JP2018150242A - Cellulose composite - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a cellulose composite, etc. that has compression moldability comparable to that of cellulose powder and that quickly disintegrates under high striking pressure although containing starch which is an elastic body.SOLUTION: The cellulose composite contains cellulose and starch and light anhydrous silicic acid, where the mass ratio of cellulose to starch is 90:10 to 40:60, the content of light anhydrous silicic acid is 0.1 to 2% by mass, the bulk density is 0.10 to 0.50 g/cm, the angle of repose is 35 to 54°, and the residue remaining on the sieve when sieved with a sieve having an opening of 32 μm is 50 mass% or less.SELECTED DRAWING: None

Description

  The present invention relates to a cellulose composite containing cellulose, starch, and light anhydrous silicic acid, and a molded body containing the cellulose composite and one or more active ingredients.

  Pharmaceutical products are produced in various dosage forms depending on the route of administration. Particularly in recent years, the development of orally disintegrating tablets that can be taken without water has been active. Orally disintegrating tablets that disintegrate by saliva in the oral cavity are easy to take even in patients with weak swallowing functions, such as children and the elderly, and have the advantage that they can be taken quickly even in places without water. In the production of orally disintegrating tablets, there is a problem of how quickly the orally disintegrating time can be achieved simultaneously with the provision of practical tablet hardness and friability without using a special manufacturing method. When the impact pressure is increased to give practical hardness, the disintegration time in the oral cavity is delayed. Therefore, an excipient having a quick disintegration property under high impact pressure is desired.

On the other hand, conventionally, in pharmaceuticals, health foods, foods, and other chemical industries, it is widely known to prepare a molded body containing an active ingredient, for example, a tablet by using cellulose powder as an excipient. Yes. For example, Patent Document 1 discloses a cellulose crystallite having an average level-off polymerization degree of 15 to 375, an apparent specific volume of 1.84 to 8.92 cm ³ / g (apparent density of 7 to 34 lb / ft ³ ), and a particle size of 300 μm or less. The use of agglomerates as a tablet excipient is described. In Patent Document 2, the average L / D (average length of [major axis length] / [minor axis length]) of particles having an average degree of polymerization of 150 to 450 and 75 μm or less is 2.0 to 4. 0.5, the average particle size is 20 to 250 μm, the apparent specific volume is 4.0 to 7.0 cm ³ / g, the apparent tapping specific volume is 2.4 to 4.5 cm ³ / g, and the angle of repose is 55 ° or less. Cellulose powder is disclosed in Patent Document 3, in which an average degree of polymerization of 150 to 450, an average particle size of 30 to 250 μm, an apparent specific volume of more than 7 cm ³ / g, and a molecular weight of 400 and a polyethylene glycol retention rate of 190% or more, respectively. It is described that the compression moldability is good and that a tablet with high hardness can be formed under high impact pressure. Patent Document 4 has a secondary aggregate structure of the primary cellulose particles formed by agglomerating, the pore volume within a particle is 0.265cm ³ /g~2.625cm ³ / g, containing type I crystals The average particle size is more than 30 μm and less than 250 μm, the specific surface area is 0.1 m ² / g or more and less than 20 m ² / g, the angle of repose is 25 ° or more and less than 44 °, the degree of swelling is 5% or more, and disintegrates in water. It is described that the porous cellulose agglomerates are excellent in mixing uniformity with the active ingredient, and by using this as an excipient, it is possible to form tablets with no tableting trouble and low friability. In Patent Document 5, cellulose powder having an average degree of polymerization of 150 to 450, an average particle size of 10 μm or more and less than 100 μm, and a primary particle ratio of 50% or more is excellent in compression moldability, and is suitable for orally disintegrating tablets. It is described that it can be used as a dosage form. In Patent Document 6, cellulose powder having an average degree of polymerization of 75 to 375, an apparent specific volume of 1.6 to 3.1 cc / g, and a component of 200 mesh or more is 2 to 80% by mass has good fluidity. In addition, it is described that when mixed with an active ingredient, the variation in the content of the ingredient is small and suitable as an excipient.

  A complex containing cellulose and starch is also used as an excipient. For example, Patent Document 7 contains celluloses and saccharides, the mass ratio of celluloses to saccharides is 100: (0.1 to 30.0), and excipient components other than the cellulose and the saccharides. It is described that at least one composite composition of starches or inorganic compounds has good moldability, and by using this as an excipient, an orally disintegrating tablet with good dosing feeling can be obtained. Has been. Patent Document 8 includes a starch-disintegrating composition having an average particle size of 1 to 15 μm, starches having a mixing ratio of amylopectin and amylose of 85:15 to 100: 0, and an average particle size of 10 to 500 μm. Yes, by using a disintegrating composition in which the compounding ratio of starch and inorganic substance is 100: 1 to 100: 20 and the compounding ratio of starch and crystalline cellulose is 100: 1 to 100: 30 In addition, it is described that a tablet having a high hardness without tableting trouble can be formed. Further, Patent Document 9 describes that a spray-dried suspension of synthetic aluminum silicate, hydroxypropyl starch, and crystalline cellulose was used as an excipient for orally disintegrating tablets.

Japanese Patent Publication No.40-26274 International Publication No. 2002/02643 International Publication No. 2004/106416 International Publication No. 2006/115198 International Publication No. 2016/024493 Japanese Patent Publication No.56-2047 JP 2014-218447 A International Publication No. 2012/001977 JP 2011-246428 A

  The cellulose powders described in Patent Documents 1 to 5 are insufficient in disintegration under high impact pressure, and thus were obtained when used as excipients for orally disintegrating tablets. Even if the orally disintegrating tablet has good hardness and friability, satisfactory disintegration properties may not be obtained in the oral cavity. Moreover, since the cellulose powder described in patent document 6 is inferior in moldability compared with the cellulose powder described in patent documents 1-4, there existed a subject that hardness and friability were not fully provided. Thus, the conventional cellulose powder has not been known that can simultaneously provide the high compression moldability and quick disintegration required for orally disintegrating tablets. In addition, cellulose has a problem in that it has a high water absorption and has a poor texture and cannot be blended in a large amount.

  In the case of a complex containing cellulose and starch, the saccharide absorbs moisture during storage, and there is a problem that storage stability is not sufficient or sufficient moldability cannot be imparted depending on the type of active ingredient. . For example, in the cellulose composite of Patent Document 7, it is pregelatinized starch that is specifically disclosed as starches, but the disintegration under high impact pressure is delayed because it contains a water-soluble component. There was a problem that the storage stability was not sufficient. None of the cellulose composites containing raw starch that is sugar-free and not pregelatinized starch has high moldability comparable to cellulose powder. Also in Patent Document 8, the starches specifically disclosed are waxy rice starch, and corn starch is not preferred. Moreover, since there are many compounding quantities of starches, the composite_body | complex described in the said literature had the subject that it was poor in compression moldability. The complex described in Patent Document 9 contains synthetic aluminum silicate, which has a problem of compounding with drugs. Furthermore, since the hydroxypropyl starch is contained, the complex has a problem of delay of disintegration under high impact pressure.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have sprayed and dried a specific cellulose dispersion, starch, and light anhydrous silicic acid by a fluid nozzle method. The present inventors have found that it is possible to impart disintegration quicker than powder, and have completed the present invention. That is, the present invention is as follows.

[1] Cellulose, starch and light anhydrous silicic acid are contained, the weight ratio of cellulose and starch is 90:10 to 40:60, and the content of light anhydrous silicic acid is 0.1 to 2% by mass; The bulk density is 0.10 to 0.50 g / cm ³ , the angle of repose is 35 to 54 °, and the residual content on the sieve when sieved with a sieve having an opening of 32 μm is 50% by mass or less. A cellulose composite that is characterized.
[2] The cellulose composite according to [1], wherein a molded body obtained by compressing 0.5 g of a mixture of 30% by mass of the composite and 70% by mass of acetaminophen at 7 kN has a hardness of 40 to 120N.
[3] With a disintegration tester (manufactured by Toyama Sangyo Co., Ltd., NT-40HS type, without disk), a compact obtained by compressing 0.5 g of a mixture of 30% by mass of the composite and 70% by mass of acetaminophen at 7 kN, 37 The cellulose composite as described in [1] or [2] above, wherein the disintegration time in pure water is 100 seconds or less.
[4] A molded article comprising the cellulose composite of any one of [1] to [3] and one or more active ingredients.
[5] Hydrolysis of natural cellulosic material, cellulose aqueous dispersion containing cellulose having an average degree of polymerization of 150 to 450 and a number average particle size in a volume frequency particle size distribution measured by a laser diffraction particle size distribution meter of 50 μm or more Obtaining a liquid;
Preparing an aqueous dispersion containing the aqueous cellulose dispersion, starch, and light anhydrous silicic acid;
A spray drying step of spray drying the aqueous dispersion by a fluid nozzle method;
A method for producing a cellulose composite, wherein the cellulose composite according to any one of [1] to [3] is produced.
[6] A natural cellulosic substance is hydrolyzed, the average degree of polymerization is 150 to 450, the number average particle size in the volume frequency particle size distribution measured by a laser diffraction particle size distribution analyzer is 10 μm or more and less than 50 μm, and the average width is 2 to 30 μm. And a step of obtaining a cellulose aqueous dispersion containing cellulose having an average thickness of 0.5 to 5 μm,
Preparing an aqueous dispersion containing the cellulose aqueous dispersion, starch, and light anhydrous silicic acid;
Spray drying the aqueous dispersion by a fluid nozzle method;
A method for producing a cellulose composite, wherein the cellulose composite according to any one of [1] to [3] is produced.

