SE458586B - CHEMICAL AND PHYSICAL STABLE ANTIPLAQUET DETAILS AND PROCEDURES FOR ITS PREPARATION - Google Patents

Description

458 586 10 15 20 25 30 is called the water gel phase. The dental polish can be added to the combined phases as a final step or it can be added to the water gel phase before the combination with the oil gel phase. The end product has improved chemical and cosmetic stability and improved taste.

A conventional method of preparing antibacterial dentifrices containing a quaternary ammonium compound as active material is described in U.S. Patent No. 4,118,476 and U.S. Patent No. 4,188,372 and comprises the formation of a gel with humectant (glycerin, sorbitol, polyethylene glycol), thickener (hydroxyethylcellulose). ) and sweeteners, and the addition thereof of polishing agents, flavoring agents, antibacterial agents, additional water and, finally, an anti-discolouring agent (a phosphono-containing compound or enelhexinic acid-containing compound).

Prior art also discloses processes for stabilizing dentifrice against precipitation and flocculation due to the intolerance of an antibacterial agent and an alkali metal carboxyalkylcellulose, as shown in U.S. Patent Nos. 3,842-168 and 3,843,779. The former patent utilizes the steps of addition of the antibacterial agent dissolved in water to a non-aqueous mixture of carboxymethylcellulose, sodium saccharin and humectant and then adding the surfactant to form a gel to which the polishing material and flavor are added as a final step. In the latter step, the antibacterial agent is added separately or together with the surfactant to a mixture of glycerin, water, sodium saccharin, carboxymethylcellulose and surfactant, followed by the addition of a polishing material and flavoring.

The addition of the surfactant must precede or occur simultaneously with the addition of the antibacterial agent to avoid precipitation in the dentifrice. However, the prior art does not disclose a cosmetically and chemically stable plaque inhibiting dentifrice containing as main ingredients a quaternary plaque inhibiting ammonium compound, a zwitterionic betaine surfactant, a glycerin and / or sorbitol cap. mectant and a nonionic gelling agent produced by a novel process utilizing a specific step sequence, which comprises the formation of two separate gel phases, an oil gel phase consisting of the quaternary ammonium compound, betaine surfactant and flavoring agent; and a water gel phase consisting of water, humectant and gelling agent; combining the two gel phases into a single parent gel and adding a dental abrasive to the combined gel phase as a final step or to the water gel phase before the addition of the oil gel phase. It has shown extremely stable formulations of a plaque inhibiting dentifrice containing a quaternary ammonium compound and a betaine surfactant can be prepared with glycerin or sorbitol as humectant using a specific step sequence, comprising the formation of a separate oil gel phase of the quaternary the ammonium compound, betaine and flavoring agent, a separate water gel phase of humectant, nonionic gelling agent and water (preferably containing the salts, i.e. sodium saccharin and sodium monofluorophosphate or other fluoride salt), combination of the oil and water gel phases to form a stable parent gel phase and addition of a dental abrasive as a final step. This process can be varied by adding the polish to the water gel and then adding the oil gel to the water gel abrasive mixture. This dentifrice was prepared at room temperature, i.e. each step in the step sequence is performed at room temperature.

Thus, a principal object of the present invention is to provide a stable plaque inhibiting dentifrice 458 based on quaternary active ingredients and a betaine surfactant with improved tolerability of all components by the formation of two separate gel phases which are combined into formation of a stable overall gel system.

Another object of the present invention is to provide a cosmetically and chemically stable plaque inhibiting dentifrice containing glycerin and / or sorbitol as a humectant, which is compatible with the active quaternary active ingredients. and Yet another object of the invention is to provide a stable plaque inhibiting dentifrice containing a nonionic rubber such as hydroxyethylcellulose, as a gelling agent to stabilize the betaine-quaternary system and to prevent deactivation of the active quaternary ingredient.

Another object of the invention is to provide a cosmetically (physically) and chemically stable plaque inhibiting dentifrice which also contains a fluorine-releasing compound without adversely affecting the cosmetic stability of the dentifrice.

