JP3429065B2 - Oral liquid composition - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a stable blend of gellan gum, which has been proposed as a new material for oral compositions.
In addition, the present invention relates to an oral liquid composition having an improved retention of a medicinal component at a target site in the oral cavity. [0002] Conventionally, various medicinal ingredients have been blended into oral compositions such as mouthwashes, dentifrices and the like as preventive and therapeutic agents for gingivitis and periodontitis. However, simply blending these medicinal ingredients into oral compositions such as mouthwashes, dentifrices, etc., causes the medicinal ingredients to rapidly flow out of the oral cavity due to the secretion of saliva in the oral cavity, resulting in gingiva, gingival sulcus, etc. The time spent in the target site is short, and the effect of the medicinal component is not sufficiently exhibited. This is particularly noticeable when the oral composition is a liquid. [0003] In recent years, various measures have been taken to keep these medicinal ingredients in the oral cavity for a long time. JP-A-05-124943 and JP-A-04-139119 disclose by blending a specific active agent into an oral composition containing a nonionic bactericide such as triclosan, and the like, and JP-A-04-139118.
No. reports that the combined use of specific polysaccharides improved the retention of nonionic fungicides in the oral cavity. In addition, in order to improve the retention of enzymes and fluorine compounds, a dry base (registration No. 1273071, registration No. 1249596) mainly composed of a polymer substance that is sticky when dissolved or gelled with water or Oral adhesive composition containing carboxyvinyl polymer and other pastes in various drugs
(Japanese Unexamined Patent Publication No. 60-237018), or an antifungal agent for sustained release ethylcellulose or an oral antifungal varnish composition having excellent sustained release containing a hydrophobic polymer (Japanese Patent Laid-Open No. 03-2126). It has been disclosed. [0004] On the other hand, gellan gum is a polysaccharide produced by Pseudomonas elodea using glucose or the like as a nutrient source, and in recent years, its use as a stabilizer or gelling agent has been proposed in the food field. In addition, in the field of oral compositions, JP-A-62-114905 discloses that the composition is formulated as a paste excellent in perfume holding ability and texture. Japanese Patent Application Laid-Open No. 05-139979 proposes the use of the composition as an oral composition having an inhibitory action on and removal of dental caries. Furthermore, gellan gum has the property of gelling with cationic ions such as calcium ions and sodium ions, and utilizing this,
A pharmaceutical composition which causes a liquid-gel phase transition upon contact with a physiological liquid (JP-A-62-181228) is disclosed. [0005] However, when the gellan gum is blended with an anionic surfactant to prepare a liquid composition for mouthwashing, the properties of the composition become unstable with time, and the viscosity of gellan gum in the oral cavity is increased. There is a problem that the consistency is lowered and the medicinal component does not sufficiently stay in the oral cavity. SUMMARY OF THE INVENTION An object of the present invention is to provide a liquid composition for oral cavity in which gellan gum is stably compounded and a medicinal component is sufficiently retained at a target site. SUMMARY OF THE INVENTION The present inventors have unexpectedly found that the addition of a nonionic surfactant to an oral liquid composition containing gellan gum stabilizes gellan gum. Then, when applied in the oral cavity, the liquid composition for the oral cavity became moderately viscous, and it was found that the medicinal component stayed in the oral cavity for a longer period of time, thereby completing the present invention. [0008] That is, the present invention provides a liquid composition for oral cavity, characterized by containing gellan gum and a nonionic surfactant. With such a liquid composition for oral cavity, a medicinal ingredient is retained in the oral cavity for a long period of time even when the oral cavity is washed. The compounding concentration of gellan gum in the liquid composition for oral cavity of the present invention is preferably 0.01 to 0.5% by weight, particularly preferably 0.05 to 0.3% by weight.
At a gellan gum concentration of less than 0.01% by weight, sufficient thickening of the oral liquid composition cannot be obtained even when a nonionic surfactant is incorporated, and at a concentration of more than 0.5% by weight, the dosage form The gel itself causes strong gelation, and the composition is hardly dispersed in the oral cavity. The concentration of total Ca ions and total Na ions in the oral liquid composition of the present invention is preferably 1 M or 5 M, respectively. If the Ca ion and Na ion concentrations exceed 1 M and 5 M, respectively, the dosage form itself gels, making it difficult for the composition to disperse in the oral cavity. The nonionic surfactants used in the present invention include sucrose fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbit fatty acid esters, Oxyethylene glycerin fatty acid ester, polyoxyethylene glycol fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene alkyl ether phosphoric acid and its salts, polyoxyethylene alkyl ether sulfate, polyoxyethylene phytosterol and phytostanol, polyoxyethylene poly Oxypropylene copolymer, polyoxyethylene alkyl phenyl ether phosphoric acid and salts thereof, polyoxyethylene castor oil and Hydrogenated castor oil, polyoxyethylene lanolin and lanolin alcohol, polyoxyethylene alkylamine and fatty acid amide, polyoxyethylene alkylphenylformaldehyde condensate, polyoxyethylene nonylphenyl ether and lauric diethanolamide, among which sucrose Fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene polyoxypropylene copolymers, and polyoxyethylene hydrogenated castor oil are particularly preferred. The concentration of the nonionic surfactant in the composition is as follows:
0.05 to 5.0% by weight is preferred, and 0.1 to 1.5% by weight.
