JP7075809B2 - Tablets - Google Patents

Description

The present invention comprises a sodium hydrogen carbonate, sodium carbonate, an organic acid, a cationized polymer, a beating tablet having a specific tableting hardness and a liquid absorption time A, sodium hydrogencarbonate as a raw material thereof, and sodium hydrogencarbonate thereof. The present invention relates to a method for producing a beating tablet using.

Conventionally, tableting tablets containing sodium hydrogen carbonate have been widely used as bath salts, cleaning agents, pesticide preparations, pharmaceutical preparations, confectionery and the like. As for bath salts, in recent years, it is common to add bath salts to bath water for the purpose of giving aroma and color to the bath water to refresh the feeling of bathing, activating metabolism, improving sensitivity to cold, and obtaining a hot bath effect. It is widely used, and various forms such as bath salts, tablets, and liquids are sold. Among them, bathing agents containing carbon dioxide gas generators that combine carbonates and acids expand the capillaries by the carbon dioxide gas generated in the bath water and promote metabolism, so that blood circulation is promoted and fatigue is recovered. The effect of carbon dioxide is expected, and most of them are distributed in the form of beaten tablets.
In general, a tableting method is a manufacturing method in which a powdered raw material is formed by applying a high pressure to form a formulation. In this manufacturing method, tableting hardness is an important point for improving the shape retention of tableted tablets. If the tableting hardness is low, cracks and cracks are likely to occur, and damage occurs during manufacturing, storage, transportation, etc. On the other hand, if the tableting hardness is too high, the disintegration property deteriorates and the function as a tableting tablet is deteriorated. This is because there is a problem that it cannot be exerted. Although various approaches have been proposed in the fields of bath salts, cleaning agents, pesticide preparations, pharmaceutical preparations, confectionery, etc. (for example, Patent Documents 1 to 5 etc.) in order to obtain appropriate tableting hardness, these Since the proposal is to improve the tablet hardness and disintegration property of a specific tablet in each field, it has been difficult to apply it to other tablets having different compositions.

Japanese Unexamined Patent Publication No. 2012-092031 Japanese Unexamined Patent Publication No. 06-122900 Japanese Unexamined Patent Publication No. 06-157203 Japanese Unexamined Patent Publication No. 2015-21258 Japanese Unexamined Patent Publication No. 2011-030437

Among the bath salts, the bath salt containing a cationized polymer is one of the bath salts that imitates a natural hot spring, as it gives the skin a feeling of wearing bath water and a moist feeling after bathing. It has been well received as a bath salt. In addition, the cationized polymer is generally used as one of the conditioning bases in the cosmetics / cosmetics field, especially in shampoos. However, the present inventor has found through experiments that the tableting hardness of tableted tablets is significantly reduced by blending the cationized polymer.
Therefore, it is an object of the present invention to provide a tableted tablet having high formulation stability and good disintegration property by combining this cationized polymer with a carbon dioxide gas generator composed of a carbonate and an acid.

As a result of various studies on tableting tablets containing sodium hydrogencarbonate, sodium carbonate, organic acid, and cationized polymer, the present inventor surprisingly made the tableting hardness equal to or higher than a specific value, which is described in detail below. By setting the liquid absorption time A to be described within a specific range, the shape-retaining property is excellent in that damage does not occur during manufacturing, storage, and transportation, and further, the disintegration property becomes higher as the tableting hardness increases. Despite the common technical knowledge in the field of tableting, the tableting of the present invention is also excellent in tablet disintegration, that is, both shape retention and disintegration can be obtained with a specific tableting hardness. The present invention was completed.
In addition, the present inventor specifically beats sodium hydrogencarbonate containing a specific crystal and having a specific bulk specific gravity as a raw material for a tablet containing the cationized polymer of the present invention. It was also found that the tablet hardness could be improved.

Specifically, the present invention has the following gist.
1. 1. A tableting tablet containing sodium hydrogen carbonate, sodium carbonate, an organic acid, and a cationized polymer, having a tableting hardness of 2 kgf or more, and having a liquid absorption time A of 45 minutes or more and 65 minutes or less.
Liquid absorption time A: At an environmental temperature of 25 ° C., a cylindrical hammered tablet having a diameter of 30 mm and a total volume of 15 g in a charley containing 5 ml of liquid paraffin and having a circular top and bottom with respect to the liquid surface of liquid paraffin. 2. The time from when the paraffin is placed vertically until the liquid paraffin reaches the top of the beaten tablet. 1. The average ratio of the following a line to the following b line (a line / b line) is 2 or more and 4 or less, and the bulk specific density is 1.05 g / mL or less. Sodium hydrogen carbonate as a raw material for tableting as described in 1.
Line a: Opposite line with the longest straight line connecting the ends of one sodium hydrogen carbonate crystal b line: Opposite line with the longest straight line orthogonal to line a 3. Use sodium hydrogencarbonate having an average ratio of the following a line to the following b line (a line / b line) of 2 or more and 4 or less and a bulk specific gravity of 1.05 g / mL or less as a raw material. Characteristic 1. The method for producing a tablet as described in 1.
Line a: Opposite line with the longest straight line connecting the ends of one sodium hydrogen carbonate crystal b line: Opposite line with the longest straight line orthogonal to line a 4. Sodium hydrogen carbonate, sodium carbonate, organic acid, the average of the ratio of the following a line to the following b line (a line / b line) is 2 or more and 4 or less, and the bulk specific gravity is 1.05 g / mL or less. 1. Obtained by tableting cationized cellulose. The tablet as described in.
Line a: Opposite line with the longest straight line connecting the ends of one sodium hydrogen carbonate crystal b line: Opposite line with the longest straight line orthogonal to line a

The tableted tablet of the present invention is not damaged such as cracks and cracks during its manufacture, storage and transportation, and not only exhibits excellent shape-retaining property, but also exhibits excellent shape-retaining property with air. Since the contact surface of the product can be suppressed to the minimum, the storage stability is also improved, and the effect of extremely excellent formulation stability is exhibited.
It is known that when the tableting hardness of an effervescent tablet is improved, the disintegration property of the tablet when it is put into water deteriorates, and the generated carbon dioxide gas cannot be efficiently dissolved in water. Despite its high tableting hardness, good tablet disintegration property can be obtained, and the generated carbon dioxide gas can be efficiently dissolved in water.
That is, the tableted tablet of the present invention is extremely useful because it has both pharmaceutical stability and disintegration property.

