GB2090137A - Oral composition - Google Patents

Abstract

A fluorine-free local oral composition, for example, a toothpaste comprising a lower alkyl para-hydroxybenzoate and a mesoinositol phosphate ester or its salt is highly antiseptic even in plastic containers.

Description

SPECIFICATION Oral composition This invention generally relates to oral compositions having improved antiseptic properties and aging stability, and more particularly, the oral compositions comprising a lower alkyl parahydroxybenzoate and a meso-inositol phosphate ester or its salt. The compositions are prepared in paste or liquid forms and are useful as dentifrices, for example, toothpastes and liquid dentifrices, gingival massage creams, topical solutions and pastes, mouthwashes, prophylactic pastes, cavity sealers, dental flosses, densensitizers, gels for ultrasonic treatment, 6r the like.

Oral hygienic products should be free of contamination with bacteria and fungi because of their intended application. Attempts were made to preclude contamination of oral compositions by incorporating various antiseptics or preservatives therein or by severely controlling the raw material quality and manufacturing process.

Such attempts succeeded in manufacturing contamination-free products. Commercial oral products, which are contamination-free immediately after manufacture, are often contaminated with bacteria or the like in the course of commercial distribution or particularly when consumers are using the products. Oral compositions tend to be more easily contaminated when contained in plastic containers than in metal containers such as aluminum tubes. More detailedly, if contaminants are accidentally introduced into a toothpaste container from the environment, plastics containers capable of more or less restoring their shape immediately after the pressure applied to squeeze a desired amount of toothpaste out of the container is released allow aerobic bacteria to grow or propagate easily in their contents or toothpaste as compared with aluminum tubes.Although aerobic bacteria are not pathogenic, the presence of such bacteria in a substantial quantity would have undesired influence on the flavor and stability of toothpaste compositions.

Alkyl para-hydroxybenzoates have been the predominant choice among antiseptics to be incorporated in oral compositions. These alkyl para-hydroxybenzoates, however, are not satisfactorily high in antiseptic activity as demonstrated by experiments to be described later. An increase in the amount of such an ester added is effective to enhance antisepsis, but will impair the taste and stability of oral compositions and, in some cases, will give rise to a safety problem.

It is widely known in the art to blend in oral compositions a fluoride such as stannous flouride, sodium fluoride and an alkali metal salt of monofluorophosphoric acid. Such fluoride-containing oral compositions give rise to no substantial problem with respect to antiseptic properties of fluorine-free oral compositions.

U.S. Patent No. 3,934,002 and British Patent Nos. 1,222,197, 1,384,375 and 1,408,922 disclose the addition of phytic acid compounds or other phosphoric compounds to oral compositions.

However, these oral compositions contain fluorides.

It is an object of the present invention to provide fluorine-free oral compositions which are highly antiseptic and do not allow aerobic bacteria to propagate.

Making extensive investigations to enhance the antiseptic properties of fluorine-free oral compositions, the inventors have discovered that a synergistic antiseptic effect is obtained when a lower alkyl para-hydroxybenzoate is combined with a meso-inositol phosphate ester or its salt such as phytic acid and sodium phytate in oral compositions, and this combination continues to effectively prevent contamination with bacteria even when the oral compositions are actually being used, in spite of no existence of fluorides therein.

According to the present invention, there is provided a fluorine-free oral composition comprising a lower alkyl para-hydroxybenzoate and a meso-inositolphosphate ester or its salt. Lower alky! in this context means C15 alkyl.

The use of a combination of a lower alkyl para-hydroxybenzoate and a meso-inositol phosphate ester or its salt can provide an improved oral composition which is highly antiseptic and is not contaminated with bacteria or does not allow bacteria to propagate although no fluoride is blended in the composition. In addition, since the amount of a lower alkyl para-hydroxybenzoate added can be reduced to a level at which the ester does not adversely affect the taste, aging stability and safeness of the oral composition.When the oral composition of the present invention is contained in a plastic container the contents of which are more susceptible to contamination than in metallic containers (the plastic containers including plastic tubes, laminate tubes comprising a metal foil such as aluminum foil having a plastic coating laminated at least on the inner surface, and plastic bottles), the synergistic antiseptic effect achieved by the lower alkyl para-hydroxybenzoate in combination with the mesoinositol phosphate ensures to prevent the fluorine-free oral composition from being contaminated with bacteria. That is, plastic containers may be advantageously filled with the oral compositions of the present invention .

The above and other objects, features and advantages of this invention will become more apparent and understandable from the following description.

