JP5434023B2 - Oral composition - Google Patents

Description

  The present invention relates to a composition for oral cavity that is a microgel preparation excellent in retention in the oral cavity and can be stably stored.

  Long-term use of medicinal ingredients contained in oral compositions such as bactericides such as triclosan and isopropylmethylphenol, anti-cariogenic agents such as sodium fluoride and monofluorophosphate, and refreshing agents such as menthol and peppermint oil It is very effective to improve these effects. In addition, retaining a moisturizing agent or moisture on the oral mucosa to alleviate xerostomia greatly contributes to improving the patient's QOL. In particular, when head and neck radiation therapy, where the oral cavity is included in the irradiation field, hematopoietic stem cell transplantation, chemotherapy, etc., the salivary glands are damaged as side effects, and saliva is hardly secreted, and severe dry mouth In many cases. Severe dry mouth causes an increase in dental caries, exacerbation of periodontitis, an increase in oral troubles such as bad breath, difficulty in speaking, difficulty in food intake, abnormal taste, and the like, and significantly lowers the patient's QOL. In addition to oral mucositis that frequently occurs in these treatments, the condition in the oral cavity is significantly worsened, leading to decreased food intake and malnutrition due to difficulty swallowing, delaying the schedule of cancer treatment plans, and prognosis Adversely affect the health of the patient and eventually increase the medical economic burden (see Non-Patent Document 1). For these patients, it is very beneficial to easily retain various medicinal ingredients corresponding to troubles in the oral cavity, mucous membrane moisturizing ingredients, moisture and the like in the oral cavity.

  As a method for retaining a medicinal component in the oral cavity, it is known to add a cationic bactericide such as chlorhexidine hydrochloride having high adsorptivity to hydroxyapatite which is a component of teeth. However, this method lacks versatility because the medicinal component itself is limited to those adsorbed in the oral cavity. Moreover, although the method of raising the intraoral retention of a chemical | medical agent with a highly viscous mouthwash is disclosed (refer patent document 1 and 2), sufficient retention in an oral cavity is obtained with these mouthwashes. It is not possible.

  As means for solving these problems, microgel particles prepared by shearing a solution obtained by dissolving a specific gelling agent in an aqueous solvent while gelling with a crosslinking agent, which is discharged from a spray container The composition for oral cavity used is disclosed (refer patent document 3). However, the composition for oral cavity using the microgel particles can be easily separated from the gel, or the microgel particles are bonded to each other to form large gel particles, which are apparently non-uniform gels (below) Deterioration of the feeling of use accompanying the deterioration of the appearance due to the phenomenon that the entire composition becomes a jelly and solidifies (hereinafter referred to as jelly). There is a problem that occurs easily. For this reason, a more stable composition has been desired as an oral composition using microgel particles.

JP-A-8-333227 Japanese Patent Laid-Open No. 11-12144 JP 2005-104966 A Yojiro Ota et al., Nursing Technology 52, p10-51, 2006

  An object of the present invention is to provide a composition for oral cavity which is a microgel preparation excellent in retention in the oral cavity and has improved storage stability.

  As a result of intensive studies in view of such circumstances, the inventors of the present invention blended gellan gum as a gelling agent in an amount of 0.3 to 0.4% by weight, and 1 g of gellan gum as a crosslinking agent with a divalent metal ion as 1 To obtain a composition for oral cavity with excellent retention in the oral cavity and improved storage stability such as water separation and appearance, by preparing microgel particles by adding ~ 6 mmol and constructing the preparation as an aggregate I found out that I can.

That is, the present invention uses 0.3 to 0.4% by weight of gellan gum as a gelling agent, and 1 to 6 mmol of divalent metal ions supplied by calcium chloride and / or calcium lactate per 1 g of gellan gum. Made of an aggregate of microgel particles having an average particle diameter of 15 to 200 μm, prepared by using calcium ions as a crosslinking agent, and selected from the group consisting of glycerin, propylene glycol and 1,3-butylene glycol 10 to 25% by weight of one or more polyhydric alcohols, 10 to 20% by weight of glycerin as the above-mentioned polyhydric alcohol as an essential component , 0.01% of α, α-trehalose carbohydrate derivative An oral composition characterized by containing -20% by weight and a moisture content of 50-85% by weight .

  According to the present invention, 0.3 to 0.4% by weight of gellan gum as a gelling agent, 1 to 6 mmol of divalent metal ion as a crosslinking agent is added to 1 g of gellan gum to produce microgel particles, By constructing a preparation using this as an aggregate, it is possible to provide an oral composition having excellent retention in the oral cavity and improved storage stability such as water separation and appearance. According to the composition for oral cavity of the present invention, when head and neck radiotherapy, hematopoietic stem cell transplantation, chemotherapy, etc. are performed, the salivary gland is damaged as a side effect, and the cancer patient has almost no saliva secreted. However, since various medicinal ingredients, mucous membrane moisturizing ingredients, moisture, etc. can be easily retained in the oral cavity, various oral troubles due to dry mouth are prevented, and QOL after treatment is prevented from lowering during treatment. It can contribute to eliminating delays in treatment and improving the quality of cancer treatment.

Hereinafter, the present invention will be described in more detail.
Gellan gum used in the present invention is a polysaccharide produced by Sphingomonas elodea and is mainly used as a thickening stabilizer for foods and cosmetics. Inoculate the above-mentioned bacteria (S. elodea) into a liquid medium, aseptically cultivate, recover the mucilage produced outside the cells from the culture solution, and commercialize it in a powder form through steps such as drying and crushing Is. Gellan gum includes deacylated gellan gum and native gellan gum. Deacylated gellan gum is recovered by removing (deacylated) glyceryl and acetyl groups in the process of separating mucilage. Gellan gum is recovered without processing. In the present invention, deacylated gellan gum is preferable from the viewpoint of gelation, and one kind can be used alone, or two kinds can be used in appropriate combination. Gellan gum melts at around 70 ° C., and after adding divalent metal ions, it cools and starts to form a strong and brittle gel at around 40 ° C. Deacylated gellan gum is available under the trade name “Kelcogel” (Kelco). The amount of gellan gum is 0.3-0.4% by weight. If the amount of gellan gum is out of this range, the stability of the microgel, the dischargeability from the spray container, and the retention in the oral cavity will deteriorate.

  The divalent metal ion can be supplied from a water-soluble divalent metal salt. A water-soluble divalent metal salt can be appropriately blended so that 1 to 6 mmol of divalent metal ions is contained in 1 g of gellan gum. As the divalent metal ion, calcium ion, magnesium ion, and zinc ion are preferable from the viewpoint of safety. Furthermore, calcium ions are most preferable from the viewpoint of taste. Examples of water-soluble metal salts that supply calcium ions include calcium lactate, calcium chloride, calcium gluconate, calcium glycerophosphate, calcium glutamate, calcium citrate, calcium gluconate, and calcium hydroxide. Of these, calcium chloride and calcium lactate are preferable from the viewpoint of usability and taste. One or two or more of these water-soluble divalent metal salts can be appropriately blended.

  Here, the microgel particles of the present invention are gel-like particles prepared so as to have an average particle diameter of 0.01 to 1000 μm. Among these, those having an average particle diameter of 15 to 200 μm are particularly preferable. When the average particle size is larger than 1000 μm, the fluidity is remarkably deteriorated. When the average particle size is less than 0.01 μm, the particle size is too small to obtain a gel product having sufficient commercial value.

  The microgel particles are prepared by charging the gellan gum in an aqueous solvent, heating and dissolving at 70 ° C. or higher, adding a divalent metal ion as a cross-linking agent, and quenching or quenching and applying shear. be able to. At this time, the cooling rate is 0.05 ° C./min or more, and the shearing force is preferably 2 m / s or more, and the apparatus for performing the shearing is not particularly limited, and examples thereof include a homogenizer.

The oral composition of the present invention comprises an aggregate of the microgel particles, and the yield value as the oral composition is ² to 100 dyn / cm ² , preferably 5 to 70 dyn / cm ² , more preferably 10 to 10 dyn / cm ² . 60 dyn / cm ² . When the yield value is less than ² dyn / cm ² , the retention in the oral cavity is deteriorated, and when the yield value exceeds 100 dyn / cm ² , the fluidity is deteriorated.

  Glycerin, propylene glycol or 1,3-butylene glycol can be used alone or in combination of 10 to 25% by weight. In order to suppress partial regelation or jelly formation of microgel particles, it is desirable to contain 10 to 20% by weight of glycerin. The content of propylene glycol or 1,3-butylene glycol is preferably 5% by weight or less because the taste is poor.

  The amount of water contained in the present invention is 50 to 85% by weight as the sum of the water to be blended and the water contained in the raw materials, such as ion-exchanged water, distilled water, city water, and mineral water. When the water content exceeds 85% by weight, water separation is observed, and when the water content is less than 50% by weight, it becomes difficult to produce microgel particles.

  The oral composition using the microgel particles of the present invention can be made into dosage forms such as a mouthwash, a liquid dentifrice, and a spray formulation. Among these, the oral composition of the present invention can be sucked into a nozzle and ejected by spraying from its physical properties, and a spray formulation is particularly preferable from the viewpoint of usability.

  In the composition for oral cavity of the present invention, the microgel particles form an aggregate as an individual solid that is independent of each other. Therefore, even if the spray formulation is sucked into a nozzle, the composition may be stringed. In addition, after discharge, adjacent microgel particles adhere to each other to build regelation as a whole, enabling long-term residence in the oral cavity that was not suitable with conventional viscous liquids It is. For this reason, the use of dry mouth is particularly preferable because of the above characteristics.

  In addition to gellan gum, water-soluble divalent metal salt, glycerin, propylene glycol, 1,3-butylene glycol and water, the oral composition of the present invention is formulated with additives commonly used in this field. It can mix | blend suitably according to it. Examples of such additives include gelling agents, pH adjusters, abrasives, foaming agents, surfactants, wetting agents, sweeteners, fragrances, plant extracts, preservatives, colorants, and various active ingredients. It can be illustrated. The blending amount of the additive is not particularly limited and can be appropriately set as long as the effects of the invention are not impaired.

  Gelling agents include gellan gum, agar, carrageenan, pectin, farseleran, alginic acid and its salts, glucomannan, tara gum, locust bean gum, tamarind, celluloses, xanthan gum, pullulan, guar gum, starch phosphate, polyacrylic Examples thereof include acid salts, gum arabic, curdlan, gati gum and aeromonas gum, cellulose derivatives such as carboxymethyl cellulose and hydroxyethyl cellulose, or salts thereof. These gelling agents can be used in a range that does not affect the microgel particles by appropriately combining one or more gellan gums.

  Moreover, it is also possible to add humectants other than glycerin, propylene glycol, and 1,3-butylene glycol to the oral composition of the present invention, specifically, sorbit, polyethylene glycol, polypropylene glycol, xylitol, Examples of the wetting agent include maltitol, lactitol, erythritol, palatinose, and palatinit. Moreover, these wetting agents can be used individually by 1 type or in combination of 2 or more types as appropriate. The blending amount of the wetting agent can be appropriately set according to at least one kind of wetting agent, but it can be usually blended in an amount of about 0 to 40% by weight based on the total amount of the composition.

  As pH of the composition for oral cavity in this invention, about 3-10 are preferable, More preferably, it is about 5.5-8.5. When the pH is out of the range of 3 to 10, irritation is strong, which is not preferable. Further, if the pH is lower than 5.5, there is a concern about the solute of calcium from the teeth, and if the pH is higher than 8.5, the bitterness is strong and the commercial value as a product is lost. Buffering agents can also be used to adjust the pH. Examples of the buffer include citric acid and its salts (such as sodium salt), phosphoric acid and its salts (such as sodium phosphate and sodium hydrogen phosphate), malic acid and its salts, gluconic acid and its salts, maleic acid and Salts thereof, aspartic acid and salts thereof, gluconic acid and salts thereof, succinic acid and salts thereof, glucuronic acid and salts thereof, fumaric acid and salts thereof, glutamic acid and salts thereof, adipic acid and salts thereof, hydrochloric acid, sodium hydroxide, Examples thereof include potassium hydroxide and sodium silicate. These buffering agents can be used singly or in appropriate combination of two or more. The blending amount of the buffer is not particularly limited as long as the desired pH is obtained, but is usually about 0 to 5% by weight, preferably about 0.1 to 3% by weight, based on the entire composition.

