JP2012236823A - Tablet excellent in moisture-resistant stability - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a rapidly disintegrating tablet in the oral cavity, having hardness sufficient for production and transportation together with rapid disintegration properties in the oral cavity, and little reduction of the hardness, even under high humidity, and capable of maintaining good oral disintegration properties.SOLUTION: The rapidly disintegrating tablet in the oral cavity comprises a porous basic inorganic material having pH 7-13 in 4% pH slurry and 30-500 m/g BET specific surface area, sugar, a disintegration agent and a pharmaceutical agent, wherein the blending ratio of the porous basic inorganic material and the sugar is 1:200-1:5. The performance can be much more enhanced, when the sugar contains ≥1% amorphous material.

Description

  The present invention relates to an orally rapidly disintegrating tablet in which a decrease in hardness and disintegration time delay of the tablet under moisture are suppressed, a method for easily producing the intraorally rapidly disintegrating tablet and excellent in production, and hardness of the tablet under moisture The present invention relates to a method in which a decrease and an increase in decay time are suppressed.

  Conventional tablets and capsules are difficult to be taken by elderly people and children with low swallowing ability. In particular, elderly people often take a plurality of kinds of medicines, which is a particular problem. So far, chewable tablets, powders and granules have been used for patients with low swallowing ability. In recent years, as a dosage form suitable for these elderly people and children, an orally rapidly disintegrating tablet that rapidly disintegrates or dissolves in the oral cavity and can be ingested without water has been proposed (16th revision Japanese Pharmacopoeia). ing. Moreover, even if it is a conventional tablet, when it sticks to the throat, it can be improved by easily disintegrating, so it is preferable to shorten the disintegration time. In the case of elderly people, intraoral quick disintegrating tablets are packaged together with a plurality of types of pharmaceuticals, or placed in a pill case in advance. Therefore, there is a need for an orally rapid disintegrating tablet in which cracks and chips due to hardness reduction and delay in disintegration time are suppressed by moisture in the air.

  Intraoral rapidly disintegrating tablets have the same properties as conventional tablets, that is, hardness that does not cause tablet chipping or pulverization during tablet production or transportation, and are produced without causing any tableting problems during compression molding. It must be possible and must have a disintegration time in the oral cavity of no more than 120 seconds, preferably no more than 60 seconds, with more difficulties in tablet design than conventional tablets. In particular, tablet hardness and disintegration time are conflicting factors.

  Since the intraoral quick disintegrating tablet needs to disintegrate immediately upon contact with water, it easily absorbs moisture (humidity) in the air, and the tablet hardness tends to decrease and the disintegration time increases. The cause of these tablet physical properties is that disintegrants with excellent disintegration properties such as polyvinylpyrrolidone, croscarmellose sodium, carboxymethyl starch sodium, carmellose calcium, and low-substituted hydroxypropylcellulose absorb water and swell. It is considered that sugars absorb moisture and the particle shape changes, deliquescence, and solidification.

  To date, in order to prevent tablet deterioration due to humidity of orally disintegrating tablets, (1) a method of increasing the hardness of tablets during manufacture, (2) a method of devising tablet components, and (3) a method of devising manufacturing steps Etc. have been done.

  As a method for devising (selecting) the components of the tablet, it contains a rapidly disintegrating buccal tablet (Patent Document 1) consisting of crystalline cellulose, calcium hydrogen phosphates, natural starches, and a lubricant, and a water-soluble binder. An orally disintegrating tablet containing no disintegrant (Patent Document 2), having an average particle size of 10 to 500 μm, and at least one granular base component selected from saccharides and amino acids, and a swelling ratio at the time of water absorption of 1.3 or less An orally disintegrating tablet (Patent Document 3) comprising a disintegrant, a water-soluble binder and a lubricant is known.

  The present applicant also proposed an intraoral quick disintegrating tablet using a disintegrating particle composition in which an inorganic excipient, a disintegrant and carmellose are homogeneously dispersed in a composite particle of mannitol and xylitol (Patent Document 4). )doing.

International Publication 2009/66773 Pamphlet JP 2001-342128 A JP 2010-270040 A International Publication 2011/19045 Pamphlet

  The object of the present invention is to provide an orally rapidly disintegrating tablet that suppresses a decrease in hardness and a delay in disintegration time even if it is kept for a long time under humidity (humidification). Moreover, the manufacturing method which can manufacture the said intraoral quick disintegrating tablet easily is provided.

  As a result of intensive studies to achieve the above-mentioned problems, the present inventors have shown that an orally rapidly disintegrating tablet obtained by mixing and compression-molding a porous basic inorganic substance with an amorphous saccharide has excellent disintegration properties. It has been found that it has sufficient hardness that does not cause problems during production and transportation, and decreases in hardness and increases in disintegration time due to moisture.

  The present invention provides an orally rapidly disintegrating tablet that has sufficient hardness that does not cause problems during production and transportation, good oral disintegration time, and that suppresses a decrease in hardness and an increase in disintegration time under moisture. Moreover, the simple manufacturing method of the said intraoral quick disintegrating tablet is provided.

It is an X-RD chart before the acceleration test of Example 1 and Comparative Example 1 and after the acceleration test.

  The present invention is an intraoral quick disintegrating agent containing a drug, a saccharide containing an amorphous substance, a porous basic inorganic substance, and optionally a swellable disintegrating agent.

  Saccharides are widely used as excipients for tablets because they are excellent in fluidity and moldability at the time of preparation and are excellent in disintegration in tablets. Among them, saccharides containing amorphous have excellent effects. However, saccharides containing an amorphous substance undergo a structural change to a stable particle shape of the saccharide under moisture, and the strength of the tablet increases, but the disintegration time increases because the bonds between the constituent particles become stronger.

  The saccharide containing amorphous in the present invention is wet granulation such as spray drying, fluidized bed granulation, stirring granulation and rolling bed granulation, and once the saccharide is dissolved in water, it is dried again in a short time. Sugar obtained. The amorphous part is 1 to 100%, preferably 10 to 100%, more preferably 20 to 100%, and still more preferably 30 to 100% of the entire saccharide. When granulating the amorphous saccharide, it may contain a disintegrant, other excipients, and a binder.

  The sugar may be any of sugar alcohol and sugar, for example, mannitol, xylitol, sorbitol, erythritol, maltitol, lactose, sucrose, glucose, fructose, maltose, trehalose, palatinit and palatinose. Can be combined. From the viewpoint of moldability and disintegration, mannitol, xylitol, erythritol and lactose are preferable, and mannitol is most preferable. Further, Fmelt (manufactured by Fuji Chemical Industry Co., Ltd.), which is an excipient for an intraoral quick disintegrating tablet, in which a disintegrant and an inorganic substance are uniformly dispersed in composite particles of mannitol and xylitol may be used.

  Saccharides have an average particle diameter of 20 to 200 μm, preferably 50 to 150 μm, from the viewpoint of easy coating when mixed with a porous basic inorganic substance and a feeling of roughness in the oral cavity.

The porous basic inorganic substance used in the present invention has a hydroxyl group on the particle surface, and is a salt of magnesium, aluminum or calcium. For example, magnesium aluminate silicate, magnesium metasilicate aluminate, hydrotalcite, calcium silicate, aluminum silicate, magnesium silicate and magnesium hydroxide,
Preferred are magnesium aluminate silicate, magnesium aluminate metasilicate, hydrotalcite, and calcium silicate, and more preferred are magnesium aluminate silicate, magnesium aluminate metasilicate, and basic magnesium aluminate metasilicate.

  The basicity of the basic inorganic substance means that the acidity / basicity of the surface is basic, and can be measured at the pH when added to water. When adding 4% of an inorganic substance to water, pH is 7-13, Preferably pH is 8-12, More preferably, it is 8-11. A high pH is not preferable because it reacts with other additives and drugs. Even if the structural formula is the same, an inorganic substance showing basicity can be used.

  The porosity of these porous basic inorganic substances means that the specific surface area is large due to the particle size of the primary particles being small, the particles themselves being irregular and having many holes, and the like. The larger the surface area of the inorganic substance, the larger the contact surface with the air and the higher the ability to prepare moisture in the air layer, and the easier it is to coat the sugar surface. However, it is not preferable that the surface area is large, because a problem occurs during tablet production. As a specific surface area, it is 30-500 m <2> / g, Preferably it is 50-500 m <2> / g, More preferably, it is 100-400 m <2> / g, Most preferably, it is 200-400 m <2>.

It can also be shown by the oil absorbency of the degree of porosity oil, and the oil absorption of oil is 0.2 to 10 ml / g, preferably 0.5 to 8 ml / g, more preferably 0.5 to 6 ml / g. is there.

  The porous basic inorganic material not only has porosity, but also an equilibrium state with water molecules in the air is important, and it is preferable that moisture adsorption at a general living temperature is large. The moisture adsorption amount under conditions of a temperature of 37 ° C. and a relative humidity of 90% is 10 to 70%, preferably 20 to 60%.

  The porous basic inorganic substance should not be deliquescent with water and is preferably insoluble in water. Since the porous basic inorganic material uniformly disperses and coats the surface of the saccharide constituting the tablet, the average particle size is preferably smaller, and the average particle size is 1 to 30 μm, preferably 1 to 20 μm.

  The disintegrant in the present invention refers to a disintegrant usually used for tablet production. Preferably, it is a swellable disintegrant, and the swellable disintegrant is an essential component particularly for an intraoral quick disintegrating tablet in order to impart excellent disintegration to the tablet. Swellable disintegrants swell as soon as they come into contact with water, and disintegrate the tablet by pushing away adjacent particles. However, since the water is easily absorbed, even if the tablet is left for a long time under humidity, the swelling disintegrant absorbs water from the air and swells to some extent. Result in an increase.

  The swelling disintegrant used in the present invention is crospovidone, low-substituted hydroxypropylcellulose, croscarmellose sodium, carboxymethyl starch sodium, carmellose, crystalline cellulose, and starch. In particular, crospovidone and low-substituted hydroxypropylcellulose are preferable because of high swelling when in contact with water.

  The mixing ratio of the porous basic inorganic substance and the saccharide is 1: 400 to 1: 2, preferably 1: 200 to 1: 5, more preferably 1:50 to 1: 7, and further preferably 1:30 to 1. 1:10. When the ratio of the porous basic inorganic substance is small, stability (hardness and disintegration time) under moisture is not preferable, and when it is large, problems such as moldability occur.

  When a disintegrating agent is included, the mixing ratio of the porous basic inorganic substance and the disintegrating agent is 1:50 to 1: 1, preferably 1:30 to 1: 1, more preferably 1:20 to 1: 2. When the proportion of the porous basic inorganic substance is small, the stability under moisture is not sufficient, and when it is large, the problem of moldability occurs.

  In the tablet of the present invention, the surface of the saccharide and disintegrant particles are covered with fine particles of a porous basic inorganic substance. For this reason, it is thought that it works to regulate the change in moisture in the outside air, and suppresses the change in the particle structure (solidification) of saccharides, the swelling of the disintegrant, and the like.

  In the manufacturing process of an intraoral rapidly disintegrating tablet, manufacturing which raises tablet hardness by humidifying and heating in a short time and solidifying the saccharide in a tablet is also performed. However, when the saccharide containing amorphous is contained by leaving it under moisture for a longer time, the structure of the surface portion, particularly the bonded portion with other particles, is changed due to the moisture. Causes the decay time delay. By blending the porous basic inorganic substance of the present invention into a tablet, there is an effect of promoting the crystal change of the amorphous part of the saccharide to a stabilized crystal. For example, in amorphous D-mannitol, a change from amorphous to β-type crystal occurs. This is the same effect as warming and humidification in the tablet manufacturing process. It is considered that the performance degradation due to moisture is suppressed by the performance improvement due to crystal growth. That is, the porous basic inorganic substance acts as an accelerator for the growth of stable crystals of saccharide under moisture in a tablet containing saccharide.

  The drug is not particularly limited, and is a drug for central nerves such as a peripheral nerve agent, antipyretic analgesic / anti-inflammatory agent, hypnotic sedative, and neuropsychiatric agent; peripheral nerve agent such as skeletal muscle relaxant and autonomic nerve agent; Cardiovascular drugs such as antiarrhythmic agents, diuretics and vasodilators; respiratory organs such as bronchodilators and antitussives; gastrointestinal drugs such as digestives, intestinals and antacids; metabolism of hormones and antihistamines Anti-ulcer agents; antibiotics; chemotherapeutic agents; crude drug extracts; microorganisms and vitamins.

  As the drug having a bitter taste or causing the drug to be released in the digestive tract, a drug treated by a known method such as coating can be used. For example, the method described in JP-A No. 11-263723, that is, an active ingredient, a readily soluble substance such as xylitol, sorbitol, and sucrose, and a water-soluble binder such as polyvinylpyrrolidone, pullulan, hydroxypropylcellulose, hydroxypropylmethylcellulose, gum arabic, and gelatin , And mannitol, lactose, and mannose can be coated with an active ingredient by spray drying, fluidized bed granulation, stirring granulation, kneading granulation, or the like.

  In addition to the above ingredients, general pharmaceutical additives can be blended. As a pharmaceutical additive, one or more kinds of pharmaceutical additives such as an excipient, a binder, a surfactant, a sour agent, a sweetener, a corrigent, a fragrance, a colorant, and a stabilizer are blended. Each blending ratio is 0.01 to 1000 parts by weight of one or more components of other pharmaceutical additives with respect to 100 parts by weight of the saccharide containing amorphous, and 0.1 to 0.1% of the active ingredient as necessary. 250 parts by weight is blended.

  The “orally-fast disintegrating tablet” in the present invention means a tablet that can disintegrate rapidly in the oral cavity, for example, within 120 seconds, preferably within 60 seconds, more preferably within 30 seconds. The orally disintegrating time here is the time obtained by the conditions of the orally disintegrating tablets described later and the methods of the examples. The disintegration time in the oral cavity varies depending on the tablet size and tablet shape, and this is also included in the present invention.

  In the present invention, moisture refers to moisture in the air. High humidity stability (high humidity stability) satisfies both suppressing hardness reduction under humidity and suppressing disintegration time delay under humidity That is.

In the present invention, “decrease in hardness under humidity” means “after 3 months under the condition of 75% relative humidity at 25 ° C. in an accelerated test, which will be described later, or under open condition at a temperature of 40 ° C. relative humidity 75%. In one week, the hardness maintenance rate is 65% or more, preferably 70% or more, most preferably 80% or more, and the hardness is 30N or more.
The tablet retention rate is expressed as a percentage by dividing the hardness after the acceleration test by the hardness before the acceleration test.

  In the present invention, “increase in disintegration time under humidity is suppressed” means that after 3 months under an acceleration test at a temperature of 25 ° C. and a relative humidity of 75%, described later, or at a temperature of 40 ° C. and a relative humidity of 75%. After 1 week below, the disintegration time is within 60 seconds, preferably within 50 seconds, and most preferably within 30 seconds.

  It can be produced by mixing a porous basic inorganic substance with a drug, an saccharide containing an amorphous substance, and if necessary, a swellable disintegrant or a pharmaceutical additive, followed by compression molding. The saccharide is preferably granulated in the presence of water by adding a porous basic inorganic substance, a disintegrant, and a drug as necessary. The granulation method in the presence of water is wet granulation such as spray drying, fluidized bed granulation, stirring granulation, and rolling bed granulation. Moreover, an external lubrication method can be performed at the time of compression molding.

  The compression molding is preferably performed by the direct tableting method, and the molding pressure at that time varies depending on the size of the tablet, but is usually 200 to 2000 kgf, preferably 250 to 1600 kgf, more preferably 250 to 1200 kgf. is there.

  The collapsible compression-molded product of the present invention usually has a hardness of 20 to 200N, preferably 30 to 150N. Since the collapsible compression-molded product of the present invention uses the particle composition of the present invention, it has good hardness at a low molding pressure. The molding pressure varies depending on the size of the tablet. For example, when a 200 mg tablet is pressed using a 8 mm diameter punch, the hardness is 30 to 150 N when the molding pressure is 100 to 1200 kgf, and the molding pressure is When it is 100 to 1000 kgf, it has a hardness of 30 to 100 N.

The orally disintegrating tablet of the present invention can be used as other solid preparations such as a tablet other than those intended for orally disintegrating tablets, such as a chewable tablet or a disintegrating tablet in the stomach. In the case of a chewable tablet type or a general tablet, the hardness may be higher than the above-mentioned hardness.
Since the orally disintegrating tablet of the present invention disintegrates immediately with a small amount of water, it can be used for foods that disintegrate in the oral cavity.

EXAMPLES The present invention will be described below with reference to examples, but these examples do not limit the scope of the present invention.
Evaluation about each tablet obtained in the Example was performed by the following method.
[4% pH slurry]
The inorganic substance was added to water to a concentration of 4%, and the pH was measured with a pH meter (HM-30V, manufactured by Toa DKK Corporation).
[BET specific surface area]
It was measured with a BET specific surface area measuring instrument (Monosorb, manufactured by Yuasa Ionics).
[Oral disintegration time]
The tablet disintegration time was measured with a tablet disintegration tester (ODT-101, manufactured by Toyama Sangyo Co., Ltd.).
[Tablet hardness]
It measured using the load cell type tablet hardness meter (PC-30, Okada Seiko Co., Ltd. product).
[Tablet retention rate]
The hardness after the acceleration test was divided by the hardness before the acceleration test and expressed as 100 minutes.

[Reference Example 1] Manufacture of disintegrating excipient Mannitol (Mannit P, Towa Kasei Kogyo Co., Ltd.) 65 parts by weight, Xylitol 4 parts by weight, Crystalline cellulose (Theolas FD101: Asahi Kasei Chemicals) 17 parts by weight, Crospovidone ( After 9 parts by weight of Kollidon CL-SF (manufactured by BASF) and 5 parts by weight of anhydrous calcium hydrogen phosphate (Fujicalin SG, manufactured by Fuji Chemical Industry Co., Ltd.) are uniformly dispersed in water, a spray dryer (S-50N / R) , Manufactured by Niro Co., Ltd.) and spray-dried at an outlet temperature of 90 to 100 ° C. to obtain a white spherical particle composition having good fluidity. The average particle size was 114 μm. The α-type crystal of D-mannitol was 6.4%, the β-type crystal was 31.2%, and the amorphous type was 31.2%.

[Reference Example 2] Manufacture of magnesium aluminate metasilicate A white powder of magnesium aluminate metasilicate was manufactured according to the method described in JP-B 36-023163. The 4% slurry pH was 10.0, the oil absorption capacity was 3.5 ml / g, the BET specific surface area was 300 m ² / g, and the average particle size was 24 μm.

[Example 1] Basic oral inorganic rapidly disintegrating tablet 97.6 parts by weight of granulated product of Reference Example 1, 2.0 parts by weight of magnesium aluminate silicate, magnesium stearate (manufactured by Taihei Chemical Industrial Co., Ltd.) After mixing 5 parts by weight, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine to obtain tablets with a weight of 200 mg, a diameter of 8 mm, and 9R. The results are shown in Table 2.

[Examples 2 to 4, Comparative Examples 1 to 3]
By replacing the magnesium aluminate silicate with the basic inorganic material shown in Table 1, the same production method as in Example 1. The results are shown in Table 2.

[Table 1] Blended inorganic substances

[Accelerated test]
The obtained tablets were left for 3 months under an open temperature of 25 ° C. and a relative humidity of 75%. The results are shown in Table 2.

[Table 2] Test results

  From Examples 1 to 4 and Comparative Example 1, the increase in the disintegration time was suppressed by adding and mixing the basic porous inorganic material within 60 seconds, and the hardness retention rate was 65% or more, and the hardness was 30N. It is understood that the stability in humidification is high. The acidic porous inorganic materials of Comparative Examples 2 to 3 have a disintegration time of 60 seconds or more and a hardness retention rate of 65%, which proves difficult to use as an intraoral quick disintegrating tablet under humidification.

[Crystal structure analysis]
For Example 1 and Comparative Example 1, the tablets were subjected to X-ray measurement (X-RD) using an X′Pert-MPD type (manufactured by Spectrum), and the change in β-type crystals of mannitol was analyzed. The results are shown in Table 3 and FIG.

各値はマンニトールのβ型結晶の代表的なピークでのＸＲＤ強度を示す。 [Table 3] β-type crystal peak intensity

Each value represents the XRD intensity at a typical peak of the mannitol β-type crystal.

  It can be seen that the β-type crystals of D-mannitol increased in Example 1 compared to Comparative Example 1. It shows that the amorphous part of D-mannitol has transitioned to a β-type crystal.

[Examples 1 and 4-6] Orally rapidly disintegrating tablets of basic inorganic substances According to the blending amounts in Table 4, the granulated product of Reference Example 1, magnesium silicate aluminate, and 0.5 parts by weight of sucrose stearate ester were added. After mixing, the tablets were tableted with a set hardness of 50 N using a rotary tableting machine to obtain tablets having a weight of 200 mg, a diameter of 8 mm, and 9R.

[Table 4] Compounding amount

[Accelerated test]
The obtained tablets were left for 3 months under opening at a temperature of 25 ° C. and a relative humidity of 75%. The results are shown in Table 5.

[Table 5] Test results

  When the addition amount of magnesium aluminate silicate is 1 to 5 parts by weight, the hardness retention rate is 70% or more, and the disintegration time is 20 seconds or less, indicating that the deterioration of the physical properties of the tablet due to humidification is suppressed. .

Claims (18)

An intraoral quick disintegrating tablet comprising a porous basic inorganic substance, drug, saccharide and disintegrant having a 4% pH slurry pH of 7 to 13 and a BET specific surface area of 30 to 500 m 2 / g. The intraoral quick disintegrating tablet according to claim 1, wherein the saccharide comprises an amorphous saccharide. The intraoral quick disintegrating tablet according to claim 1 or 2, wherein the porous basic inorganic substance is 0.2 to 10 ml / g. The intraoral quick disintegrating tablet according to any one of claims 1 to 3, wherein a mixing ratio of the porous basic inorganic substance and the saccharide is 1: 200 to 1: 5. The intraoral quick disintegrating tablet according to any one of claims 1 to 3, wherein a mixing ratio of the porous basic inorganic substance and the saccharide is 1:50 to 1: 7. The intraoral rapidly disintegrating tablet according to any one of claims 1 to 5, wherein the mixing ratio of the porous basic inorganic substance and the disintegrant is 1:50 to 1: 1. The stability against humidity is such that the tablet hardness retention rate is 65% or more and the disintegration time is 60 seconds or less when held for 3 months at a temperature of 25 ° C. and a relative humidity of 75%. The intraorally rapidly disintegrating tablet described. The porous basic inorganic substance is at least one selected from magnesium aluminate silicate, magnesium aluminate metasilicate, hydrotalcite, aluminum silicate, calcium silicate, magnesium silicate, magnesium hydroxide and magnesium aluminate hydroxide. The intraoral quick disintegrating tablet according to any one of claims 1 to 7. The intraoral quick disintegrating tablet according to any one of claims 1 to 8, wherein the saccharide comprises at least one selected from mannitol, xylitol, erythritol and lactose. The intraoral quick disintegrating tablet according to any one of claims 2 to 9, wherein an amorphous saccharide is wet-granulated and has an average particle size of 20 to 200 µm. The saccharide containing amorphous or the granulated product containing amorphous saccharide and the porous basic inorganic substance are mixed without using water substantially, and obtained by compression molding. The intraorally rapidly disintegrating tablet described. Any one of claims 2 to 10 obtained by mixing an amorphous saccharide or a granulated product containing an amorphous saccharide, a porous basic inorganic substance, and a disintegrant without substantially using water and compression molding. The intraoral rapidly disintegrating tablet according to Item 1. After mixing 4% pH slurry with porous basic inorganic substance, saccharide, drug, disintegrant with BET specific surface area of 7-13, BET specific surface area of 30-500m2 / g, oil absorption capacity of 0.2-10ml / g The manufacturing method of the intraoral quick disintegrating tablet obtained by compression molding. The production method according to claim 13, wherein the mixing of the porous basic inorganic substance, saccharide, drug, and disintegrant does not substantially use water. The method according to claim 13 or 14, wherein the saccharide is an amorphous saccharide or a granulated product containing an amorphous saccharide. 14. A saccharide, if necessary, a drug, a disintegrant, and a porous basic inorganic substance are granulated in the presence of water, and the drug, disintegrant, and porous basic inorganic substance not added in the granulation are mixed. The manufacturing method of any one of -15. A porous basic inorganic material having a 4% pH slurry having a pH of 7 to 13, a BET specific surface area of 30 to 500 m2 / g, and an oil absorption capacity of 0.2 to 10 ml / g is blended in a tablet containing amorphous sugar. A method for improving moisture stability of an intraorally rapidly disintegrating tablet. Crystals of saccharides under moisture containing, as an active ingredient, a porous basic inorganic material having a 4% pH slurry having a pH of 7 to 13, a BET specific surface area of 30 to 500 m 2 / g, and an oil absorption capacity of 0.2 to 10 ml / g Growth agent.

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