The oral compositions of the present invention may be prepared in paste or liquid forms and used as dentifrices such as toothpastes, liquid dentrifrices and toothpowders, gingival massage creams, topical solutions and pastes, cavity sealers, dental flosses, desensitizers, gels for ultrasonic treatment, or the like. Briefly stated, the oral compositions of the present invention contain a lower alkyl parahydroxy-benzoate in admixture with a meso-inositol phosphate as an antiseptic agent, but not any fluoride.

The lower alkyl para-hydroxybenzoates which can be used in the present invention include methyl para-hydroxybenzoate. The esters ethyl para-hydroxybenzoate, propyl para-hydroxybenzoate, isopropyl para-hydroxybenzoate, butyl para-hydroxybenzoate, and isobutyl pa ra-hydroxybenzoate. The esters may be used alone or in admixture of two or more. The lower alkyl para-hydroxybenzoate may be present in amounts of 0.0001 to 1% by weight of the total weight of the composition. The preferred range is 0.01 to 1% by weight particularly because enhanced antisepsis is obtained and the taste of the composition is not impaired.

The meso-inositol phosphates which can be used in the present invention preferably include meso-inositol pentaphosphate and meso-inositol hexaphosphate which is also known as phytic acid, because the activity depends on the number of phosphate groups esterified with the hydroxyl groups of inositol. The salts of meso-inositol phosphates include sodium salts, potassium salts, ammonium salts, calcium salts, magnesium salts, aluminum salts, barium salts and the like. Particularly preferred are penta- and hexa-sodium salts, penta- and hexa-potassium salts, tetra-calcium salts, penta-magnesium salts and penta-barium salts. Complex salts are also included. The alkali metal salts are most preferred because of their high solubility in water.

These meso-inositol phosphate esters and their salts may be used alone or in admixture of two or more. These esters and salts may be present in amounts of 0.01 to 10% by weight, preferably 0.1 to 5% by weight of the total weight of the oral composition.

The oral composition of this invention may further include other well-known ingredients depending on a particular type of the composition. Differently stated, the oral composition of this invention may be formulated into any desired form of paste and liquid by a conventional preparation method using suitably selected ingredients.

When the oral composition of the present invention forms a dentifrice composition, it may contain generally 10 to 90% by weight of an abrasive, particularly 20 to 60% by weight of an abrasive in the case of toothpastes. The abrasive may be selected from dicalcium phosphate dihydrate and anhydride, calcium carbonate, calcium pyrophosphate, insoluble sodium metaphosphate, calcium sulfate, amorphous silica, crystalline silica, hydrous silicic acid, alumina, aluminum silicate, aluminum hydroxide, microcrystalline cellulose, magnesium tertiary phosphate, magnesium carbonate and synthetic resins, and mixtures thereof.

In preparing paste-type compositions, a binder may be blended generally in an amount of 0.55% by weight, including cellulose derivatives such as sodium carboxymethyl cellulose, sodium carboxymethyl hydroxyethyl cellulose, and hydroxyethyl cellulose, carrageenan, propylene glycol alginate, alkali metal alginates such as sodium alginate, gums such as tragacanth gum, guar gum, karaya gum, gum arabic and xanthan gum, synthetic binding agents such as polyvinyl alcohol, inorganic binding agents such as silica gel, veegum, aluminum silicate gel, coloidal magnesium aluminum silicate, etc. and mixtures thereof.

In oral compositions, a humectant may also be blended generally in an amount of 585%, preferably 1070% by weight, including sorbitol, glycerine, ethylene glycol, propylene glycol, 1,3- butylene glycol, polyethylene glycol, xylitol, maltitol, lactitol, etc. and mixtures thereof.

