KR920007830B1 - Stable antiplaque dentifrices - Google Patents

Abstract

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Description

Stable anti-plaque toothpaste and preparation method thereof

The present invention provides an anti-plaque toothpaste with improved foamability, improved taste, solubilized active ingredient, improved fluoride stability, improved compatibility of all ingredients, improved extrusion properties from various containers and increased cost efficiency. It is about formulation.

It has been difficult to produce a cosmetically available anti-plaque toothpaste consisting of a moisturizing system all glycerin or all sorbitol and a quaternary ammonium compound and a betaine surfactant. In addition, the use of a mixture of glycerin / polyethylene glycol or sorbitol / polyethylene glycol provides the lowest cosmetic stability when glycerin or sorbitol is present in at least 10% by weight of the composition. However, extensive solubility tests of various mixtures of ingredients in benzethonium chlorite (BTC) toothpastes have shown that compatible systems of water, BTC, betaine, salts and glycerin are dependent on the order in which these ingredients are added. .

Accordingly, it has been found that stable anti-plaque toothpaste compositions containing quaternary ammonium compounds and betaine surfactants can be made by specific methods using glycerin or sorbitol as moisturizers. An essential feature of this method is that after forming two separate phases, the two phases are subsequently mixed to form a stable system. One of these phases contains an active quaternary component (benzetonium chloride or cetylpyridinium chloride) dissolved in a betaine surfactant (cocamidopropyl betaine) and a flavourant and is called an oily gel phase. The second phase contains water, humectants and nonionic gelling agents such as hydroxyethylcellulose and optionally sodium saccharin and fluorine containing compounds such as sodium monofluorophosphate and is called an aqueous gel phase. The tooth polishing agent can be added to the mixed phase as a final step or to the aqueous gel prior to mixing with the oily gel phase. The final product has improved chemical and cosmetic stability and improved taste.

Conventional preparations of antimicrobial toothpastes containing quaternary ammonium compounds as active substances are known from US Pat. No. 4,118,476 and US Pat. No. 4,188,372, which are moisturizers (glycerine, sorbitol, polyethylene glycol), thickeners (hydro) Consisting of hydroxyethyl cellulose) and a sweetener followed by the addition of an abrasive, a flavourant, an antimicrobial agent, additional water, and finally a colorant (phospho-containing compound or melic acid-containing compound) to the device.

The prior art also discloses methods of stabilizing toothpaste against precipitation and flocculation due to incompatibility with antimicrobial agents and alkali metal carboxyalkyl celluloses, as shown in US Pat. Nos. 3,842,168 and 3,843,779. The former patent adds an antimicrobial agent dissolved in water to a non-aqueous mixture of carboxymethyl cellulose, sodium saccharin, and a moisturizer, followed by the addition of a surfactant to form a gel, followed by the addition of abrasives and flavors. In the latter patent, an antimicrobial agent is added to the mixture of glycerin, water, sodium saccharin, carboxymethyl cellulose and surfactant together with or separately from the surfactant, followed by the addition of abrasives and flavors. The surfactant should be added prior to or concurrent with the addition of the antimicrobial agent to avoid the formation of precipitates in the toothpaste.

However, in the prior art, cosmetically and chemically prepared by a novel method using a specific step sequence containing quaternary ammonium antiprat compound, zwitterionic betaine surfactant, glycerin and / or sorbitol moisturizer and nonionic gelling agent as essential ingredients. No stable anti-plaque toothpaste is known, and this novel method forms two separate gel phases consisting of an oily gel phase consisting of a quaternary ammonium compound, a betaine surfactant and a flavoring agent, and an aqueous gel phase consisting of water, a humectant and a gelling agent. These two gel phases are then mixed into a single parent gel and the tooth polishing agent is added as a final step on the mixed gels or on the aqueous gel prior to the addition of the oily gel phase.

It has now been found that stable anti-plaque toothpaste formulations containing quaternary ammonium compounds and betaine surfactants together with glycerin or solitol as moisturizers can be prepared using the steps of the characteristic sequence, which method is quaternary ammonium May contain separate oily gel phases of compounds, betaines and flavoring agents and separate aqueous gel phases of moisturizers, nonionic gelling agents and water (preferably salts such as sodium saccharin, sodium monofluorophosphate or other fluoride salts) ) And then oily and aqueous gel phases are mixed to form a stable parent gel phase and the final step is to add a tooth polishing agent. This method can be modified by adding the abrasive to the aqueous gel and then adding the oil gel to the aqueous gel-polishing mixture. This toothpaste is manufactured at ambient temperature, ie each step in the overall sequence of steps is carried out at ambient temperature (room temperature).

Therefore, the first object of the present invention is to form two separate gel phases and then mix them to form a stable total gel system, based on the quaternary active ingredient and betaine surfactants, stable compatibility of all components with improved compatibility To make toothpaste.

Another object of the present invention is to provide a cosmetically and chemically stable anti-plaque toothpaste containing glycerin and / or sorbitol as a moisturizing agent compatible with betaine and quaternary active ingredients.

Another object of the present invention is to provide a stable anti-plaque toothpaste containing a nonionic gum such as hydroxy ethylcellulose as a gelling agent to stabilize the betaine-4 system and prevent inactivation of the quaternary active ingredient. To provide.

It is another object of the present invention to provide a cosmetic (physical) and chemically stable anti-plaque toothpaste containing a fluoride providing compound without adversely affecting the cosmetic stability of the toothpaste.

Other objects, advantages and novel features of the invention are 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 will be apparent from the combination or use of particular emphasis on the appended claims.

The above and still further objects of the present invention are quaternary ammonium antiplaque compounds, zwitterionic betaine surfactants, flavoring agents and; The novel and stable antiplaque toothpaste of the present invention consisting of a moisturizing agent selected from the group consisting of glycerin, sorbitol and mixtures thereof and a nonionic gelling agent consists of two separate gel phases, quaternary ammonium antiplaque compounds, betaines and flavoring agents. Forming an oily gel phase and an aqueous gel phase consisting of water, a humectant and a nonionic gelling agent; The two gel phases are combined to form a single gel phase; A tooth polishing agent is prepared at ambient temperature by a method consisting of adding onto the mixed gel described above. The order of addition can be changed by adding a tooth polishing agent on the aqueous gel before combining with the oily gel phase. However, it is essential to prepare two separate gel phases prior to the addition step. The addition of salts, such as fluorine-containing compounds and / or sodium saccharin, which are preferred components, is achieved by dissolving water in the prescribed amount of water before mixing with a moisturizer and gelling agent in forming the aqueous gel phase.

More specifically, the present invention relates to a novel method for preparing a cosmetic and chemically stable anti-plaque toothpaste consisting essentially of the formation of two phases, an oily gel phase and an aqueous gel phase.

(a) dispersing the prescribed amount of quaternary ammonium antiplaque compound in the prescribed amount of flavoring agent, and (b) mixing the quaternary ammonium-flavor dispersion with the prescribed amount of betaine surfactant to give an oily Forming a gel phase, (c) dispensing the prescribed amount of nonionic gelling agent in the prescribed amount of glycerin and / or sorbitol moisturizing agent, and (d) mixing the gelling agent-humidifying agent dispersion described above with the prescribed amount of water Form an aqueous gel phase, (e) mix the two gel phases to form a stable parent gel phase, (f) add a tooth polishing agent to the mother gel or aqueous gel phase while mixing, and (g) a stable antiplaque toothpaste Recover.

The oily gel phase is in the form of a viscous translucent gel. The aqueous gel phase is transparent. The stable parent gel phase is similar to the emulsified system.

The present invention can be modified by adding a tooth polishing agent to the aqueous gel and then mixing the oily gel phase to a mixture of the tooth polishing agent and the aqueous gel phase.

Any preferred additive, sodium saccharin and / or fluorine-containing compound, is added to the moisturizer-gelling agent dispersion and dissolved in the prescribed amount of water prior to forming the aqueous gel phase.

The novel formulations of the present invention using only glycerin and / or sorbitol moisturizers in the quaternary-betaine system not only provide chemical cosmetic stability of the toothpaste but also provide improved taste. Benzetonium chloride (BTC) and betaine toothpaste containing 20% glycerin or sorbitol moisturizer have improved taste characteristics compared to 20% polyethylene glycol (PEG 600) BTC toothpaste. The stability obtained with glycerin and / or sorbitol moisturizers does not extend to other moisturizers such as polyethylene glycol. Precipitation was observed on 20% PEG600 moisturizer gel of BTC toothpaste. The precipitate was analyzed by I. R. spectroscopy and found to consist of BTC, saccharin and betaine.

In the fluoride stability test for BTC toothpaste, most of the MFP loss was found to be due to hydrolysis in the entire PEG600 humectant system. Other shapes (ie adsorption or insolubilization) may of course be responsible.

Solubility problems with PEG600 and monofluorophosphate (MFP) were observed. Stability testing of MFP in BTC toothpaste showed that hydrolysis of MFP occurs to a significant extent in all moisturizer systems of PEG600. However, the glycerin moisturizer system in all BTC toothpastes showed much less MFP loss. In fact, all glycerin moisturizer systems meet the MFP shelf life requirements (more than 600 ppm total soluble fluoride, half of which are MFP), but not all moisturizer systems made of PEG600 (see Table 1 below).

TABLE 1

* W = week

It can be seen from the table that the stability of MFP is inferior in all PEG600 humectants and that MFP is very good in pure glycerin formulations.

HPLC (high pressure liquid chromatography) analysis was performed on both glycerin and sorbitol BTC toothpaste initially and after 9 weeks of accelerated aging at 49 ° C. Extraction of BTC by two extraction methods (water and acetone) did not show a decrease in BTC recovery after accelerated aging (see Table 2).

TABLE 2

The glycerin and / or sorbitol humectant system makes up about 18-23% by weight of the toothpaste composition.

Cationic antimicrobials are well known in the art (eg, section on “Quarterium Ammonium and Related Compounds” in the article on “Preservatives and Disinfectants” in Kirk-Othmer Encyclopedia fo Chemical Technology, 2nd edition (Vol. 2, pp. 1)). 632-635) Cationic materials (eg, fungicides) with antimicrobial activity have been used in oral compositions that counteract the formation of plaques caused by bacteria in the oral cavity because they resist bacteria.

The most common of these antibacterial antiplaque quaternary ammonium compounds are benzetonium chloride (also known as Hyamine 1622) or diisobutylphenoxyethoxymethyl diethylbenzylammonium chloride and cetylpyridinium chloride.

In oral preparations, this material is very effective in promoting oral hygiene by reducing the formation of dental plaque and tartar, thereby entailing a reduction of the periodontal membrane disease. Other types of cationic antimicrobials are those mentioned in, for example, US Pat. Nos. 2,984,639, 3,325,402, 3,431,208 and 3,703,583 and British Patent No. 1,319,396.

In other antimicrobial antiplaque quaternary ammonium compounds, one or two of the substituents on the quaternary nitrogen have a carbon chain length (usually an alkyl group) of 8-20, typically 10-18 carbons, while the remaining substituents are ethyl or Examples include methyls having 1 to 7 carbon atoms, such as alkyl or benzyl groups. Dodecyltrimethylammonium bromide, benzyldimethylstearyl ammonium chloride, cetylpyridinium chloride and quaternized 5-amino-1,3-bis (2-ethylhexyl-5-methylhexahydro-pyrimidine are typical quaternary ammonium antimicrobials to be.

The toothpaste composition of the present invention contains an antiplaque quaternary ammonium compound in an effective amount, preferably in an amount corresponding to about 0.1-1% by weight of the composition.

The ability of quaternary ammonium compounds to inhibit tooth plaque production is already known. However, they are inactivated by anionic surfactants such as sodium lauryl sulfate commonly used in dentifrice compositions. Substitution of the anionic surfactant with a nonionic surfactant eliminates the problem of inactivation, but results in an inferior foam product. However, incorporation of betaine surfactant into anti-Praq tooth preparations based on quaternary active ingredients unexpectedly improved the foaming properties of these preparations without causing inactivation of the quaternary antimicrobial agents.

The betaine component of the toothpaste composition of the present invention has the following general structure:

의 아미도라디칼이며(여기서 R은 C_10-20알킬기이며, a는 1-3의 정수이다), R₂및 R₃는 각기 C_1-3, 바람직하게는 C₁의 알킬기이며; R₄는 C_1-4알킬렌 또는 하이드록시 알킬렌기 및 임의로 하이드록실기이다. 전형적인 알킬 디메틸베타인에는 데실베타인 또는 2-(N-데실-N,N-디메틸암모니오)아세테이트, 코코베타인 또는 2-(N-코코-N,N-디메틸암모니오)아세테이트, 미리스틸 베타인, 팔미틸베타인, 라우릴베타인, 세틸베타인, 스테아릴베타인 등이 포함된다. 아미도베타인에는 코코 아미도 에틸베타인, 코코아미도 프로필베타인, 라우르아미도 프로필베타인 같은 것이 포함된다.Wherein R ₁ is C _10-20 , preferably C _12-16 alkyl group or structure

Amidoradical wherein R is a C _10-20 alkyl group, a is an integer of 1-3, and R ₂ and R ₃ are each an alkyl group of C _1-3 , preferably C ₁ ; R ₄ is a C _1-4 alkylene or hydroxy alkylene group and optionally a hydroxyl group. Typical alkyl dimethylbetaines include decylbetaine or 2- (N-decyl-N, N-dimethylammonio) acetate, cocobetaine or 2- (N-coco-N, N-dimethylammonio) acetate, myristyl beta Phosphorus, palmitybetaine, laurylbetaine, cetylbetaine, stearylbetaine and the like. Amidobetaines include such things as coco amido ethylbetaine, cocoamido propylbetaine, and lauramido propylbetaine.

Betaine, a zwitterionic material, acts as a foam in quaternary-containing toothpaste compositions. They act as cations over a wide pH range and do not inactivate quaternary antimicrobial activity.

In addition to betaine's incoherence in quaternary compound activity, in-lab foam tests showed that quaternary ammonium compounds (quat) and betaine-containing compositions were 2-3 times more than nonionic / quaternary ammonium compounds. Good bubble.

Zwitterionic betaines can be fully compatible with quaternary antimicrobial antiplaque agents and impart improved foaming and detergency to the quaternary-containing toothpaste compositions without inactivating their antimicrobial properties. The amount of betaine effective in improved foaming varies from about 3-5% by weight of the total composition.

Cosmetic stability issues, such as flavoring crimp leakage, occur with all zwitterion-containing toothpastes. The flavourant counts out and does not dissolve in zwitterionic surfactants. However, the stability evaluation of the novel anti-plaque toothpaste of the present invention containing glycerin and / or sorbitol moisturizer showed satisfactory flavor stability after aging for 9 weeks at 49 ° C. The flavor component, which is an essential component of toothpaste, constitutes about 0.5-2% by weight of the toothpaste. Any suitable flavoring agent may be used. Examples of suitable flavoring ingredients include flavor oils such as spearmint oil, peppermint oil, gingko oil, sasapras oil, clover oil, sage oil, eucalyptus oil, marjoram oil, cinnamon oil, lemon oil and orange oil and methyl salicylate .

Sweeteners can also be used as a supplement to flavors. Suitable sweeteners are water soluble, including sucrose, lactose, maltose, sorbitol, sodium cyclate and saccharin and are used in amounts of 0.01-0.5% by weight.

Another essential ingredient in the toothpaste of the present invention is a gelling agent which is a nonionic gum, which is present in an amount of about 0.8-1.5% by weight.

Large organic anion molecules, such as carboxymethylcellulose, for example, have been found to be capable of inactivating quaternary antimicrobial activity. Thus, hydroxyethylcellulose, which is a small nonionic organic molecule, forms a stable mucogel in the betaine--4-class system of the present invention, which is a preferred gelling agent. Other nonionic gelling agents can also be used, such as hydroxymethylcellulose and the like.

Another preferred component of the toothpaste of the present invention is the fluoride-providing compound, which is characterized in that it releases fluoride ions in water and does not substantially react with other compounds in the toothpaste. Among these materials are inorganic fluoride salts such as soluble alkali metals, alkaline earth metals and heavy metal salts such as sodium fluoride, potassium fluoride, ammonium fluoride, lead fluoride, copper fluoride such as cuprous fluoride, zinc fluoride, tin fluoride or tin chloro fluoride. Such as tin fluoride, barium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorosiliconate, sodium monofluorophosphate, aluminum mono- and di-fluorophosphate and sodium fluoride calcium pyrophosphate. Alkali metals and tin fluorides such as sodium fluoride and tin fluoride, sodium monofluorophosphate and mixtures thereof are preferred.

The amount of fluoride-providing compound will vary to some extent depending on the type of compound, solubility and toothpaste, but should be non-toxic. The amount of fluoride-providing compounds in solid oral formulations, such as tooth pastes or dental creams, for example, is quite satisfactory if one can release up to 1% by weight of the formulation. Such compounds may be used in modest amounts, but it is preferred to use enough compounds to release 0.005-1%, preferably about 0.1%, of fluoride ions. Typically in alkali metal fluorides and stannous fluoride this component is present in an amount of up to weight percent based on the weight of the formulation. For sodium monofluorophosphate the compound may be present in amounts up to 7.6% by weight, usually 0.76%.

Toothpastes prepared according to the present invention contain conventional water-insoluble polishes or tooth polishing agents in amounts of about 35-65% by weight of the total composition. Suitable examples of tooth polishes or polishes include sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, calcium phosphate dihydrate, dicalcium phosphate anhydrous, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, calcium carbonate, calcium nitrate, silica, Bentonite and mixtures thereof. Preferred abrasives include alumina containing abrasives such as calcined alumina and hydrated alumina and mixtures thereof. The abrasive is mixed with the oily gel phase and the aqueous gel phase and then added to the single gel or onto the aqueous gel phase.

The toothpaste of the present invention may contain conventional additives such as colorants or whitening agents, preservatives and ammonialation materials such as monoammonium glycylinate. These additives may be added to the toothpaste in minimum amounts of up to 5% by weight, preferably up to 1%, so long as they do not interfere with the foam, anti-fragility and stability of the finished product. The oil phase usually comprises about 3.6-8% by weight of the toothpaste.

In the practice of the present invention for promoting oral hygiene, the toothpaste according to the present invention is regularly used in tooth enamel by brushing the teeth for 30-90 seconds at least once a day.

The following examples are intended to illustrate the invention, but the invention is not limited thereto. The compositions are prepared by conventional methods and all amounts and proportions herein and in the claims are by weight unless otherwise noted.

Example 1

Glycerin Moisturizer Antiplaque Toothpaste

Benzetonium chloride was dispersed in the flavoring agent and then the dispersion was mixed with betanin to form an oily gel. Sodium saccharin and sodium monofluorophosphate (MFP) were dissolved in water. Hydroxyethylcellulose was dispersed in glycerin and the mixture was stirred and added to the water-saccharin-MFP solution to form an aqueous gel. The oily gel and the aqueous gel were mixed to form a stable mother gel. Calcined alumina and hydrated alumina were mixed with the mother gel to obtain toothpaste products having effective chemical cosmetic stability and sufficient foaming properties against plaque-related bacteria. This toothpaste was prepared at room temperature.

Example 2

The procedure of Example 1 was repeated except that 20% sorbitol was used instead of 20% glycerin. The resulting product has an equivalent effect on plaque associated bacteria and has excellent chemical and cosmetic stability and sufficient foaming.

MFP stability studies have shown that both new glycerin and sorbitol toothpastes have excellent MFP stability. Example 1 (20% glycerin) had an initial total soluble fluoride concentration of 990 ppm and an MFP concentration of 950 ppm. Example 2 (20% sorbitol) had an initial total soluble fluoride concentration and MFP concentrations as F 1020 ppm and 980 ppm, respectively (see Table 3).

TABLE 3

The pH of both compositions only rose slightly after aging at 490 ° C. for 9 weeks. After accelerated aging, the total soluble fluoride concentration and MFP concentrations as F were 820 ppm and 730 ppm in Example 1 and 960 ppm and 910 ppm in Example 2, respectively.

Modifications may also be made to the above compositions. For example, other embodiments may use other betaines such as lauamidopropyl betaine, coco betaine instead of cocoamidopropyl betaine. Similarly, embodiments may use other abrasives instead of specific abrasives. Likewise, in certain embodiments other fluorine-containing compounds such as sodium fluoride, potassium fluoride and the like may be used instead of sodium monofluorophosphate. Similarly, cetylpyridinium chloride or other quaternary ammonium antiplaque agents may be used in place of benzetonium chloride. Sodium saccharin can also be substituted with sodium cyclomate.

