JP2018083763A - Intraoral foaming formulation and production method thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide intraoral foaming formulations that are stable even if they are stored for long period of time, in intraoral foaming formulations that contain organic acid and one or more selected from carbonate and bicarbonate.SOLUTION: The present invention provides a method for producing an intraoral foaming formulation which contains (a) one or more selected from carbonate and bicarbonate, (b) organic acid, (c) trisodium phosphate, and which comprises following steps (1) and (2), trisodium phosphate being added to at least one of a powder raw material that comprises one or more selected from carbonate and bicarbonate, or a powder raw material that comprises organic acid, in the step (1). (1) Separately providing a powder raw material that contains at least one selected from carbonate and bicarbonate and a powder raw material that contains an organic acid. (2) Integrating and mixing the powder raw material that is separately prepared in the step (1).SELECTED DRAWING: None

Description

  The present invention relates to a foamed preparation that dissolves by generating carbon dioxide in the oral cavity and a method for producing the same.

  The carbonated foam preparation is prepared by blending a carbonate such as sodium hydrogen carbonate as a foaming component and an organic acid as a neutralizing agent, and appropriately compressing or granulating. When this is put into water or the mouth, the components cause a neutralization reaction and generate carbon dioxide gas, which has the advantage of dissolving quickly, so it is used for pharmaceuticals, mouthwashes, foods, detergents, baths, etc. ing.

  For example, in the field of pharmaceuticals and foods, foaming solid compositions for oral cavity (Patent Documents 1, 2, etc.) that dissolve directly on the tongue and cause medicinal ingredients to act on the tongue coating and tongue mucosa, and the throat are adversely affected. There have been reported candy (Patent Document 3) and the like imparting effervescence effective for capturing (inclusion) the flame bacterium and eliminating the causative bacteria adhering to the throat.

  However, since the neutralization reaction occurs in the foamed preparation due to the small amount of moisture inherent in the preparation, the internal pressure of the sealed storage container rises during storage, causing deformation and breakage of the container, and the use of products. There was a problem that caused carbon dioxide not to be generated.

The reaction during storage accelerates when the temperature rises, and the reaction is further accelerated by moisture generated by the reaction. For commercialization, an additive for the foaming component and neutralizing agent, an additive for suppressing the reaction, a desiccant Use is essential. For example, Patent Document 4 reports that an effervescent tablet detergent containing an anhydrous phosphate such as disodium phosphate anhydrous as a stabilizer is stable under storage conditions at 50 ° C. for 100 hours. Yes.
However, especially in the case of drugs taken from the oral cavity into the body, such as pharmaceuticals, supplements, and mouthwashes, it is better because it is necessary to ensure sufficient quality such as the period until use, taste, flavor and safety. Storage stability is required.

JP-A-4-327526 Japanese Patent Laid-Open No. 7-238008 Japanese Patent Laid-Open No. 2002-184 Japanese Patent Laid-Open No. 10-204500

  An object of the present invention is to provide a buccal foam preparation that contains one or more selected from carbonates and bicarbonates and an organic acid and is stable even when stored for a long period of time.

  As a result of various investigations on the stability of an oral foam preparation, the present inventors have suppressed the generation of carbon dioxide gas even when stored for a long time in a high temperature environment when trisodium phosphate is used as a stabilizer. The present inventors have found that excellent storage stability that cannot be obtained with other phosphates can be imparted.

That is, the present invention relates to the following 1) to 3).
1) The following steps (1) and (2), including (a) one or more selected from carbonates and bicarbonates, (b) organic acids and (c) trisodium phosphate A method for producing a preparation, wherein in step (1), trisodium phosphate is added to at least one of a powder raw material containing one or more selected from carbonates and bicarbonates or a powder raw material containing an organic acid. ,Method.
(1) A step of separately preparing a powder raw material containing at least one selected from carbonates and bicarbonates and a powder raw material containing an organic acid. (2) Powders prepared in step (1), respectively. The step of combining and mixing the raw materials 2) (a) one or more selected from carbonate and bicarbonate, (b) an organic acid, and (c) an oral foam preparation containing trisodium phosphate, An oral cavity containing (c) trisodium phosphate (0.8) to 12% by mass in terms of phosphoric acid with respect to a mixture of (a) one or more selected from carbonates and bicarbonates, and (b) organic acids. Inner foam preparation.
3) The stabilization method of the said buccal foam preparation including the process of mix | blending trisodium phosphate in the buccal foam preparation containing 1 or more types chosen from carbonate and bicarbonate, and an organic acid.
4) A stabilizer for an intraoral foam preparation containing at least one selected from carbonates and bicarbonates, and an organic acid, containing trisodium phosphate as an active ingredient.

  According to the present invention, even when stored for a long time in a high-temperature environment, the generation of carbon dioxide gas is suppressed, the quality of the preparation is ensured, and deformation and breakage of the hermetically sealed storage container during storage can be prevented.

The intraoral foam preparation of the present invention contains (a) one or more selected from carbonates and bicarbonates, (b) organic acids and (c) trisodium phosphate, and generates carbon dioxide in the oral cavity. It is a preparation that dissolves.
The intraoral foam preparation of the present invention containing each of the above components may be in the form of a granulated product such as a granule or may be in the form of a powder that has not been granulated. Moreover, the tablet prepared by tableting the said powder or granulated material may be sufficient. Specific examples include tablets such as orally disintegrating tablets, chewable tablets, troche tablets, sublingual tablets, and buccal tablets, granules, powders, and the like.

The “carbonate and bicarbonate” of the component (a) is a component that generates carbon dioxide gas by neutralization with an organic acid.
Examples of the carbonate and bicarbonate include sodium carbonate, sodium hydrogen carbonate, sodium sesquicarbonate, potassium carbonate, potassium hydrogen carbonate, calcium carbonate, ammonium carbonate and the like. Among these, sodium carbonate, sodium hydrogen carbonate, sodium sesquicarbonate, Potassium carbonate is preferred. These may be used singly or in combination of two or more.

  The content of one or more selected from carbonate and bicarbonate in the buccal foam preparation is preferably 4% by mass or more, more preferably 10% by mass or more, and still more preferably from the viewpoint of carbon dioxide generation amount and flavor. Is 15% by mass or more, and preferably 35% by mass or less, more preferably 30% by mass or less, and still more preferably 25% by mass or less. Moreover, Preferably it is 4-35 mass%, More preferably, it is 10-30 mass%, More preferably, it is 15-25 mass%.

The “organic acid” of component (b) is a component for neutralizing carbonates and generating carbon dioxide.
Examples of the organic acid include citric acid, tartaric acid, ascorbic acid, malic acid, fumaric acid, succinic acid, malonic acid, adipic acid, and the like, and citric acid, tartaric acid, ascorbic acid, and malic acid are preferable.

  The content of the organic acid in the intraoral foam preparation is preferably 5% by mass or more, more preferably 8% by mass or more, and further preferably 10% by mass or more from the viewpoint of foaming amount and flavor. To 50% by mass or less, more preferably 30% by mass or less, and still more preferably 20% by mass or less. Moreover, Preferably it is 5-50 mass%, More preferably, it is 8-30 mass%, More preferably, it is 10-20 mass%.

  In addition, the content of one or more selected from (a) carbonate and bicarbonate in the buccal foam preparation and (b) the content of the organic acid is the component (a) and the component ( The total of b) is preferably 20% by mass or more, more preferably 25% by mass or more, further preferably 30% by mass or more, and preferably 60% by mass from the viewpoint of securing good tableting properties and moldability. % Or less, More preferably, it is 50 mass% or less, More preferably, it is 45 mass% or less. Moreover, Preferably it is 20-60 mass%, More preferably, it is 25-50 mass%, More preferably, it is 30-45 mass%.

  In addition, the content ratio of (a) one or more selected from carbonates and bicarbonates and (b) organic acids is (b) when the component (a) is 1 in terms of equivalent ratio from the viewpoint of tablet foaming. ) Component is preferably 1 or more, more preferably 1.1 or more, more preferably 1.2 or more, and preferably 5 or less, more preferably 3 or less, more preferably 2 or less from the viewpoint of flavor. is there. Moreover, (a) 1 or more types chosen from carbonate and bicarbonate: (b) The organic acid (equivalent ratio) is preferably 1: 1 to 1: 5, more preferably 1: 1.1 to 1: 3, more preferably 1: 1.2 to 1: 2.