Additional objects, advantages and novel features of the invention will become apparent from the following description and will also be apparent to those skilled in the art upon study of the following and in the practice of the invention. The objects and advantages of the invention may be realized and attained by means of the aids and combinations particularly pointed out in the appended claims.

To achieve the above and other objects and in accordance with the present invention, the novel stable plaque inhibiting dentifrice of the invention is prepared comprising a quaternary plaque inhibiting ammonium compound, a zwitterionic betaine surfactant, flavoring agent and a humectant. selected from the group consisting of glycerin, sorbitol and mixtures thereof, and a nonionic gelling agent, at room temperature by the process comprising the formation of two sepanemagel phases, an oil gel phase consisting of the quaternary plaque-inhibiting ammonium compound, betaine and a flavoring agent; and a water gel phase consisting of water, humectant and nonionic gelling agent; combining the two gel phases to form a single gel phase; addition of a dental abrasive to said combined gel phase. The sequence of the additives can be varied by adding the dental abrasive to the water gel phase before the combination with the oil gel phase. However, it is essential that the two separate gel phases be prepared before the addition steps.

The addition of salts such as a fluorine-containing compound and / or sodium saccharin, which are preferred components, was carried out by dissolving in the preparation water amount before mixing the water with the humectant and the gelling agent in the formation of the water gel phase.

More specifically, the invention relates to a novel process for the preparation of a cosmetically and chemically stable plaque inhibiting dentifrice mainly consisting of the formation of two phases, an oil gel phase and a water gel phase comprising the following step sequence: a. Dispersing the preparation amount of a quaternary ammonium antiplaque. b. mixture of said dispersion in the formulation betaine surfactant to form the oil gel phase, c. dispersing the formulation nonionic gelling agent in the formulation glycerin and / or sorbitol humectant, 458 586 10 15 20 25 Mixing said gelling-humectant dispersion with the preparation amount of water to form the aqueous gel phase, e. Combining the two gel phases to form a stable parent gel phase, adding the dental abrasive to the water gel phase or to the parent gel phase with mixing, and g. of a stable plaque-inhibiting dentifrice.

The oil gel phase is in the form of a viscous transparent gel.

The water angel phase is transparent. The stable parent gel phase resembles an emulsified system.

This process can be modified by adding and mixing the dental abrasive with the water gel phase and then adding the oil gel phase to the mixture of dental abrasive and water gel phase.

Sodium saccharin and / or a fluorine-containing compound, which are optional preferred additives, are dissolved in the preparation amount of water prior to its addition to the aqueous solvent dispersion and the formation of the aqueous gel phase.

The new formulation method of the present invention using only glycerin and / or sorbitol humectant in a quaternary betaine system provides chemical and cosmetic stability to the dentifrice as well as improved taste. The taste properties of a 20% glycerin or sorbitol humectant containing benzethonium chloride (BTG) betaine dentifrice are intended to be improved over a 20% polyethylene glycol (PEG 600) BTC dentifrice.

The stability provided by the glycerin and / or sorbitol humectant is not obtained with other humectants such as polyethylene glycol. A precipitate was observed in the 20% PEG 600 humectant gel phase of the BTC dentifrice. The precipitate was analyzed by an IR spectrophotometric method and found to consist of BTC, saccharin and betaine.

Fluoride stability studies on the BTC dentifrice confirm that a large part of the MFP loss is due to hydrolysis in the PEG 600 humectant system. Other phenomena (ie absorption or insolubilization) may also be responsible. A solubility problem with PEG 600 and monofluorophosphate (MFP) has been identified. Stability studies for MFP in the BTC dentifrice indicate that hydrolysis of MFP occurs largely in a humectant system consisting of PEG 600 alone. However, the presence of glycerin in the BTC dentifrice alone shows a significantly lesser loss of MFP.

In fact, a glycerin-only humectant system meets the present requirements for MFP sustainability (more than 600 ppm total soluble fluoride, half of which is MFP) while a humectant-only PEG 600-containing system does not meet the requirement (see Table I below ).