  The composite containing cellulose, starch, and light anhydrous silicic acid according to the present invention can impart quicker disintegration than cellulose powder, particularly under high compression pressure, while having high compression moldability similar to that of cellulose powder. For this reason, the composite is particularly suitable as an excipient for a pharmaceutical product in a dosage form that requires a balance between moldability and disintegration, such as an orally disintegrating tablet.

  Hereinafter, the present invention will be described in detail together with specific embodiments. The following embodiment is an example for explaining the present invention, and is not intended to limit the present invention to the following contents. The present invention can be implemented with appropriate modifications within the scope of the gist.

<Cellulose composite>
The cellulose composite according to the present invention contains cellulose, starch and light anhydrous silicic acid (silicon dioxide, CAS number: 7631-86-9), and the mass ratio of cellulose to starch is 90:10 to 40:60. Yes, the content of light silicic anhydride is 0.1 to 2% by mass. By making the mass ratio of cellulose and starch within a specific range and further containing a small amount of light anhydrous silicic acid, when the cellulose composite was used as an excipient, it was produced under high moldability and high impact pressure. Excellent disintegration can be achieved even with tablets.

  The mass ratio of cellulose and starch of the cellulose composite according to the present invention is 80:20 to 50 in terms of the balance between hardness and disintegration of tablets produced under high impact pressure using the cellulose composite as an excipient. Is preferably within the range of 50:50, more preferably within the range of 70:30 to 50:50, and even more preferably within the range of 70:30 to 60:40.

  The cellulose content relative to the whole cellulose composite according to the present invention is preferably less than 90% by mass for good fluidity, and preferably 40% by mass or more for good moldability. Further, the content ratio of starch with respect to the whole cellulose composite according to the present invention is preferably less than 60% by mass because of good moldability, and the tablet obtained using the cellulose composite as an excipient is preferable. Since disintegration is good, the content is preferably more than 10% by mass.

  In the cellulose composite according to the present invention, the flowability is improved when the content of the light anhydrous silicic acid with respect to the entire composite is 0.1% by mass or more. Further, when the content of light silicic acid is 2% by mass or less with respect to the whole complex, the mixing property between the complex and the active ingredient is improved, and the tablet is produced using the complex as an excipient. The uniformity of the active ingredient content is improved. The content of light anhydrous silicic acid with respect to the whole cellulose composite according to the present invention is in the range of 0.2 to 2% by mass because both the fluidity and the content uniformity of the active ingredient of the manufactured tablet are improved. Is preferably within the range of 0.3 to 2% by mass.

The cellulose composite according to the present invention has a bulk density of 0.10 to 0.50 g / cm ³ . The cellulose composite according to the present invention has good flowability because the bulk density is 0.10 g / cm ³ or more, and good moldability because the bulk density is 0.50 g / cm ³ or less. . The bulk density of the cellulose composite according to the present invention is preferably in the range of 0.10 to 0.40 g / cm ³ , since the balance between fluidity and moldability is better. more preferably in the range of ~0.35g / cm ^3, and even more preferably within the range of 0.20~0.35g / cm ^3. The bulk density of the cellulose composite according to the present invention is calculated by dividing the volume when the container is filled with a predetermined mass of cellulose particles by the mass.

  The cellulose composite according to the present invention has an angle of repose of 35 to 54 °. The cellulose composite according to the present invention has an angle of repose of 35 ° or more and thus has good moldability, and since the repose angle is 54 ° or less, the cellulose composite was obtained using the cellulose composite as an excipient. Tablet disintegration is good. The angle of repose of the cellulose composite according to the present invention is preferably in the range of 38 to 54 °, more preferably in the range of 40 to 50 °, since the balance between moldability and disintegration is better. It is more preferable. The angle of repose of the cellulose composite according to the present invention can be measured by a conventional method using a Sugihara type angle of repose measuring instrument.

  The cellulose composite according to the present invention has a residual content on the sieve of 50% by mass or less when sieved with a sieve having an opening of 32 μm. When cellulose, starch, and light anhydrous silicic acid are mixed with each other in dry powder form, depending on the amount of starch, there is a granulated product in which cellulose aggregates. The remaining particles exceed 50% by mass. On the other hand, the cellulose composite according to the present invention can be obtained by preparing an aqueous dispersion containing cellulose, starch and light silicic acid, and then spray drying the aqueous dispersion. In this aqueous dispersion, cellulose is present in individual fibers, so that aggregation of cellulose is unlikely to occur during spray drying. As a result, the amount of particles remaining on a sieve having an opening of 32 μm is 50% by mass or less. . The cellulose composite according to the present invention preferably has a residual content on a sieve of 48% by mass or less, more preferably 46% by mass or less, when sieved through a sieve having an opening of 32 μm, more preferably 42% by mass. % Or less is more preferable.

  The cellulose composite according to the present invention is a tablet having both good hardness and easy disintegration in the oral cavity by mixing with an active ingredient as an excipient and compressing the obtained mixed powder under high compression pressure. Can be manufactured. For example, 30% by mass of the cellulose composite according to the present invention and 70% by mass of acetaminophen are mixed, 0.5 g of the mixed powder is put into a mortar, and compressed with a hydrostatic press (manufactured by Aiko Engineering) at a pressure of 7 kN. In this case, a molded body having a hardness of 40 N or more and a disintegration time of 100 seconds or less can be produced. The hardness of the molded body is preferably as hard as possible, but is limited to 120N, preferably 50 to 120N, because the formability of cellulose is limited. In the case of a mixed powder obtained by simply mixing dry powders of cellulose, starch and light anhydrous silicic acid, the hardness of the molded body produced under the same conditions is less than 40N. Moreover, although the disintegration time of the said molded object is so preferable that it is quick, a lower limit is about 1 second at most.

  In addition, the disintegration time of the tablet or cylindrical molded body produced using the cellulose composite according to the present invention as an excipient is the 16th revised Japanese Pharmacopoeia (published by Yodogawa Shoten Co., Ltd.), General Test Method “Disintegration Test Method”. It can measure by the method according to. Specifically, the length is 77.5 ± 2.5 mm, the inner diameter is 20.7 to 23 mm, the thickness is 1.0 to 2.8 mm, the upper end is open, and the mesh opening is 1.8 to 6 transparent tubes with a flat stainless steel net of 2.2 mm and wire diameter of 0.57 to 0.66 mm, and a diameter of 88 to 92 mm for holding these tubes vertically between the top and bottom. A disintegration tester equipped with a tester made of two plastic plates having a thickness of 5 to 8.5 mm is used. One sample per tube is put in six tubes of the tester, and the tester containing the sample is placed in pure water at 37 ° C. 29 to 32 reciprocations per minute with an amplitude of 53 to 57 mm. The time taken for the sample to disintegrate by shaking is taken as the disintegration time. In addition, when the sample residue is not recognized at all in the tester, or when the sample residue is a soft substance that does not clearly retain its original shape, or is a fragment of an insoluble coating, Is assumed to have collapsed. The average value of the disintegration times of the six samples is taken as the disintegration time of the sample.

  The cellulose composite according to the present invention preferably has a degree of swelling defined by the following formula of -2.0 to 20%. It is preferable that the degree of swelling of the cellulose composite is −2.0% or more because the disintegration becomes faster. The larger the degree of swelling, the better, but it is about 20% at most.

Swelling degree (%) = (V ₀ −V ₁ ) / V ₀ × 100
V ₀ : Volume when 10 g of powder is weighed and put into a 100 mL settling tube V ₁ : After adding 10 g of powder and 50 mL of pure water to the 100 mL settling tube, the powder is sufficiently wetted and allowed to stand for 8 hours. Volume of

(Average particle diameter of cellulose composite)
The volume frequency particle size distribution of the cellulose composite according to the present invention is measured by a laser diffraction particle size distribution meter. In the following, “number average particle size in volume frequency particle size distribution obtained by laser diffraction particle size distribution meter” may be referred to as “average particle size”.

  The cellulose composite according to the present invention preferably has an average particle size of 30 μm or more and 250 μm or less, more preferably 30 μm or more and 150 μm or less, and further preferably 30 μm or more and 120 μm or less. The cellulose composite according to the present invention has better fluidity when the average particle size is 30 μm or more, and better moldability when it is 250 μm or less.

(L / D of cellulose composite)
The cellulose composite according to the present invention preferably has a major axis / minor axis (L / D) ratio in the range of 2.0 to 4.0. A cellulose composite having an L / D of 2.0 or more is preferable because of high moldability, and a cellulose composite having 4.0 or less is preferable because of good fluidity. In addition, L / D of a cellulose composite carries out image analysis processing of the optical microscope image of at least 400 or more cellulose composites (product made from Interquest Co., Ltd., apparatus: Hyper700, software: Imagehyper), and each cellulose composite Can be calculated as an average value after obtaining the ratio (long side / short side) of the long side and the short side of the rectangle with the smallest area among the circumscribed rectangles.

  The appearance of aggregation of the cellulose composite according to the present invention can be observed with an electron microscope. As the cellulose composite according to the present invention, the cellulose composite forming an aggregate is preferably less than 50%, more preferably less than 20% by mass.

  The cellulose composite according to the present invention is used in the fields of medicine, food, and other chemical industries, and is particularly useful as an excipient for pharmaceutical tablets. In addition, powders, granules, and tablets containing these powders or granules prepared using the cellulose composite are excellent in moldability and disintegration. Therefore, the cellulose composite is particularly disintegrated in the oral cavity. It is very suitable as an excipient for dosage forms such as tablets, which require a balance between moldability and disintegration.

<Method for producing cellulose composite>
The cellulose composite according to the present invention can be produced, for example, by the following method.
The cellulose composite according to the present invention includes a step of hydrolyzing a natural cellulosic material to obtain a cellulose aqueous dispersion containing cellulose having an average degree of polymerization of 150 to 450, the obtained cellulose aqueous dispersion, and starch And a step of preparing an aqueous dispersion containing light anhydrous silicic acid, and a spray drying step of spray drying the obtained aqueous dispersion by a fluid nozzle method.

  Although starch contributes to disintegration, it is an elastic body, and if it is simply mixed with cellulose powder, the moldability of cellulose powder is impaired by the amount of starch mixed. On the other hand, the cellulose powder obtained by dispersing cellulose reduced to a specific size by hydrolysis in water and spray-drying the obtained aqueous dispersion by a fluid nozzle method is the same as the aqueous cellulose dispersion. The formability of the cellulose powder itself is increased 1.3 to 1.5 times as compared with the cellulose powder obtained by spray drying by the method. For this reason, even after the starch is blended by spray-drying an aqueous dispersion in which cellulose of a specific size, starch, and light anhydrous silicic acid are dispersed by a fluid nozzle method, it is molded in the same manner as cellulose powder. The cellulose composite which has the property and can provide quick disintegration can be manufactured. The reason why a cellulose composite having both moldability and disintegration suitable by spray drying using a fluid nozzle method is not clear, but the mist diameter is smaller in the fluid nozzle method than in the disk method. This is presumed to be due to drying without agglomeration.

(Natural cellulosic material)
The cellulose used as the raw material of the cellulose composite according to the present invention is a hydrolyzate of a natural cellulosic substance (a fibrous substance derived from a natural product containing cellulose). The natural cellulosic material may be plant or animal and may be derived from microorganisms. Examples of natural cellulosic materials include fiber materials derived from natural products containing cellulose such as wood, bamboo, wheat straw, rice straw, cotton, ramie, squirts, bagasse, kenaf, beet, and bacterial cellulose. Examples of commonly available natural cellulosic materials include natural cellulosic materials (powdered cellulose) that are in powder form, such as cellulose floc and crystalline cellulose.

  Known crystal forms of cellulose include type I, type II, type III, and type IV. Among them, type I and type II are widely used, and types III and IV are obtained on a laboratory scale. However, it is not widely used on an industrial scale. As a natural cellulosic material used as a raw material of the cellulose composite according to the present invention, the structural mobility is relatively high, the plastic deformability at the time of compression is sufficient, and it is easy to impart sufficient hardness to the molded body. Therefore, it preferably has a cellulose I type crystal structure.

  As a raw material of the cellulose composite according to the present invention, one kind of natural cellulosic substance may be used, or a mixture of two or more kinds of natural cellulosic substances may be used. The natural cellulosic material is preferably used in the form of a refined pulp, but the pulp refining method is not particularly limited, and any pulp such as dissolving pulp, kraft pulp, NBKP pulp, etc. may be used.

(Average degree of polymerization of cellulose)
The cellulose used as the raw material of the cellulose composite according to the present invention has an average degree of polymerization of 150 to 450. When the average degree of polymerization of cellulose is 150 or more, a cellulose composite having high moldability can be obtained. In addition, if the average degree of polymerization is 450 or less, hydrolysis of the natural cellulosic material is sufficient, and the obtained cellulose composite has a low content of the amorphous part of cellulose and a strong fiber property appears. There is no tendency to easily recover the elasticity, and the moldability tends to be excellent.

  The average degree of polymerization of cellulose can be measured according to the reduced specific viscosity method using a copper ethylenediamine solution described in the confirmation test (3) for crystalline cellulose in the 16th revised Japanese Pharmacopoeia (published by Yodogawa Shoten Co., Ltd.). However, when the average degree of polymerization exceeds 350, the sample amount is measured as 0.25 g of drug.

(Hydrolysis of cellulose)
The method for hydrolysis of the natural cellulosic material is not particularly limited, and examples thereof include acid hydrolysis, alkali oxidation decomposition, hydrothermal decomposition, steam explosion, and microwave decomposition. These methods may be used alone or in combination of two or more. In the acid hydrolysis method, for example, α-cellulose obtained as a pulp from a fibrous plant is used as a cellulose raw material, and this is dispersed in an aqueous medium, and an appropriate amount of proton acid, carboxylic acid, Lewis acid, heteropoly acid, etc. In addition, the average degree of polymerization can be easily controlled by heating while stirring. The reaction conditions such as temperature, pressure, and time at this time vary depending on the cellulose species, cellulose concentration, acid species, and acid concentration, but are appropriately adjusted so as to achieve the desired average degree of polymerization. For example, the conditions of using 2 mass% or less mineral acid aqueous solution and processing a cellulose for 10 minutes or more under 100 degreeC or more and pressurization are mentioned. Under these conditions, a catalyst component such as an acid penetrates into the inside of the cellulose fiber, the hydrolysis is accelerated, the amount of the catalyst component to be used is reduced, and subsequent purification is facilitated. In addition, the dispersion liquid of the cellulose raw material at the time of hydrolysis may contain a small amount of an organic solvent in a range not impairing the effects of the present invention, in addition to water.

(Cellulose aqueous dispersion)
In the production of the cellulose composite according to the present invention, first, a natural cellulosic material is hydrolyzed to obtain a cellulose aqueous dispersion containing cellulose having an average degree of polymerization of 150 to 450. This cellulose aqueous dispersion has an average polymerization degree of 150 to 450, an average particle diameter (number average particle diameter in volume frequency particle size distribution measured by a laser diffraction particle size distribution meter) of 50 μm or more, or This is an aqueous cellulose dispersion having an average degree of polymerization of 150 to 450, an average particle diameter of 10 μm or more and less than 50 μm, an average width of 2 to 30 μm, and an average thickness of 0.5 to 5 μm. When a cellulose aqueous dispersion having an average degree of polymerization of 150 to 450 and an average particle diameter of 50 μm or more is used, a cellulose composite having a low bulk density and a large angle of repose is obtained. On the other hand, when an aqueous cellulose dispersion having an average degree of polymerization of 150 to 450, an average particle size of 10 μm or more and less than 50 μm, an average width of 2 to 30 μm, and an average thickness of 0.5 to 5 μm is used, the bulk density is high. A cellulose composite having a small angle of repose is obtained. The bulk density and angle of repose can be arbitrarily controlled by changing the blending ratio of cellulose, starch and light silicic acid, and the solid content concentration during spray drying.

(Average particle size of cellulose)
The volume frequency particle size distribution of cellulose that is a raw material of the cellulose composite according to the present invention is measured by a laser diffraction particle size distribution meter.

  When an aqueous cellulose dispersion having an average degree of polymerization of 150 to 450 and an average particle diameter of 50 μm or more is used, the average particle diameter of cellulose in the aqueous dispersion is preferably 50 μm to 120 μm, preferably 50 μm to 100 μm. Or less, more preferably 60 μm or more and 80 μm or less. On the other hand, when using a cellulose aqueous dispersion having an average particle diameter of 10 μm or more and less than 50 μm, an average width of 2 to 30 μm, and an average thickness of 0.5 to 5 μm, the average particle diameter of cellulose in the aqueous dispersion is The thickness is preferably 15 μm or more and less than 50 μm, and more preferably 20 μm or more and 45 μm or less.

  When using an aqueous cellulose dispersion having an average particle diameter of 10 μm or more and less than 50 μm, an average width of 2 to 30 μm, and an average thickness of 0.5 to 5 μm, the average width of cellulose in the aqueous dispersion is 5 to 30 μm. It is preferable that it is 10-30 micrometers. The average thickness of cellulose in the aqueous dispersion is preferably 1.0 to 4.0 μm, and more preferably 2.0 to 3.0 μm.

(Average width of cellulose)
In the present invention and the specification of the present application, the average width (μm) of cellulose means the average value of the width (μm) of particulate cellulose (cellulose primary particles) obtained by hydrolyzing a natural cellulosic substance. . The width of the cellulose primary particles corresponds to the length of the short side when the cellulose primary particles are fibrous (cuboid), and corresponds to the length of the short axis when the cellulose primary particles are elliptical.

  The width of the cellulose primary particles is measured from a scanning microscope image of the cellulose primary particles. Specifically, cellulose primary particles made of a natural cellulosic material are dried as necessary, placed on a sample table with a carbon tape, and platinum palladium is vacuum-deposited (the film thickness of the deposited film at this time is 20 nm or less) ) Is observed with a scanning electron microscope, the width of three typical cellulose primary particles is measured, and the average of these is defined as the average width (μm) of the cellulose primary particles. For example, the width of the particle can be measured by using “JSM-5510LV (trade name)” manufactured by JASCO Corporation as a scanning electron microscope and observing at an acceleration voltage of 6 kV and a magnification of 250 times.

(Average thickness of cellulose)
In the present invention and the present specification, the average thickness (μm) of cellulose is the average value of the thickness (μm) near the center of particulate cellulose (cellulose primary particles) obtained by hydrolyzing a natural cellulosic substance. Means.

  The thickness of a cellulose primary particle is measured from the scanning microscope image of the cross section of a cellulose primary particle. Specifically, cellulose primary particles made of a natural cellulosic material are dried as necessary, placed on a sample table with a carbon tape, and gold is vacuum-deposited. After cutting out the cross section of the cellulose primary particles by the beam, this cross section is observed with a scanning electron microscope of the apparatus, the thickness of three typical cellulose primary particles is measured, and the average value of these is determined for the cellulose primary particles. The average thickness (μm). For example, using “FB-2100 (trade name)” manufactured by Hitachi, Ltd. as a focused ion beam processing apparatus, and cutting a section of cellulose primary particles with a Ga ion beam, this section is subjected to an acceleration voltage of 6 kV and a magnification. By observing at 1500 times, the thickness of the particles can be measured.