The intraoral foam preparation of the present invention contains (c) trisodium phosphate (Na ₃ PO ₄ ) as a stabilizer.
From the viewpoint of storage stability, trisodium phosphate is converted into phosphoric acid (PO ₄ ) with respect to the total amount of (a) one or more selected from carbonates and bicarbonates and (b) organic acids. Preferably it is 0.8% by mass or more, more preferably 1.0% by mass or more, further preferably 1.5% by mass or more, and from the viewpoint of flavor, it is preferably 12% by mass or less, more preferably 6% by mass. Hereinafter, it is more preferably 3% by mass or less. Moreover, Preferably it is 0.8-12 mass%, More preferably, it is 1.0-6 mass%, More preferably, it is 1.5-3 mass%.

Further, trisodium phosphate is preferably 3% by mass or more, more preferably 4% by mass or more, and still more preferably from the viewpoint of storage stability in terms of phosphoric acid (PO ₄ ) relative to (b) organic acid. Is 5% by mass or more, and from the viewpoint of flavor, it is preferably 30% by mass or less, more preferably 20% by mass or less, and still more preferably 15% by mass or less. Moreover, Preferably it is 3-30 mass%, More preferably, it is 4-20 mass%, More preferably, it is 5-15 mass%.

  In addition, in the oral foam preparation of the present invention, the pH of a 25% by weight aqueous solution is preferably 2 or more, more preferably 3 or more, more preferably 4 or more, and still more preferably from the viewpoint of irritation to the oral mucosa and teeth. It is 5.5 or more, and preferably 7 or less from the viewpoint of flavor. Moreover, it is preferably pH 2 to 7, more preferably pH 3 to 7, more preferably pH 4 to 7, and still more preferably pH 5.5 to 7.

As shown in Examples below, in an oral foam preparation containing one or more selected from carbonates and bicarbonates and organic acids, trisodium phosphate is added to the amyl pillow packaging at 50 ° C. for one month. Even when stored, no expansion of the container is observed (Example 1, Table 1). On the other hand, even with the same phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium pyrophosphate, and sodium metaphosphate hardly give a stabilizing effect under the same conditions (Comparative Examples 1 to 9, Table 1).
Thus, in an oral foam preparation containing at least one selected from carbonate and bicarbonate and an organic acid, it is extremely effective to incorporate trisodium phosphate, and the high temperature of the oral foam preparation Long-term stabilization can be achieved under the environment.
That is, trisodium phosphate can be used as a stabilizer in an oral foam preparation containing at least one selected from carbonates and bicarbonates and organic acids.

The buccal foam preparation of the present invention can contain an excipient that is a formulation additive in addition to the components (a), (b) and (c) described above, whereby the buccal foam of the present invention. When the preparation is made into a powder, granule or tablet, the dispersibility, moldability and disintegration of the solid preparation can be further improved.
Excipients include sugar alcohols such as mannitol, sorbitol, xylitol, erythritol, maltitol, lactitol, reduced palatinose, isomalt; sugars such as lactose hydrate, fructose, sucrose, glucose, trehalose; corn starch, potato Starches such as starch, wheat starch, rice starch and tapioca starch; amino acids such as glycine and alanine; silicic acids such as light anhydrous silicic acid, synthetic aluminum silicate, magnesium aluminate metasilicate and calcium silicate; crystalline cellulose; Celluloses such as powdered cellulose; talc; titanium oxide and the like. One type of excipient may be used alone, or two or more types may be used.

Further, the oral foam preparation of the present invention is an additive generally used for pharmaceuticals and supplements such as lubricants, binders, coloring agents, corrigents, sweeteners, fragrances, preservatives and the like as other additives. An appropriate amount of one or more agents can be included.
Here, examples of the lubricant include magnesium stearate, calcium stearate, silicon dioxide, talc, sucrose fatty acid ester, sodium stearyl fumarate and the like.
Examples of the sweetening agent include aspartame, acesulfame potassium, saccharin, saccharin sodium, dipotassium glycyrrhizinate, stevia, thaumatin, and sucralose.

  Moreover, the intraoral foam preparation of this invention can contain a medicinal component. The medicinal component may be any kind and amount that does not impair the dispersibility, disintegration, moldability and the like of the preparation of the present invention, and is not particularly limited.