Table I MFP stability in BTC dentifrice with 20% PEG 600 humectant system and 20% glycerin humectant system Eg Soluble F IonicF MFP as F Humectant I Qw * I 3w 6w 9w * I 3w 6w Sw * I 3w 6w 9w * PEG 8, 2 10.1 980 660 S70 520 57 289 439 431 920 370 130 Glycerin 7.8 8.3 980 870 790 790 26 55 85 106 950 810 700 680 à w = weeks 4ss sas 10 15 20 25 This table clearly shows MFP's poor stability in a PEG 600 humectant and the very good stability of MFP in a glycerin preparation.

HPLC (High Pressure Liquid Chromatography) analysis on both a glycerin and a sorbitol-BTC dentifrice composition was performed initially and after 9 weeks of accelerated aging at 49 ° C. Two extraction methods for BTC (water and acetone) suggest no reduction in BTC recovery after accelerated aging (see Table II).

Table II HPLC analysis on a glycerin and a sorbitol-BTC dentifrice formulation initially and after 9 weeks of accelerated aeration (49 ° c) Initial analysis Water analysis after aging Acetone water - Acetone Humectant extraction extraction extraction 20% glycerin 0.42 0.54 0.47 0.52 20% sorbitol 0.36 0.48 0.45 0.46 The glycerin and / or sorbitol humectant system constitutes about 1 8 - 23% by weight of the dentifrice composition.

Cationic antibacterial materials are well known in the art, see, for example, the section "Quaternary Ammonium and Related Compounds" ants "in the article" Antiseptics and Dísinfect- in Kirk-Othmer Encyclopedia of Chemical Technology, Second Edition (Vol. 2, pages 632-635). . Cationic materials which possess antibacterial activity (ie they are germicides) have been used against bacteria and have been used in oral compositions to counteract plaque formation causing bacteria in the oral cavity.

Among the most common of these antibacterial antiplaque quaternary ammonium compounds are benzethonium chloride, also known as hyamine 1622 or diisobutylphenoxyethoxyethyldimethylbenzylammonium chloride, and cetylpyridinium chloride. In an oral preparation, this material is highly effective in promoting oral hygiene by reducing the formation of dental plaque and calculus, which is usually accompanied by a reduction in periodontal disease. Other cationic antibacterial agents of this type are mentioned, for example, in U.S. Patent Nos. 2,984,639, 3,325,402, 3,431,208 and 3,703,583 to British Patent 1,319,396.

Other antibacterial plaque inhibiting quaternary ammonium compounds include those in which one or two of the substituents on the quaternary nitrogen have a carbon chain length (typically alkyl group) of 8 to 20, typically 10 to 18 carbon atoms, while the remaining substituents have a lower number of carbon atoms (typically alkyl or benzyl group), such as 1-7 carbon atoms, typically methyl or ethyl groups. Dodecyltrimethylammonium bromide, benzyldimethylstearylammonium chloride, cetylpyridinium chloride and quaternized S-amino-1,3-bis (2-ethylhexyl) -5-methylhexahydropyrimidine are typical quaternary ammonium antibacterial agents.

The dentifrice composition of the present invention contains an effective amount of the plaque inhibiting quaternary ammonium compound, preferably about 0.1 to 1% by weight of the composition.

The ability of the quaternary ammonium compounds to involve the formation of dental plaque is well known. However, they are deactivated by anionic surfactants such as sodium lauryl sulfate conventionally used in dentifrice formulations. The exchange of nonionic surfactants against the anionic surfactants eliminates the deactivation problem but results in products with poor foaming. However, the incorporation of betaine surfactants into dental antiplaque formulations based on quaternary active ingredients unexpectedly improves the foaming of these formulations without inactivating the quaternary antibacterial agents.

The betaine component of the present dentifrice composition has the general formula 'R, 2 + _ R1-§ -R4-C00 Rs in which R1 is an alkyl group having 10 to about 20 carbon atoms, preferably 12 to 16 carbon atoms or the amido radical: OH RcN- (cH2) a 'in which R is an alkyl group having about 10 to 20 carbon atoms and a is an integer from 1 to 3; R 2 and R 3 are each alkyl groups having 1 to 3 carbons and preferably 1 carbon; R 4 is an alkylene or hydroxyalkylene group having 1 to 4 carbon atoms and optionally a hydroxyl group. Typical alkyl dimethyl betaines include decyl betaine or 2- (N--decyl-N, N-dimethylammonio) -acetate, coconut betaine or 2- (N-coconut-N, N-dimethylammonio) -acetate, myristyl betaine, palmityl betaine, lauryl betaine, cetyl betaine etc, stearyl betaine, etc. The amido betaines similarly include coconut amidoethyl betaine, coconut amidopropyl betaine, lauramidopropyl betaine and the like. 10 15 20 25 30 45s (sss 11 The betaines, which are zwitterionic materials, act as a foaming agent in the quaternary agent-containing dentifrice compositions. They act cationically over a wide pH range but do not inactivate the quaternary antimicrobial activity.