  The solid content concentration of the cellulose aqueous dispersion is preferably 20% by mass or less, more preferably 15% by mass or less, and more preferably 10% by mass or less with respect to the entire aqueous dispersion in order to suppress aggregation of the respective particles of cellulose. Further preferred.

  Next, by adding starch and light anhydrous silicic acid to the obtained aqueous cellulose dispersion, and further adding water as required, water dispersion containing cellulose, starch, and light anhydrous silicic acid Prepare the solution. The solid concentration of the aqueous dispersion after adding starch and light anhydrous silicic acid to the cellulose dispersion is higher than the solid concentration of the cellulose aqueous dispersion, and is preferably 15 to 25% by mass. The viscosity of the aqueous dispersion (slurry) containing the three components is about 100 to 600 mPa · s. When the solid content concentration of the aqueous dispersion containing the three components is low, a cellulose composite having higher moldability is obtained by spray drying, and when the solid content concentration of the aqueous dispersion containing the three components is high A cellulose composite having better fluidity can be obtained.

(Starch)
The starch used as the raw material of the cellulose composite according to the present invention is preferably raw starch, and more preferably corn starch. Raw starch has a lower content of water-soluble components than modified starches such as partially pregelatinized starch, pregelatinized starch, and starch derivatives such as hydroxypropyl starch. This is because it is difficult.

(Spray drying)
The obtained aqueous dispersion is spray-dried by a fluid nozzle method to obtain the cellulose composite of the present invention. The method of spray drying is not particularly limited as long as it is a fluid nozzle method, and may be a one-fluid fluid nozzle method or a two-fluid fluid nozzle method. In the production of the cellulose composite of the present invention, it is preferable to spray-dry with a pressurizing one-fluid nozzle or a pressurizing two-fluid nozzle. By spray-drying with a pressurized fluid nozzle method, a cellulose composite with better moldability can be obtained.

  Fluid nozzle type spray drying can be performed using a spray dryer generally called a spray dryer. Such a spray dryer is a drying device that instantly dries a cellulose dispersion to form particles, such as devices such as Okawara Kako, Matsubo, GEA Process Engineering, Powdering Japan, Nippon Chemical Machinery, Fujisaki Electric, etc. Can be used.

<Molded body>
The molded body according to the present invention contains the cellulose composite according to the present invention and one or more active ingredients. More specifically, the molded body according to the present invention is mixed with the cellulose composite according to the present invention and at least one active ingredient as necessary, and mixed, stirred, granulated, and punched. It refers to a molded product obtained by appropriately selecting a known method such as tableting, sizing or drying. Examples of molded articles include solid preparations such as tablets, powders, fine granules, granules, extracts, pills, capsules, troches, and poultices when used for pharmaceuticals. The present invention includes not only pharmaceuticals but also foods such as confectionery, health foods, texture improvers, dietary fiber reinforcing agents, solid foundations, bath preparations, animal drugs, diagnostic agents, agricultural chemicals, fertilizers, ceramic catalysts, etc. include. The molded product of the present invention can be produced by a conventional method.

(Active ingredient)
The active ingredient contained in the molded product according to the present invention is not particularly limited, and examples thereof include medicinal medicinal ingredients, health food ingredients, food ingredients, agricultural chemical ingredients, fertilizer ingredients, feed ingredients, cosmetic ingredients, catalyst ingredients, and the like. It is done. The shape of the active ingredient in the molded body is not particularly limited, and may be any shape such as powder, crystal, oil, liquid, and semisolid. Further, it may be coated for elution control and bitterness reduction. Moreover, the active ingredient contained in the molded object which concerns on this invention may be used independently, and may use 2 or more types together.

  Among the active ingredients, the medicinal medicinal ingredients include, for example, antidepressants, antipyretic analgesics, antipsychotic drugs, skeletal muscle relaxants, hypnotic sedatives, hypnotic sedatives, antipruritics, pediatric analgesics, gastric drugs, Acid, digestive, cardiotonic, arrhythmic, antihypertensive, vasodilator, diuretic, antiulcer, intestinal, osteoporosis, antitussive expectorant, antiasthma, antibacterial, frequent urination Orally administered, such as nourishing tonics and vitamins. The medicinal components may be used alone or in combination of two or more. Specifically, for example, antidepressants (phenytoin, acetylphenetride, trimethadione, phenobarbital, primidone, nitrazepam, sodium valproate, sultiam, etc.), antipyretic analgesic / anti-inflammatory drugs (acetaminophen, phenylacetylglycine methylamide, mefenam) Acid, diclofenac sodium, fructophenine, aspirin, aspirin aluminum, etenzaamide, oxyphenbutazone, sulpyrine, phenylbutazone, ibuprofen, alclofenac, naloxene, ketoprofen, tinolidine hydrochloride, benzydamine hydrochloride, thiaramide hydrochloride, indomethacin, piroxicam, salicylamide, etc.) , Antipruritic drugs (dimenhydrinate, meclizine hydrochloride, diphenidol hydrochloride, etc.), narcotics (opium alkaloid hydrochloride, hydrochloric acid) Ruhine, codeine phosphate, dihydrocodeine phosphate, oxymethebanol, etc.), neuropsychiatric drugs (chlorpromazine hydrochloride, levomepromazine maleate, perazine, maleic acid, perphenazine, chlorprothixene, haloperidol, diazepam, oxazepam, Oxazolam, mexazolam, alprazolam, zotepine, etc.), skeletal muscle relaxants (chlorzoxazone, chlorphenesin carbamate, chlormezanone, pridinol mesylate, eperisone hydrochloride, etc.), drugs for autonomic nerves (betanechol chloride, neostigmine bromide, pyridostigmine bromide, etc. ), Antispasmodic drugs (atropine sulfate, butropium bromide, butyl scopolamine bromide, propanterin bromide, papaverine hydrochloride, etc.), antiparkinsonian drugs (biperiden hydrochloride, trihexifif hydrochloride) Nidyl, amantadine hydrochloride, levodopa, etc.), antihistamines (diphenhydramine hydrochloride, chlorpheniramine dl-maleate, promethazine, mequitazine, clemastine fumarate, etc.), cardiotonic agents (aminophylline, caffeine, dl-isoproterenol hydrochloride, ethylephrine hydrochloride) , Norphenelin hydrochloride, ubidecarenone, etc.), arrhythmic drugs (procainamide hydrochloride, pindolol, metoprolol tartrate, disoviramide, etc.), diuretics (potassium chloride, cyclopentiazide, hydrochlorothiazide, triamterene, acetazolamide, furosemide, etc.) Hexamethonium hydride, hydralazine hydrochloride, silosingopine, reserpine, propranolol hydrochloride, captopril, methyldopa, etc.), vasoconstrictors (dihydroergotamine mesylate, etc.) Vasodilators (etaphenone hydrochloride, diltiazem hydrochloride, carbochromen hydrochloride, pentaerythritol tetranitrate, dipyridamole, isosorbide nitrate, nifedipine, nicamethate citrate, cyclandrate, cinnarizine, etc.), arteriosclerotic drugs (ethyl linoleate, lecithin, Clofibrate, etc.), circulatory organ drugs (nicardipine hydrochloride, meclofenoxate hydrochloride, cytochrome C, pyridinol carbamate, pinbocetin, calcium hopantenate, pentoxifylline, idebenone, etc.), respiratory accelerator (dimefrine hydrochloride, etc.), Antitussive expectorant (codeine phosphate, dihydrocodeine phosphate, dextromethorphan hydrobromide, noscapine, L-methylcysteine hydrochloride, bromhexine hydrochloride, theophylline, ephedrine hydrochloride, amlexanox ), Bile drugs (osalmide, phenylpropanol, hymechromone, etc.), intestinal drugs (berberine chloride, loperamide hydrochloride, etc.), digestive drugs (metoclopramide, phenipentol, domperidone, etc.), vitamins (retinol acetate, dihydro Taxolol, etretinate, thiamine hydrochloride, thiamine nitrate, fursultiamine, octothiamine, chicotiamine, riboflavin, pyridoxine hydrochloride, pyridoxal phosphate, nicotinic acid, pantethine, cyanocobalamin, biotin, ascorbic acid, phytonadione, menatetrenone), antibiotics ( Benzylpenicillin benzathine, amoxicillin, ampicillin, cyclacillin, cefaclor, cephalexin, cefuroxime axetil, erythromycin, kitasamycin, josamycin Chloramphenicol, tetracycline, griseofulvin, cefuzonam sodium, etc.), chemotherapeutic agents (sulfamethoxazole, isoniazid, ethionamide, Chiazosuruhon, nitrofurantoin, enoxacin, ofloxacin, norfloxacin, etc.).

  Other active ingredients include caffeine, lansoprazole, famotidine, omeprazole, mosapride citrate, voglibose, zolpidem tartrate, loratadine, imidapril hydrochloride, mizoribine, cefcapene pivoxil hydrochloride, levofloxacin, risperidone, sumatriptan succinate, fumaric acid Quetiapine, solifenacin succinate, glucosamine, glucosamine hydrochloride, N-acetylglucosamine, γ-aminobutyric acid (GABA), coenzyme Q10, gymnema, agaricus, collagen, psyllium husk powder, chondroitin, chondroitin sulfate, turmeric, alginic acid, sodium alginate , Alginate, zinc alginate, potassium alginate, calcium alginate, ammonium alginate, windbreak pain, Day leaves, astaxanthin, alpha-lipoic acid, ginkgo biloba, elastin, L-carnitine, chitosan, chlorella, spirulina, ceramide, konogi palm, hyaluronic acid, bilberry, β-glucan, maca, pine bark extract, lutein, African mango, Citrus fruit extract, mushroom chitosan, kuzu flower extract, green coffee bean extract, green rooibos, black vinegar, ornithine, amino acids, olives, curcumin, agaricus, ganoderma fungi, phospholipids, oligolactic acid, ferulic acid, blue Examples include soybean powder, lactobionic acid, cat's claw, and polyphenol.

  Other oily and liquid active ingredients include, for example, teprenone, indomethacin farnesyl, dimethicone, menatetrenone, phytonadione, vitamin A oil, phenipentol, vitamin D, vitamin E and other vitamins, DHA (docosahexaenoic acid), EPA ( Eicosapentaenoic acid), higher unsaturated fatty acids such as liver oil, coenzyme Q, oil-soluble flavors such as orange oil, lemon oil, peppermint oil, etc. "16th revision Japanese Pharmacopoeia" (published by Yodogawa Shoten Co., Ltd.) ), “External group”, “USP26”, “NF21” (all issued by UNITED STATES PHARMOPEIAL CONVENTION, INC), pharmaceutical active ingredients described in “EP”, and the like. Vitamin E has various homologues and derivatives, but is not particularly limited as long as it is liquid at normal temperature. For example, dl-α-tocopherol, dl-α-tocopherol acetate, d-α-tocopherol, d-α-tocopherol acetate and the like may be mentioned, and one kind selected from the above may be used alone or two kinds You may use the above together.

  Semi-solid active ingredients include, for example, earth dragons, licorice, keihi, peonies, buttonpi, valerian, salamander, ginger, chimpi, maoh, nantenjitsu, ohhi, onji, kyoukyo, shazenshi, shazenso, sarcophagus, seneca, baimo , Fennel, amber, auren, gadget, chamomile, gentian, goo, beast gall, shajin, ginger, sojutsu, clove, chinhi, sandalwood, chiketsu carrot, carrot, kakkonyu, katsushiyu, kososan, purple katsura Mention herbal or herbal extracts such as hot water, small purple hot water, small blue dragon hot water, Mumon winter hot water, half summer Koboku hot water, Mao hot water, oyster meat extract, propolis and propolis extract, coenzyme Q, etc. One kind selected from the above may be used alone, or two or more kinds may be used in combination.

  The content of the cellulose composite contained in the molded product according to the present invention is not particularly limited, but is preferably 1% by mass or more and 99% by mass or less with respect to the total mass of the molded product, and is 3% by mass or more and 99% by mass or less. It is more preferable that it is 5 mass% or more and 99 mass% or less. If it is in the said range, sufficient hardness which is hard to produce abrasion and destruction can be provided to the molded object (tablet) shape | molded under the high impact pressure.

  Although content of the active ingredient which the molded object which concerns on this invention contains is not specifically limited, It is preferable that they are 50 to 99 mass%. By sufficiently increasing the proportion of the active ingredient in the entire molded article, the size of the molded article of the active ingredient that requires a high dose can be reduced extremely efficiently.

  Furthermore, in addition to the cellulose composite and the active ingredient according to the present invention, the molded product according to the present invention includes a disintegrant, a binder, a fluidizing agent, a lubricant, a corrigent, a fragrance, a colorant, as necessary. Other additives such as sweeteners and surfactants can also be contained.

  Disintegrants include croscarmellose sodium, carmellose, carmellose calcium, carmellose sodium, celluloses such as low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, hydroxypropyl starch, rice starch, wheat starch, corn starch, potato Starches, starches such as partially pregelatinized starch, crospovidone and the like can be mentioned.

  Binders include sugars such as sucrose, glucose, lactose, fructose, sugar alcohols such as mannitol, xylitol, maltitol, erythritol, sorbitol, gelatin, pullulan, carrageenan, locust bean gum, agar, konjac mannan, xanthan gum, tamarind Water-soluble polysaccharides such as gum, pectin, sodium alginate and gum arabic, crystalline cellulose, powdered cellulose, celluloses such as hydroxypropylcellulose, hydroxypropylmethylcellulose and methylcellulose, starches such as pregelatinized starch and starch paste, polyvinylpyrrolidone, Synthetic polymers such as carboxyvinyl polymer and polyvinyl alcohol, calcium hydrogen phosphate, calcium carbonate, synthetic hydrotalcite, aluminate silicate Inorganic acids such as Neshiumu like.

  Examples of the fluidizing agent include hydrous silicon dioxide and light anhydrous silicic acid.

  Examples of the lubricant include magnesium stearate, calcium stearate, stearic acid, sucrose fatty acid ester, talc and the like. Examples of the corrigent include glutamic acid, fumaric acid, succinic acid, citric acid, sodium citrate, tartaric acid, malic acid, ascorbic acid, sodium chloride, 1-menthol and the like.

  Examples of the fragrances include oranges, vanilla, strawberry, yogurt, menthol, fennel oil, cinnamon oil, spruce oil, mint oil, and green tea powder.

  Examples of the colorant include food colors such as Food Red No. 3, Food Yellow No. 5, and Food Blue No. 1, copper chlorophyllin sodium, titanium oxide, riboflavin, and the like.

  Examples of sweeteners include aspartame, saccharin, dipotassium glycyrrhizinate, stevia, maltose, maltitol, starch syrup, and amacha powder.

Examples of the surfactant include phospholipid, glycerin fatty acid ester, polyethylene glycol fatty acid ester, sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, and the like.

  Since the cellulose composite according to the present invention is useful as an excipient capable of simultaneously imparting moldability and disintegrability, the molded article according to the present invention is a pharmaceutical product in a dosage form that requires a balance between moldability and disintegration. Or a food or drink, and more preferably an orally disintegrating tablet.

  When the molded body according to the present invention is an orally disintegrating tablet, the tablet hardness is preferably 50N or more and less than 200N, more preferably 50N or more and less than 150N, and even more preferably 50N or more and less than 100N. It is preferable that the tablet hardness is 50 N or more because the side surface of the tablet is not easily hung or broken during transportation or storage. On the other hand, when it is less than 200 N, the disintegration property of the tablet is not slow, and satisfactory disintegration property as an orally disintegrating tablet is obtained.

  Orally disintegrating tablets are pharmaceuticals and health food preparations that can be taken without water. For example, the disintegration time of tablets performed according to the 16th revised Japanese Pharmacopeia, general test method "disintegration test method" is less than 60 seconds Is preferable, and within 30 seconds is more preferable. In an oral disintegration test in which a tablet is actually put into a human mouth and disintegrated only with saliva, the disintegration is preferably less than 60 seconds, and more preferably within 30 seconds.

  The invention is illustrated by the following examples. However, these do not limit the scope of the present invention. In addition, the measuring method of each physical property in an Example and a comparative example is as follows.

<Average polymerization degree>
The average degree of polymerization of cellulose was a value measured by the copper ethylenediamine solution viscosity method described in the 16th revised Japanese pharmacopoeia, confirmation test (3) for crystalline cellulose.
Specifically, first, about 1.3 g of a sample was accurately weighed and placed in a 125 mL Erlenmeyer flask, and 25 mL of water and 25 mL of a 1 mol / L copper ethylenediamine reagent solution were respectively added accurately. Next, nitrogen was immediately passed through the tube, and the sample was dissolved by shaking with a shaker. Appropriate amount of the obtained solution is accurately measured and measured at 25 ± 0.1 ° C. according to the first viscosity measurement method (capillary viscometer method), the Ubbelohde viscometer whose approximate constant (K) is 0.03. Was used to determine the kinematic viscosity ν. The kinematic viscosity ν is the product of the time (t) and constant (K) required for a constant volume to flow down through the capillary. Separately, 25 mL of water and 25 mL of 1 mol / L copper ethylenediamine test solution were accurately weighed, and the mixture was tested in the same manner using an Ubbelohde viscometer with an approximate constant (K) of 0.01. The kinematic viscosity ν ₀ was determined. The kinematic viscosity ν ₀ is the product of the time (t ₀ ) required for a constant volume to flow down through the capillary tube and a constant (K).
The relative viscosity (η _rel ) of this sample was determined by the following equation.

η _rel = ν / ν ₀

Relative viscosity calculated based on "Table for obtaining product [η] C of concentration from intrinsic viscosity to relative viscosity (η _rel )" described in 16th revision Japanese Pharmacopoeia, Crystalline Cellulose Confirmation Test (3) The product ([η] C) of the intrinsic viscosity [η] (mL / g) and the concentration (C) (g / mL) was obtained from (η _rel ), and the average degree of polymerization (P) was calculated by the following equation. In the following formula, M _T is a weighed amount of this product samples in terms of dry matter (g).

P = 95 [η] C / [M _T ]

When the average degree of polymerization (P) exceeds 350, it is carried out in the same manner as above except that the sample amount is about 0.25 g, and the average degree of polymerization (P) is calculated.

<Average particle diameter [μm]>
The average particle diameter of each particle of cellulose or cellulose composite was measured using a laser diffraction / scattering particle size distribution meter (LA-910, manufactured by Horiba, Ltd.). The average particle diameter was calculated as the number average of volume frequency.

<Bulk density [g / cm ³ ]>
The bulk density of the powder of cellulose or cellulose composite was determined by reading the volume of a particle layer obtained by loosely filling 30 g of particles in a 100 mL graduated cylinder and dividing the volume by 30. The number of repetitions was 3, and the average value was taken.

<Repose angle [°]>
Sugihara-style repose angle measuring device (slit size: depth 10 mm x width 50 mm x height 140 mm, protractor installed at a position of width 50 mm) was used, a quantitative feeder was used, and the powder was dropped into the slit at 3 g / min. The dynamic self-fluidity was measured. At this time, the angle between the bottom of the apparatus and the cellulose powder forming layer is the angle of repose of the powder.