One or more types selected from (a) carbonates and bicarbonates of the present invention, (b) organic acid and (c) trisodium phosphate intraoral foam preparations include the following steps (1) and ( 2) In the step (1), trisodium phosphate is added to at least one of a powder raw material containing one or more selected from carbonates and bicarbonates, or a powder raw material containing an organic acid. It can manufacture by adding.
(1) A step of separately preparing a powder raw material containing at least one selected from acid salts and bicarbonates, and a powder raw material containing an organic acid. (2) Powders prepared in step (1), respectively. Step of mixing raw materials In other words, the oral foam preparation of the present invention is prepared by separately preparing a powder raw material containing one or more selected from carbonates and bicarbonates and a powder raw material containing an organic acid. , By adding trisodium phosphate to at least one of them and mixing them together.
By adopting a method in which one or more selected from carbonate and bicarbonate, organic acid and trisodium phosphate do not contact at the same time, the stabilizing effect by trisodium phosphate can be effectively exhibited (Table 5, Implementation) Example 6 and Comparative Example 15).

Step 1 is a step of separately preparing powder raw materials for one or more selected from (a) carbonates and bicarbonates and (b) organic acids.
The powder raw material can be prepared by adding one or more selected from (a) carbonate and bicarbonate and (b) an organic acid alone, but appropriately adding formulation additives such as excipients. It is preferable to do this. Here, examples of the formulation additive include the above-described excipients, lubricants, sweeteners, and the like.
In the present invention, at least one of a powder raw material containing one or more selected from carbonates and bicarbonates, or a powder raw material containing an organic acid, that is, either or both, trisodium phosphate is present. Added and prepared.
The preparation can be carried out using a known apparatus or the like by a known mixing and stirring method in the art. The mixing at this time is preferably performed without being wetted or humidified.

The powder raw material may be in the form of a non-granulated powder, but may be in the form of a granulated product such as a granule. In this case, it is preferable to use a powder raw material containing trisodium phosphate as a granulated product. The granulation treatment for obtaining the granulated product is roughly classified into a dry method and a wet method, and a wet method is preferable. The wet method is a process in which each component is kneaded with a solvent and then granulated, and a method and an apparatus used for production of a general preparation can be used as necessary. In addition, as a solvent used in this treatment, alcohols such as ethanol and isopropanol used for production of general preparations and water can be used as a solvent.
Examples of the granulation method include an extrusion granulation method, a rolling granulation method, a pulverization granulation method, a fluidized bed granulation method, a spray granulation method, and a crushing granulation method. Among these, the fluidized bed granulation method is preferable from the viewpoints of the dissolution characteristics and tableting characteristics of the granules obtained by granulation. The fluidized bed granulation method is a process of granulating each component while spraying a solvent or a mixed solution of a solvent and a binder, and a method or an apparatus used for producing a general preparation as necessary. Can be used.

  In step 2, a powder material containing one or more selected from carbonates and bicarbonates prepared separately in step 1 and a powder material containing an organic acid, at least one of which contains trisodium phosphate In such a manner, they are combined and mixed.

  Also in this step, appropriate amounts of additives such as lubricants, colorants, sweeteners, fragrances, preservatives can be added as appropriate. In addition, when manufacturing a granulated material or a tablet using the same, it is preferable to add a sweetener and a fragrance | flavor in this process from a viewpoint of the fall prevention of flavor.

  In addition, when the oral foam preparation of the present invention is a tablet, for tableting, a mixture of granulated powder raw materials is compressed (wet granule compression method), and a powder raw material not granulated In the case of tableting the mixture by direct compression (direct powder compression method), it is preferable to use the direct powder compression method because of the simplicity of the process. In any case, other components such as a binder and a disintegrant may be added to the powder raw material and mixed as necessary, and compression molded.

  Here, as the binder, povidone, hydroxypropyl cellulose, hypromellose phthalate ester, hydroxypropyl methylcellulose acetate succinate, magnesium metasilicate aluminate, synthetic aluminum silicate, light anhydrous silicic acid, calcium silicate, carmellose Sodium, ethylcellulose, methylcellulose, hypromellose, gum arabic, sodium alginate, dextrin, corn starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, pregelatinized starch, crystalline cellulose, powdered cellulose, low substituted hydroxypropylcellulose, Examples thereof include gelatin, pullulan, polyvinyl alcohol, and carboxyvinyl polymer. Among them, magnesium aluminate metasilicate, synthetic aluminum silicate, light anhydrous silicic acid, calcium silicate and the like can be mentioned.

  Disintegrants include crospovidone, carmellose calcium, carmellose, croscarmellose sodium, low-substituted hydroxypropylcellulose, corn starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, pregelatinized starch, carboxy Examples include methyl starch sodium.