In oral compositions, also included are anionic surfactants such as water-soluble salts of higher alkyl sulfates having 8 to 1 8 carbon atoms in the alkyl group (e.g., sodium lauryl sulfate and sodium mirystyl sulfate), water-soluble salts of sulfonated monoglycerides of higher fatty acids having 10 to 1 8 carbon atoms in the fatty acid group (e.g., sodium lauryl monoglyceride sulfonate and sodium coconut monoglyceride sulfonate), a-olefine sulfonates, salts of amides of higher fatty acids having 1 2 to 1 8 carbon atoms in the fatty acid group with lower aliphatic amino acids (e.g. sodium-N-methyl-Npalmitoyl tauride, sodium N-lauroyl sarcosinate, sodium N-acyl amino and sodium N-lauroyl- -alanine), soaps, etc.; nonionic surfactants such as alkanoyl diethanol amides (e.g. lauroyl diethanol amide), stearyl monoglyceride, surcose fatty acid esters having 1 2 to 1 8 carbon atoms in the fatty acid group (e.g. sucrose monolaurate and dilaurate), lactose fatty acid esters, lactitol fatty acid esters, maltitol fatty acid esters, condensates of sorbitan monostearate with approximately 60 moles of ethylene glycol condensates of ethylene oxide with propylene oxide, condensates of propylene glycol and their derivatives (e.g. polyoxyethylene polyoxypropylene monolauryl ester), etc.; amphoteric surfactants such as those of betaine and amine acid types, etc., alone or in admixture in an amount of 0-7%, preferably 0.57% by weight; and a sweetener such as sodium saccharin, stevioside, neohesperidin dihydrocalcone, thaumatin, glycyrrhizin, perillartine, p-methoxycinnamic aldehyde, etc. in an amount of 0-5%, preferably 0.015% by weight. Also included are flavors in an amount of 0-5%, preferably 0.1 to 5% by weight, such as spearmint oil and peppermint oil, clove oil, cassia oil, sage oil, coriander oil, anise oil, wintergreen oil, eucalyptus oil, and fruit flavors. Such a natural essential oil may be partially or entirely replaced by a synthetic or isolated flavor, for example, 1-menthol, anethole, carvone, eugenol, etc.

The oral composition of this invention may further include other active ingredients, for example, enzymes such as dextranase, amylase, protease, mutanase, lysozyme chloride, lytic enzyme, bacteriolytic enzyme, etc., sorbic acid, hinokitiol, alkyl glycine, E-aminocaproic acid, tranexamic acid, aluminum chlorohydroxyallantoinate, dihydrocholesterol, glycyrrhetinates, glycerophosphate, sodium chloride, sodium bromide, water-soluble inorganic primary and secondary phosphates, quaternary ammonium compounds, and the like alone or in admixture. Examples of the water-soluble inorganic phosphate are potassium and sodium salts of orthophosphoric acid, pyrophosphoric acid and polyphosphoric acid, while the potassium salts are preferred.

For example, the compositions in the form of paste such as toothpastes may be prepared by kneading the desired ingredients selected from the foregoing ingredients with a proper amount of water or other solvents.

Other types of oral compositions may be prepared in accordance with conventional formulations and methods using a well-known base material. For example, the oral compositions in the form of liquid such as liquid mouthwashes and topical solutions may be prepared by adding any of the abovementioned active ingredients, a sweetener and a flavor to a suitable solvent such as distilled water, ionized water, ethanol, etc. and blending a lower alkyl para-hydroxybenzoate and a meso-inositol phosphate ester or its salt therein. Any type of oral compositions may be prepared by selectively blending any suitable agent depending on the nature of a particular composition.

The oral compositions of the present invention are generally adjusted to pH 2-10 when they are paste or liquid. The pH adjustment may be made by adding an organic acid such as citric acid, tartaric acid, lactic acid, malonic acid, malic acid, L-ascorbic acid, acetic acid, succinic acid, etc. or an alkali metal salt thereof, an inorganic acid, such as hydrochloric acid, phosphoric acid, etc., or a base such as sodium hydroxide so as to give a desired pH value. The pH adjustment may also be achieved by varying the amount of the meso-inositol phosphate ester or its salt blended.

The thus prepared composition may be packed into any desired container including aluminum tubes, laminate tubes comprising an aluminum foil having a plastic coating laminated at least on the inner surface, plastic tubes, bottle-shaped containers and aerosol containers. When the oral composition of the present invention is packed in a plastic container the contents of which are more susceptible to contamination than in metallic containers (the plastic containers including plastic tubes, laminate tubes comprising a metal foil such as aluminum foil having a plastic coating laminated at least on the inner surface, and plastic bottles), the synergistic antiseptic effect achieved by the lower alkyl para-hydroxybenzoate in combination with the meso-inositol phosphate ensures to prevent the fluorinefree oral composition from being contaminated with bacteria.Plastic containers may be advantageously filled with the oral compositions of the present invention.

The plastics container includes a plastics tube formed solely of plastics material, an aluminum foilplastics coating laminate tube which comprises an aluminum foil coated with a plastics layer on an inner or each surface and formed into a tube, and a plastic bottle. Plastic material of the plastic containers may be selected from ethylene-vinyl alcohol copolymer, polyvinylidene chloride, polyvinyl chloride, nylon, polyester, polyethylene, polypropylene, etc.