<Resistance on sieve when sieved with sieve of 32 μm openings [% by mass]>
About 10 g of the powder was placed on a sieve having an opening of 32 μm and sieved with an air jet sieve (manufactured by ALPINE, model A200LS) for 10 minutes, and the mass of the powder remaining on the sieve was determined as a percentage of the total mass.

<Tablet hardness>
The hardness of the tablets was measured with a tablet hardness tester (Tablet Tester 8M / DR. SCHLEUNIGER) that is generally used. The tablet hardness was measured for each tablet, and the average value of the tablet hardness for 20 tablets was calculated.

<Tablet friability>
Measure the mass (W _a ) of 20 tablets, put it in a tablet friability tester (PTFR-A, manufactured by PHARMA TEST), rotate at 25 rpm for 4 minutes, and then remove the fine powder adhering to the tablets. The mass was measured again (W _b ) and calculated from the following formula.
Friction = 100 × (W _a −W _b ) / W _a

<Tablet disintegration test>
It was carried out in accordance with the 16th revision Japanese Pharmacopoeia, General Test Method "Disintegration Test Method". Water was used as the test solution, and “NT-40HS type” (without disk) manufactured by Toyama Sangyo Co., Ltd. was used as the disintegration tester. Specifically, one sample per tube is put in six transparent tubes of the tester, and the tester in which the sample is put in pure water at 37 ° C. has 29 to 32 reciprocations per minute. The time required for the sample to collapse was measured by shaking up and down at 53 to 57 mm. The average value of the disintegration time of 6 samples was defined as the disintegration time of the sample.

<Tablet oral disintegration test>
Using three healthy adult male subjects as subjects, the time required for the tablet to completely disintegrate with saliva in the oral cavity was measured. Each person was measured twice, and the average value of three people was calculated.

[Example 1]
2 kg of pulverized commercial pulp (degree of polymerization 790) and 30 L of 4N hydrochloric acid aqueous solution were put into a low speed stirrer (Ikebukuro Sakai Kogyo Co., Ltd., 30 L GL reactor), hydrolyzed at 40 ° C. for 48 hours, average An acid-insoluble residue having a degree of polymerization of 270 was obtained. The obtained acid-insoluble residue was filtered using Nutsche so as to have a solid content of 40%, and the filter residue was further washed with pure water, neutralized with ammonia water, put into a 90 L plastic bucket, and purified water. And stirring with a three-one motor (made by HEIDON, type 1200G) to obtain a cellulose dispersion having a solid content concentration of 10%. The average particle size of the cellulose particles in the cellulose dispersion was 67 μm.
The cellulose dispersion, starch and light anhydrous silicic acid (SiO ₂ ) are mixed so that the mass ratio of cellulose / starch / SiO ₂ is 88.2 / 9.8 / 2, and the solid content concentration is 9.9 mass. % Aqueous dispersion was prepared. This aqueous dispersion was spray-dried with a feed rate of 20 kg / h and a pressurized one-fluid nozzle system to obtain a composite A containing cellulose, starch and SiO ₂ .
30% by mass of the composite A thus obtained and 70% by mass of acetaminophen were mixed, 0.5 g of the mixed powder was put into a mortar, and compressed with an impact pressure of 7 kN using a hydrostatic press (manufactured by Aiko Engineering). A tablet containing 70% by mass aminophen was obtained, and the hardness and friability were measured.
Tables 1 to 3 show the powder physical properties of the cellulose, the composite A, and the tablet containing 70% by mass of acetaminophen.

[Example 2]
By subjecting hardwood to known pulping treatment and bleaching treatment, the average fiber width of the primary cellulose particles is about 19 μm, the average thickness is about 3 μm, the level-off polymerization degree is 140 to 220, the moisture is 5 to 10%, the whiteness is 92 to 92%. A pulp having 97%, a viscosity of 5 to 40 cps, S105 to 15%, S181 to 8%, a copper value of 0.5 to 1.5, and a dichloromethane extract of 0.03 ppm or less was obtained. 2 kg of the pulp and 30 L of 4N hydrochloric acid aqueous solution were hydrolyzed at 40 ° C. for 48 hours while stirring in a low-speed stirrer (Ikebukuro Sakai Kogyo Co., Ltd., 50 L GL reactor) to obtain an acid-insoluble residue. . The obtained acid-insoluble residue is thoroughly washed with pure water, filtered, introduced into a 90 L-poly bucket, and pure water is added so that the total solid concentration is 15% by mass. The mixture was neutralized with aqueous ammonia while stirring at pH (pH after neutralization was 7.5 to 8.0). The average fiber width of the primary cellulose particles in the cellulose aqueous dispersion having a solid content concentration of 15% by mass was 22 μm, the average thickness was 2.5 μm, and the average particle size was 38 μm.
The obtained aqueous cellulose dispersion, starch and SiO ₂ are mixed so that the mass ratio of cellulose / starch / SiO ₂ is 69.3 / 29.7 / 1, and water having a solid content concentration of 18.3% by mass is mixed. A dispersion was prepared. This aqueous dispersion was spray-dried by a pressurized 1-fluid nozzle system with a feed rate of 30 kg / h to obtain a composite B containing cellulose, starch and SiO ₂ .
30% by mass of the obtained complex B and 70% by mass of acetaminophen were mixed, 0.5 g of the mixed powder was put into a mortar, and compressed with a hydrostatic press (manufactured by Aiko Engineering) at a pressure of 7 kN. A tablet containing 70% by mass aminophen was obtained, and the hardness and friability were measured.
Tables 1 to 3 show the powder physical properties of the cellulose, the composite B, and the tablet containing 70% by mass of acetaminophen.

[Example 3]
A cellulose aqueous dispersion, starch and SiO ₂ are mixed so that the mass ratio of cellulose / starch / SiO ₂ is 59.4 / 39.6 / 1 to prepare an aqueous dispersion having a solid content concentration of 19.4% by mass. The composite C containing cellulose, starch and SiO ₂ was obtained in the same manner as in Example 2 except that a tablet containing 70% by mass of acetaminophen was produced, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of the cellulose, the composite C, and the tablet containing 70% by mass of acetaminophen.

[Example 4]
A cellulose aqueous dispersion and starch are mixed so that the mass ratio of cellulose / starch is 60/40 to prepare an aqueous dispersion having a solid content concentration of 19.3% by mass, and the feed amount is 90 kg by a pressurized one-fluid nozzle method. A composite D containing cellulose, starch and SiO ₂ was obtained in the same manner as in Example 2 except that it was changed to / h, and a tablet containing acetaminophen 70% by mass was produced, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of the cellulose, the composite D, and the tablet containing 70% by mass of acetaminophen.

[Example 5]
A cellulose aqueous dispersion, starch and SiO ₂ were mixed so that the mass ratio of cellulose / starch / SiO ₂ was 49.75 / 49.75 / 0.5, except that the solid content concentration was 19.3 mass%. Were operated in the same manner as in Example 2, to obtain a complex E containing cellulose, starch and SiO ₂ , to produce a tablet containing 70% by mass of acetaminophen, and to measure hardness and friability. Tables 1 to 3 show the powder physical properties of the cellulose, the complex E, and the tablet containing 70% by mass of acetaminophen.

[Example 6]
A cellulose aqueous dispersion, starch and SiO ₂ were mixed so that the mass ratio of cellulose / starch / SiO ₂ was 36.6 / 59.4 / 1, and the solid content concentration was 18.9% by mass. In the same manner as in No. ₂ , a composite F containing cellulose, starch and SiO ₂ was obtained, and a tablet containing 70% by mass of acetaminophen was produced, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of the cellulose, the composite F, and the tablet containing 70% by mass of acetaminophen.

[Example 7]
A composite G containing cellulose, starch and SiO ₂ was obtained in the same manner as in Example 3 except that the cellulose aqueous dispersion of Example 1 was used as the cellulose dispersion, and a tablet containing 70% by mass of acetaminophen was obtained. Manufactured and measured for hardness and friability. Tables 1 to 3 show the powder physical properties of the cellulose, the composite G, and the tablet containing 70% by mass of acetaminophen.

[Comparative Example 1]
Commercially available crystalline cellulose (Theorus KG-1000: manufactured by Asahi Kasei Co., Ltd.) was pulverized using an airflow pulverizer (manufactured by Seishin Enterprise Co., Ltd., single track jet mill STJ-200 type), with a pulverization pressure of 0.4 MPa and a powder supply rate of 10 kg. / H was pulverized to obtain cellulose powder G (corresponding to Example 4 of Patent Document 5), and a tablet containing 70% by mass of acetaminophen was produced, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of cellulose, cellulose powder G, and acetaminophen 70% by mass-containing tablets.

[Comparative Example 2]
After adjusting the cellulose aqueous dispersion of Example 1 to a solid content concentration of 10% by mass, the feed rate was 6 kg / h and spray-dried by a disk method to obtain cellulose powder H (corresponding to Example 1 of Patent Document 3). A tablet containing 70% by mass of acetaminophen was produced, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of cellulose, cellulose powder H, and acetaminophen-containing 70% by mass tablet.

