NZ212257A

NZ212257A - Stable foamable dentifrice containing dextranase

Info

Publication number: NZ212257A
Application number: NZ212257A
Authority: NZ
Inventors: A Gaffar; P Ren; A Esposito; V P Gelsomino; T R Dring; D Mcpherson; D Moy
Original assignee: Colgate Palmolive Co
Priority date: 1984-06-12
Filing date: 1985-05-30
Publication date: 1988-03-30
Also published as: IT8548203A0; GB8514601D0; GB2160098A; GB2160098B; DK264485A; DK264485D0; IT1181681B; FR2565485A1; AU4360485A; SE8502540D0; ES8700051A1; BR8502769A; SE8502540L; AR241518A1; CH668360A5; FR2565485B1; ES544047A0; PT80600A; NO852352L; BE902641A

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £12257 2 1225 " ."ATE NT ;-iC£ 3 C MAY 1935 RECEtVTQ NO DRAWINGS f ;ri. ...~ S;;-sc;':cation Filad^C Ciai.; • 8<ol Publication Date: ... ?. S !???. P.O. Journal. No: . Patents Form No. 5 Number PATENTS ACT 1953 Dated COMPLETE SPECIFICATION STABLE DENTIFRICE CONTAINING DEXTRANASE tfWe COLGATE-PALMOLIVE COMPANY of 300 Park Avenue, New York, New York 10022, United States of America, a corporation organised under the laws of the State of Delaware, United States of America do hereby declare the invention for which i/we pray that a Patent may be granted to nut/us, and the method by which it is to be performed, to be particularly described in and by the following statement: . l . (followed by page la) 21225 \.r. r-vrcxroH" r M A V '< ~ ^ K \jv\c\-- rs-oo 5 BACKGROUND AND PRIOR ART The present invention relates to novel oral y 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 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 -1a- c. 12257 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 et al, in JADA, vol. 76, pp. 301-304, (February 1968); and an article by Duany et al, in Journal of Perventive 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 hugiene products such as toothpastes, rinses and chewing gum containing surface active cleansing and foaming agents, as shown 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 -2- 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 sulfate. 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. It is known to utilize eugenol and 1-menthol as dextranase stabilizers in the presence of anionic surfactants. It is also known to utilize a mixture of dextranase and omega-amino acids in oral compositions to prevent bacterial plague formation. U.K. Patent Application No. 2,061,727/A utilizes aluminas and hydrated aluminas as the abrasive, in order to stabilize the dextranase in the dentifrice composition. N.Z. Patent No. 158659 discloses dental antiplaque and anticalculus compositions containing a mixture of a bis- biguanido compound, dextranase and sodium hexametaphosphate. N.Z. Patent No. 157359 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 N.Z. Patent Nos. 158679; 153131 and US Patent No. 3,751,561. Oral compositions containing dextranase in combination with other enzymes are disclosed in N.Z. Patent No. 167969. 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 is disclosed in N.Z. Patent No. 168427. The addition of a Group IIA metal ion to the neutral protease and hydrolyzed protein combination provides additional stability as disclosed in N.Z. Patent No. 168247. 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 2 1225 7 agents as aforecited, there is no disclosure of the use of a polycationic stabilizer selected from the group consisting of proteins, polypeptides and polyamines, vjhich more specifically 1 include a quaternized hydrolyzed protein (Crotein Q), polylysine, polyarginine, protamine sulfate, polyacryloxyalkyl ammonium salt, polyvinyl pyridir.ium ammonium salt, polyoxyethylene (dimethyl amino) ethylene dichloride (Busan-77) and poly h"-(2-hydroxypropyl methacrylamide). Summary of the Invention 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 aetergency of the anionic surfactant. Accordingly, a primary object of present invention is to provide a stable dentifrice containing an anionic surfactant, a dextranase enzyme and a polycationic stabilizer* 2 12257 |; Another object of present invention is to provide a j; foaming and stable dextranase-containing dentifrice in the jj presence of anionic and nonionic surfactants. Still another object of present invention is to provide a foaming and stable dextranase-containing dentifrice in the presence of anionic and amphoteric surfactants. Another object of present invention is to provide a physically and cosmetically stable dextranase-containing dentifrice with retention of enzyme activity during aging. otill another object of present invention is to provide a stable dextranase-containing dentifrice without adversely affecting the foaming property of the anionic surfactant system. Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims. To achieve the foregoing and other objects and in accordance with the present invention, as embodied and broadly described herein, the stable dentifrice of this invention com- Z1ZZO / I I i i prises an anionic surfactant system, a dextranase, and a polycationic stabilizer selected from the group consisting of proteins, polypeptides and polyamines, in a dental vehicle. Typical stabilizers may be selected from the group consisting of a ! i quaternary derivative of hydrolyzed protein, polylysine, poly- j arginine, protamine sulfate, polyacryloxyalkyl ammonium salt, j t polyvinyl pyridiniun ammonium salt, polyoxyethylene (dimethyl ; amino) ethylene dichloride and poly K-(2-hydroxypropyl methacryl- amide). I I J-iore specifically, present invention relates 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. i t. Dextranase enzymes are produced from a variety of sources all of which are useful in the present invention. Dex- i tranase enzymes are commonly produced by growing Penicillium funiculosun or other fungal sources in a dextran-containing medium. The dextran is commonly a commercial grade obtained from Leuconostoc mesenterioides. This commercial grade of i Si 2257 dextran contains about 95 percent *<-l,6-glucoside linkages and about 5 percent ©c-l,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. 6, dated Apr. 16, 1968, pages 343-349. A further procedure is described in U. 3. Patent No. 2,742,399 to Tsuchiya et al. (Kote also Tsuchiya et al, "Journal of Bacteriology,11 Vol. 64, page 513 )• In the procedure of Bowen, dextran may be prepared from noncariogenic streptococcal strains such as ATCC 10558, 903-1600, IIA2 + 3f or Leuconostoc mesenterioides and purified according to the method described by Wood et al, "Archives of Oral Biology,M Vol. 11, 1066, pages 1039 ct seq., except that L. mesenterioides is grown at 25°C. Dextranase may be prepared by inoculating Penicillium funiculosum into flasks containing 250 ml of a medium containing 0.5j» yeast extract and 1& dextran. The flasks are incubated at 30°C on a shaking incubator for 4 days. The tt*2 5T? culture is then centrifuged at 3,000 g for 20 minutes and filtered through Whatman 42 filter paper. Dialysis in 16 mm "Visiting" tubing against deionized water and concentrating fifty fold by dialysis against polyethylene glycol (molecular weight 20,000) follows. 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 sulfate. Additional procedures for preparing dextranase include that described in U. 3. Patent No. 2,742,399 to Tsuchiya et al. j Dextranases of bacterial origin are also useful in the ' i 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 coagulans NRRL B-3977 (Beckman dextranase catalogue #680000). Bacterial-origin dextranase may be obtained by the addition of -1,3-dextran or a mixture of oC-l»6-t o^-l»3-» and o(-l,4-dextrans. The bacterial strain may be innoculated into a shaker flask or fsraer.tator for a period of 1 to 5 days at 25°-40°C. The sterile growth medias can consist of the aforementioned \N r-9 OCT 1985 j dextran or mutan combined with a mixture of carbohydrate (starch, | glucose, sucrose, cellulose), nitrogeneous compounds (protein ♦ j 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 sulfate, acetone, sodium sulfate, 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 (D2A2, Sephodex, SCTSOLA, hydroxy apatite) chromatography methods and frozen or stabilized by the addition of protein, dextran, salt, etc. (The purification steps are usually conducted at refrigerated temperatures.) The amount of dextranase employed in the oral compositions of the invention is at least such amount as is effective in promoting oral hygiene. This amount is dependent upon the j 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 212257 sugar from 1 microgram of maltose monohydrate or native dextran per minute at 35°C and pH 6.0. Vihile 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 0.05-4JS 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 100°F). 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 sulfonate, sulfate, 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 tallowv 212257 grease, coconut oil, tall oil and mixtures thereof; and the sulfated and sulfonated synthetic detergents, particularly those having about 8-26, and preferably about 12-22, carbon atoms to the molecule. Examples of suitable synthetic anionic detergents include the higher alkyl mononuclear aromatic sulfonates such as the higher alkyl benzene sulfonates containing from 8-16 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 sulfonate and the alkyl toluene, xylene and phenol sulfonates: Cg-Cl6 alkyl naphthalene sulfonate, ammonium diamyl naphthalene sulfonate, and sodium dinonyl naphthalene sulfonate; sulfated aliphatic alcohols such as sodium lauryl and hexadecyl sulfates, triethanolamine lauryl sulfate, and sodium oleyl sulfate; sulfated alcohol ethers, such as lauryl, tridecyl, or tetradecyl sulfates including 1-5 ethylene oxide moieties; ammonium lauryl ether sulfate; sulfated and sulfonated fatty oils, acids or esters, such as the sodium salts of sulfonated castor oil and sulfated red oil; sulfated hydroxyamides such as sulfated hydroxyethyl lauramide; sodium salt of lauryl sulfoacetate; sodium salt of dioctyl sulfosuccinate, the sodium salt of oleyl 2 1225 7 ! methyl tauride, and sodium K-lauryl sarcosinate. i aIso included within the ambit of the invention are the sulfuric acid esters of polyhydric alcohols incompletely i ■ j esterified with higher fatty acids, e.g., coconut oil monoglycer-ide monosulfate, tallow diglyceride monosulfate; and the hydroxy sulfonated higher fatty acid esters such as the higher fatty acid esters of low molecular weight alkylol sulfonic 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 sulfonates, the higher alkyl sulfates, the higher fatty acid monoglyceride ■ sulfates and the sulfated ethoxylatea alcohols, ammonium lauryl ether sulfate, sodium IJ-lauroyl sarcosinate, dioctyl sodium , sulfosuccinate, and mixtures thereof. i It is preferred to use the anionic surfactant(s) in an , i! amount of about 0.1 to 5/» by weight of the carrier or dental 1 | |! vehicle. i. !; Other suitable surface active materials include nonionic! j agents such as condensates of sorbitan monostearate with approxi- | mately 20-60 moles of ethylene oxide, condensates of ethylene i oxide with propylene oxide condensates of propylene glycol ("Pluronics*'); condensates of higher fatty alcohols or ethers 2 12257 with ethylene oxide; condensates of alkyl thiophenols with 10 to 15 ethylene oxide units, and ethylene oxide addends of monoesters of hexahycric alcohols and inner esters thereof such j| as sorbitan monolaurate, sorbitol monooleate, nannitan mono- ii 11 palmitate, and sorbitan monoisostearate. Specific examples include polyoxyethylene 20 sorbitan monooleate (Tween 60), i polyoxyethylene 20 sorbitan monoisostearate. The weight ratio i, of anionic to nonionic surfactant of 1:1, 1:2, and 2:1 have I beer, found to afford good dextranase stability in the presence i i of a polycationic stabilizer such as Crotein Q. ; The amphoteric surfactant, which is a preferred i! !■ additional surfactant, has both anionic and cationic groups, I . j: is ionically balanced, and its isoelectric point is at a pH ji of about 7 and includes the betaines and sulfobetaines. The ji betaines are a class of amphoteric surfactants which include ji alkyl betaines, alkylaraido betaines and alkylamino betaines h having the general formula: R,-N+-ft,-300" 2 12257 wherein R^ is an alkyl group having 10 to about 20 carbon atons, preferably 12 to 16 carbon atoms or the amido radical: 0 H n • R-C-N-(CH-) -* a or an amino radical: R-NH-(CH,) -2 a wherein R is an alkyl group having about 10 to 20 carbon atoms and a is the Integer 1 to 3; and **3 are ®ach alkyl groups having 1 to 3 carbons and preferably 1 carbon; is an alkylene or hydroxyalkylene group having from 1 to U carbon atoms and, optionally, one hydroxyl group* Typical alkyldimethyl betaines Include deeyl betaine or 2-(N-decyl-N,N-dimethylaiwaonio) acetate, coco betaine or 2-(N-coco-N,N-dimethylammonio) acetate, myristyl betaine, palmityl betaine, lauryl betaine, cetyl betaine, stearyl betaine, etc. The amidobetaines similarly include cocoamidoethyl betaine, cocoamidopropyl betaine, laurami-dopropyl betaine and the like. li I! The sulfobetaines, which are similar in structure to the betaines, have sulfonate groups in place of the carboxy-late groups, as represented by the general formulas *2 R2-1: H3 wherein E^, Rji R^ and R^ have the same meanings as above, and include alkylsulfobetaines, alkylamidosulfobetaines and alkylarainosulfobetaines. The molar ratio of anionic to amphoteric surfactant of 1.2:1 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 sulfate. 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 -16- !;rji \^9GCri985 21225 7! i i i i and complete dispersion of the composition throughout the oral cavity. J. Garcia Dominguez, International Journal of Cosmetic Science. Volume 3» pp. 57-66 (1961), discloses that amphoteric j i betaine inhibits soaiun lauryl sulfate from denaturing dextra- I nase in an aqueous solution, by the formation of mixed micelles j through ionic interaction with SLS. However, its use in a i dentifrice together with the cationic protein stabilizer affords j unexpected and unusual formula stability and the retention of j enzyme activity upon aging. j i It is preferred to use the amphoteric surface active j I agent in an amount of about 2-6>j by weight of the carrier or j i dental vehicle. j I The inactivation of the dextranase due to the presence | of anionic surfactant in the dentifrice makes it essential to ! i add about 0.5-5/» by weight of a cationic stabilizer, having multiple positive charges, to interact with the anionic surfactant sodium lauryl sulfate (3L3), 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 is selected from the group consisting of a quaternary derivative of hydrolyzed collagen protein, polylysine, polyarginine, protamine \ I I i1 2 1225 7 sulfate, polyacryloxy alkyl ammonium salt, polyvinyl pyridinium ammonium salt, polyoxyethylene (dimethyl amino) ethylene dichlor-ide (Busan-77), poly N-(2-hydroxypropyl methacrylamide). Cationic surfactants do not function as a stabilizer for the dextranase The ratio of stabilizer:anionic surfactant is preferably within r the weight range of 1:1 to 2:1 respectively in order to bind the anionic surfactant and prevent its interaction with dextra-i nase. The quaternary derivative of hydrolyzed collagen product, a preferred polycationic stabilizer, is a product of Croda Inc. of Kew York, known as Crotein Q, having a minimum pi 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 pro-tonation of NH groups in the protein chain, as shown diagrammati-cally in the Crodata circular 7778, page 2. -18- t 212257 +N(CH3) y X « +N(CH_) t S NH, 'fNH2-x-+N(CH3 ) +N(CH7) 3 3 At pH 9-5» Crotein Q*s quaternary group is still positively charged. +N(CH,) • 3 3 'n(ch3). +K(CH,) « 3 3 ;-x-+N( ch^ >9 OCT 1985 • 212257 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 3 concentrations were evaluated. The time required for 50/s loss of activity (t|) were calculated and are used for comparison. Representative data from each study are presented. Effect of SLS concentration on enzyme activity: 3L3 Concentration ti - 26°C 0.5>i 2.8 hr. 1.05* 0.8 hr. Enzyme inactivation increases with SLS concentration. Influence of temperature on enzyme inactivation: Experimental conditions j l£ SLS t . l£ SLS + Crotein : l'/i SLS + 0.5£ Pluronic (Mixed deterg.) j Mixed deterg. + 15» Crotein 1 i I tj - 0 hr. 1.5 hr. 1.1 hr. 5.3 hr. ti - 26°C 0.8 hr. 22.0 hr. 14.6 hr. 31.7 hr. -20- 212257 Enzyme activity is stabilized by lower temperatures. Stability of Enzyme Activity as a function of Crotein Q: t* - 3B°C 1*8 hr. 14*8 hr. In the presence of detergents(s), enzyme stability increases with Crotein Q concentration. > System Description l£ SLS, l£ Crotein 1# SLS. 2& Crotein -21- 2 12257 Stability studies conducted on dextranase enzymes have shown that the enzyme inactivating effects of anionic surfactants such as sodium lauryl sulfate (SLS), can be lessened in the presence of a polycationic stabilizer, such as Crotein although the exact mechanism by which the stabilizer effects this function is not known, 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 units/ml, is added 0.95 ml dextran (110,000 av. mol. wt) dissolved in 0.1M sodium acetate, and digested for 30 minutes at 37°C. At the end of the digestion period, 1 ml color 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— -22- 2 122o 1000 ug/ml) ana 1 ml color reagent are boiled for 15 minutes, cooled and read O.D. at 540 nM after addition of 10 ml H^O. The color reagent comprises 5 g 3,5 dinitrosalicylic acid, 1 g phenol, 0.25 g sodium sulfite and 100 g potassium sodium tartrate dissolved in 500 ml of 2?» HaOH. 1 unit of dextranase activity is defined as the release of 1 ug maltose monohydrate (Baker) per minute at 37°C. Examples 1-7 inclusive are more fully defined hereinafter. -23- K) O n H ■>) ■fji TnDLE I it ACTIVITIES UfT (Weeks at 38°C) Dentifrices 1 2 3 4 5 6 7 8 9 Control* 64.6I2.I 48.2-1.2 46.9-2.6 4l.6ll0.1 33.2^0.6 26.7I0.3 26.2I2.O 26.5-0.1 24.9-1.0 (1) 0.5> 3Li> 4.8-0.2 3.5-0.3 5.4-1.2 2.8±o.o 2.0I0.4 3.2^0*3 1.610.3 2.010.0 2.llo.2 MM (2) 0.5* Pluronic 83.9-2.1 76.613.1 75.713.1 62.ill.8 56.912.1 49.5-2.2 46.5ll.3 • 51,3-2.8 47.ll0.1 (3) 0.5/i SLS + Pluronic • 5/1 68.4-1.9 55.3-1.6 43.7-1.0 32.7-1.7 28.7-0.4 21.5-0*6 18.9-1.0 16.0^0.6 13.6^2.7 (4) 0«5^ SLd + Pluronic + ««« Polyox .5* 93.9ll.9 88.3-1.1 81.8 -5.0 75.d2.4 73.4*1.7 68,912.9 61.3-1.7 63.7^2.0 54.1-1.8 (5) 0.5* SLS + Pluronic + Crotein Q .5;i lit 94.8-0.8 95.2-1.1 92.6I3.2 98.2-1.9 94.7-2.5 60.210.3 84.6-1.2 88.3-2.2 8O.2I4-9 (6) 0.5?