  As abrasives, dicalcium phosphate dihydrate and anhydrous, calcium phosphate, tricalcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, silica gel, aluminum silicate, precipitated silica, zirconosilicate, etc. Examples thereof include silica compounds, insoluble sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate, calcium sulfate, polymethyl methacrylate, bentonite, zirconium silicate, hydroxyapatite, and synthetic resin. An abrasive | polishing agent is normally mix | blended about 0-30 weight% with respect to the whole composition.

  Examples of the foaming agent include higher alkyl sulfate esters having 8 to 18 carbon atoms in the alkyl group such as sodium lauryl sulfate and sodium myristyl sulfate, sulfosuccinic acid surfactants, N-long chain acylamino acid salts, α- Olefin sulfonate salt, higher fatty acid sodium monoglyceride monosulfate, N-acyl sarcosine salt, N-acyl glutamate, N-methyl-N-acyl taurine salt, N-methyl-N-acylalanine salt, α-olefin sulfonate, etc. An anionic surfactant can be blended. These anionic surfactants may be used alone or in combination of two or more. The blending amount of the foaming agent is usually about 0 to 5% by weight, preferably about 0.01 to 2% by weight, based on the entire composition.

  Moreover, you may mix | blend the nonionic surfactant, amphoteric surfactant, and cationic surfactant which are normally used for an oral composition other than the said anionic surfactant. Examples of such surfactants include polyoxyethylene fatty acid esters such as polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monolaurate, polyoxyethylene hydrogenated castor oil, lauric acid monoethanolamide, and myristic acid monoester. Ethanolamide, polyoxyethylene higher alcohol ether, polyoxyethylene polyoxypropylene copolymer, polyoxyethylene polyoxypropylene fatty acid ester alkyl glycoside (for example, alkyl chain of fatty acid moiety: about C8 to C16), polyglycerin fatty acid ester (for example, Nonionic surfactant such as alkyl chain of fatty acid part: about C8 to C16), sucrose fatty acid ester (for example, alkyl chain of fatty acid part: about C8 to C16); N-alkyl Amphoteric surfactants such as aminoethylglycine, alkylbetaine, fatty acid amidopropylbetaine (for example, alkyl chain of fatty acid moiety: about C8 to C16), alkylsulfobetaine, imidazolium betaine; alkyltrimethylammonium chloride, alkyltrimethylammonium bromide, Examples thereof include cationic surfactants such as alkyldimethylammonium chloride. Among these, polyoxyethylene hydrogenated castor oil and alkyl glycoside are preferable. The compounding quantity of surfactants other than anionic surfactant is about 0 to 5 weight% normally with respect to the whole composition, Preferably, it is 0.01 to 2 weight%.

  Examples of the sweetener include saccharin, saccharin sodium, stevioside, acesulfame potassium, glycyrrhizic acid and its salt, aspartylphenylalanine methyl ester, perilartin, thaumatin, xylitol, palatinose, palatinit, erythritol, maltitol and the like. Sweetening agents may be used alone or in combination of two or more. The blending amount of the sweetener can be appropriately set according to the desired sweetness, but is usually about 0 to 15% by weight with respect to the whole composition.

  As fragrances, menthol, anethole, carvone, eugenol, limonene, peppermint oil, spearmint oil, wintergreen, methyl salicylate, cionel, thymol, clove oil, eucalyptus oil, rosemary oil, sage oil, lemon oil, orange oil, ocimen oil , Citronellol, methyl eugenol, water-soluble fragrances of various fragrances and the like, as long as they are commonly used flavoring agents, they can be blended without particular limitation. Although the compounding quantity of a fragrance | flavor can be set suitably, it is about 0 to 5 weight% normally with respect to the whole composition.