Both the left and right figures are micrographs illustrating lines a and b in the present invention.

Hereinafter, the tableted tablet of the present invention will be described in detail.
The tableting of the present invention is a combination of sodium hydrogen carbonate, sodium carbonate, an organic acid, and a cationized polymer to form a tablet having a tableting hardness of 2 kgf or more and a liquid absorption time A of 45 minutes or more and 65 minutes or less. However, it is important to achieve both formulation stability and disintegration.
In the tableting tablet of the present invention, any sodium hydrogen carbonate, sodium carbonate, organic acid, or cationized polymer can be used as long as the tableting hardness can be 2 kgf or more and the liquid absorption time A can be 45 minutes or more and 65 minutes or less. can do.

<Sodium hydrogen carbonate>
Among them, sodium hydrogencarbonate contains the specific crystals described below, and when sodium hydrogencarbonate having a specific bulk specific gravity is used, the tableting hardness of the tablet of the present invention is 2 kgf or more and the liquid absorbing liquid. The time A can be 45 minutes or more and 65 minutes or less, which is preferable.
It is preferable to use sodium hydrogencarbonate having an average of 2 or more and 4 or less in the “ratio of a-line to b-line (a-line / b-line)” described below in terms of improving the hardness of the tableting tablet of the present invention. ..
(About line a / line b)
For lines a and b in the present invention, sodium hydrogen carbonate is observed with a microscope and image analysis is performed focusing on one crystal. More specifically in FIG. 1, line a means the opposite end line having the longest straight line connecting the ends of one sodium hydrogen carbonate crystal, as shown by the solid lines in both the left and right views of FIG. Lines b and b mean the opposite end lines having the longest straight line orthogonal to the line a, as shown by the dotted lines in both the left and right figures of FIG.
The ratio of the a line to the b line (a line / b line) is a value calculated by dividing the value of the a line by the value of the b line. This observation and measurement calculation were performed for 15 crystals different depending on the microscope, and the average value was taken as the average of the ratio (a line / b line) of the a line and the b line of the present invention.
The average ratio of a-line to b-line (a-line / b-line) of sodium hydrogen carbonate is preferably 2 or more and 4 or less, but more preferably 2 or more and 3 or less, and 2 or more and 2.5. The following is particularly preferable.
Further, the sodium hydrogen carbonate used in the tableting of the present invention contains 30% or more of crystals in which the ratio of a-line to b-line (a-line / b-line) is 2 or more and 4 or less with respect to the total amount of sodium hydrogen carbonate. It is preferably contained in an amount of 40% or more, more preferably 50% or more, and particularly preferably 50% or more. The content of the crystal can be determined by analyzing an image obtained by observing sodium hydrogen carbonate with a microscope.

It is preferable to use sodium hydrogencarbonate having a "bulk specific gravity" of 1.05 g / mL or less, which will be described below, in terms of improving the hardness of the tableting tablet of the present invention.
(About bulk specific density)
The bulk specific gravity of the present invention is generally called a loose bulk specific density (density). It can be calculated by filling a container with a capacity of 100 mL with sodium hydrogen carbonate "loosely" without tapping and measuring the weight of the filled sodium hydrogen carbonate.
The upper limit of the bulk specific gravity of sodium hydrogen carbonate is preferably 1.05 g / mL or less, more preferably 1.01 g / mL or less, and particularly preferably 0.95 g / mL or less. The lower limit of the bulk specific gravity is preferably 0.70 g / mL or more, more preferably 0.75 g / mL or more, and particularly preferably 0.80 g / mL or more.

Further, the sodium hydrogen carbonate used in the tableting tablet of the present invention preferably has a specific compressibility.
The compression ratio in the present invention is calculated by the following measurement method and calculation formula.
(1) 15 g of sodium hydrogen carbonate was weighed and filled in a cylindrical mortar having a base area of 7.11 cm ² .
(2) The height of the filled sodium hydrogen carbonate of (1) was calculated from the bulk specific gravity of the present invention and used as the thickness before compression.
(3) The thickness of sodium hydrogen carbonate after compression at a pressure of 25 kN was measured with a hydraulic pump type tableting machine and used as the thickness after compression.
[Compression rate calculation formula]
Compression rate (%) = (thickness before compression-thickness after compression) ÷ thickness before compression The lower limit of this compression rate is preferably 35% or more for the sodium hydrogen carbonate used in the tableting tablet of the present invention. , 36% or more is more preferable, and 37% or more is particularly preferable. Further, the upper limit of the compression rate is preferably 50% or less, more preferably 48% or less, and particularly preferably 45% or less.
Further, the sodium hydrogen carbonate used for the tableting of the present invention preferably has an average particle size of larger than 150 μm in terms of improving the tableting hardness.

Sodium hydrogen carbonate used in the tableting of the present invention, in particular, the average ratio of a-line to b-line (a-line / b-line) is 2 or more and 4 or less, and the bulk specific gravity is 1.05 g / mL or less. As long as the sodium hydrogen carbonate of is satisfied with these regulations, any one including commercially available products can be adopted. Further, even sodium hydrogencarbonate that does not satisfy the regulations can be made into sodium hydrogencarbonate that satisfies these regulations by means such as classification by a sieve or crushing.
7.11 cm using only 15 g of sodium hydrogen carbonate with an average ratio of a-line to b-line (a-line / b-line) of 2 or more and 4 or less and a bulk specific gravity of 1.05 g / mL or less. The hardness of the tableting tablet obtained by filling the cylindrical mortar of No. ² and compressing it with a hydraulic pump type tableting machine at a pressure of 25 kN was in the range of 4.0 kgf or more and 6.0 kgf or less.
In the tableting tablet of the present invention, the sodium hydrogen carbonate is preferably in the range of 20% by weight or more and 75% by weight or less, more preferably 40% by weight or more and 65% by weight or less, based on the total weight of the tableting tablet. ..

<About sodium carbonate>
In the tableting tablet of the present invention, it is preferable to use an anhydride for sodium carbonate, preferably in the range of 3% by weight or more and 20% by weight or less with respect to the total weight of the tableting tablet, and 5% by weight or more and 10% by weight or less. Is more preferred.
The sodium carbonate used in the tableting tablet of the present invention preferably has an average particle size of larger than 150 μm in terms of improving tableting hardness.
<About organic acids>
The organic acid contained in the beaten tablet of the present invention is selected from fumaric acid, citric acid, malic acid, tartaric acid, succinic acid, maleic acid, phthalic acid, glutaric acid, adipic acid, benzoic acid, salicylic acid and oxalic acid. One kind or two or more kinds can be mentioned. Of these, fumaric acid and / or succinic acid are more preferable from the viewpoint of pharmaceutical stability.
In the tableting tablet of the present invention, the blending amount of the organic acid is preferably in the range of 10% by weight or more and 75% by weight or less, and more preferably in the range of 20% by weight or more and 55% by weight or less with respect to the total weight of the tableting tablet. Further, it is particularly preferable that the content is less than 30% by weight.

<About cationized polymers>
Examples of the cationized polymer that can be used in the tableting of the present invention include those available on the market.
Examples of the cationized cellulose include O- [2-hydroxy-3- (trimethylammonio) propyl] hydroxyethyl cellulose chloride, O- [2-hydroxy-3- (lauryldimethylammonio) propyl] hydroxyethyl cellulose chloride, and chloride. As the cationized guar gum, for example, O- [2-hydroxy-3- (trimethylammonio) propyl] guar gum chloride, and as the cationized dextran, for example, dimethyldialylammonium / hydroxyethylcellulose copolymer and the like, for example, dextran chloride. The hydroxypropyltrimethylammonium ether is, for example, the cationized acrylamide copolymer, for example, dimethyldiallylammonium chloride / acrylamide copolymer, and the cationized collagen is, for example, N- [2-hydroxy-3- (trimethylammoni) chloride. E) propyl] Hydrolyzed collagen, and other examples include cationized starch.
Among these, cationized cellulose, cationized guar gum or cationized dextran is preferable in that when used as a bath agent, the feel of a bath water imitating a natural hot spring can be obtained and the solubility in water is obtained. In particular, the cationized cellulose preferably has a molecular weight of 100,000 to 2 million and a degree of cationization (the number of moles of cation groups added per glucose) of 0.1 to 0.4 from the viewpoint of solubility in water. .. In the tableting tablet of the present invention, the blending amount of the cationized polymer is preferably 0.01 to 3.0% by weight, more preferably 0.1 to 2.0% by weight, based on the total weight of the tableting tablet. , More preferably 0.5 to 1.0% by weight.

<About tableting>
The tableting tablet of the present invention is produced by mixing the above components and tableting, and a well-known tableting machine can be used. A well-known locking machine is a device that fills a mortar with a powder mixture and compresses it between the lower and upper pestle. The tableting machine is a single-shot tableting machine in which a pair of upper and lower mortars move up and down in one mortar to compress it. There is a rotary tableting machine in which a series of operations of filling, compression, and ejection are continuously performed while rotating. As a well-known locking machine, a single-shot locking machine such as a Shiga Seisakusho tableting machine can be used, and a rotary locking machine such as Kikusui Seisakusho Co., Ltd. can be used. Further, it is also possible to produce a tablet by single-shot tableting using a die according to the weight of the tablet to be produced and, for example, a hydraulic pump of Labonect Co., Ltd., RIKEN Equipment Co., Ltd., or the like. The tableting method should not be limited, and it can be produced by a direct powder tableting method (direct pressing method) or a granule tableting method (indirect compression method). In addition, the mixing order and mixing method of each component are appropriately selected.
When using a tableting machine, the size of the tablet is preferably 80 mm or less in diameter (length of one side in the case of polygon) in the case of a columnar shape, more preferably 60 mm or less, and 10 mm. The above is preferable, and 30 mm or more is more preferable. The thickness of the tablet is preferably 20 mm or less, more preferably 17 mm or less, more preferably 5 mm or more, still more preferably 8 mm or more, still more preferably 10 mm or more. The shape of the tablet is not particularly limited, but is selected from a columnar shape, a block shape, a spherical shape, a hemispherical shape, a polygonal shape, and the like, but a columnar shape is preferable.

<About tableting hardness>
The tableting hardness of the tablet of the present invention is determined by applying a pressure to the vertical direction (diameter direction) of the tablet using a force gauge (for example, digital force gauge: MODEL-RZ-50, manufactured by Aiko Engineering Co., Ltd.). It means the maximum pressure when cracks and cracks occur.
Specifically, the measurement is carried out according to the tableting hardness measuring method with a 15 g tablet described below.
<Method for measuring tableting hardness with 15 g tablet>
When pressure is applied to the side surface (diameter direction) of a columnar tablet that has been tableted with a pressure of 25 kN with a diameter of 30 mm, a thickness of about 15 mm, and a total volume of 15 g under the following measurement conditions, and cracks or cracks occur. Measure the maximum pressure of.
[Measurement condition]
-Digital force gauge: MODEL-RZ-50 (manufactured by Aiko Engineering Co., Ltd.)
-Electric stand: MODEL-1308U (manufactured by Aiko Engineering Co., Ltd.)
-Measurement attachment: 012B (circular, diameter 15 mm)
・ Electric stand speed at the time of measurement: 5 mm / min
The tableting tablet of the present invention has a tableting hardness of 2 kgf or more measured by the above-mentioned measuring method. Among them, those having a weight of 2.5 kgf or more are preferable, and those having a weight of 3 kgf or more are more preferable. The upper limit of the tableting hardness of the tablet of the present invention is preferably 6.5 kgf or less, more preferably 6.0 kgf or less.

<About liquid absorption time A>
The tableting tablet of the present invention is characterized in that the liquid absorption time A described below is 45 minutes or more and 65 minutes or less.
The liquid absorption time A is a columnar punched tablet compacted with a pressure of 25 kN having a diameter of 30 mm, a thickness of about 15 mm, and a total volume of 15 g, and a circular top and bottom flow in a charley containing 5 ml of liquid paraffin and having a diameter of 90 mm. It is placed so as to be perpendicular to the liquid surface of paraffin, and means the time from immediately after placement until the liquid paraffin reaches the top of the beaten tablet.
The liquid paraffin used for measuring the liquid absorption time A may have a kinematic viscosity of 8 to 17 mm ² / s at 37.8 ° C., for example, Liquid Paraffin No. 1 manufactured by Sanko Chemical Industry Co., Ltd. 70-S and the like can be exemplified.
The liquid absorption time A of the tableting tablet of the present invention is characterized by being 45 minutes or more and 65 minutes or less, and more preferably 45 minutes or more and 60 minutes or less.
<About void area and porosity>
The method for measuring the void area of the tablet in the present invention is not particularly limited, but can be calculated, for example, by image analysis of the cross section thereof. Specifically, the following measurement method can be used, which will be described in detail by a specific example described later. That is, a columnar stamped tablet compacted with a pressure of 25 kN having a diameter of 30 mm, a thickness of about 15 mm, and a total area of 15 g is roughly divided into two at the diameter portion, and an image of the cross section thereof is divided into a raw material phase and a bubble phase (void portion). The area of the bubble phase (void portion) (mm ² ) can be regarded as the void area of the present invention, and the void ratio (%) can be calculated from this image analysis.
The tableting tablet of the present invention preferably has an actual void area of 0.15 mm ² or less in the specific examples described later. Further, the porosity in the specific examples described later is preferably in the range of 2 to 15%, and more preferably in the range of 5 to 15%.

The beating tablet of the present invention is used for bathing agents, artificial tooth cleaning agents, cleaning agents for washing toilets, foaming cleaning agents such as cleaning agents for drains, pesticide preparations such as jumbo agents for paddy fields, effervescent confectionery, and head spa applications. Can also be used.
When the beaten tablet of the present invention is used as a bath agent, in addition to the above-mentioned sodium hydrogen carbonate, sodium carbonate, organic acid, and cationized polymer, various components known in the field of bath salts are required. (Hereinafter referred to as "arbitrary component") may be contained alone or in combination of two or more. Hereinafter, optional components that can be contained when the tableted tablet of the present invention is used as a bath agent are illustrated, but it goes without saying that the components are not limited to those described here.

<Inorganic salts (excluding sodium hydrogen carbonate and sodium carbonate)>
Sulfides such as sodium chloride, potassium chloride, ammonium chloride, carbonates such as sodium sesquicarbonate, calcium carbonate, potassium carbonate, magnesium carbonate, heavy magnesium carbonate, sodium sulfate, magnesium sulfate, aluminum sulfate, iron sulfate, potassium aluminum sulfate , Sulfides such as sodium thiosulfate, calcium thiosulfate, potassium thiosulfate, sodium hyposulfate, nitrates such as sodium nitrate, potassium nitrate, calcium nitrate, phosphates such as sodium phosphate, calcium hydrogen phosphate, calcium silicate, Magnesium silicate, calcium sulfide, calcium bicarbonate, potassium sulfide, sodium sulfide, ammonium sulfide, barium sulfide, zinc sulfide, tin sulfide, antimony sulfide, iron sulfide, carbon disulfide, sulfides such as phosphorus sulfide, sodium hydroxide, Hydrooxides such as calcium hydroxide, borosand, boric acid, calcium oxide, potassium bromide, potassium permanganate and the like can be mentioned. Among the above-mentioned inorganic salts, sodium chloride, sodium sulfate, potassium aluminum sulfate, magnesium sulfate, calcium carbonate, and calcium silicate are suitable, and in particular, when the tablet of the present invention is used as a bathing agent, sodium sulfate and silica are suitable. It preferably contains calcium acid, which is also suitable as a formulation aid.
<Oil components>
Natural fats and oils such as nuka oil, jojoba oil, olive oil and soybean oil; hydrocarbons such as vaseline, squalane and squalane; alcohols such as stearyl alcohol and cetyl alcohol; fatty acids such as myristic acid, lauric acid and palmitic acid; monoglyceride, triglyceride and the like. Synthetic oils and fats; silicone and the like. These can also be contained as a moisturizing ingredient.
<Polymer substances (excluding cationized polymers)>
Carboxymethyl cellulose and its salts, hydroxyethyl cellol and its salts, alginic acid and its salts, polyphosphoric acid and its salts, polyacrylic acid and its salts, pyrophosphate and its salts, crystalline cellulose, arabic rubber, xanthan gum, guar gum, locust beans Examples thereof include gum, gelatin, styrene polymer emulsion, dextrin, polyethylene glycol, liquid paraffin, casein, polyoxyethylene polyoxypropylene glycol, polyethylene glycol monostearate and the like. Among the above-mentioned polymer substances, when the tablet of the present invention is used as a bath agent, it preferably contains liquid paraffin, dextrin, and polyethylene glycol, and these are also suitable as a pharmaceutical auxiliary.