In addition to the non-interfering property of the betaines with quaternary activity, laboratory foam tests have shown that preparations containing both the quaternary ammonium compound (quat) and the betaine foam 2-3 times better than the nonionic / quat preparations.

The zwitterionic betaines are fully tolerable with the quaternary antimicrobial antiplaque agents and impart detersive and improved foaming properties to the quaternary agent containing the dentifrice composition without deactivating its antimicrobial properties. The effective amount of betaine in providing improved foaming can be varied from about ß to about 5% by weight of the total formulation. u Cosmetic stability problems occur with all zwitterionic agents containing dentifrices, such as crimp leakage of flavor. The flavor seeps out and is not solubilized in the zwitterionic surfactant. However, stability evaluations of the present novel antiplaque dentifrice containing glycerin and / or sorbitol humectant suggest satisfactory flavor stability during 9 weeks of aging at 49 ° C.

The flavoring ingredient, which is an essential ingredient in a dentifrice, makes up about 0.5 - 2% by weight.

Any suitable flavoring can be used. Examples of suitable flavoring ingredients are flavoring oils, e.g. oils of mint, peppermint, evergreen, sassafras, cloves, sage, eucalyptus, marjoram, cinnamon, lemon and orange, and methyl salicylate. 458 10 15 20 25 30 586 12 A sweetener can also be used as a complement to the flavoring material. Suitable sweeteners are water soluble and include sucrose, lactose, maltose, sorbitol, sodium cyclamate and saccharin in an amount of 0.01 to 0.5% by weight.

Another essential ingredient in the present dentifrice is a gelling agent, which is a nonionic gum, in an amount of about 0.8 to 1.5 weight percent. Large organic anionic molecules such as carboxymethylcellulose have been shown to have the potential to inactivate quaternary antibacterial activity. Thus, hydroxyethylcellulose, which is a nonionic small organic molecule, provides a stable slimy gel in the betaine-quat system of the present invention, and is the preferred gelling agent. Other nonionic gelling agents may be used such as hydroxymethylcellulose and the like.

The fluoride-releasing compounds, which are preferred additional ingredients in the present dentifrice, are characterized by their ability to release fluoride ions into water and by the fact that they do not substantially react at all with other compounds in the dentifrice. These materials include inorganic fluoride salts such as soluble alkali metal, alkaline earth metal and heavy metal salts, for example sodium fluoride, potassium fluoride, ammonium fluoride, lead fluoride, a copper fluoride such as copper (I) fluoride, zinc fluoride, a stannous fluoride such as stannous fluoride or stannous fluoride. , barium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorosirconate, sodium monofluorophosphate, aluminum mono- and difluorophosphate and fluorinated sodium calcium pyrophosphate.

Alkali metal and tin fluorides, such as sodium and stannous fluorides, sodium monofluorophosphate and mixtures thereof are preferred. The amount of the fluoride-releasing compound depends to some extent on the type of compound, its solubility and the dentifrice, but it must be a non-toxic amount.

In a solid oral preparation such as a toothpaste or dental cream, the amount of such a compound which releases a maximum of 1% by weight of the preparation is considered satisfactory.

A suitable minimal amount of such a compound may be used, but it is preferred to utilize a sufficient amount of the compound to release from 0.005% to 1% by weight and preferably about 0.1% by weight of fluoride ion. Typically, in the case of alkali metal fluorides and stannous fluoride component, the component is present in an amount of up to 2% by weight, based on the weight of the preparation. In the case of sodium monofluorophosphate, the compound may be present in an amount of up to 7.6% by weight, more typically 0.76%.

The dentifrice prepared in accordance with the present invention contains conventional water-insoluble polishes or dental abrasives in amounts of about 35-65% by weight of the total formulation. Suitable examples of dental abrasives or polishing materials include sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dihydrated calcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphonium, silicon carbonate, zirconium siliconium, zirconia. The preferred abrasives are alumina-containing abrasives such as calcined alumina and hydrated alumina and mixtures thereof. The abrasive is added to the water gel phase or to the single gel after combining the oil gel and water gel phases.

The dentifrice of the present invention may also contain conventional additional ingredients such as coloring or whitening agents, preservatives and ammonia-treated materials such as monoammonium glycyrrhitzinate.

These additional ingredients can be added to the dentifrice in minimal amounts of up to 5% by weight, and preferably up to 1%, provided that they do not have the anti-plaque and stability properties of the final product. The oil phase typically makes up about 3.6 - 8% by weight of the dentifrice. In the use of the present invention for the promotion of oral hygiene, the dentifrice according to the invention is regularly applied to the tooth enamel by brushing the teeth for 30-90 seconds at least once daily.

The following examples further illustrate the present invention, but of course the invention is not limited thereto. The compositions are prepared in the usual manner and all amounts and proportions set forth herein and also set forth in the claims are by weight unless otherwise indicated.

Example 1 Glycerin humectant containing antiplaguite dentifrice Ingredients Water (deionized) 19.34 Sodium saccharin 0.30 Sodium monofluorophosphate 0.76 Hydroxyethylcellulose 1.10 Glycerin 20.00 Benzetonium chloride 0.50 Flavor content Ammonium oxide Oxydium The benzethonium chloride is dispersed in the flavoring and that dispersion is mixed into the betaine to form an oil gel. The sodium saccharin and sodium monofluorophosphate (MFP) are dissolved in the water. Hydroxyethylcellulose is dispersed in the glycerin and this mixture is added to the water-saccharin MFP solution with stirring to form a water gel. The oil and water gels are mixed to form a stable parent gel. The calcined alumina and hydrated alumina are mixed with the parent gel to form the final dentifrice, which is effective against plaque-related bacteria while exhibiting excellent chemical and cosmetic stability and also possesses sufficient foaming properties. This dentifrice is prepared at room temperature.

Example 2 Example 1 is repeated except that 20% sorbitol replaces the 20% glycerin. The resulting product is equally effective against plaque-related bacteria and also possesses excellent chemical and cosmetic stability and sufficient foaming properties.

MFP stability studies indicate that both the new glycerin and sorbitol dentifrices have an excellent MFP stability profile. Example 1 (20% glycerin) had an initial total soluble fluoride value of 990 ppm and an MFP as an F value of 950 ppm. Example 2 (20% sorbitol) had an initial totally soluble fluoride value and an MFP as an F value of 1,020 ppm and 980 ppm, respectively (see Table III). u 458 see '_' - 10 15 20 25 16 Table III MFP stability profile for a new glycerin-BTC dentifrice and a new sorbito1-BTC dentifrice (9 weeks (w) aging via 49%) on Soluble F Ionic F MFP = as F 2- .._____ H “mek1 = a fl t E. _91”. _ï. is _I_ .L ._I. 221. 1 Glycerin alone 7.8 8.0 990 820 43 94 950 730 2 Sorbitol alone 7.6 7.7 1020 960 43 45 980 910 The pH profiles of the two preparations showed only a slight increase after 9 weeks of age at 49 ° C. After accelerated aging, the values for total soluble fluoride and MFP as F were 820 and 730 ppm for Example 1 and 960 ppm and 910 ppm for Example 2, respectively.

Variations in the above preparations can be made.

For example, other betaines such as lauramidopropyl betaine, coconut betaine and the like may be used in place of the coconut amidopropyl betaine in the examples. Similarly, other abrasives can be used for the specific abrasives in the examples. Likewise, other fluoride-releasing compounds such as sodium fluoride, potassium fluoride, etc. can be used instead of sodium monofluorophosphate in the specific examples. Likewise, cetylpyridinium chloride and other quaternary ammonium antiplaque agents can be used in place of benzethonium chloride.