« SL3 + Pluronic + Celatin • 5/i lvi 76.5-1.1 78.210.5 71.ll0.9 75.214.7 74.4ll.9 66.9I2.3 64,0^0,9 70,0^1.4 64.6-0.8 (7) 0.5> SLS ♦ .5/ Pluronic + lj4 Polyvinyl Pyrroli-done 70.7-0.6 55.8ll.S 49.2±1.9 48.1-3,5 38.5*0.3 34.9ll.7 32.9ll.O 30.9ll.6 26.4^1.7 p Control dentifrice containing enzyme but no SLS or stabilizer 5f03i2!ol^Lii4bfrSB8&F0i}23S51cS! ab0Ut 2C* poly°xypropylene' the latter radical having a «o.V»cular w Water soluble ream. a high mni«euii»r ««<Eh* of PQXyetlurXflM oxide, obtained from Union Carbide Corp. ! 2 1 2257 ii ii I :' 1 !i t • i: I It is clear from the table that the enzyme per se in the absence of detergent is unstable in dental cream. An addition of SLS increased deactivation rate (1). The addition of f-luronic to the SLS/enzyme dentifrice (3) does |i not stabilise the dextranase. The further addition of Polyox I provides inadequate stabilization (4), as compared to Crotein Q, ii (5) gave better stability of the enzyme in the dentifrice than . i gelatin , (compare 5 vs. 6). Polyvinyl pyrrolidone (7) is not j| effective in stabilizing dextranase in the dentifrice. i j !i The stability of the dextranase-containing dentifrice, •J measured by the retention of enzyme activity over a protracted ii period of time is also shown in Table II, wherein comparative J : |. samples of said dentifrice containing anionic and amphoteric I' surfactants are evaluated using the manual method of Tsuchiya !j et al, Journal of Bacteriology. Vol. 64 (4) pp. 513-514, (1952), ii ii which may be modified for the Technicon autoanalyzer, both using ! the coloriraetric reagent dinitro-salicylic acid. Aged samples ! solubilized in water and buffer were incubated for 11.5 minutes I i with dextran substrate, the reaction stopped by boiling, the solution reacted with color reagent, and the absorbance read and compared to a glucose standard curve to determine the percent 2 1 2257 J 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. 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 fornrulae utilizing conventional humectants, thickening agents, flavors and the like, in conventional amounts ; as set forth in this specification. r 2 a 10 1.1 12 13 14 / TABLE II SLS/Betaine/Dextranase Formulations and Aging Data Ex. Ingredients 3«6£ Dextranase (0*83 mg protein/ml), 2£ Crotein Q, 1.8^ SLS, 53» Betaine, Silica 3.6}t Dextranase (0.83 mg Jrotein/ml), 2£ Crotein Q, •8jt SLS, Betaine, Alumina 0«65£ Dextranase (0.83 mg protein/ml), l£ Crotein Q, 1.29C SLS, Alumina Initial Enzyme Activity 53,130 49,392 5,340 Alumina, 2£ Crotein Q, 1.20 4,570 SLS, Betalnel, 0.55^ Dextranase Silica, 2i» Crotein Q, 1.2JC SLS, 18,600 1*1* Betaine, 1 i» Amide, 2.1> Dextranase Alumina, 2J& Crotein Q, 1.2^ SLS, 13,800 4J* Betaine, l«8jt Dextranase Alumina, 2* Crotein Q, 0.3* SLS. 13,400 0*9^ AI.RS,* Betaine, 1.8^ Dextranase jt of Initial Enzyme Activity j wks b wks 9 wks 12 wks 104 100 110 98 98 101 84 71 99 88 91 95 103 87 95 67 107 116 9? 7? 31 107 ». 1 :.i3 -27- f 2 7 Ex. Ingredients Initial Enzyme Activity % of Initial Enzyme Activity 3 wks 6 wks 9 wks 12 wks 15 Alumina, 2+ Crotein Qf 0.3^ SLS, 27,000 0«9Jt ALES, 4^ Betaine, 3.6^ Dextranase 103 99 123 121 16 Silica, 2* Crotein Q, 0*33* SLS, 28,300 0*9J& ALES, Betaine, 3.696 Dextranase 102 99 120 119 17 Alumina, 3* Crotein Q, 1.2* SLS, 23,200 5£ Betaine, 3*6£ Dextranase 104 141 139 148 ^Sulfated amido-betaine 2 Ammonium laurylether sulfate Samples were aged at 100°F. Activities determined by colorlmetrlc spectrophotometry using 3,5 *l»itro- salicylic acid* Calculations! SLS (94jt active, F*W* 288*38) 18 grams x 0*94 ■ 16*9 g * 0.0587 moles Betaine (271* active, F*V. 283) 50 grams x 0*27 * 13*5 g m 0*0477 moles Molar ratio SLSt Betaine ■ 0.06*0.05 ■ l*2sl C "28- * O rt-A 212257 The interactions 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 accord ing to standard foam height procedure. This analysis was conducted at 37°C in both distilled and hard water (105 ppm CaC^, and 70 ppm Solutions were prepared to contain singularly or combinations of 0.1^ 5LS, and 0.2-/o Crotein Q. Foam volume was measured in ml after 30 inversions of the grad' uate cylinder. Ta3LS III 0.1™ SLS + 0.1/» SLS 0.2;» Crotein Q 0.2>* Crotein (j distilled water 500 ml 12 ml 475 ml hard water 236 ml 12 ml 425 ml f This data shows that Crotein Q, which is nonfoaming, 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. The following graph shows the relative foam volumes in distilled water and hard water. -29- FOAH VOLUME (ML) £ S s ro s e s s DISTILLED MATER HARD WATER DISTILLED WATER HARD WATER DISTILLED WATER HARD WATER DISTILLED WATER HARD WATER DISTILLED WATER HARD WATER! g i £ I ' 1 DISTILLED WATER HARD WATER H ! If If If / i? UU if 1 U Z Z ' T. » » ' • : ; • : f i DISTILLED WATER 1 HARD WATERS r- M II M HIH U fl i f i I !un| -12XJS if J i g 30. 