For the compression molding, a method and an apparatus generally used for tablet formation such as a rotary tableting machine and a single tableting machine can be used.
In the case of using a granulated product, prior to the compression molding, the granulated product was dried using a fluidized bed dryer, a shelf dryer, etc., a screen mill, a jet mill, a hammer mill, a pin mill, etc. You may attach to operation required for manufacture of tablets, such as sieving using a sizing and a vibration sieve.

  The intraoral foam preparation of the present invention is sealed in a package formed of a moisture-proof material, and is packaged so that moisture intrusion from the outside of the package can be suppressed, and an effervescent oral product (pharmaceutical, food, supplement, etc.) and It is desirable to do. Here, examples of the moisture-proof material include a polyvinylidene chloride single layer, a multilayer material including polyvinylidene chloride, a multilayer material including aluminum foil, silica vapor deposition, or aluminum vapor-deposited single layer or multilayer material. Among them, a multilayer material including aluminum foil is preferable. Examples of the packaging form include SP packaging, PTP packaging, pillow packaging, and stick packaging, and a plurality of these may be combined.

With respect to the above-described embodiment, the following aspects are further disclosed in the present invention.
<1> Including the following steps (1) and (2), (a) one or more selected from carbonates and bicarbonates, (b) organic acids, (c) trisodium phosphate A method for producing a foamed preparation, wherein in step (1), trisodium phosphate is added to at least one of a powder raw material containing one or more selected from carbonates and bicarbonates, or a powder raw material containing an organic acid. How to add.
(1) A step of separately preparing a powder raw material containing at least one selected from carbonates and bicarbonates and a powder raw material containing an organic acid. (2) Powders prepared in step (1), respectively. The method according to <1>, wherein the preparation of the powder raw material in the step <2> step (1) of combining and mixing the raw materials includes a granulation treatment.
<3> The method according to <1> or <2>, further comprising a step of tableting the mixture obtained in the step (2).
<4> An oral foaming preparation containing (a) one or more selected from carbonate and bicarbonate, (b) an organic acid, and (c) trisodium phosphate, (c) triphosphate An oral foam preparation containing 0.8 to 12% by mass of sodium in terms of phosphoric acid with respect to a mixture of (a) one or more selected from carbonates and bicarbonates, and (b) organic acids.
<5> The pH of the 25% by weight aqueous solution of the intraoral foam preparation is preferably 2 or more, more preferably 3 or more, more preferably 4 or more, still more preferably 5.5 or more, and preferably 7 or less. Or Preferably it is pH 2-7, More preferably, it is pH 3-7, More preferably, it is pH 4-7, More preferably, it is pH 5.5-7.
<6> The content of (c) trisodium phosphate is preferably 3% by mass or more, more preferably 4% by mass or more, and still more preferably, in terms of phosphoric acid (PO ₄ ), relative to (b) the organic acid. Is 5% by mass or more, and preferably 30% by mass or less, more preferably 20% by mass or less, still more preferably 15% by mass or less, or preferably 3 to 30% by mass, more preferably 4%. The oral foam preparation according to <4> or <5>, which is ˜20 mass%, more preferably 5 to 15 mass%.
<7> The content ratio (equivalent ratio) of one or more selected from (a) carbonate and bicarbonate and (b) organic acid is preferably 1: 1 to 1: 5, more preferably 1: 1. The oral foam preparation according to any one of <4> to <6>, which is 1-1: 3, more preferably 1: 1.2-1: 2.
<8> The total content of (a) one or more selected from carbonates and bicarbonates and (b) organic acids is preferably 20% by mass or more, more preferably 25% by mass or more, and still more preferably. 30% by mass or more, and preferably 60% by mass or less, more preferably 50% by mass or less, still more preferably 45% by mass or less, or preferably 20 to 60% by mass, more preferably 25 to 25% by mass. The oral foam preparation according to any one of <4> to <7>, which is 50% by mass, more preferably 30 to 45% by mass.
<9> (a) The oral cavity according to any one of <4> to <8>, wherein at least one selected from carbonate and bicarbonate is sodium hydrogen carbonate, sodium sesquibicarbonate, sodium carbonate, or calcium carbonate. Inner foam preparation.
<10> (b) The oral foam preparation according to any one of <4> to <9>, wherein the organic acid is citric acid, malic acid, tartaric acid, or ascorbic acid.
<11> One or more types selected from carbonates and bicarbonates, and an oral foam preparation containing an organic acid, the method for stabilizing the oral foam preparation comprising a step of blending trisodium phosphate.
<12> A stabilizer for an intraoral foam preparation containing at least one selected from carbonates and bicarbonates, containing trisodium phosphate as an active ingredient, and an organic acid.

