JP2016183232A - Powdered cellulose - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide powdered cellulose for tablets which is formed into a tablet having high breaking strength and has good powder flowability.SOLUTION: Powdered cellulose for tablets obtained by pulverizing pulp derived from wood acid-hydrolyzed with a mineral acid has an average particle diameter of 30-45 μm, a polymerization degree of 300-1,300, and a crystallinity of 75-90%. The powdered cellulose for tablets has excellent high whiteness, powder flowability, and tablet breaking strength.SELECTED DRAWING: None

Description

  The present invention relates to powdered cellulose for tablets obtained by acid hydrolysis treatment of pulp derived from wood with mineral acid.

  Powdered cellulose has characteristics such as thickening, emulsification stability, water retention, oil absorption, shape retention, etc., so food additives, tablet excipients, dispersants, shape retention agents, water retention agents, filter aids It is used in a wide range of fields such as foods, medicines, cosmetics, building materials, ceramics, rubber, plastics, etc. as fillers, additives for paints and adhesives.

  There are two methods for producing this powdery cellulose: a production method using chemical treatment and a production method using mechanical treatment. The production method using chemical treatment is a production method in which a cellulose raw material is hydrolyzed using sulfuric acid or a mineral acid such as hydrochloric acid and, if necessary, pulverized. Specifically, a method of acid hydrolysis with dilute acid at a high temperature of 120 to 160 ° C. for 20 to 45 minutes to obtain powdered cellulose (Patent Document 1), 2.5 regulations (hereinafter, regulations are abbreviated as N) There are a method of acid hydrolysis with hydrochloric acid for about 15 minutes to obtain powdered cellulose (Patent Document 2), a method of obtaining a powdered cellulose by high-temperature treatment with various concentrations of aqueous hydrochloric acid (Patent Document 3), and the like.

  Powdered cellulose is used in various applications, but is particularly used as an excipient because of its high safety. Excipients are additives that are added to facilitate the handling of pharmaceuticals, agricultural chemicals, etc., or to improve molding and convenience, and when the amount of active ingredients is low in the manufacturing process of tablets and pills. Used for the purpose of a certain size and concentration.

  In preparations such as tablets and pills, the quality required of excipients is that the molded product (tablets and pills) has sufficient strength, and good workability (powder in the manufacturing process) It is important to have fluidity.

US Pat. No. 3,954,727 U.S. Pat. No. 3,141,875 JP-A-53-127553 JP2013-177528A

  However, when conventional powdery cellulose is used as an excipient, there is a problem that the strength of the formed tablet is insufficient or the fluidity of the powder is insufficient. In addition, workability | operativity at the time of forming a tablet will fall even if powder fluidity (powder fall speed) is too low or too high.

  Therefore, an object of the present invention is to provide a powdery cellulose for tablets in which the formed tablet has high breaking strength and good powder flowability.

The present invention provides the following [1] to [3].
[1] In powdered cellulose obtained by pulverizing pulp hydrolyzed with mineral acid, the average particle size of the powdered cellulose is 30 to 45 μm, the degree of polymerization is 300 to 1300, and the degree of crystallinity is 75. Powdered cellulose for tablets, characterized in that it is -90%.
[2] The powdery cellulose for tablets according to [1], wherein the whiteness of the powder or more cellulose is 80% or more.
[3] The powdery cellulose for tablets according to [1] or [2], wherein the pulp is a pulp derived from wood.

  ADVANTAGE OF THE INVENTION According to this invention, the powdery cellulose for tablets in which the breaking strength of the formed tablet is high and powder fluidity | liquidity is favorable can be provided.

  The powdery cellulose of the present invention is obtained by pulverizing pulp hydrolyzed with a mineral acid such as hydrochloric acid, sulfuric acid, nitric acid, etc., and has an average particle size of 30 to 45 μm, a degree of polymerization of 300 to 1300, and a crystallinity. Is 75 to 90%.

In the present invention, if the average particle size is smaller than 30 μm, the tablet breaking strength becomes insufficient, and if it is larger than 45 μm, the powder dropping speed becomes too low. On the other hand, if the degree of polymerization is less than 300, the tablet breaking strength is insufficient, and if it is greater than 1300, the average particle size is increased and the powder dropping speed is too low. Furthermore, if the crystallinity is smaller than 75%, the tablet breaking strength becomes insufficient. The tablet breaking strength is preferably in the range of 65 to 130 kg / cm ² , and the powder falling speed is preferably in the range of 0.1 to 0.35 g / sec.

