use thereof |
US7939306B2 (en) | 2002-05-10 | 2011-05-10 | Colgate-Palmolive Company | Antibacterial dentifrice exhibiting antiplaque and breath freshening properties |
DE102011077040A1 (en) * | 2011-06-07 | 2012-12-13 | Beiersdorf Ag | Drug combinations of å-polylysine (epsilon-polylysine) and one or more ethoxylated and / or propoxylated alkanols |
US8628690B2 (en) | 2004-02-23 | 2014-01-14 | The Texas A&M University System | Nanoemulsion compositions and methods of use thereof |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102005033663A1 (en) * | 2005-07-12 | 2007-01-25 | Beiersdorf Ag | Particularly mild shower formulation |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3981989A (en) * | 1973-11-26 | 1976-09-21 | The Lion Dentifrice Co., Ltd. | Oral preparation |
US4058596A (en) * | 1971-10-13 | 1977-11-15 | Colgate-Palmolive Company | Stabilized toothpastes containing an enzyme |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2038107A1 (en) * | 1970-07-31 | 1972-02-10 | Henkel & Cie Gmbh | Liquid stabilized enzyme preparations which can optionally be used as washing or cleaning agents |
FR2156149A1 (en) * | 1971-10-13 | 1973-05-25 | Colgate Palmolive Co | Dentifrice contg protease and protein - stable on storage |
US3944470A (en) * | 1973-06-29 | 1976-03-16 | The Procter & Gamble Company | Stabilization and enhancement of enzymatic activity |
JPS5249055B2 (en) * | 1973-11-26 | 1977-12-14 | ||
CA1063357A (en) * | 1974-05-21 | 1979-10-02 | James J. Benedict | Abrasive composition |
JPS58172310A (en) * | 1982-04-02 | 1983-10-11 | Akira Endo | Preventive and remedy for dental caries |
JPS58225007A (en) * | 1982-06-23 | 1983-12-27 | Lion Corp | Composition for oral cavity |
AU5068985A (en) * | 1984-11-08 | 1986-06-03 | Zetachron, Inc. | Dentifrice containing alginate calcium chelating agent |
-
1985
- 1985-05-23 SE SE8502540A patent/SE8502540L/en not_active Application Discontinuation
- 1985-05-30 NZ NZ212257A patent/NZ212257A/en unknown
- 1985-06-05 PT PT80600A patent/PT80600B/en unknown
- 1985-06-08 DE DE19853520584 patent/DE3520584A1/en not_active Withdrawn
- 1985-06-10 GB GB08514601A patent/GB2160098B/en not_active Expired
- 1985-06-11 IT IT48203/85A patent/IT1181681B/en active
- 1985-06-11 NO NO852352A patent/NO852352L/en unknown
- 1985-06-11 BR BR8502769A patent/BR8502769A/en unknown
- 1985-06-11 GR GR851416A patent/GR851416B/el unknown
- 1985-06-11 ES ES544047A patent/ES8700051A1/en not_active Expired
- 1985-06-12 DK DK264485A patent/DK264485A/en not_active Application Discontinuation
- 1985-06-12 BE BE0/215173A patent/BE902641A/en not_active IP Right Cessation
- 1985-06-12 AU AU43604/85A patent/AU577864B2/en not_active Ceased
- 1985-06-12 AR AR85300702A patent/AR241518A1/en active
- 1985-06-12 FR FR8508899A patent/FR2565485B1/en not_active Expired
- 1985-06-12 CH CH2503/85A patent/CH668360A5/en not_active IP Right Cessation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4058596A (en) * | 1971-10-13 | 1977-11-15 | Colgate-Palmolive Company | Stabilized toothpastes containing an enzyme |
US3981989A (en) * | 1973-11-26 | 1976-09-21 | The Lion Dentifrice Co., Ltd. | Oral preparation |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4828824A (en) * | 1986-09-15 | 1989-05-09 | L'oreal | Dentifrice containing a poly(hydroxypropyl ether) non-ionic surfactant and a salt of a specific derivative of a protein degradation product |
BE1001095A4 (en) * | 1986-09-15 | 1989-07-11 | Oreal | TOOTHPASTE CONTAINING A POLY NON-IONIC SURFACTANT (HYDROXYPROPYLETHER) AND A SALT OF A SPECIFIC DERIVATIVE OF A PROTEIN DEGRADATION PRODUCT |
FR2603800A1 (en) * | 1986-09-15 | 1988-03-18 | Oreal | TOOTHPASTE CONTAINING A POLY NON-IONIC SURFACTANT (HYDROXYPROPYLETHER) AND A SALT OF A SPECIFIC DERIVATIVE OF A PROTEIN DEGRADATION PRODUCT |
US4927625A (en) * | 1987-08-21 | 1990-05-22 | Lever Brothers Company | Toothpastes |
US5073292A (en) * | 1990-06-07 | 1991-12-17 | Lever Brothers Company, Division Of Conopco, Inc. | Heavy duty liquid detergent compositions containing enzymes stabilized by quaternary nitrogen substituted proteins |
EP0518608A1 (en) * | 1991-06-12 | 1992-12-16 | Block Drug Company, Inc. | Taste preserving, mild oral hygiene compositions |
US7939306B2 (en) | 2002-05-10 | 2011-05-10 | Colgate-Palmolive Company | Antibacterial dentifrice exhibiting antiplaque and breath freshening properties |
WO2004019899A1 (en) * | 2002-08-28 | 2004-03-11 | Colgate-Palmolive Company | Dual component dental composition containing enzyme |
CN100435776C (en) * | 2002-08-28 | 2008-11-26 | 高露洁-棕榄公司 | Dual component dental composition containing enzyme |
EP2172187A1 (en) * | 2002-08-28 | 2010-04-07 | Colgate-Palmolive Company | Dual component dental composition containing enzyme |
US6927053B2 (en) | 2002-08-28 | 2005-08-09 | Colgate-Palmolive Company | Dual component dental composition containing enzyme |
US8628690B2 (en) | 2004-02-23 | 2014-01-14 | The Texas A&M University System | Nanoemulsion compositions and methods of use thereof |
EP1973986A2 (en) * | 2006-01-03 | 2008-10-01 | The Texas A & M University System | Bioactive complex compositions and methods of use thereof |
EP1973986A4 (en) * | 2006-01-03 | 2011-08-10 | Texas A & M Univ Sys | Bioactive complex compositions and methods of use thereof |
DE102011077040A1 (en) * | 2011-06-07 | 2012-12-13 | Beiersdorf Ag | Drug combinations of å-polylysine (epsilon-polylysine) and one or more ethoxylated and / or propoxylated alkanols |
Also Published As
Publication number | Publication date |
---|---|
AU4360485A (en) | 1985-12-19 |
GB8514601D0 (en) | 1985-07-10 |
IT1181681B (en) | 1987-09-30 |
PT80600A (en) | 1985-07-01 |
NO852352L (en) | 1985-12-13 |
BR8502769A (en) | 1986-02-18 |
DK264485A (en) | 1985-12-13 |
DE3520584A1 (en) | 1985-12-12 |
FR2565485B1 (en) | 1988-02-19 |
BE902641A (en) | 1985-12-12 |
SE8502540L (en) | 1985-12-13 |
NZ212257A (en) | 1988-03-30 |
GR851416B (en) | 1985-11-25 |
ES544047A0 (en) | 1986-10-01 |
PT80600B (en) | 1987-01-16 |
CH668360A5 (en) | 1988-12-30 |
ES8700051A1 (en) | 1986-10-01 |
IT8548203A0 (en) | 1985-06-11 |
FR2565485A1 (en) | 1985-12-13 |
AR241518A1 (en) | 1992-08-31 |
AU577864B2 (en) | 1988-10-06 |
DK264485D0 (en) | 1985-06-12 |
SE8502540D0 (en) | 1985-05-23 |
GB2160098B (en) | 1988-01-06 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PCNP | Patent ceased through non-payment of renewal fee |