<Fragrance ingredients / essential oil ingredients>
Hakka, Eucalyptus, Lemon, Barbena, Citronella, Kayapte, Salvia, Thyme, Clove, Rosemary, Hisop, Jasmine, Chamomile, Neroli, Yomogi, Perilla, Majorum, Laurel, Juniperberry, Natsumegu, Ginger, Onion, Garlic, Lavender, Bergamotte, Clary Sage, Peppermint, Basil, Rose, Petit Glen, Cinnamon, Mace, Citral, Citronellal, Borneol, Linaroll, Geraniol, Nerol, Loginol, Orange, Artemisia, Camphor, Mentor, Cineol, Eugenol, Hydroxy Citronellal, Sandalwood, Costas, Labdanum, Amber, Musk, α-Pinen, Limonen, Methyl salicylate, Sojutsu, Byakujutsu, Chamomile, Keigai, Koboku, Senkyu, Tohi, Touki, Shokyo, Shakuyaku, Oubaku, Ogon, Sanshin, Keihi, Carrot Essential oils such as dok cutlet, shobu, gaiyou, matsubusa, byakushi, juyaku, uikyo, chimpi, chamomile, amyl nitrite, trimethylcyclohexanol, allylsulfide, nonyl alcohol, decyl alcohol, phenylethyl alcohol, methyl carbonate, ethyl carbonate, phenyl "Perfume and Flavor Materials of Natural Origin", Stephen Arctander, Allure, such as acetic acid ester, guaiacol, indole, cresol, thiophenol, p-dichlorobenzene, p-methylquinoline, isoquinoline, pyridine, absins oil acetic acid, acetic acid ester. Co. (1960), "Encyclopedia of Fragrances", edited by Japan Fragrance Association, Asakura Shoten (1989), "Flower oils and Floral Compounds In Company", Danute Pajaujis Anonys, Allured Pub. Co. (1993), "Perfume and Flavor Chemicals (aroma chemicals)", Vols. I and II, Stephen Arctander, Allured Pub. Co. (1994), "Basic knowledge of fragrances and fragrances", edited by Motoki Nakajima, Sangyo Tosho (1995), "Synthetic fragrance chemistry and product knowledge", Motokazu Indo, Chemical Industry Daily (1996), "Encyclopedia of fragrances" Examples include the fragrance component and the essential oil component described in "Encyclopedia", edited by Mitsuyoshi Yatagai, and Maruzen (2005). These fragrance components and essential oil components may be used alone or in combination of two or more as a compounded fragrance. Further, a solvent, a fragrance stabilizer and the like can be appropriately mixed and used as a fragrance composition.

<Crude drugs>
Examples include chamomile, gaiyou, kampi, fennel, schizonepeta, cinnamon, iris, chimpanzee, cinnamon, iris, touki, touhi, houttuynia cordata, pepper, white hippo, gobo, carrot, garlic, clove, rosemary, yuzu, thyme and the like. These may be contained as an extract. It can also be contained as a fragrance or a moisturizing ingredient.
<Enzymes>
Examples thereof include trypsin, α-chymotrypsin, bromelain, papain, protease, proctase, seratiopeptidase, lysozyme, pepsin and the like.
<Pigments and minerals>
Titanium oxide, talc, clay, kaolin, red iron oxide, yellow iron oxide, mica, mica, titanium, titanium dioxide, zinc oxide, bentonite, zeolite, anhydrous silicic acid, metasilicic acid, neutral white clay, etc. And so on. Among the above pigments and minerals, when the tablet of the present invention is used as a bath agent, it preferably contains titanium oxide, which is also suitable as a pharmaceutical aid.
<Dyes>
Blue No. 1, Blue No. 2, Red No. 102, Red No. 106, Red No. 227, Red No. 230 (1), Yellow No. 4, Yellow No. 5, Yellow No. 202 (1), Green No. 3, Green No. 201 Examples include legal pigments such as No., Green No. 204, and Orange No. 205, and natural pigments such as chlorophyll, riboflavin, annat, and anthocyanin.
<Vitamins and their derivatives>
Examples thereof include vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, vitamin F, vitamin H, pantothenic acid, nicotinic acid or a derivative thereof, vitamin E nicotinic acid ester, tocopherol acetate, sodium ascorbate and the like. These can also be contained as a moisturizing ingredient.

<Seaweed extracts>
Green algae such as Anaaosa, Mill, Usbaaonori, Hitoegusa, Sujiaonori, Kasanori, Heraiwazuta, Hanemo, Nagamil, etc. , Hondawara, brown algae plants such as sea urchin, malva amanori, asakusanori, susabinori, sea elephant, hirakusa, maxa, triashi, hanafunori, owl funori, tosakanori, splinter, green laver, red algae Examples thereof include extracts obtained from red algae plants and the like. These can also be contained as a moisturizing ingredient.
<Plant extracts>
Examples thereof include aloe extract, green tea extract, hechima water, chamomile extract, citrus extract, comfrey extract, eucalyptus extract, royal jelly extract, lemon extract, rose hip extract, and peach leaf extract. There are no particular restrictions on the extraction method. These can also be contained as a moisturizing ingredient.
<Cooling substances>
Examples thereof include menthol derivatives such as menthol, camphor and thymol, monocyclic compounds, bicyclic alcohols, tricyclic alcohols, tricyclic amides, and peppermint oil.
<Moisturizing ingredients>
Ceramides such as ceramides, ceramide derivatives and ceramide-like substances; organic acid salts such as sodium lactate, disodium tartrate, sodium pyrrolidonecarboxylate, disodium glutamate; isoprene glycol, propylene glycol, 1,3-butylene glycol, glycerin, Polyhydric alcohols such as xylose, xylitol, sorbitol; water-soluble polymers such as polyvinyl alcohol, sodium alginate, polyvinylpyrrolidone, mucopolysaccharides such as chondroitin sulfate and hyaluronic acid, collagen and its derivatives, proteins, keratin, fibroin and Hydrolysates thereof: fatty acid esters such as isopropyl myristate and isopropyl palmitate, shea butter, squalane, placenta, albutin, casein, silk, honey and the like.