  As plant extract, plants such as Kyodo, Mokko, Guiyo, Japanese biloba, Japanese cypress, Rosin, Fujibaka, Canary tree, Elderberry, Centavo, Psyllium, Acacia, sterile flower, birch, rosemary and other organic plants such as methanol and ethyl acetate Examples thereof include those extracted with a solvent, aloe extract, gentian pepper extract, tea extract, and hamamelis extract. The plant extract may be used alone or in combination of two or more. The compounding quantity of a plant extract is about 0 to 5 weight% normally with respect to the whole composition.

  Examples of the preservative include benzoates such as sodium benzoate; parabens such as methylparaben, ethylparaben, and butylparaben, phenoxyethanol, and potassium sorbate. The preservatives may be used alone or in combination of two or more, and the blending amount of the preservatives can be appropriately set, but is usually about 0 to 3% by weight with respect to the whole composition.

  Examples of the colorant include legal pigments such as Blue No. 1, Yellow No. 4, Red No. 202, and Green No. 3; mineral pigments such as ultramarine blue, enhanced ultramarine blue, and bitumen; and titanium oxide. The blending amount of the colorant is usually about 0 to 1% by weight with respect to the whole composition.

  Active ingredients include cationic bactericides such as chlorhexidine hydrochloride, cetylpyridinium chloride, benzethonium chloride and benzalkonium chloride, nonionic bactericides such as triclosan and isopropylmethylphenol, and anionic bactericides such as sodium n-lauroyl sarcosine. Drugs, dextranase, amylase, mutanase, lysozyme, enzymes such as lytic enzyme (Litec enzyme), tranexamic acid and epsilon aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholesterol, vitamin E derivatives such as tocopherol acetate, glycyrrhizin salts, Active ingredients such as glycyrrhetinic acid, glycerophosphate, chlorophyll, potassium nitrate, sodium chloride, and caropeptide may be used alone or in combination. . Further, as a mucosal moisturizing agent, trehalose, a carbohydrate derivative of α, α-trehalose, xylitol, erythritol, xanthan gum, hyaluronic acid, hyaluronic acid salt, chondroitin sulfate, etc. may be used alone or in combination. In terms of the mucosal moisturizing effect, α, α-trehalose sugar derivatives are preferred. The carbohydrate derivative of α, α-trehalose is one or more carbohydrates selected from non-reducing oligosaccharides composed of 3 or more glucoses having an α, α-trehalose structure in the molecule. Among them, terminal of molecules such as α-glucosyl α, α-trehalose, α-maltosyl α, α-trehalose, α-maltotriosyl α, α-trehalose and α-maltotetraosyl α, α-trehalose In addition, carbohydrates with a trehalose structure can be used. In particular, it contains α-maltosyl α, α-trehalose as a main component, and in addition, α-glucosyl α, α-trehalose, α-maltotriosyl α, α-trehalose, α-maltotetraosyl α, α- Carbohydrates containing one or more selected from trehalose are desirable. In this case, a sugar containing α-maltosyl α, α-trehalose in an amount of about 5% by mass or more, preferably about 10% by mass or more, and more preferably about 30% by mass or more in terms of anhydride with respect to the total carbohydrates. Quality is desirable. Examples of the saccharide include commercially available syrup-like α, α-trehalose-containing saccharide derivative-containing saccharide (trade name “Hellodex”, sold by Hayashibara Corporation) and reducing properties coexisting by hydrogenation thereof. It is possible to use a saccharide obtained by converting a saccharide into its sugar alcohol (trade name “Tornale” (47% saccharide derivative of α, α-trehalose, 26% water)) it can. These active ingredients may be used alone or in combination of two or more. The amount of the active ingredient is not particularly limited as long as the desired effect is obtained, but is usually about 0.001 to 30% by weight, preferably about 0.01 to 20% by weight, based on the entire composition. is there.