  In this invention, it is preferable that the pulp used as a raw material is a pulp derived from a wood, and the pulp derived from a hardwood and the pulp derived from a conifer are mentioned. The pulping method (digestion method) of these wood-derived pulps is not particularly limited, and examples thereof include a sulfite cooking method, a kraft cooking method, a soda / quinone cooking method, and an organosolv cooking method. However, among these, kraft pulp is preferable from the viewpoint of environment.

  The pulping method (digestion method) dissolves and removes the lignin, which is a coloring substance in the pulp, but a bleaching treatment can be performed to further increase the whiteness. The bleaching method is not particularly limited, and a generally used method can be used. For example, pulverized (C), chlorine dioxide bleached (D), alkali extracted (E), hypochlorite bleached (H), hydrogen peroxide bleached (P) ), Alkaline hydrogen peroxide treatment stage (Ep), alkaline hydrogen peroxide / oxygen treatment stage (Eop), ozone treatment (Z), chelate treatment (Q), etc., in combination with D / E / P-D, C / D-E-H-D, Z-E-D-P, Z / D-Ep-D, Z / D-Ep-DP, D-Ep-D, D-Ep-DP, D- Ep-P-D, Z-Eop-D-D, Z / D-Eop-D, Z / D-Eop-D-E-D, etc. can be performed in sequence ("/" This means that the treatment before and after “/” is performed continuously without washing). The whiteness of the cellulosic material is desirably 80% or more based on ISO 2470.

  In the method for producing powdered cellulose of the present invention, the acid concentration in the acid hydrolysis treatment of pulp is not particularly limited. However, from the viewpoint of maintaining the degree of polymerization and the whiteness, an acid for producing conventional powdered cellulose is used. It is desirable to be 0.1 to 1.0 N, which is lower than the concentration. When the acid concentration in the acid hydrolysis treatment is lower than 0.1 N, the depolymerization of cellulose due to the acid is suppressed, so that a decrease in the degree of polymerization can be reduced, but it is very difficult to miniaturize. On the other hand, if it is higher than 1.0 N, depolymerization of cellulose proceeds and finer is facilitated, so that the powder fluidity is improved, but the tablet breaking strength is lowered as the degree of polymerization is lowered.

  Below, the manufacturing method of the powdery cellulose of this invention is illustrated.

  Powdered cellulose is produced through a raw material pulp slurry preparation step, an acid hydrolysis reaction step, a neutralization / washing / liquid removal step, a drying step, a pulverization step, and a classification step.

  The pulp raw material that can be used in the present invention can be in a fluidized state or in a sheet form. When fluidized pulp from the pulp bleaching process is used as a raw material, it is necessary to increase the concentration before it is put into the hydrolysis reaction tank, and it is concentrated by a dehydrator such as a screw press or a belt filter. It is thrown. When a pulp dry sheet is used as a raw material, the pulp is loosened with a crusher such as a roll crusher and then put into a reaction vessel.

  Next, a dispersion having a pulp concentration of 3 to 10% by weight (converted to solid content) adjusted to an acid concentration of 0.10 to 1.0 N is treated under conditions of a temperature of 80 to 100 ° C. and a time of 30 minutes to 3 hours. After the hydrolysis of the pulp, solid-liquid separation is performed on the pulp hydrolyzed in the dehydration step and the waste acid. The hydrolyzed pulp is neutralized by adding an alkaline agent and washed. Then, it is dried with a dryer and mechanically pulverized and classified to a specified size with a pulverizer.

  As the pulverizer used in the present invention, a cutting mill: mesh mill (manufactured by Horai Co., Ltd.), Atoms (manufactured by Yamamoto Momoma Co., Ltd.), knife mill (manufactured by Pulman), cutter mill (manufactured by Tokyo Atomizer Manufacturing Co., Ltd.) , CS cutter (Mitsui Mining Co., Ltd.), rotary cutter mill (Nara Machinery Co., Ltd.), turbo cutter (Freund Sangyo Co., Ltd.), pulp crusher (Zuikou Co., Ltd.) shredder (Shinko Pantech Co., Ltd.) ) Hammer type mill: Jaw crusher (manufactured by Makino Co., