ORAL COMPOSITIONS

Abstract: Oral compositions comprising tranexamic acid or its salt and an aldehyde flavor such as citral, trans-2-hexenal and trans-2-octenal are improved in taste and discoloration by blending menthone, isomenthone or pulegone therein.

Description: This invention relates to an oral composition having tranexamic acid and/or a salt thereof blended therein, and more particularly, to such an oral composition whose bitter and pungent tastes due to the inclusion of tranexamic acid and its salt are mitigated to provide a pleasant feel in use and which experiences controlled coloring during an extended period of storage and thus exhibits excellent shelf stability. It is well known in the art to blend tranexamic acid or its salts in oral compositions, typically dentifrices,as an active ingredient effective for preventing paradental diseases. Oral compositions having tranexamic acid or its salts blended therein, however, taste bitter and hot or pungent and will be undesirably colored during an extended period of shelf storage. In UK Patent No. 207309 by the same applicant as the present invention, it was proposed to mitigate the bitter taste of tranexamic acid-containing oral compositions by blending carvone therein. It was also disclosed that the shelf stability of tranexamic acid-containing oral compositions is improved by blending carvone in combination with l-menthol. It is believed that discoloration of oral compositions having tranexamic acid or its salts blended therein is caused by reaction of tranexamic acid or its salts with an aldehyde group in a flavor (see Japanese Patent Publication No. 55-5484 and Japanese Patent Application Laid-Open No. 56-122308). The same applicant as the present invention proposed to blend a specific aldehyde flavor in an oral composition having tranexamic acid or its salts blended therein (see UK Patent No. 2122491), based on the discovery that the specific aldehyde flavor is effective in preventing discoloration of the oral composition having tranexamic acid or its salts blended therein. However, it is sometimes desired to blend in oral compositions aldehyde flavors which would probably cause discoloration of tranexamic acid-containing oral composition, for example, citral, atrans-2-hexenal, and trans-2-octenal because the aldehyde flavors impart a more pleasant feel to the oral compositions. It is thus needed to prevent discoloration of oral compositions having such aldehyde flavors blended therein along with tranexamic acid and its salts and to control the bitter and pungent tastes characteristic of tranexamic acid and its salts. A primary object of the present invention is to provide a novel and improved oral composition having tranexamic acid and/or a salt thereof blended therein, which tastes less bitter or pungent, thus giving a pleasant feel in use, and experiences controlled coloring during an extended period of storage, thus possessing excellent shelf stability. Continuing our investigations to improve the feel and shelf stability of oral compositions having tranexamic acid or its salts blended therein and to prevent discoloration of such tranexamic acid-containing oral compositions having incorporated therein aldehyde flavors probably causing discoloration of tranexamic acid or its salts, for example, citral, tans-2-hexenal, and trans-2-octenal, we have discovered that menthone, isomethone and pulegone have the unique effect of improving the inherent bitter and pungent tastes of oral compositions having tranexamic acid or its salts blended therein, and prohibiting discoloration of the tranexamic acid-containing oral compositions having incorporated therein an aldehyde flavor which will otherwise cause discoloration of such compositions. As previously described, carvone can improve the bitter taste due to tranexamic acid or its salts, but cannot prevent discoloration of tranexamic acid or its salts when used alone. Combination of carvone with l-menthol provides a synergistic effect of preventing discoloration. Without any assisting agent, menthone, isomenthone and pulegone can mitigate the bitter and pungent tastes of tranexamic acid or its salts to impart a favorable feel in use, and have such a specific interaction with an aldehyde flavor including citral, trans-2-hexenal and trans-2-octenal as to cause no discoloration of tranexamic acid-containing oral compositions even when they contain any of these aldehyde flavors which will otherwise cause discoloration of such composition. By formulating menthone, isomenthone or pulegone having such improved discoloration control, it is possible to blend any aldehyde flavors which may cause discoloration in tranexamic acid-containing oral compositions without any problem or rather with an improved feel in use. Therefore, the present invention provides an oral composition comprising tranexamic acid and/or a salt thereof, an aldehyde flavor, and at least one cyclic ketone selected from the group consisting of menthone, isomenthone, and pulegone. The amount of tranexamic acid and/or a salt thereof blended in the oral composition preferably ranges from 0.01 to 5%, more preferably from 0.01 to 1% by weight of the total weight of the composition. The aldehyde flavor used in the invention is selected from aldehyde flavors which would probably cause discoloration of tranexamic acid-containing oral compositions. Examples of such aldehyde flavors include citral, trans-2-hexenal, trans-2-octenal, and trans-2-pentenal. The flavors may be used alone or in combination of two or more. A compatible aldehyde flavor which would not cause discoloration of tranexamic acid-containing oral compositions as disclosed in UK Patent No. 207309 may also be blended. The amount of the aldehyde flavor blended in the oral composition preferably ranges from 0.001 to 10%, more preferably from 0.005 to 5% by weight of the total weight of the composition for the purpose of imparting a pleasant feel. In addition to the above-mentioned flavors, the oral compositions of the present invention may further contain other flavors such as carvone, l-menthol, anethole, methyl salicylate, etc. alone or in admixture of two or more. According to the present invention, a specific cyclic ketone selected from menthone, isomenthone and pulegone is blended in the oral composition in order to mitigate the bitter and pungent tastes inherent to tranexamic acid or its salts and to prevent discoloration of the composition which is otherwise caused by the aldehyde flavor. The amount of the cyclic ketone blended in the oral composition preferably ranges from 0.0001 to 1%, more preferably from 0.001 to 0.1% by weight of the total weight of the composition. The oral compositions according to the present invention encompass a variety of oral compositions, for example, dentifrices such as toothpaste, tooth powder and liquid dentifrice, liquid oral refreshers such as mouthwash, and solid oral refreshers such as troches, chewing gums and oral pastes. In addition to the above-mentioned ingredients, any suitable ingredients may be selected and blended in the oral compositions of the present invention depending on their type. More specifically, for dentifrices, abrasives may be blended in an amount of 20 to 90% by weight (for toothpastes, 20 to 60% by weight), including dicalcium phosphate dihydrate and anhydride, calcium primary phosphate, calcium tertiary phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, silicic anhydride, silica, silica gel, aluminosilicate, aluminum silicate, insoluble sodium metaphosphate, magnesium tertiary phosphate, magnesium carbonate, calcium sulfate, polymethyl methacrylate, bentonite, zirconium silicate and mixtures thereof. For pasty compositions, for example, toothpastes, a binder may be blended in an amount of 0.3 to 5% by weight, including synthetic binders such as carrageenan, cellulose derivatives such as sodium carboxymethylcellulose, methyl cellulose, hydroxyethylcellulose, sodium carboxymethylhydroxyethylcellulose, alkali metal alginates such as sodium alginate, propylene glycol alginate, gums such as xanthane gum, tragacanth gum, karaya gum and gum arabic, polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, polyvinyl pyrrolidone, and inorganic binders such as silica gel, aluminum silicate gel, veegum, laponite and mixtures thereof. In preparing pasty and liquid oral compositions such as toothpastes and mouthwashes, a humectant may be blended in an amount of 10 to 70% by weight, including sorbitol, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylitol, maltitol and lactitol and mixtures thereof. There may also be included anionic surfactants such as water-soluble salts of higher alkyl sulfates (e.g., sodium lauryl sulfate), sodium salts of higher fatty acids, water-soluble salts of sulfonated monoglycerides of higher fatty acids having 10 to 18 carbon atoms in the fatty acid group (e.g., sodium lauryl monoglyceride sulfonate and sodium coconut monoglyceride sulfonate), higher fatty acid sodium monoglyceride monosulfates, olefin sulfonates, paraffin sulfonates; nonionic surfactants such as fatty acid mono- and di-ethanol amides (e.g., lauroyl mono- and diethanol amides), stearyl monoglyceride, sucrose fatty acid esters having 12 to 18 carbon atoms in the fatty acid group (e.g., sucrose mono laurate and dilaurate), lactose fatty acid esters, lactitol fatty acid esters, maltitol fatty acid esters, stearic acid monoglyceride, polyoxyethylene sorbitan monolaurate, polyoxyethylene-hardened castor oil, condensates of sorbitan monostearate with approximately 60 moles of ethylene glycol, condensates of ethylene oxide with propylene oxide and their derivatives (e.g., polyoxyethylene polyoxypropylene monolauryl ester); and amphoteric surfactants such as those of betaine type alone or in admixture of two or more in an amount of 0 to 10% by weight, preferably 0.1 to 5% by weight. Also includable in the oral compositions according to the present invention are sweeteners such as sodium saccharin, stevioside, neohesperidin dihydrocalcone, glycyrrhizin, perillartin, thaumatin, fructose and sodium cyclamate in an amount of 0 to 1% by weight, preferably 0.01 to 0.5% by weight; an antiseptic agent such as p-hydroxymethylbenzoic acid, p-hydroxyethylbenzoic acid, p-hydroxypropyl benzoic acid, p-hydroxybutylbenzoic acid, sodium benzoate and lower fatty acid monoglycerides; titanium dioxide, ethanol, liquid paraffin, coloring matter, and other additives. For example, toothpastes may be prepared by kneading the desired ingredients selected from the foregoing ingredients with a proper amount of water. Other types of oral compositions may also be prepared in a conventional manner by selecting commonly used ingredients for the respective types. In this case, the pH of pasty and liquid oral compositions generally falls in the range of from 5 to 10 although not particularly limited thereto. In the practice of the invention, one or more active ingredients may also be blended. Antiphonal agentshave already been mentioned. Others may include, for example, alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, chlorohexidine salts, aluminum chlorohydroxylallantoin, dihydrocholesterol, glycyrrhizin salts, glycyrrhetinic acid, glycerophosphate, chlorophyll, sodium chloride, caropeptide, quaternary ammonium compounds and water-soluble inorganic phosphoric acid compounds. Because of having menthone, isomenthone or pulegone blended therein, the oral compositions of the present invention exhibit minimized bitter and pungent tastes due to tranexamic acid or its salts and minimized discoloration due to an aldehyde flavor which will otherwise cause discoloration of the oral composition, thus having a more pleasant feel in use and an extended shelf stability. In the present disclosure, all parts and percents are by weight unless otherwise stated. Several experiments are given below to demonstrate the effectiveness of the present invention. Experiment 1 Mouthwashes having the following composition were prepared. Mouthwash composition % by weight Tranexamic