<13> The content of one or more selected from carbonates and bicarbonates in the preparation is preferably 4% by mass or more, more preferably 10% by mass or more, and further preferably 15% by mass or more. Is 35% by mass or less, more preferably 30% by mass or less, still more preferably 25% by mass or less, or preferably 4 to 35% by mass, more preferably 10 to 30% by mass, and still more preferably 15%. The intraoral foam preparation according to <4>, which is ˜25% by mass.
<14> The content of the organic acid in the preparation is preferably 5% by mass or more, more preferably 8% by mass or more, still more preferably 10% by mass or more, and preferably 50% by mass or less from the viewpoint of flavor. More preferably, it is 30 mass% or less, More preferably, it is 20 mass% or less, or Preferably it is 5-50 mass%, More preferably, it is 8-30 mass%, More preferably, it is 10-20 mass%. The intraoral foam preparation according to <4>.
<15> The oral foam preparation according to any one of <4> to <10>, which is a tablet selected from orally disintegrating tablets, chewable tablets, troche tablets, sublingual tablets, and buccal tablets.
<16> The oral foam preparation according to any one of <4> to <10>, which is a granule or powder.

  EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example.

<Evaluation method>
(1) Storage stability (expansion of container)
The test preparation was hermetically sealed in an aluminum pillow (size: 85 mm long × 150 mm wide, seal width: 10 mm, layer structure: PET 12 μm / PE 15 μm / AL 7 μm / PE 20 μm / PE 60 μm), and a constant temperature and humidity chamber (Platinum K) set to 50 ° C. and 50%. The product was stored in Espec Corp.) and the expansion of the aluminum pillow was observed for a maximum of 30 days. An aluminum pillow whose thickness changed by 1 mm or more from the initial thickness was defined as expansion, and the number of days without expansion was recorded. The thickness of the aluminum pillow was measured using a dial gauge.
In addition, the calculated amount of baking soda 2.5 g is about 600 cc of carbon dioxide gas generated. The aluminum pillow has a filling capacity of about 120 cc, so the reaction proceeds even a little. The filling amount was such that the container would eventually rupture as it progressed. The longer the days that do not swell, the better the storage stability and the better.

(2) Foaming amount A closed vessel such as a flask having two or more inlets and outlets with cocks, a water tank containing ion-exchanged water, and a collection vessel were prepared. 4.5 g of the test preparation was placed in a sealed container, and 13.5 g of ion-exchanged water was injected from one cock. After injection, tighten the cock filled with ion-exchanged water, put the glass tube attached to the other outlet into a water tank containing ion-exchanged water with a water temperature of 20 ± 1 ° C, release the cock, and generate in a sealed container The recovered gas was recovered in a recovery container by a water replacement method. Gas was collected until the test formulation was completely dissolved. A 300 mL graduated cylinder was used as the collection container, and the volume of the gas substituted in the graduated cylinder was read from the memory of the graduated cylinder to obtain the amount of foaming of the test preparation. The measured amount of foaming was expressed as the amount of foaming per gram of sodium bicarbonate by dividing by the weight of carbonate. By measuring the amount of foaming before storage and after storage at 50 ° C. for 30 days, the presence or absence of a reaction during storage was confirmed. The smaller the difference between the amount of foam before storage and the amount of foam after storage, the higher the storage stability.

(3) pH
4.5 g of the test preparation was dissolved in 13.5 g of purified water (25% by mass aqueous solution), and the pH was measured using a compact pH meter B-712 (manufactured by Horiba, Ltd.). The water in which the test preparation is dissolved is purified water and means that it also includes distilled water or ion exchange water.

(4) Flavor One expert panel evaluated the oral carbonic acid foamed preparations described in Comparative Examples and Examples according to the following criteria.
<Bitterness> 5: Strong, 4: Slightly strong, 3: Slightly weak, 2: Weak, 1: Almost not felt <Acid> 5: Strong, 4: Slightly strong, 3: Slightly weak, 2: Slightly, 1: Almost do not feel

Example 1 Production of Oral Foam Formulation (Powder) After weighing 2.5 g of sodium bicarbonate and 10 g of maltitol, these raw materials were put into a plastic bag and mixed to obtain a mixed raw material (1). On the other hand, separately from this, 1.9 g of citric acid and 0.07 g of trisodium phosphate were weighed and put into a plastic bag and mixed to obtain a mixed raw material (2). Next, the mixed raw material (2) was charged into the mixed raw material (1) and mixed to obtain a powdery intraoral foam preparation. The total amount of the obtained preparation was enclosed in an aluminum pillow.