Is more preferred. Although an anionic surfactant may be used in combination, the amount thereof is preferably small, and is preferably 0.5% by weight or less. Among the active ingredients used in the present invention, examples of anti-inflammatory agents include tranexamic acid, epsilon aminocaproic acid, allantoins, dihydrocholesterol, epidihydrocholesterol, glycyrrhetinic acid, glycyrrhizin salts, azulene and the like. , Glycyrrhetinic acid, glycyrrhizin salts, and azulene are preferred. Examples of the blood flow promoting agent include tocopherol acetate, tocopherol nicotinate, sodium chloride and the like, and among them, tocopherol nicotinate is preferable. Also, as the fluoride, sodium fluoride,
Examples thereof include sodium monofluorophosphate and stannous fluoride. In addition, examples of the disinfectant include cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, isopropylmethylphenol, triclosan, hinokitiol, thymol, and the like.
Among them, triclosan is preferred. The concentration of each medicinal ingredient in the composition is as follows:
It is preferably 0.001 to 5.0% by weight, and more preferably 0.01 to 1.0% by weight. The liquid composition for oral cavity of the present invention is prepared in a dosage form such as a mouthwash, a liquid dentifrice, a mouse spray and the like according to a method known per se, and in addition to gellan gum and a nonionic surfactant, the composition of the composition Various components can be appropriately blended depending on the conditions. Examples of the humectant include glycerin, sorbite, polyethylene glycol and the like, and the compounding amount is usually 2 to 50% by weight. Examples of the solvent include ethanol, hexylene glycol, and the like, and the compounding amount is usually 2 to 30% by weight. In addition, sweeteners such as saccharin and stevia and preservatives such as sodium benzoate and methyl paraoxybenzoate can be blended in an amount of usually 1% by weight or less. The present invention will be described in more detail with reference to the following examples, experimental examples and comparative examples, but the present invention is not limited to these examples. Unless you know the amount,
Indicated by weight%. Experimental Example 1 Examples 1 to 8 and Comparative Examples 1 to 5 After gellan gum was dissolved in water at 90 ° C., Examples 1 to 8 and Comparative Examples 1 to 8 were prepared according to a conventional method using the formulation shown in Table 1.
5 was prepared and used as a sample for the thickening test. 5 ml of the prepared mouthwash and 15 ml of saliva collected from the subject on the day of the experiment were added to a dedicated BL-type viscometer container,
After stirring with a vortex mixer for 2 seconds, the viscosity was measured immediately after contact with saliva and 5 minutes after contact with a BL type viscometer (6 rpm, rotor no. 1). Further, as a control, the viscosity of the mouthwash containing no saliva was similarly measured. Table 1 shows the results. [Table 1] From the test results in Table 1, it can be seen that when the anionic surfactant alone is blended, the viscosity does not increase even when it is brought into contact with saliva. It was recognized that the viscosity was increased by the contact of the polymer. Experimental Example 2 Examples 9 to 11 and Comparative Examples 6 and 7 Gellan gum was dissolved in water at 90 ° C., and then the formulations shown in Table 2 were used to prepare Examples 9 to 11 and Comparative Examples 6 according to a conventional method.
To 7 were prepared and used as samples for the thickening test.