2 12257 This data shows 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 optim- I al enzyme stabilization, SLS + Crotein + 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 ensymatic-ally, physically and cosmetically stable dentifrices containing approximately 5,OOC 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. i-251/ TABLE IV Retention Aged of Enzyme at_ •Height of Sample Ingredients Activity 100 F Foam unl) 1 Alumina - 1.2* 95 9 wks 54 Betaine, 1.2* SLS, 2f> Crotein Q 2 Alumina - 0.9* 96 9 wks 34 Betaine, 0.8* SLS, 1* Crotein Q 3 Alumina - 1.2* 96 9 wks 30 Betaine, 0.6* SLS, 1?( Crotein Q 4 Silica - 1.2* 104 6 wks 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 foaa was measured after shaking 1 gram of dentifrice in 10 ml of 175 PPM hard water (900F) for 15 sec. ' o ** <> N i* •9 OCT1985 -32- 2 12257 i: i- t ii i i Toothpastes and toothpowders conventionally contain a substantially water insoluble polishing agent or abrasive which is compatible with the formulation. Preferred compatible J ; materials which do not adversely affect the dentifrice composi-i tion include aicalcium phosphate dihydrate, silica and hydrated alumina. The polishing a^ent may be the sole carrier material as in a toothpowaer, and is present in an amount up to about BOA : 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, aluminum or i 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 I j of both water and a humectant or binder such as glycerin or sorbitol. The total liquid content will generally be about 20-75c/i of the vehicle. The amount of water is generally about 10-25:/i of the vehicle. It is preferred to also use a gelling } agent in toothpastes such as the natural and synthetic gums ana gum-like materials such as Irish moss, gum tragacanth, starch, sodium alginate, carboxymethyl cellulose, Viscarin GM3, Iota carrageenan, and the like, usually in an amount up to i about 10,of and preferably about 0.2-55*, of the carrier or vehicle, ! The carrier suitably nay contain a 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. 3 Various other materials may also be incorporated into the carrier. Examples thereof are coloring or whitening agents (for example, titanium dioxide), preservatives (for •r 9 OCT 1985 n • 212257 example, sodium benzoate), silicones, chlorophyll compounds, ammoniated materials such as urea, diammonium phosphate, and mixtures thereof, alcohol, menthol, and other constituents. These adjuvants are incorporated into the instant compositions 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. Flavoring 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 flavor in the manner desired. Examples of such additional materials include the flavoring 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 flavor 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 2 12257 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 flavor are then added. The toothpaste is then thoroughly deaerated (e.g., in vacuo) and tubed. The formulation may be deaeratea during mixing or after mixing. Detailed Description of the Invention 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 1-7 The stabilization properties of Examples 1-7, which are measured by the retention of enzyme activity over a period -36- 257 of time and recorded in Table I, 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. Ii -37- 2 12257 Ingredients Dentifrice (1) (2) (3) (U) (5) (6) (7) Glycerine 15 15 Sodium Alginate 1.0 1.0 Sorbitol 70jo soln. 15 15 Sodium Saccharin 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 — ■ - ... - >■ Flavor 1 1 — ■ - - > Dextranase 5000 5000 — ■ — units/g units/g Crotein Q - - - - 1*0 - - Gelatin ----- 1.0 - Polyox^ - - -1.0 - - - Polyvinyl - - - - - - 1*0 Pyrrolidone Water Q* S. 1Block polymer of about &<& polyoxyethylene and about 20£ poly-oxypropylene, the latter radical having a molecular weight of 3,250, obtained from BASF Wyandotte Co. ^Water soluble resin, a high molecular weight polymer of polyethylene oxide, obtained