Sodium cyclamate can also replace sodium saccharin.

It is to be understood that the foregoing detailed description has been given for illustrative purposes only and that variations may be made therein without departing from the invention.

Claims (21)

10 15 20 25 458 586 17 P a t e n t k r a v Chemically and physically stable antiplaquet dentifrice, characterized in that it comprises a quaternary antiplaque ammonium compound, a betaine surfactant, a flavoring agent, a humectant system of glycerin and / or sorbitol and a nonionic gelling agent, prepared by a process comprising the preparation of two separate gel phases, an oil gel phase and an aqueous gel phase, combining said gel phases into a single gel and adding a dental abrasive thereto as a final step, or adding said abrasive to the water gel phase before adding the oil gel phase. Dental preservative according to claim 1, characterized in that the oil gel phase consists of the quaternary anti-plaque ammonium compound, a betaine surfactant and a flavoring agent: and that the water gel phase consists of water, humectant and nonionic gelling agent. k ä n n e t e c k - n a t of a fluorine-containing compound being dissolved in Dental care agent according to claim 2, the preparation amount of water before the addition of the water to the humectant and the gelling agent in the formation of the water-gel phase. Dental care agent according to claim 2 or 3, characterized in that a water-soluble sweetener is dissolved in the preparation amount of water before the addition of the water to the humectant and the gelling agent in the formation of the water gel phase. Dental care product according to claim 4, characterized in that the sweetener is sodium saccharin. 458 586 10 15 20 25 18 Process for the preparation of a cosmetically and chemically stable antiplaquet dentifrice, characterized in that it consists mainly of the formation of two phases, an oil gel phase and an aqueous gel phase, comprising the following step sequence: a. Dispersing the preparation amount of a quaternary ammonium antiplaque agent in the flavoring agent of the formulation, b. mixing said quaternary ammonium flavoring dispersion in the formulation betaine surfactant to form the oil gel phase, mixing said gelling-humectant dispersion with the preparation amount of water to form the water-gel phase, e. combining the two gel phases to form a stable parent gel phase, f. adding the dental abrasive to the water-gel phase or to the parent gel phase while mixing, and g. recovery of a stable antiplaquet dentifrice. Process according to claim 6, characterized in that a water-soluble sweetening material, a fluorine-containing compound or both are dissolved in the preparation amount of water before its addition to the humectant gelling agent dispersion in the formation of the aqueous gel phase. Process according to claim 7, characterized in that said sweetening material is sodium saccharin and that said fluorine-containing compound is sodium monofluorophosphate. Process according to any one of claims 6 to 8, characterized in that said nonionic gelling agent is hydroxyethylcellulose. Dental care product according to claim 1, characterized in that the betaine content constitutes about 3 - 5% by weight of the preparation. Dental care agent according to claim 10, characterized in that the nonionic gelling agent is hydroxyethylcellulose in amounts of about 0.8 - 1.5% by weight. Dental care product according to claim 11, characterized in that it contains about 18 to 23% by weight of glycerin, sorbitol or a mixture thereof as the humectant system. Dental care agent according to claim 1, characterized in that it contains about 35 - 65% by weight of a water-insoluble dental abrasive. Dental care agent according to claim 13, characterized in that the dental abrasive is an alumina-containing abrasive. Dental care agent according to claim 14, characterized in that the antiplaque agent is benzethonium chloride in an amount of about 0.1 - 1% by weight. Dental care agent according to claim 3, characterized in that the fluoride-releasing compound is present in an amount sufficient to release about 0.00S - 1% by weight of fluoride ion into the dental care agent. 10 586 _ 20 Dental care product according to claim 16, characterized in that the fluoride-releasing compound is sodium monofluorophosphate. Dental care product according to claim 10, characterized in that the betaine is coconut amidopropyl betaine. Dental care product according to claim 14, characterized in that the abrasive is a mixture of hydrated alumina and calcined alumina. Dental care product according to claim 2, characterized in that the flavoring substance constitutes about 0.5 - 2% by weight. Dental care products according to claim 5, characterized in that the sodium saccharin constitutes about 0.01 - 0.5% by weight.