[Comparative Example 3]
Hydrolysis was performed by the same operation as in Example 1 except that the hydrolysis conditions were a 3N hydrochloric acid aqueous solution, 40 ° C., and 20 hours to obtain an acid-insoluble residue having an average degree of polymerization of 440. The obtained acid-insoluble residue was filtered using Nutsche so as to have a solid content of 70% by mass. The obtained filtration residue was further washed with pure water, neutralized with ammonia water, put into a 90 L plastic bucket, pure water was added, and the same procedure as in Example 1 was followed to obtain cellulose water having a solid content concentration of 6% by mass. A dispersion was obtained. The average particle diameter of the cellulose particles in the cellulose aqueous dispersion was 41 μm. The obtained aqueous cellulose dispersion was spray-dried by a disk method to obtain cellulose powder I (corresponding to Example 7 of Patent Document 2).
Using the obtained cellulose powder I, a tablet containing 70% by mass of acetaminophen was produced in the same manner as in Example 1, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of cellulose, cellulose powder I, and acetaminophen 70% by mass-containing tablets.

[Comparative Example 4]
Hydrolysis was performed by the same operation as in Example 1 except that the hydrolysis conditions were 0.14N hydrochloric acid aqueous solution, 121 ° C., 1 hour, and the stirring speed during the reaction was 30 rpm, and an acid-insoluble residue having an average degree of polymerization of 220. Got. The obtained acid-insoluble residue was filtered using Nutsche so as to have a solid content of 70% by mass. The obtained filtration residue was further washed with pure water, neutralized with ammonia water, put into a 90-liter plastic bucket, pure water was added, and the same procedure as in Example 1 was followed to obtain cellulose water having a solid content concentration of 17% by mass. A dispersion was obtained. The average particle diameter of the cellulose particles in the cellulose aqueous dispersion was 29 μm. After the obtained cellulose aqueous dispersion was spray-dried by a disk method, coarse particles were removed with a sieve having a mesh opening of 325 mesh, and cellulose powder J (loss on drying 4.1% by mass, corresponding to Example 1 of Patent Document 1) Got.
Using the obtained cellulose powder J, a tablet containing 70% by mass of acetaminophen was produced in the same manner as in Example 1, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of cellulose, cellulose powder J, and acetaminophen-containing 70% by mass tablet.

[Comparative Example 5]
Commercially available KP pulp (degree of polymerization 840) is hydrolyzed in a 0.7% aqueous hydrochloric acid solution at 125 ° C for 150 minutes, and then the hydrolysis residue is neutralized, washed and filtered to form a wet cake, and then sufficiently ground in a kneader After that, ethanol having a volume ratio of 1 was added, and the mixture was squeezed and air-dried. The obtained dry powder was pulverized with a hammer mill, and then coarse particles were removed with a 40 mesh sieve to obtain cellulose powder K (dry mass: 3.0% by mass, corresponding to Example 1 of Patent Document 6).
Using the obtained cellulose powder K, tablets containing 70% by mass of acetaminophen were produced in the same manner as in Example 1, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of cellulose, cellulose powder K, and acetaminophen-containing 70% by mass tablet.

[Comparative Example 6]
The cellulose dispersion, starch and SiO ₂ were mixed so that the mass ratio of cellulose / starch / SiO ₂ was 34.65 / 6.35 / 1.0, and the solid content concentration was 19.2% by mass. By operating in the same manner as in Example 2, a complex L containing cellulose, starch and SiO ₂ was obtained, and a tablet containing 70% by mass of acetaminophen was produced, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of the cellulose, the complex L, and the tablet containing 70% by mass of acetaminophen. The complex L had a small cellulose mass and a small angle of repose, and the hardness of a tablet containing 70% by mass of acetaminophen was as low as 33N.

[Comparative Example 7]
The cellulose dispersion, starch, and SiO ₂ are mixed so that the mass ratio of cellulose / starch / SiO ₂ is 94.1 / 4.9 / 1, the solid content concentration is 9.9% by mass, and the feed rate is 6 kg / h. In the same manner as in Example 2, except for the above, a composite M of cellulose, starch and SiO ₂ was obtained, and a tablet containing 70% by mass of acetaminophen was produced, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of the cellulose, the complex M, and the tablet containing 70% by mass of acetaminophen. The composite M had a large cellulose mass and bulk density, and an angle of repose exceeded 54 °. The hardness of the tablet containing 70% by mass of acetaminophen was as good as 119N, but the disintegration time exceeded 100 seconds.

[Comparative Example 8]
Crystalline cellulose, starch and SiO ₂ were mixed in a plastic bag so that the mass ratio of cellulose / starch / SiO ₂ was the same as in Example 1. Using the obtained mixed powder, a tablet containing 70% by mass of acetaminophen was produced in the same manner as in Example 1, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of cellulose, mixed powder, and acetaminophen-containing 70% by mass tablet. This mixed powder had an angle of repose exceeding 54 °, and the hardness of the tablet containing 70% by mass of acetaminophen was lower than that of Example 1.

[Comparative Example 9]
Crystalline cellulose, starch and SiO ₂ were mixed in a plastic bag so that the mass ratio of cellulose / starch / SiO ₂ was the same as in Example 2. Using the obtained mixed powder, a tablet containing 70% by mass of acetaminophen was produced in the same manner as in Example 1, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of cellulose, mixed powder, and acetaminophen-containing 70% by mass tablet. In this mixed powder, the hardness of the tablet containing 70% by mass of acetaminophen in the mixed powder was less than 50N.

[Comparative Example 10]
Crystalline cellulose, starch and SiO ₂ were mixed in a plastic bag so that the mass ratio of cellulose / starch / SiO ₂ was the same as in Example 3. Using the obtained mixed powder, a tablet containing 70% by mass of acetaminophen was produced in the same manner as in Example 1, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of cellulose, mixed powder, and acetaminophen-containing 70% by mass tablet. This mixed powder had an average particle size of less than 30 μm, and the hardness of a tablet containing 70% by mass of acetaminophen was less than 50N.

[Comparative Example 11]
Crystalline cellulose, starch and SiO ₂ were mixed in a plastic bag so that the mass ratio of cellulose / starch / SiO ₂ was the same as in Example 5. Using the obtained mixed powder, a tablet containing 70% by mass of acetaminophen was produced in the same manner as in Example 1, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of cellulose, mixed powder, and acetaminophen-containing 70% by mass tablet. This mixed powder had an average particle size of less than 30 μm and an angle of repose of less than 35 °, and the hardness of a tablet containing 70% by mass of acetaminophen was less than 50N.

[Comparative Example 12]
Crystalline cellulose, starch and SiO ₂ were mixed in a plastic bag so that the mass ratio of cellulose / starch / SiO ₂ was in the range described in Patent Document 8. Using the obtained mixed powder, a tablet containing 70% by mass of acetaminophen was produced in the same manner as in Example 1, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of cellulose, mixed powder, and acetaminophen-containing 70% by mass tablet. This mixed powder had an average particle size of less than 30 μm and an angle of repose of less than 35 °, and the hardness of a tablet containing 70% by mass of acetaminophen was less than 50N.

[Comparative Example 13]
Crystalline cellulose, starch and SiO ₂ were mixed in a plastic bag so that the mass ratio of cellulose / starch / SiO ₂ was in the range described in Patent Document 8. Using the obtained mixed powder, a tablet containing 70% by mass of acetaminophen was produced in the same manner as in Example 1, and the hardness and friability were measured. Tables 1 to 3 show the powder physical properties of cellulose, mixed powder, and acetaminophen-containing 70% by mass tablet. This mixed powder had an average particle size of less than 30 μm and an angle of repose of less than 35 °, and the hardness of a tablet containing 70% by mass of acetaminophen was less than 50N.

  In Table 3, the “residue on sieve [wt%]” column is the result of sieve residue (wt%) when sieved with a sieve having an opening of 32 μm. “Hardness when compressed at 7 kN” In the column [N], a tablet obtained by compressing a mixture of acetaminophen and a composite or cellulose powder ([acetaminophen] / [composite or cellulose powder] = 70/30) at 7 kN is shown. It is a result of hardness [N], and the column of “Disintegration time when compressed at 7 kN [seconds]” is a column of tablets obtained by compressing the mixture of acetaminophen and a composite or cellulose powder at 7 kN. This is the result of the decay time [seconds].

  The composites obtained in Examples 1 to 7 have hardness comparable to the cellulose powders of Comparative Examples 1 to 4 in spite of containing starch that is an elastic body. For Comparative Examples 1 and 2 of a certain cellulose powder, the disintegration time of the tablets was short and the disintegration was excellent. More specifically, the composite A of Example 1 and the mixed powder of Comparative Example 8, the composite B of Example 2 and the mixed powder of Comparative Example 9, and the composite C of Example 3 and Comparative Example 10 were mixed. The powder, the composite E of Example 5 and the mixed powder of Comparative Example 11 have the same composition, but the composite of the example was spray-dried with a pressurized one-fluid nozzle. Whereas the residue on the sieve when sieving was less than 50% by mass, the mixed powder of the comparative example was prepared by powder mixing. The minute exceeded 50% by mass. Since the mixed powders of Comparative Examples 12 and 13 have a high starch content, the residual content on the screen when sieved with a sieve having an opening of 32 μm was less than 50% by mass, but the angle of repose was less than 35 °, High moldability was not obtained.

When comparing the tablets of Example 1 and Comparative Example 2, they both use the same aqueous cellulose dispersion and the tablet of Example 1 contains starch, even though it contains starch. Since the tablet was harder than the tablet of Comparative Example 2, it was suggested that the moldability was better when the spray drying was performed by the fluid nozzle method than by the disk method. Also, using the composite G of Example 7 produced using a cellulose dispersion having an average degree of polymerization of 300 and an average particle size of 67 μm, and a cellulose dispersion having an average degree of polymerization of 240 and an average particle size of 38 μm. Comparing with the composite C produced in Example 3, the composite G in Example 7 was carried out even though the mass ratio of cellulose / starch / SiO ₂ and the production process of the composite were the same. The bulk density was lower than the composite C of Example 3, the angle of repose was large, and the degree of swelling was small. From this result, it was shown that the bulk density and angle of repose of the composite of cellulose, starch and SiO ₂ are affected by the cellulose dispersion as a raw material.