from Union Carbide Corp* -38- 212257 i. EXAMPLE 8 Gel Toothpaste \ " Ingredients ± Glycerine l! CMC- ; Ka Benzoate ! Na Saccharin • Monofluorophosphate (I-IFP) Sorbitol ! i Carbowax — PEG 600 25 0.35 0.5 0.2 0.76 24.09 3 -39- 212257 Ingredients FDC Blue #1 *S l£ Deionized water ■» Silica containing combined alumina Colloidal silica aerogel^ Sodium lauryl sulfate (SLS) Betaine tego-S-1066^ Crotein Q Flavor Dextranase (20,000 units/g) PH 6.5 Foam &L ml 1 Carboxymethyl cellulose 2 Polyethylene glycol, mol. weight 600 3 Zeo 49B, ex J. M. Huber * Syloid 244 5 A sulfated amphoteric surfactant manufactured by Goldschmidt Chemical Corp., Actives 27£ 40- 0.1 6.6 18 8 1.8 5 2 1 3.6 EXAMPLE 9 Toothpaste Ingredients i* Iota carrageenan 0.9 Glycerine 22 Na Benzoate 0.5 Na Saccharin 0*2 Sodium Monofluorophosphate 0*76 Deionized water 12*24 Hydrated alumina 50 SLS 1*8 Sulfated amldobetaine (1*5£ active) 5 Crotein Q 2 Flavor 1 Dextranase (20,000 units/g) 3*6 pH 7.41 Foam 83 ml | •'OCT/ags 2 12257 EXAMPLE 10 Toothpaste Ingredients Iota carrageenan Glycerin Ma Saccharin Methyl Paraben MFP Crotein Q Deionized water Hydrated alumina SLS Dextranase (20,000 units/g) pH 8.08 The omission of the betaine reduces the enzyme stability of this composition to zero. -VZ- 0.9 22 0.2 0.1 0.76 1 23.19 50 1.2 0.65 2 12257 EXAMPLE 11 Toothpaste Ingredients % Iota carrageenan 0*9 Glycerin 22*0 MFP 0.76 Na Benzoate 0.5 Na Saccharin 0.2 Hydrated alumina 50 SLS 1.2 Betaine 4.0 Crotein Q 2 Flavor 1 Dextranase (10,000 units/g) 1.6 Deionized water 15.64 pH 7*44 Foam 56 ml -43. 2 1 225 7 EXAMPLE 12 Toothpaste Ingredients ft Iota carrageenan 0*9 Glycerin 22 Na Bensoate 0.5 Na Saccharin 0.2 MFP 0.76 i Hydrated alumina $0 Deionized water 13*64 SLS 1*2 Betaine tego-S 1066 5 Crotein Q 3 Flavor 1 Dextranase (10,000 units/g) 1.8 pH 7.17 Foam 71 ml -44— EXAMPLE 13 Toothpaste Ingredients ^ Iota carrageenan 0.9 Glycerin 22 Ma Benzoate 0*5 Na Saccharin 0.2 MFP 0.76 Hydrated alumina 50 Deionized water 11.84 SLS 1-2 Betaine 5 Crotein Q 3 Flavor * Dextranase (20,000 units/g) 3*6 pH 7.28 Foam 60 ml f EXAMPLE 1L Mouthwash Ingredients # Ethanol (90/S) 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 Sulfate (SLS) 0.1 -0.5 Crotein Q 0.5 - 3 Flavoring 0.22-0.5 Water Q»S. EXAMPLE 15 Toothpowder Ingredients * Hydrated Alumina 70-80 Glycerin 10 SLS 0.1-0.5 ii 2 1225 7 ! Ingredients . # Sodium Saccharin 0.1 Flavoring 1.0 Dextranase 1,000-20,000 units/g Crotein Q 0.5-3 Water Q.S. EXAMPLE 16 Chewing Gum Ingredients Gum base (Natural or Synthetic 20-35 elastomer filler i*e. gum arabic) Sorbitol 10-20 Dextranase (5,000-20,000 units/g) 0.1-1.0 Sodium Lauryl Sulfate 0.1-0.5 Crotein Q 0.5-3 Flavoring 0.5-2 ' Dextrose Q«S. I I j- i i J ii 2 1225 7 i: H I l! I ' j SXACTLE 17 Toothpaste jj Ingredients ■ i 1 Glycerin Carrageenan L»icalcium phosphate dihydrate i ■ Sodium Benzoate ooaium Saccharin Crotein Q oLo Fluronic (F108) '■ i Flavor j| Dextranase 1; Water i! I |l I : 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 comprise an aqueous vehicle i i • ; 5 I t j I > \ ? 4 t -48- j 22 1-3 50 0.5 0.2 1.3 0.75 0.5 1 5,000-20,000 units/g Q • 5 • 2 12257 containing a suitable flavor material. Examples 18-21 inclusive contain 1.8£ dextranase. Example 22 contains 2.1£, Example 23 contains 2.5/» and Examples 24-26 inclusive contain 3*6-/" dextranase. Conventional humectants or mixtures thereof in suitable amounts as defined in this specification, are utilized. Examples I i 16, 19, 21, 24 and 26 comprise glycerin, whereas Examples 20, 22, 23 ana 25 comprise a mixture of glycerin and sorbitol. -49- Ex. Ingredients 18 Iota7Alumina, 1«2* SLS, 491 Betaine 2* Crotein Q 19 Iota/Alumina, 3* SLS, 0.9* ALES, 4% Betaine, 2* Crotein Q 20 Silica, 0.3* SLS, 0.9* ALES, 4* Betaine, 2* Crotein Q 21 Iota/Alumina, 1.2* SLS, 5* Betaine, 3* Crotein Q 22 Silica, 1.2* SLS, 4* Betaine, 2* Crotein Q, 1* Amide 23 Silica, 0.6* SLS, 4* Betaine, 2* Crotein Q, 1* Aside 24 lota/Alumina, 0.3* SLS, 0.9* ALES, 4* Betaine, 2* Crotein Q 25 Silica, 0.3* SLS, 0.9* ALES, 4* Betaine, 2* Crotein Q 26 Iota/Alumina, 1.2* SLS, 5* Betaine, 3* Crotein Q ^ * Carrageenan EXAMPLES 10 - id Toothpastes Initial Enzyne Activity After0 Foam (al) Activity (units) 12 Weeks 100 F * of Initial- 58 13,800 15,200 110 58 13,400 15,100 113 46 14,000 . 15,800 113 71 12,500 16,100 129 55 18,600 15,000 81 37 23,800 18,700 79 50 27,000 32,700 121 51 28,300 33,800 119 60 23,200 34,300 148 -50- </div>

Claims

<div class="application article clearfix printTableText" id="claims"> 3-\l.2S7 I • I Variations in the above formulations may be made.
For example, other anionic surfactants such as higher alkyl benzene sulfonates, fatty acid soaps such as tallow soap, sulfated alcohol ethers and the like may be substituted for the specific anionic surfactants in the examples.
Similarly, other betaines and sulfated betaines may be substituted for the specific betaine surfactants in the examples.
Likev;ise, other nonionic surfactants I; may be substituted for the specific nonionic surfactants in the • : examples. ti 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. j1 Likewise, other polycationic stabilizers such as j i polylysine, polyarginine, protamine sulfate, polyvinyl pyridinium ammonium salts, poly K-(2-hydroxypropyl methacrylarnide) may be ! substituted for the Crotein Q used in the examples. ji It is understood that the foregoing detailed descrip tion is given merely by way of illustration and that variations may be made therein without departing from the spirit of the invention as defined in the appended claims. "51- WHAT WE CLAIM IS : 1, 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 said enzyme activity against loss during aging, and against inactivation due to the presence of said 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. 2, An oral composition according to Claim 1, wherein the polycationic stabilizer is selected from the group consisting of a quaternary derivative of hydrolyssed collagen protein, polylysine, polyarginine, protamine sulfate, polyacryloxy-alkyl ammonium salt, polyvinyl pyridinium ammonium salt, polyoxyethylene (dimethyl amino) ethylene dichloride, poly N-(2-hydroxypropyl methacrylamide). 3, An oral composition according to Claim 1, containing a nonionic surfactant in the weight ratio of 2:1 to 1:2 of nonionic to anionic surfactant. PA r " V 52 4.
An oral composition according to Claim 1, containing an amphoteric surfactant selected from the group consisting of betaines and sulfobetaines, in the molar ratio of 1.2:1 to 1:2 11 of anionic to amphoteric surfactant. ' i I ' '5. hn oral composition according to Claim 4» wherein the : amphoteric surfactant has the general formula: 1 -C00~ , or 1 , 4 R3 ?2 *i-r-v5°3- !i r3 ii il i| f wherein R^ is an alkyl group having 10 to 20 carbon atoms, the amido radical: 0 H n • R-C-N-(CH,) - » or * a £/s' /X ''q V ^ r -9 OCT 19851 the amino radical: R-NH-(CH2)a- , wherein R is an alkyl radical of 10 to 20 carbon atoms and a is an integer 1 to 3; R2 and R3 are each alkyl radicals having 1 to 3 carbons; and R^ is an alkylene or hydroxyalkylene group having 1 to 4 carbon atoms, and constitutes 2-6% by weight of the composition.
6. An oral composition according to Claim 1, wherein the polycationic stabilizer constitutes 0.5 to 5% by weight of the composition.
7. An oral composition according to Claim 1, wherein the dextranase constitutes 0.05 to 4% weight of the composition.
8. An oral composition according to Claim 1, wherein the anionic surfactant is sodium lauryl sulfate. c. "■ o r\ r- ~h t <c ^ u .
9. An oral composition according to Claim 1, wherein the anionic surfactants are sodium lauryl sulfate and ammonium lauryl ether sulfate.
10. An oral composition according to Claim 3, wherein the nonionic surfactant is a block polymer of 80% polyoxyethylene and 20% polyoxypropylene having a molecular weight of 3,250.
11. An oral composition according to Claim 1, in the form of a toothpaste containing 30-75% by weight of a water insoluble polishing agent.
12. An oral composition according to Claim 1, in the form of a toothpowder containing 70-80% water insoluble polishing agent.
13. An oral composition according to Claim 1, in the form of an aqueous mouthwash containing 5-10% ethanol.
14. An oral composition according to Claim lf in the form of a chewing gum, comprising 20-35% of a gum base containing a natural or synthetic elastomer filler. -55- * r/A/ ^v. H -V; 17FEBI988 .*>// ? r i M : ? OKI {-■ K O .
15. An oral composition according to Claim 11, wherein the polishing agent is hydrated alumina.
16. An oral composition according to Claim 11, wherein the polishing agent is dicalcium phosphate dihydrate.
17. An oral composition according to Claim 11, wherein the polishing agent is silica.
18. An oral composition according to Claim 11, containing a liquid content of 20-75% by weight of the composition.
19. An oral composition according to Claim 4, wherein the polycationic stabilizer is a quaternary derivative of hydrolyzed collagen protein. 17 FEB 1988 V 21225 7
20. An oral composition according to Claim 11v wherein the polycationic stabilizer is a quaternary derivative of hydrolyzed collagen protein. WEST-WALKER, McCABE Pen ATTORNEYS FOR THE APPLICANT </div>