<Solvent>
Purified water, ion-exchanged water, alcohols such as ethanol, propanol and benzyl alcohol, polyhydric alcohols such as ethylene glycol, diethylene glycol, dipropylene glycol, glycerin and 1,3-butanediol, ethylene glycol monomethyl ether and ethylene glycol monoethyl ether. , Ethylene glycol monopropyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, diethylene glycol monoisobutyl ether, triethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol dimethyl ether, Dipropylene glycol monomethyl ether, tripropylene glycol monomethyl ether, tripropylene glycol monobutyl ether, propylene glycol monopropyl ether, dipropylene glycol monopropyl ether, propylene glycol monobutyl ether, propylene glycol-tert-butyl ether, dipropylene glycol monobutyl ether, di Glycol ethers such as propylene glycol dimethyl ether, phenylcarbitol, phenylcellosolve, benzylcarbitol, paraffins such as n-paraffin, esters such as diethylphthalate, benzylbenzoate, triethylcitrate, isopropyl myristate, and other 3-methyl Examples thereof include -4-methoxybutanol, N-methylpyrrolidone, propylene carbonate and the like.
<Surfactant>
Nonionic activators such as polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene copolymer, polyoxyethylene fatty acid ester, sorbitan fatty acid ester; fatty acid ester such as soap base, α- Anionic surfactants such as sodium olefin sulfonate, sodium lauryl sulfate, sodium polyoxyethylene lauryl sulfate, sodium coconut oil fatty acid methyl taurine; alkyl betaine, alkylamide propyl betaine, 2-alkyl-N-carboxymethyl-N-hydroxy Amphoteric surfactants such as ethylimidazolinium betaine; cationic surfactants such as alkylamine salts and quaternary ammonium salts can be mentioned.

<Anti-fading agent>
Amino acids such as glycine, alanine and glutamic acid; salicylic acid and salts thereof and the like can be mentioned.
<pH adjuster>
Examples thereof include disodium hydrogen phosphate, disodium phosphate, disodium hydrogen citrate, and trisodium citrate.
<Fungicide>
Examples thereof include isopropylmethylphenol, triclosan, dichloroisocyanuric acid, silver zeolite, cetylpyridinium chloride, benzalkonium chloride, benzenetonium chloride, chlorhexidine chloride, hinokithiol, phenol, glycyrrhizinate and derivatives thereof.
<Others>
Glucose, sucrose, trehalose, phytocollage, isoflavone, paraoxybenzoic acid ester, vegetable or fruit extract (extract), deep sea water and the like can be mentioned.
The content of the above-mentioned optional component may be appropriately set as long as the effect of the present invention is not impaired. Further, the tableted tablet of the present invention may be covered with a known water-soluble film or the like, depending on the intended use and needs.

Hereinafter, the present invention will be specifically described in Examples, but the present invention is not limited to these Examples.

<Reference test>
[Test sample]
A columnar hammered tablet containing sodium hydrogen carbonate, sodium carbonate, succinic acid, and cationized cellulose and having a diameter of 50 mm, a thickness of about 15 mm, and a total amount of 45 g at a pressure of about 98 kN (about 10 t) was used as test sample A. ..
Further, a columnar tablet which is different only from the test sample A in that it does not contain cationized cellulose was designated as the test sample a.
[Evaluation of test specimen]
Using a digital force gauge (manufactured by Aiko Engineering Co., Ltd., attachment for measurement: pressing part, circular shape with a diameter of 15 mm) so that pressure is applied to the center of the top surface of test specimens A and a, in the side surface (thickness) direction. Pressure was applied to it, and the maximum pressure when cracks or cracks occurred was defined as the tableting hardness. The evaluation test was performed three times, and the average value was taken as the tableting hardness of each.
The tableting hardness of the test sample a was 5.4 kgf, whereas the tableting hardness of the test sample A was 2.0 kgf.

From the results of the above "reference test", it was clarified that the tableting hardness of the tablet was reduced to about 40% by blending the cationized polymer such as cationized cellulose. When the tableting hardness under the above-mentioned tableting conditions is about 2.0 kgf, damage is expected during manufacturing, storage, transportation, etc., so it is necessary to improve the tableting hardness.
As a result of examining each of sodium hydrogen carbonate, sodium carbonate, succinic acid, and cationized cellulose, we obtained a new finding that the tableting hardness of the tablet can be changed by changing the main compounding component, sodium hydrogen carbonate. , Sodium hydrogen carbonate was examined in detail.

<Detailed study test on sodium hydrogen carbonate>
[Preparation of test sample]
Commercially available sodium hydrogen carbonate and 7 kinds of sodium hydrogen carbonate were obtained by classifying or crushing the sodium with a sieve, and these were used as test samples 1 to 7. The average particle size of the test samples 1 to 7 was larger than 150 μm.
[Evaluation of test specimen]
As for the tableting hardness, the hardness of the tableting tablet containing only sodium hydrogen carbonate was measured according to the above-mentioned method for measuring the tableting hardness of a 15 g tableting tablet.
Further, "the average of the ratio (a line / b line) of the a line and the b line", the "bulk specific gravity", and the "compression rate" were calculated according to the above-mentioned measurement method.
Furthermore, by analyzing the microscopic observation image of the test sample, crystals with a "average ratio of a-line to b-line (a-line / b-line)" of 2 or more and 4 or less are included with respect to the total amount of sodium hydrogen carbonate. The ratio was measured.
The evaluation results are shown in Table 1.