acid 0.1 85% Glycerin 10 Ethanol 10 Polyoxyethylene (60) hardened castor oil 1 Saccharin sodium 0.05 l-Menthol 0.2 Cyclic ketone shown in Table 1 0.2 Water balance 100.0% The mouthwashes were subjected to a sensory tests as to bitter and hot tastes. Using a panel of ten specialists, evaluation was made by examining the taste of samples into the following five grades, and classifying the average according to the following criterion. The results are shown in Table 1. Grade The following five grades were given in comparison with a control mouthwash, that is, mouthwash having the same composition as above except that the flavor shown in Table 1 was omitted. 5: markedly improved 4: improved 3: somewhat improved 2: not improved 1: rather worse Criterion E: averaging between 5 and 4 G: averaging between 4 and 3 F: averaging between 3 and 2 B: averaging between 2 and 1 Flavor Bitter Hot Menthone E G Isomenthone E G Piperitone E G Pulegone E G Piperitenone G F Cis-jasmone E G 3-Methylcyclohexanone G F Cryptone G G Acetophenone G F Camphor G G Anisylacetone F F β-Methylionone B F As seen from the data of Table 1, particularly menthone, isomenthone, piperitone, pulegone, and cis-jasmone make a noticeable improvement in the bitter and hot tastes of tranexamic acid-containing oral compositions. Experiment 2 Mouthwashes having the following composition, that is, having blended the cyclic ketone shown in Table 2, were prepared. Mouthwash composition % by weight Tranexamic acid 0.2 85% Glycerin 12.0 Ethanol 12.0 Polyoxyethylene (60) hardened castor oil 4.5 Saccharin sodium 0.5 Citral 0.4 Cyclic ketone shown in Table 2 0.4 Water balance 100.0% The mouthwashes were charged in transparent glass bottles and shelf stored for 5 days at 50°C whereupon they were evaluated for discoloration. Evaluation was made in comparison with a control mouthwash, that is, mouthwash having the same composition as above except that the cyclic ketone shown in Table 2 was omitted. The results are shown in Table 2. Samples with "NO" are those samples exhibiting controlled discoloration. Flavor Discoloration Menthone NO Isomenthone NO Piperitone Discolored Pulegone NO Piperitenone Discolored Cis-jasmone Discolored 3-Methylcyclohexanone Discolored Cryptone Discolored Acetophenone No Camphor NO Anisylacetone NO As seen from the data of Table 2, menthone, isomenthone, pulegone, acetophenone, camphor, and anisyl acetone are effective in controlling discoloration due to blending of citral. From the combined results of Experiments 1 and 2, menthone, isomenthone and pulegone are recognized as outstandingly mitigating the bitter and hot tastes of tranexamic acid and controlling discoloration of tranexamic acid-containing oral compositions which is otherwise caused by blending of citral. Experiment 3 There were prepared mouthwashes having the same composition as shown in Experiment 2 except that 0.4% of menthone as the cyclic ketone and aldehyde flavors shown in Table 3 were blended. The mouthwashes were examined for discoloration by the same procedure as in Experiment 2. The results are shown in Table 3. Aldehyde flavor Discoloration Citral NO Trans-2-hexenal NO Trans-2-octenal NO As seen from the data of Table 3, menthone makes such a specific interaction with citral, trans-2-hexenal and trans-2-octenal as to control discoloration of tranexamic acid-containing oral compositions which is otherwise caused by blending of these aldehyde flavors. Similar results were obtained with isomenthone and pulegone used instead of menthone. Examples of the present invention are given below by way of illustration and not by way of limitation. Example 1: Toothpaste Ingredient % by weight Silicic anhydride 25.0 Sodium carboxymethyl cellulose 0.8 Sodium alginate 0.4 Sorbitol 30.0 Glycerin 10.0 Propylene glycol 3.0 Sodium lauryl sulfate (C₁₀-C₁₆) 1.5 Sodium lauroyl sarcosinate 0.3 Polyoxyethylene sorbitan monolaurate 0.1 Tranexamic acid 0.1 -aminocaproic acid 0.05 Allantoinate 0.1 Sodium benzoate 0.1 Saccharin sodium 0.1 Flavor blend