  Although the container filled with the composition for oral cavity of this invention is not specifically limited, What is necessary is just to be used for containers for oral compositions, such as a plastic which consists of synthetic resins, and a glass bottle. In particular, since the composition for oral cavity of the present invention can be discharged by suction and spraying to a nozzle due to its physical properties, it is preferable to use a spray-type container that can be discharged in a mist form among the containers. The material of the plastic constituting the container is not particularly limited, but polyethylene, polyester, polypropylene, polyethylene terephthalate, ethyl vinyl alcohol, and the like are preferably used. Moreover, it does not specifically limit as a spray type container, A push type, an aerosol type, a trigger type etc. are mentioned. In addition, if it is other than the container of the said shape, bottle filling, pillow pack shape, stick shape, tube shape, cup shape, etc. are mentioned.

  Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto. In the following examples, unless otherwise specified, “%” is expressed in weight%.

[Example 1-6, Comparative Example 1-6]
With the formulation shown in Table 1, pH, average particle size, appearance evaluation, and retention evaluation were performed. The results are shown in Table 1.
The formulation in the table is as follows. While stirring at 500 rpm with a stirrer (IKA: EUROSTAR digital), a gelling agent is added to water and heated to about 90 ° C., and then a buffer, a wetting agent, and a preservative are added. Finally, a crosslinking agent is added and cooling is started. The volatile substance is added at 60 to 50 ° C., and then forcedly cooled to about 5 ° C., and further, a high-speed emulsifier / disperser (manufactured by Primics Co., Ltd. K. HOMOMIXER MARK II) was sheared and defoamed at 8000 rpm to obtain an oral composition.

[PH measurement]
It measured by the usual method using the Horiba make, pH meter 6366C.

[Measurement of average particle size]
Measured with a laser diffraction / scattering particle size distribution analyzer LA-700 (particle size measurement range: 0.04 to 262 μm, flow cell circulation pump speed: 3, stirring motor speed: max, sample amount: 100 mL) manufactured by HORIBA, Ltd. .

[Appearance evaluation]
The microgel produced by the production method described above was put on a 70 mL glass container with a lid, and visually observed after 2 months at 40 ° C. and 75% RH. The evaluation criteria are described below.
<Water separation>
X: Water separation is observed in the upper layer and the lower layer.
○: No water separation is observed.
<Partial regelation>
It was evaluated whether or not the microgel particles were partially bonded in an apparently non-uniform state.
X: Partial regelation is recognized.
○: Partial regelation is not observed.
<Jellyification>
Evaluation was performed based on whether or not the liquid level moved when tilted at 45 ° C. at a speed of 15 ° C./sec or less in a 70 mL cylindrical transparent container.
X: The liquid level remains horizontal and does not move.
○: The liquid level moves.

[Residence test]
1 g of the oral composition was spread on a 20 cm square stainless steel plate to a diameter of 10 cm, and after standing still for 1 minute, the length of the oral composition suspended from the lowest point of the circle was measured.
○: Less than 1 cm x 1 cm or more

[Comprehensive evaluation]
×: When there is one or more “x” in the above appearance and usability evaluation ○: When “x” is less than one in the above appearance and usability evaluation

  As shown in Table 1, 0.3 to 0.4% by weight of gellan gum, and 1 to 6 mmol of calcium ions are added to 1 g of gellan gum, from the group consisting of glycerin, propylene glycol and 1,3-butylene glycol. The composition for oral cavity comprising microgel particles having an average particle diameter of 15 to 200 μm containing 10 to 25% by weight of one or two or more selected polyhydric alcohols has no problem of water separation or appearance, and has a retention property. It was the composition for oral cavity which was excellent in.

[Example 7]
An oral composition containing microgel particles having the following formulation was prepared in the same manner as in Example 1-6.
Ingredient Amount (%)
Gellan gum 0.35
Calcium lactate pentahydrate 0.15
Glycerin 13.0
Tornale 5.0
1,3-butylene glycol 1.0
Citric anhydride 0.1
Sodium citrate 0.9
Methyl paraoxybenzoate 0.1
Water-soluble fragrance 0.2
Water balance
Total 100.0
(Moisture content 80.5%)

  The oral composition prepared according to Example 7 was a stable oral composition with no appearance problems.