Comparative Example 1
Sodium bicarbonate 2.5 g, maltitol 10 g, and citric acid 1.9 g were weighed and placed in a plastic bag and mixed to obtain a powdery intraoral foam preparation. The total amount of the obtained preparation was enclosed in an aluminum pillow.

Comparative Examples 2-9
After weighing 2.5 g of sodium hydrogen carbonate and 10 g of maltitol, it was put into a plastic bag and mixed to obtain a mixed raw material (1). Separately from this, 1.9 g of citric acid and the types of phosphates shown in Table 1 were weighed in the blending amounts shown in Table 1, and then put into a plastic bag and mixed to obtain a mixed raw material (2). Next, the mixed raw material (2) was added to and mixed with the mixed raw material (1) to obtain a powdery intraoral foam preparation. The obtained preparation was enclosed in an aluminum pillow.

  From Table 1, only when trisodium phosphate is blended among phosphates, the number of days that the container does not expand when stored at 50 ° C. exceeds 30 days, and the storage stability is particularly small with little increase in volume during storage. It was shown to be expensive.

Examples 2 to 5 Manufacture of an oral foam preparation (powder) A powdered oral foam preparation was prepared in the same manner as in Example 1 except that the amount of trisodium phosphate was changed to the amount shown in Table 2. did.

Comparative Examples 10-12
A powdery oral foam preparation was produced in the same manner as in Example 1 except that the amount of trisodium phosphate was changed to the amount shown in Table 2.

  From Table 1 (Example 1) and Table 2, in order to express the effect of storage stability, the amount of (c) trisodium phosphate added to the mixture of (a) carbonate and (b) organic acid On the other hand, in terms of phosphoric acid, it is good when it is 0.8% or more, and from the viewpoint of flavor, increasing the blending amount of trisodium phosphate increases the bitterness, so 12% or less is good. It was considered.

Example 6 Manufacture of an intraoral foam preparation (tablet) 17.04 g of sodium bicarbonate, 35.00 g of erythritol, and 22.60 g of maltitol were weighed and mixed in a plastic bag to obtain a mixed raw material (1). On the other hand, 12.96 g of citric acid and 3.00 g of trisodium phosphate were weighed separately and put into a plastic bag and mixed to obtain a mixed raw material (2). Next, 0.4 g of aspartame, 5.00 g of fine cellulose, 1.00 g of fine silicon dioxide, 3.00 g of calcium stearate, and mixed raw material (2) are added to the mixed raw material (1), mixed, and mixed raw material ( 3) was obtained.
The mixed raw material (3) was compression-molded into a cylindrical shape having a tablet of 900 mg and a diameter of 13 mm using a rotary tableting machine to obtain an intraoral foam preparation of a tablet. 15 g of the obtained preparation was enclosed in an aluminum pillow.

Comparative Example 13
An oral foam preparation was produced in the same manner as in Example 6 except that trisodium phosphate was not added.

Example 7 Production of Oral Foaming Formulation (Granule) 17.04 g of sodium bicarbonate, 35.00 g of erythritol, and 22.60 g of maltitol were weighed and mixed in a plastic bag to obtain a mixed raw material (1). . The mixed raw material (1) is charged into a fluid bed granulator (FLO-5M manufactured by Freund Corporation), the blowing temperature is 83 ° C., the air volume is 2 m 3 / min, the spray liquid temperature is 23 ° C., the spray speed is 50 mL / min, and the spray time is 25.0 min. After spraying tap water and granulating under the above conditions, drying was performed until the exhaust temperature reached 50 ° C. to prepare granules. Separately, 12.96 g of citric acid and 3.00 g of trisodium phosphate were weighed and mixed in a plastic bag to obtain a mixed raw material (2). Next, 0.4 g of aspartame and the mixed raw material (2) were added to the granulated product (granule) obtained in (1) and mixed to obtain a granular oral foaming preparation. 15 g of the obtained preparation was enclosed in an aluminum pillow.