[Example 8]
After mixing N-acetylglucosamine 50% by mass, Complex C produced in Example 3 15% by mass, Erythritol 34% by mass, and SiO ₂ 0.5% by mass in a polyethylene bag for 3 minutes. 0.5% by mass of magnesium stearate was added to the obtained mixed powder and further slowly mixed for 30 seconds. The obtained mixed powder was tableted with a rotary tableting machine (CLEANPRESSSCORRECT 12HUK, manufactured by Kikusui Seisakusho) using a punch with a diameter of 0.8 cm and 12R at a turntable rotation speed of 54 rpm to produce a tablet having a mass of 180 mg. Table 4 shows the tablet physical properties of the obtained tablets.

[Example 9]
A tablet was prepared in the same manner as in Example 8 except that the complex C was changed to the complex D produced in Example 4. Table 4 shows the tablet physical properties of the obtained tablets.

[Comparative Example 14]
A tablet was produced in the same manner as in Example 8 except that the composite C was made cellulose powder I produced in Comparative Example 3. Table 4 shows the tablet physical properties of the obtained tablets.

[Comparative Example 15]
A tablet was prepared in the same manner as in Example 8 except that the composite C was cellulose powder J produced in Comparative Example 4. Table 4 shows the tablet physical properties of the obtained tablets.

[Comparative Example 16]
A tablet was prepared in the same manner as in Example 8 except that the composite C was changed to cellulose powder K produced in Comparative Example 5. Table 4 shows the tablet physical properties of the obtained tablets.

  The tablets of Examples 8 and 9 had a hardness of 50 N or more and a friability of 0.2 or less, which met practical standards. Further, the oral disintegration time was within 30 seconds, and the disintegration property was excellent. On the other hand, the tablet of Comparative Example 14 had good hardness and friability, but the oral disintegration time was as long as 60 seconds, which was inferior to the tablets of Examples 8 and 9. The tablet of Comparative Example 15 had good hardness but was inferior to the tablets of Examples 8 and 9 in terms of friability and oral disintegration time. Although the tablet of Comparative Example 16 had good oral disintegration time, chipping of the tablet occurred during tableting and was inferior to the tablets of Examples 8 and 9 in hardness and friability.

[Example 10]
20% by weight of GABA, 29% by weight of complex C produced in Example 3, 47% by weight of fine erythritol, 3% by weight of pregelatinized starch (“Swelstar” PD-1), 0.2% by weight of orange flavor, Then, 0.2% by mass of aspartame was thoroughly mixed in a polyethylene bag for 3 minutes, and then 0.6% by mass of magnesium stearate was added to the obtained mixed powder and further slowly mixed for 30 seconds. 0.5 g of the obtained mixed powder is put into a mortar (manufactured by Kikusui Seisakusho, using material SUK2, ³ ), and a flat bowl (manufactured by Kikusui Seisakusho, material SUK2, 3) with a diameter of 1.13 cm (bottom area is 1 cm ² ). ) Was used and compressed with an impact pressure of 6 kN. The compressor used was PCM-1A manufactured by Aiko Engineering (compression speed was about 25 cm / min). Table 5 shows the tablet physical properties of the obtained tablets.

[Example 11]
A tablet was produced in the same manner as in Example 10 except that the complex C was changed to the complex D produced in Example 4. Table 5 shows the tablet physical properties of the obtained tablets.

[Comparative Example 17]
A tablet was prepared by operating in the same manner as in Example 10 except that the composite C was cellulose powder I produced in Comparative Example 3. Table 5 shows the tablet physical properties of the obtained tablets.

[Comparative Example 18]
A tablet was prepared by operating in the same manner as in Example 10 except that the composite C was cellulose powder J produced in Comparative Example 4. Table 5 shows the tablet physical properties of the obtained tablets.

[Comparative Example 19]
A tablet was produced in the same manner as in Example 10 except that the composite C was made cellulose powder K produced in Comparative Example 5. Table 5 shows the tablet physical properties of the obtained tablets.

  As shown in Table 5, the tablet manufactured using the cellulose composite according to the present invention was more disintegrating than the tablet manufactured using the conventional cellulose powder.

[Example 12]
30% by weight of curcumin, 30% by weight of complex C prepared in Example 3, 36% by weight of fine erythritol, 3% by weight of pregelatinized starch (“Swelstar” PD-1), 0.2% by weight of orange flavor, Then, 0.2% by mass of aspartame was thoroughly mixed in a polyethylene bag for 3 minutes, and then 0.6% by mass of magnesium stearate was added to the obtained mixed powder and further slowly mixed for 30 seconds. 0.5 g of the obtained mixed powder is put into a mortar (manufactured by Kikusui Seisakusho, using material SUK2, ³ ), and a flat bowl (manufactured by Kikusui Seisakusho, material SUK2, 3) with a diameter of 1.13 cm (bottom area is 1 cm ² ). (Compressor is made by Aiko Engineering, PCM-1A (compression speed is about 25 cm / min.) Table 6 shows the tablet physical properties.

[Example 13]
A tablet was prepared in the same manner as in Example 12 except that the complex C was changed to the complex E produced in Example 5. Table 6 shows the tablet physical properties of the obtained tablets.

[Comparative Example 20]
A tablet was produced in the same manner as in Example 12, except that the composite C was made cellulose powder I produced in Comparative Example 3. Table 6 shows the tablet physical properties of the obtained tablets.

[Comparative Example 21]
A tablet was produced in the same manner as in Example 12 except that the composite C was made cellulose powder J produced in Comparative Example 4. Table 6 shows the tablet physical properties of the obtained tablets.

[Comparative Example 22]
A tablet was produced in the same manner as in Example 12 except that the composite C was made cellulose powder K produced in Comparative Example 5. Table 6 shows the tablet physical properties of the obtained tablets.

  As shown in Table 6, the tablet manufactured using the cellulose composite according to the present invention has the advantage that it is as hard as a tablet manufactured using the conventional cellulose powder and has a short oral disintegration time. Had.

[Example 14]
0.5 g of the composite A produced in Example 1 was put in a mortar (manufactured by Kikusui Seisakusho, using material SUK2, ³ ), and a flat bowl (made by Kikusui Seisakusho, material SUK2) having a diameter of 1.13 cm (bottom area 1 cm ² ) was used. , 3), and compressed with a striking pressure of 2 kN. The compressor used was PCM-1A manufactured by Aiko Engineering (compression speed was about 25 cm / min). Table 7 shows the physical properties of the obtained tablets. The hardness of the tablet was almost the same after 3 months.

[Comparative Example 23]
The same operation as in Example 14 was performed except that the composite A produced in Example 1 was changed to the cellulose composite described in Example 7 of Patent Document 7. Table 7 shows the physical properties of the obtained tablets. The tablet hardness after 3 months of the tablet was clearly reduced.

  Cellulose according to the present invention The composite according to the present invention can impart quicker disintegration than cellulose powder even under high impact pressure, while having a high compression moldability comparable to that of cellulose powder. For this reason, the cellulose which concerns on this invention can use the composite which concerns on this invention as an excipient | filler, and a satisfactory thing can be manufactured in the dosage form in which the balance of a moldability and disintegration is calculated | required, such as an orally disintegrating tablet.

Claims (6)

Cellulose, starch and light anhydrous silicic acid are contained, the weight ratio of cellulose and starch is 90:10 to 40:60, the content of light anhydrous silicic acid is 0.1 to 2% by mass, and the bulk density is It is 0.10 to 0.50 g / cm ³ , the angle of repose is 35 to 54 °, and the residual content on the sieve when sieved with a sieve having an opening of 32 μm is 50% by mass or less. , Cellulose composite.   The cellulose composite according to claim 1, wherein a hardness of a molded body obtained by compressing 0.5 g of a mixture of 30% by mass of the composite and 70% by mass of acetaminophen at 7 kN is 40 to 120N.   In a disintegration tester (Toyama Sangyo Co., Ltd., NT-40HS type, no disk), a compact formed by compressing 0.5 g of a mixture of 30% by mass of the complex and 70% by mass of acetaminophen at 7 kN, pure at 37 ° C. The cellulose composite according to claim 1 or 2, wherein the disintegration time in water is 100 seconds or less.   A molded body comprising the cellulose composite according to any one of claims 1 to 3 and one or more active ingredients. Hydrolyzing natural cellulosic material to obtain an aqueous cellulose dispersion containing cellulose having an average degree of polymerization of 150 to 450 and a number average particle size in a volume frequency particle size distribution measured by a laser diffraction particle size distribution meter of 50 μm or more Process,
Preparing an aqueous dispersion containing the aqueous cellulose dispersion, starch, and light anhydrous silicic acid;
A spray drying step of spray drying the aqueous dispersion by a fluid nozzle method;
A method for producing a cellulose composite, comprising: producing the cellulose composite according to any one of claims 1 to 3. Hydrolyzes natural cellulosic material, average polymerization degree is 150-450, number average particle size in volume frequency particle size distribution measured by laser diffraction particle size distribution analyzer is 10 μm or more and less than 50 μm, average width is 2-30 μm, and average Obtaining a cellulose aqueous dispersion containing cellulose having a thickness of 0.5 to 5 μm;
Preparing an aqueous dispersion containing the cellulose aqueous dispersion, starch, and light anhydrous silicic acid;
Spray drying the aqueous dispersion by a fluid nozzle method;
A method for producing a cellulose composite, comprising: producing the cellulose composite according to any one of claims 1 to 3.