[Clinical trial example]
Nine patients who were aware of dry mouth accompanying cancer treatment by head and neck radiotherapy, hematopoietic stem cell transplantation, and chemotherapy used the oral composition shown in Example 7 for 7 days. Before use, the oral surgeon surveyed by oral surgeons and evaluated the subjective symptoms of dry mouth of the person in five stages. In addition, after use, the change in mouth dryness and the comparison with products for dry mouth currently in use were evaluated in five stages. Details of each evaluation item are shown in Table 2, and the results are shown in Table 3. Furthermore, the mouth dry feeling before and after use was evaluated by the VAS (Visual Analog Scale) method. The VAS used a 10 cm line, and the patient gave a “sign” to the current dry mouth state with the left end being “not feeling dry at all” and the right end being “very dry and cannot be tolerated”. When evaluating after use, do not look at the evaluation results before use. The difference in the distance of the mark from the left end before and after use was evaluated. The greater the positive value, the better the dry mouth, the closer it is to 0, the smaller the change, and the larger the negative value, the worse the dry mouth. Table 3 shows the results.

  As shown in Table 3, the composition for oral cavity of the present invention alleviates the feeling of dry mouth in clinical trials with severe dry mouth patients associated with cancer treatment by head and neck radiotherapy, hematopoietic stem cell transplantation, chemotherapy, etc. It was shown to be effective.

[Example 8]
An oral composition containing microgel particles having the following formulation was prepared in the same manner as in Example 1-6.
Ingredient Amount (%)
Gellan gum 0.35
Calcium lactate pentahydrate 0.15
Magnesium chloride hexahydrate 0.05
Glycerin 13.0
Propylene glycol 1.5
Xylitol 1.0
Tornale 2.0
Citric anhydride 0.01
Trisodium citrate 0.5
Methyl paraoxybenzoate 0.2
Sodium benzoate 0.2
Polyoxyethylene (40) hydrogenated castor oil 0.1
Tocopherol acetate 0.05
Sodium monofluorophosphate 0.7
Fragrance 0.05
Saccharin sodium 0.01
Water balance total 100.0
(Moisture content 80.7%)

[Example 9]
An oral composition containing microgel particles having the following formulation was prepared in the same manner as in Example 1-6.
Ingredient Amount (%)
Gellan gum 0.4
Calcium chloride pentahydrate 0.15
Zinc gluconate trihydrate 0.15
Glycerin 15.0
1,3-butylene glycol 1.0
Tornale 5.0
Citric anhydride 0.01
Trisodium citrate 0.6
Methyl paraoxybenzoate 0.1
Sodium benzoate 0.1
Polyoxyethylene (60) hydrogenated castor oil 0.1
Triclosan 0.05
Cetylpyridinium chloride 0.05
Fragrance 0.05
Saccharin sodium 0.01
Water balance total 100.0
(Moisture content 78.5%)

  As described above, the oral compositions prepared in Examples 8 and 9 were oral compositions having no problem in appearance and excellent retention.

Claims (2)

Using 0.3 to 0.4% by weight of gellan gum as a gelling agent, 1 to 6 mmol of calcium ion, which is a divalent metal ion supplied by calcium chloride and / or calcium lactate, per 1 g of gellan gum One or two kinds selected from the group consisting of glycerin, propylene glycol and 1,3-butylene glycol, which are made of an aggregate of microgel particles having an average particle diameter of 15 to 200 μm, prepared by using as a crosslinking agent. 10 to 25% by weight of the above polyhydric alcohol , 10 to 20% by weight of glycerin as the polyhydric alcohol as an essential component, and 0.01 to 20% by weight of a carbohydrate derivative of α, α-trehalose And a moisture content of 50 to 85% by weight.   The composition for oral cavity according to claim 1 for a patient during or after cancer treatment by head and neck radiotherapy, hematopoietic stem cell transplantation, chemotherapy or the like.