The following examples are set forth by way of illustration, and not by way of limitation. All percentages are by weight.

EXAMPLES 1-3 and Comparative Examples 1-10 Toothpastes having the following formulation shown in Table 1 were prepared in a conventional manner.

TABLE 1 (% by weight)

Example Comparative Example 1 2 3 1 2 3 4 5 6 7 8 9 10 Dicalcium phosphate dihydrate 50 50 50 50 50 50 50 50 50 50 50 50 50 Sorbltol 20 20 20 20 20 20 20 20 20 20 20 20 20 Sodium carboxy methyl cellulose 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 Sodium lauryl sulfate 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 Flavor 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 Sodium saccharln 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Methyl p-hydroxybenzoate 0.05 0.05 0.05 - 0.05 - - - 0.05 0.05 0.05 - Ethyl p-hydroxybenzoate - - - - - - - - - - - 0.05 0.05 Sodium phytate (40% in water) 0.5 1.0 1.5 - - 0.5 1.0 1.5 - - - - Phosphoric acid - - - - - - - - 0.05 - - - Potassium phosphate - - - - - - - - - 0.5 - - sodium pyrophosphate - - - - - - - - - - 0.5 - Methane diphosphonate - - - - - - - - - - - 1.0 Stannous ethane-1-hydroxy1,1-diphosphonate - - - - - - - - - - - - 0.3 Water Balance Balance Total 100 100 100 100 100 100 100 100 100 100 100 100 100 Aerobic bacteria isolated from a toothpaste in houshold use by carrying out a hygienic test (gramnegative bacteria resistant to sodium lauryl sulfate, and propagated in an agar culture medium containing 1 5% of the toothpaste of Comparatice Example 1) was implanted in each of the above-prepared toothpastes so that the toothpaste contained 107 bacteria per gram. Each of the implanted toothpastes was packed in a plastic tube which is made from three layers, polyethylene, poiyamide and polyethylene layers and stored at a temperature of 320C.

The number of bacteria surviving in the toothpastes was counted by the agar plate culture smear method after storage for 2, 4 and 7 days since the implantation. the results are shown in Table 2.

TABLE 2 Number of Surviving Bacteria/Gram of Toothpaste

Toothpaste Initial 2 Days 4 Days 7 Days Evaluation Example 1 5.05 x 107 6.38 x 104 2.80 x 103 0 ,, 2 2 , 7.13 x 103 0 0 3 3 .. 0 0 Comparative Example 1 .. 4.00 x 107 3.18 x 107 2.35 x 107 ,, 2 2 .. 5.20 x 106 5.33 x 105 1.52 x 105 A 3 3 . 5.32 x 106 6.43 x 105 2.75 x 105 A 4 4 .. 4.78 x 106 5.88 x 105 3.20 x 105 A ,, 5 5 .. 4.44 x 106 4.35 x 105 8.55 x 104 0 6 6 5.61 x 107 3.33 x 106 4.35 x 105 2.10 x 105 A ,, 7 .. 4.80 x 106 2.63 x 105 1.31 x 105 A 8 E 3.51 x 106 3.85 x 105 1.41 x 105 A .. 9 .. 4.12 x 1Q6 6.37 x 109 3.20 x 105 A .. 10 , 5.41 x 106 4.18 x 105 2.01 x 105 A Evaluation was made on the basis of the following criteria.

Number of bacteria Antisepsis more than 106 none # : 105 - 106 slight O : 104 - 105 good # : less than 104 excellent As seen from Table 2, methyl para-hydroxybenzoate and sodium phytate exert a synergistic effect in rendering the toothpastes antiseptic. Particularly, the antiseptic effect becomes outstanding as the amount of sodium phytate is increased.

It has been found that similar effects are obtained when phytic acid, potassium phytate and other water-soluble salts of phytic acid are used instead of sodium phytate.

EXAMPLES 4-9 and Comparative Example 11 Toothpastes having the following formulation were prepared using as the alkyl parahydroxybenzoate methyl pa ra-hydroxybenzoate (Example 4), ethyl pa ra-hydroxybenzoate (Example 5), propyl para-hydroxybenzoate (Example 6), butyl para-hydroxybenzoate (Example 7), isopropyl parahydroxybenzoate (Example 8) and isobutyl para-hydroxybenzoate (Example 9). Plastic tubes made from polyethylene, polyamide and polyethylene layers were filled with these toothpastes, respectively. The number of surviving bacteria was counted by the same method as in Example 1 after storage for the given periods.

Ingredient % by weight Aluminum hydroxide 49 Sorbitol 10 Glycerine 10 Propylene glycol 3 Carrageenan 0.5 Sodium carboxymethyl cellulose 0.6 Flavor 1.0 Sodium saccharin 0.1 Sodium phytate (40% in water) 0.5 Alkyl para-hydroxybenzoate 0.05 Water Balance Total 100.0% A toothpaste having the same formulation was prepared except that the alkyl parahydroxy benzoate was omitted (Comparative Example 11). This toothpaste was also subjected .to the same contamination test as above.

The results are shown in Table 3.

TABLE 3 Number of Surviving Bacteria /Gram of Toothpaste

Toothpaste Initial 2 Days 4 Days 7 Days Evaluation Example 4 6.30 x 107 7.56 x 104 3.00 x 103 0 # " 5 " 6.61 x 104 7.36 x 10 0 # 6 6 .. 7.31 x 104 5.18 # 104 3.66 x 103 # ,, 7 7 .. 7.21 # 104 1.05 X 109 4.86 # 103 8 ,, 5.25 x 104 2.33 x 104 6.25 x 103 # 9 9 , 8.25 x 104 9.82 x 103 3.56 x 103 Comparative Example 11 " 6.25 x 106 7.92 x 105 5.33 x 105 # EXAMPLE 10 and Comparative Example 12 Liquid dentifrices having the following formulation shown in Table 4 were prepared in a conventional manner, and plastic bottles made from polyethylene were filled therewith. The number of surviving bacteria was counted by the same method as in Example 1 after storage for the given periods.

TABLE 4

Comparative Example 10 Example 12 Ingredient Sodium polyacrylate 3.0% 3.0% Glycerine 30.0 30.0 Sodium saccharin 0.1 0.1 Flavor 0.9 0.9 Ethanol 3.0 3.0 Linoleic acid 0.05 0.05 Sodium phytate (40% in water) 0.5 Methyl para-hydroxy benzoate 0.05 Water Balance Balance Total 100.0% 100.0% Surviving bacteria /gram of dentifrice Initial 6.23 x 107 6.23 x 101 2 days 9.80 x 103 8.70 x 105 Evaluation A EXAMPLE 11 and Comparative Example 13 Gingival massage creams having the following formulation shown in Table 5 were prepared and plastic containers made from polyethylene, polyamide and polyethylene layers were filled therewith.

The number of surviving bacteria was counted by the same method as in Example 1 after storage for the given periods.

TABLE 5

Comparative Example 11 Example 13 Ingredient White vaseline 8.0% 8.0% Propylene glycol 4.0 4.0 Dextranase 1.0 1.0 Stearyl alcohol 8.0 8.0 Polyethylene glycol 4000 25.0 25.0 Polyethylene glycol 400 37.0 37.0 Sucrose stearate 0.5 0.5 Sodium phytate (40% in water) 0.5 Methyl para-hydroxybenzoate 0.05 Water Balance Balance Total 100.0% 100.0% Surviving bacteria /gram of cream Initial 8.23 x 107 6.23 x 101 2 days 6.00 x 103 5.92 x 101 Evaluation ~

Claims (8)

1. A fluorine-free oral composition comprising a lower alkyl para-hydroxybenzoate, a meso-inositol phosphate ester or its salt, and an orally acceptable carrier.

2. An oral composition according to claim 1 wherein the lower alkyl para-hydroxybenzoate is selected from the group consisting of methyl para-hydroxybenzoate, ethyl para-hydroxybenzoate, propyl para-hydroxybenzoate, isopropyl para-hydroxybenzoate, butyl para-hydroxybenzoate and isobutyl para .hydroxybenzoate, and mixtures thereof.

3. An oral composition according to claim 1 or 2 wherein the lower alkyl para-hydroxybenzoate is present in an amount of 0.0001 to 1% by weight of the total weight of the composition.

4. An oral composition according to claim 1 wherein the meso-inositol phosphate ester or its salt is selected from the group consisting of meso-inositol pentaphosphate and its salts and meso-inositol hexaphosphate and its salts.

5. An oral composition according to claim 4 wherein the meso-inositol phosphate salt is an alkali metal salt of meso-inositol phosphate.

6. An oral composition according to any preceding claim wherein the meso-inositol phosphate ester or its salt is present in an amount of 0.01 to 10% by weight of the total weight of the composition.

7. An oral composition according to any preceding claim wherein the composition is contained in a plastic container.

8. An oral composition according to claim 1 substantially as shown in any of the Examples.