As shown in Table 1, the present inventor has found that, surprisingly, the tableting hardness of sodium hydrogen carbonate changes greatly depending on its shape and the like.
When examined in detail, sodium hydrogencarbonate, which greatly improves tableting hardness, has "an average ratio of a-line to b-line (a-line / b-line) of 2 or more and 4 or less, and a bulk specific gravity of 1. It was confirmed that the requirement of "05 g / mL or less" was satisfied, and it was also clarified in Table 1 that sodium hydrogencarbonate of test samples 1 to 3 was applicable.
On the other hand, the sodium hydrogen carbonate of the test sample 4 whose bulk specific gravity is outside the range of the present invention, although the average ratio of the a-line to the b-line (a-line / b-line) is 2.0, is hit. It was clarified that the tablet hardness was 2.5 kgf, which was significantly inferior to the tableting hardness of sodium hydrogen carbonate of the test samples 1 to 3.
Further, the sodium hydrogen carbonate of the test sample 5 having a bulk specific gravity of 1.03 g / mL but an average ratio of a-line to b-line (a-line / b-line) of 1.7 has a tableting hardness. It was also revealed that the hardness was 1.2 kgf, which was significantly inferior to the tableting hardness of sodium hydrogen carbonate of the test samples 1 to 3.

<Tablet hardness confirmation test for tablets>
<Examples 1 to 3, Comparative Examples 1 to 4, Reference Examples 1 and 2>
[Preparation of test sample]
Using the sodium hydrogen carbonates of the test samples 1 to 7 of the above-mentioned "detailed study test on sodium hydrogen carbonate", the blending amount shown in Table 2 (the number in Table 2 means% by weight). The mixture was uniformly mixed to obtain a powder mixture. This powder mixture was compression-molded at a pressure of 25 kN using a hydraulic pump type tableting machine to prepare a 15 g tablet having a diameter of 30 mm and a thickness of approximately 15 mm. The tableting hardness of the obtained tablet was measured according to the above-mentioned method for measuring tableting hardness with a 15 g tablet. The average particle size of the sodium carbonate used was 300 μm. Table 2 summarizes the blending amounts of the tableting tablets of Examples 1 to 3, Comparative Examples 1 to 4, and Reference Examples 1 and 2 and the tableting hardness of each.

From the results in Table 2, the sodium hydrogencarbonate of Test Specimens 1 to 3 whose tableting hardness was confirmed to be improved in the tableting with sodium hydrogencarbonate alone was added to the tableting tablet containing cationized cellulose. It was clarified that the tableting hardness as a tablet can be improved.
The tableting tablets containing cationized cellulose (Examples 1 to 3 and Comparative Examples 1 to 4) have a lower tableting hardness than the tableting tablets not containing cationized cellulose (Reference Examples 1 and 2). However, from the comparison between Example 2 and Reference Example 1 and Comparative Example 4 and Reference Example 2, it can be understood that the tableting of Example 2 is suppressed in the decrease in tableting hardness.
From these results, by blending a specific sodium hydrogen carbonate, even in a tablet containing cationized cellulose, the tablet hardness can be 2 kgf or more, more preferably 2.5 kgf or more, and more preferably 3 kgf or more. Was confirmed.

<Confirmation test of void area and porosity>
[Measuring method of void area (150 magnification)]
The tableting tablets (Examples 1 to 3 and Comparative Examples 1 to 4) prepared in the above-mentioned "tablet tableting hardness confirmation test" were used as test samples.
Each test sample was roughly divided into two by the diameter portion, and the cross section thereof was observed with a scanning electron microscope (SEM) at a magnification of 150 times. In the image of the cross section, the solid phase derived from the raw material and the bubble phase (void portion) were binarized, and the bubble phase area was measured by image processing to obtain the void area (150 magnification).
[Calculation method of actual void area]
The void area (150 magnifications) measured at a magnification of 150 times was converted into an actual void area with a magnification of 1 times by the following calculation formula.
<Calculation formula>
Actual void area (mm ² ) = void area (150 magnification) ÷ (150 × 150)
[Calculation method of porosity]
The ratio of the void area (150 magnification) to the total area processed by the image was calculated.
<Calculation formula>
Porosity (%) = (void area (150 magnification) ÷ processed image area) x 100
The "area of the processed image" in the calculation formula means the area of the cross-sectional image in the above-mentioned "method for measuring the void area (150 magnification)". The processed image was 1280 pixels × 960.05 pixels, and the resolution was 201 dpi (dots per inch). Since 1 inch is 25.4 mm, 1280 pixels is equivalent to 161.75 mm (25.4 ÷ 201 × 1280 ≒ 161.75), and 960.05 pixels is 121.32 mm (25.4 ÷ 201 × 960. It corresponds to 05≈121.32). That is, the area of the processed image was 19623.51 mm ² (161.75 × 121.32), and the porosity (%) of each test sample was calculated.
Table 3 summarizes the void area (150 magnifications) (mm ² ), the actual void area (mm ² ), and the porosity (%) of the tableted tablets of Examples 1 to 3 and Comparative Examples 1 to 4.

From the results in Table 3, it was confirmed that the tableting tablets of Examples 1 to 3 were significantly lower in both the void area and the porosity than the tableting tablets of Comparative Examples 1 to 4.

<Liquid absorption time confirmation test for tableted tablets>
[Test details]
The above-mentioned method for measuring the liquid absorption time A using the tablets (Examples 1 to 3, Comparative Examples 1 to 4, Reference Examples 1 and 2) prepared in the above-mentioned "Tablet-stamping hardness confirmation test" as a test sample. The liquid absorption time A was measured according to the above. In addition, the amount of liquid absorbed (g) was calculated from the difference in weight of the test sample before and after the measurement. Table 4 summarizes the liquid absorption time A (minutes) and the liquid absorption amount (g) of the tableted tablets of Examples 1 to 3, Comparative Examples 1 to 4, and Reference Examples 1 and 2.