Comparative Example 14
An oral foam preparation was produced in the same manner as in Example 7 except that trisodium phosphate was not added.

  From Table 3, it was shown that the number of days when the container does not swell when stored at 50 ° C. exceeds 30 days only for the formulation containing trisodium phosphate, and the storage stability is particularly high with little volume increase during storage. .

Examples 8 to 13 Production of an oral foam preparation (powder) An oral foam preparation was produced in the same manner as in Example 1 except that the amounts of citric acid and trisodium phosphate were changed to the amounts shown in Table 4. .

From Table 4, it was considered from the results of the foaming amount and flavor before storage that the larger the acid blending ratio, the larger the foaming amount, and the organic acid / carbonate content ratio (equivalent ratio) should be 1 or more.
Moreover, it was thought that pH 2-7 was preferable from the result of pH and flavor.

Comparative Example 15 Production of Oral Foam Formulation (Tablet) Sodium hydrogen carbonate 17.04 g, erythritol 35.00 g, maltitol 22.60 g, citric acid 12.96 g, trisodium phosphate 3 g, aspartame 0.4 g, fine cellulose 5 0.000 g, fine silicon dioxide 1.00 g, and calcium stearate 3.00 g were put into a plastic bag and mixed to obtain a mixed raw material. Subsequently, the mixed raw material was compression-molded into a cylindrical shape having a tablet of 900 mg and a diameter of 13 mm using a rotary tableting machine to obtain an intraoral foaming preparation of a tablet. 15 g of the obtained preparation was enclosed in an aluminum pillow.
From Table 5, after preparing the mixture containing a component (a) and the mixture containing a component (b) and a component (c) separately, the tablet manufactured by the method of combining both and tableting is the component (a ), (B) and (c) were compared with the tablet produced by the method of tableting, it was shown that the amount of foaming after storage was small and the storage stability was particularly good.

Claims (12)

An oral foam preparation comprising (a) one or more selected from carbonates and bicarbonates, (b) an organic acid, and (c) trisodium phosphate, comprising the following steps (1) and (2): In the production method, in step (1), trisodium phosphate is added to at least one of a powder raw material containing one or more selected from carbonates and bicarbonates, or a powder raw material containing an organic acid. Method.
(1) A step of separately preparing a powder raw material containing at least one selected from carbonates and bicarbonates and a powder raw material containing an organic acid. (2) Powders prepared in step (1), respectively. Process of mixing and mixing raw materials   The method according to claim 1, wherein the preparation of the powder raw material in step (1) includes a granulation treatment.   Furthermore, the method of Claim 1 or 2 including the process of tablet-molding the mixture obtained at the process (2).   (A) one or more selected from carbonates and bicarbonates, (b) an organic acid, and (c) an oral foaming preparation containing trisodium phosphate, (c) trisodium phosphate, An oral foam preparation containing 0.8 to 12% by mass in terms of phosphoric acid with respect to a mixture of (a) one or more selected from carbonates and bicarbonates, and (b) organic acids.   The oral foam preparation according to claim 4, wherein the pH of the 25 mass% aqueous solution of the oral foam preparation is 2-7.   The oral foam preparation according to claim 4 or 5, wherein the content of (c) trisodium phosphate is 3 to 30% by mass in terms of phosphoric acid with respect to (b) the organic acid.   The content ratio of at least one selected from (a) carbonate and bicarbonate and (b) an organic acid is 1: 1 to 1: 5 in equivalent ratio. Oral foam preparation.   The oral foaming according to any one of claims 4 to 7, wherein the total content of (a) one or more selected from carbonates and bicarbonates and (b) organic acids is 30 to 60% by mass. Formulation.   The oral foam preparation according to any one of claims 4 to 8, wherein at least one selected from (a) carbonate and bicarbonate is sodium bicarbonate, sodium sesquibicarbonate, sodium carbonate or calcium carbonate.   (B) The oral acid foam preparation according to any one of claims 4 to 9, wherein the organic acid is citric acid, malic acid, tartaric acid or ascorbic acid.   The stabilization method of the said buccal foam preparation including the process of mix | blending trisodium phosphate in the buccal foam preparation containing 1 or more types chosen from carbonate and bicarbonate, and an organic acid.   A stabilizer for an intraoral foam preparation containing tri-sodium phosphate as an active ingredient and containing at least one selected from carbonates and bicarbonates and organic acids.