The test method is the same as in Experimental Example 1. Table 2 shows the results. [Table 2] According to the above test results, saliva increased the viscosity of the mouthwash containing gellan gum at a compounding concentration of 0.01% by weight or more. On the other hand, when the concentration of gellan gum exceeded 0.5% by weight, the mouthwash itself gelled, making mouthwashing impossible. Therefore, it is understood that the compounding concentration of gellan gum is preferably 0.01 to 0.5% by weight. EXPERIMENTAL EXAMPLE 3 The mouthwash of Example 1 was used to give 30 volunteers 30
For 5 seconds, 10 minutes, 15 minutes, 30 minutes
After 2 minutes, 2 ml of saliva was collected. The collected saliva was precisely weighed in an amount of 1 g into a 10-ml volumetric flask on the day, and the volume was increased with methanol. Thereafter, the concentration of tocopherol nicotinate was measured by high performance liquid chromatography. As a control, a similar experiment was carried out for a formulation (Comparative Example 5) in which gellan gum was removed from the mouthwash of Example 1. Table 3 shows the results. [Table 3] From the above test results, it was confirmed that the gellan gum formulation contained a higher concentration of tocopherol nicotinate than the control. Example 12 Gellan gum was dissolved in water at 90 ° C. according to the following formulation, and a mouthwash liquid type oral liquid composition of the present invention was obtained according to a conventional method. Component name Amount (% by weight) Gellan gum 0.3 Tocopherol nicotinate 0.2 Saccharin sodium 0.02 Citric acid 0.05 Sodium citrate 0.1 Ethanol 5.0 Polyoxyethylene sorbitan monooleate 1.0 Glycerin 15. 0 Fragrance 0.3 Sodium benzoate 0.02 Purified water Remainder Example 13 Gellan gum was dissolved in water at 90 ° C according to the following formulation, and then the oral cavity of the present invention in the form of a liquid dentifrice was prepared by the method described above. Liquid composition was obtained. Ingredient name Compounding amount (% by weight) Gellan gum 0.3 Dipotassium glycyrrhizinate 0.1 Saccharin sodium 0.02 Sodium monohydrogen phosphate 0.01 Sodium dihydrogen phosphate 0.01 Ethanol 3.0 Polyoxyethylene (200) poly Oxyfluoropropylene (70) glycol 0.5 glycerin 15.0 Perfume 0.3 Sodium benzoate 0.02 Purified water The balance Example 14 Gellan gum was dissolved in water at 90 ° C. according to the following formulation, According to the method described above, a liquid dentifrice-type oral liquid composition of the present invention was obtained. Component name Amount (% by weight) Gellan gum 0.1 Allantoin 0.1 Saccharin sodium 0.05 Sodium monohydrogen phosphate 0.01 Sodium dihydrogen phosphate 0.01 Ethanol 3.5 Polyoxyethylene hydrogenated castor oil 1.0 Glycerin 15.0 Fragrance 0.3 Sodium benzoate 0.02 Purified water Remainder Example 15 Gellan gum was dissolved in water at 90 ° C according to the following formulation, and then the mouthwash liquid of the present invention was prepared according to the method described above. A liquid composition for oral cavity was obtained. Component name Blended amount (% by weight) Gellan gum 0.3 Hinokitiol 0.1 Saccharin sodium 0.01 Citric acid 0.05 Sodium citrate 0.1 Ethanol 5.0 Polyoxyethylene sorbitan monooleate 1.0 Glycerin 15.0 Flavor 0.3 Sodium benzoate 0.02 Purified water The balance Example 16 Gellan gum is dissolved in water at 90 ° C. according to the following formulation, and then the mouthwash liquid of the present invention in the form of a mouthwash is prepared by the above-mentioned method. A composition was obtained. Component name Blended amount (% by weight) Gellan gum 0.1 Triclosan 0.05 Saccharin sodium 0.01 Sodium monohydrogen phosphate 0.01 Sodium dihydrogen phosphate 0.01 Ethanol 10.0 Polyoxyethylene hydrogenated castor oil 1.0 Glycerin 13.0 Fragrance 0.3 Purified water Remainder Example 17 Gellan gum is dissolved in water at 90 ° C. according to the following formulation, and then the mouth spray liquid composition of the present invention in the form of a mouse spray is prepared by the method described above. I got Component name Amount (% by weight) Gellan gum 0.2 Chlorhexidine hydrochloride 0.01 Polyoxyethylene hydrogenated castor oil 1.0 Glycerin 10.0 Ethanol 40.0 Fragrance 0.8 Purified water Balance ADVANTAGE OF THE INVENTION According to this invention, even if gellan gum is mix | blended stably and the inside of an oral cavity is wash | cleaned, the medicinal ingredient is retained in an oral cavity for a long time, and the liquid composition for oral cavity which shows a sufficient effect is obtained.

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-5-139979 (JP, A) JP-A-1-287015 (JP, A) JP-A-62-1114905 (JP, A) JP-A-62-1 417 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K ⁷ /00-7/50 A61K 9/00-9/72 A61K 47/00-47/48 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claim 1] 0.01 to 0.5% by weight of gellan gum,
An oral liquid composition comprising 0.05 to 5.0% by weight of a nonionic surfactant and a pharmaceutically active ingredient.