No. 1 0.8 Distilled water balance 100.0% Formulation of flavor blend No. 1 Ingredient Parts by weight l-Menthol 30.0 Peppermint oil 30.0 Spearmint oil 1.0 Anethole 6.0 Eugenol 0.1 Trans-2-hexenal 1.0 Cardamom oil 1.0 Strawberry flavor 2.5 Menthone 1.0 Isomenthone 5.0 Cis-jasmone 1.0 Ethanol 1.4 80.0 Example 2: Toothpaste Ingredient % by weight Calcium hydrogenphosphate dihydrate 25.0 Aluminum hydroxide 25.0 Silicic anhydride 2.0 Sodium carboxymethyl cellulose 0.9 Carrageenan 0.3 Sorbitol 20.0 Polyethylene glycol 3.0 Sodium lauryl sulfate 1.0 Myristoyl diethanolamide 0.5 Tranexamic acid 0.3 Chlorohexidine hydrochloride 0.01 Sodium monofluorophosphate 0.76 Dipotassium glycyrrhetinate 0.1 Paraben 0.1 Saccharin sodium 0.1 Flavor blend No. 2 0.8 Distilled water balance 100.0% Formulation of flavor blend No. 2 Ingredient Parts by weight l-Menthol 30.0 Peppermint oil 8.0 Anethole 3.0 Cineole 2.0 Methyl salicylate 18.0 Benzaldehyde 5.0 Cardamom oil 1.0 Strawberry flavor 1.0 Citral 1.0 Menthone 5.0 Isomenthone 2.0 Piperitone 1.0 Pulegone 1.0 3-Methylcyclohexanone 0.1 Cryptone 1.0 Ethanol 0.9 100.0 Example 3: Toothpaste Ingredient % by weight Aluminum hydroxide 45.0 Silicic anhydride 3.0 Sodium carboxymethyl cellulose 1.4 Sorbitol 10.0 Glycerin 10.0 Polyethylene glycol 3.0 Sodium lauryl sulfate (C₁₀-C₁₆) 1.2 Sucrose monolaurate 0.3 Tranexamic acid 0.1 Chlorohexidine gluconate 0.01 Dipotassium glycirrhetinate 0.1 Saccharin sodium 0.1 Flavor blend No. 3 0.81 Distilled water balance 100.0% Formulation of flavor blend No. 3 Ingredient Parts by weight l-Menthol 30.0 Peppermint oil 10.0 Anethole 5.0 Cineole 20.0 Citral 4.0 Cardamom oil 3.0 Laurel oil 1.0 Pulegone 5.0 Cis-jasmone 1.0 Camphor 1.0 Ethanol 1.0 81.0 Example 4: Toothpaste Ingredient % by weight Calcium hydrogenphosphate dihydrate 25.0 Calcium hydrogenphosphate anhydride 25.0 Silicic anhydride 2.0 Sodium carboxymethyl cellulose 1.0 Carrageenan 0.3 Sorbitol 10.0 Glycerin 15.0 Propylene glycol 3.0 Sodium lauryl sulfate (C₁₀-C₁₆) 1.5 Polyoxyethylene sorbitan monolaurate 0.1 Tranexamic acid 0.3 Stearyl glycirrhetinate 0.1 Saccharin sodium 0.15 Flavor blend No. 4 0.6 Distilled water balance 100.0% Formulation of flavor blend No. 4 Ingredient Parts by weight l-Menthol 8.0 Hexyl aldehyde 0.05 Trans-2-hexenal 0.05 Cardamom oil 0.05 Melon flavor 50.0 Laurel oil 0.05 Menthone 0.5 Cis-jasmone 0.5 Ethanol 0.8 60.0 Example 5: Mouthwash Ingredient % by weight Glycerin 10.0 Ethanol 10.0 Saccharin sodium 0.3 Polyoxyethylene-hardened castor oil 1.0 Tranexamic acid 0.1 Chlorohexidine hydrochloride 0.01 Flavor blend No. 5 0.68 Distilled water balance 100.0% Formulation of flavor blend No. 5 Ingredient Parts by weight l-Menthol 20.0 Peppermint oil 0.3 Anethole 2.0 Cineole 1.4 Eugenol 1.0 Methyl salicylate 40.0 Citral 1.0 Strawberry flavor 0.1 Menthone 0.1 Cis-jasmone 0.1 Ethanol 2.0 68.0

Claims: An oral composition comprising tranexamic acid and/or a salt thereof and an aldehyde flavor which would normally cause discoloration of a tranexamic acid-containing oral composition, characterized in that the composition further contains at least one cyclic ketone selected from menthone, isomenthone and pulegone. An oral composition according to claim 1 wherein the amount of tranexamic acid and/or a salt thereof blended ranges from 0.01 to 5% by weight of the total weight of the composition. An oral composition according to claim 1 or 2 wherein the amount of the aldehyde flavor blended ranges from 0.001 to 10% by weight of the total weight of the composition. An oral composition according to any one of claims 1 to 3 wherein the amount of the cyclic ketone blended ranges from 0.0001 to 1% by weight of the total weight of the composition. An oral composition according to any preceding claim wherein the aldehyde flavor is selected from citral, trans-2-hexenal, trans-2-octenal and trans-2-pentenal.

Inventors: GOMI, TETSUO, ISHII, SHIGERU, SUGANUMA, NOBUO
Applicants: LION CORPORATION
Application year: 1987
Main classification: A61K7
IPC codes: A61K8, A61Q11