From the results in Table 4, the tableting tablets of Examples 1 to 3 having a tableting hardness of 2 kgf or more have a liquid absorption time A in the range of 45 minutes or more and 65 minutes or less, and Comparative Examples 1 to 3 having a tableting hardness smaller than 2 kgf. The liquid absorption time A of Reference Example 2 is 10 minutes or more longer than the liquid absorption time A of the tablet being beaten, that is, the liquid absorbing speed is slow, and the tableting hardness is about the same. It was revealed that the liquid absorption rate was shorter than 10 minutes or more, that is, the liquid absorption rate was high.
As shown in Table 3, it has been confirmed that the tableting tablets of Examples 1 to 3 are considerably smaller in both the void area and the porosity than the tableting tablets of Comparative Examples 1 to 4, and the tableting hardness of Examples is high. Since the bath salts 1 to 3 have few internal voids and it takes time for the liquid to permeate, it is presumed that the liquid absorption time A is longer than that of the tableting tablets of Comparative Examples 1 to 4. As shown in Table 4, it was clarified that the relationship between the tableting hardness and the liquid absorption time A of Examples 1 to 3 and Comparative Examples 1 to 4 was as expected.
On the other hand, the amount of liquid absorbed between Examples 1 to 3 and Comparative Examples 1 to 4 is almost the same as 1.2 to 1.3, although the porosity is significantly different. It was clarified that the amount of liquid absorbed in No. 2 decreased by about 25%.
It is considered that the tableting tablets of Examples 1 to 3 having a high tableting hardness have less internal voids than the tableting tablets of Comparative Examples 1 to 4, and therefore the amount of liquid absorbed is also reduced. As shown in Table 4, it was confirmed that the relationship between the tableting hardness and the amount of liquid absorbed in Comparative Examples 1 to 4 was a completely unexpected result, which was unexpected.
The present inventor paid attention to the fact that the amount of liquid absorbed in Examples 1 to 3 and Comparative Examples 1 to 4 was almost the same, and then conducted an evaluation test on the disintegration property of the tablet.

<Test for confirming disintegration of tablets>
[Test details]
The tableting tablets (Examples 1 to 3, Comparative Examples 1 to 4, Reference Examples 1 and 2) prepared in the above-mentioned "tablet tableting hardness confirmation test" were used as test samples. One tablet of each test sample was put into hot water of 40 ° C./5 L, and the time (seconds) until one tablet disintegrated and completely dissolved was measured.
Table 5 summarizes the disintegration / dissolution times (seconds) of the beaten tablets of Examples 1 to 3, Comparative Examples 1 to 4, and Reference Examples 1 and 2.

From the results in Table 5, the tableting tablets of Examples 1 to 3 had a higher tableting hardness and a lower porosity (%) than the tableting tablets of Comparative Examples 1 to 4, but were completely poured into hot water. It was clarified that the time required for dissolution in the tablet was about the same, and the disintegration property was excellent.
It is known that when the tableting hardness is high, the tablet disintegration property when put into water deteriorates, and the generated carbon dioxide gas cannot be efficiently dissolved in water. However, quite surprisingly, the tableted tablet of the present invention is generated by obtaining extremely good tablet disintegration property while maintaining a good tableting hardness that does not cause damage during manufacturing, storage, transportation, etc. It was confirmed that carbon dioxide gas can be efficiently dissolved in water.

As described above, the tableted tablet of the present invention not only exhibits excellent shape-retaining property without causing breakage such as cracks and cracks, but also has excellent shape-retaining property, so that the contact surface with air is minimized. Because it can be suppressed, it is extremely excellent in pharmaceutical stability, such as improving storage stability. Moreover, although the tableting tablet of the present invention has a high tableting hardness, good tablet disintegration property can be obtained, and the generated carbon dioxide gas can be efficiently dissolved in water.
That is, the tableted tablet of the present invention is extremely useful because it has both good pharmaceutical stability and disintegration property.

Claims (3)

Hydrogen carbonate having an average ratio of the following a line to the following b line (a line / b line) of 2 or more and 2.4 or less and a bulk specific gravity of 0.89 g / mL or more and 1.05 g / mL or less. It contains 20% by weight or more of sodium, sodium carbonate, 10% by weight or more of organic acid, 0.1% by weight or more and 1.0% by weight or less of cationized cellulose , has a tableting hardness of 2 kgf or more, and is as follows. A beaten tablet having a liquid absorption time A of 45 minutes or more and 65 minutes or less.
Liquid absorption time A: At an environmental temperature of 25 ° C., a cylindrical hammered tablet having a diameter of 30 mm and a total volume of 15 g in a charley containing 5 ml of liquid paraffin and having a circular top and bottom with respect to the liquid surface of liquid paraffin. The time from when the paraffin is placed vertically until the liquid paraffin reaches the top of the beaten tablet.
Line a: The opposite end line with the longest straight line connecting the ends of one sodium hydrogen carbonate crystal.
Line b: The opposite end line with the longest straight line orthogonal to line a 2. The average of the ratio (a line / b line) between the following a line and the following b line is 2 or more . The sodium hydrogen carbonate as a raw material for tableting according to claim 1, wherein the content is 4 or less and the bulk specific gravity is 0.89 g / mL or more and 1.05 g / mL or less.
Line a: Opposite line with the longest straight line connecting the ends of one sodium hydrogen carbonate crystal b line: Opposite line with the longest straight line orthogonal to line a 2. The average of the ratio (a line / b line) between the following a line and the following b line is 2 or more . The method for producing a tablet according to claim 1, wherein sodium hydrogencarbonate having a bulk specific gravity of 0.89 g / mL or more and 1.05 g / mL or less is used as a raw material.
Line a: Opposite line with the longest straight line connecting the ends of one sodium hydrogen carbonate crystal b line: Opposite line with the longest straight line orthogonal to line a

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