It is to be understood that various changes may be made without departing from the spirit of the invention as the above detailed description has been given for purposes of illustration only.

Claims (21)

After preparing two separate gel phases, an oily gel phase and an aqueous gel phase, the gel phases are mixed into a single gel, and the abrasive is added to the aqueous gel prior to adding the tooth polishing agent or the oily gel phase as a final step. Chemically stable anti-plaque toothpaste consisting of an anti-Praque quaternary ammonium compound, a betaine surfactant, a flavourant, a moisturizer system of glycerin and / or sorbitol, and a nonionic gelling agent, prepared by a method consisting of . The toothpaste of claim 1 wherein the oily gel phase is comprised of a quaternary ammonium antiplaque compound, a betaine surfactant, and a flavoring agent, and the aqueous gel phase is comprised of water, a moisturizer, and a nonionic gelling agent. The toothpaste of claim 2 wherein the fluorine-containing compound is dissolved in a prescribed amount of water prior to the addition of water to the moisturizer and gelling agent upon formation of the aqueous gel phase. The toothpaste according to claim 2 or 3, wherein the water-soluble sweetener is dissolved in the prescribed amount of water prior to the addition of water to the moisturizer and gelling agent when forming the aqueous gel phase. The toothpaste of claim 4, wherein the sweetener is sodium saccharin. a. Disperse the prescribed amount of quaternary ammonium antiplaque in the prescribed amount of flavor, and b. Mixing the quaternary ammonium-flavor dispersion with a prescribed amount of betaine surfactant to form an oily gel phase, c. Disperse the prescribed amount of nonionic gelling agent in the prescribed amount of glycerin and / or sorbitol humectant, d. The gelling agent-humidifier dispersion is mixed with a prescribed amount of water to form an aqueous gel phase, e. Two gel phases are mixed to form a stable parent gel phase, f. Add the tooth polishing agent onto the mother gel with mixing or onto the aqueous gel, g. Preparation of cosmetic and chemically stable antiplaque toothpaste consisting essentially of two phases, the formation of an oily gel phase and an aqueous gel phase, comprising the steps of recovering a stable antiplaque toothpaste. The method of claim 6, wherein upon forming the aqueous gel phase, a water soluble sweetener, fluorine-containing compound, or both, are dissolved in the prescribed amount of water prior to addition to the moisturizer-gelling agent dispersion. 8. The method of claim 7, wherein said sweetener is sodium saccharin and said fluorine-containing compound is sodium monofluoro phosphate. The method according to any one of claims 6 to 8, wherein the nonionic gelling agent is hydroxyethylcellulose. The toothpaste of claim 1, wherein the betaine content comprises about 3-5% by weight of the composition. 11. The toothpaste of claim 10, wherein the nonionic gelling agent is hydroxyethyl cellulose and is present in an amount of about 0.8-1.5% by weight. 12. The toothpaste of claim 11, wherein the moisturizer system contains about 18-23 weight percent glycerin, sorbitol, or mixtures thereof. 10. The toothpaste of claim 1, wherein the toothpaste contains about 35-65% by weight of a water insoluble tooth polishing agent. The toothpaste of claim 13, wherein the tooth polishing agent is an alumina containing abrasive. 15. The toothpaste of claim 14, wherein the antiplaque agent is benzetonium chloride and is present in an amount of about 0.1-1% by weight. 4. The toothpaste of claim 3, wherein the fluoride providing compound is present in the toothpaste in an amount sufficient to release about 0.005-1% by weight of fluoride ion. The toothpaste of claim 16 wherein the fluoride providing compound is sodium monofluorophosphate. 11. The toothpaste of claim 10, wherein the betaine is cocoamidopropyl betaine. 15. The toothpaste of claim 14, wherein the abrasive is a mixture of hydrated alumina and calcined alumina. The toothpaste of claim 2, wherein the flavoring comprises about 0.5-2% by weight. 6. The toothpaste of claim 5, wherein sodium saccharin comprises about 0.01-0.5% by weight.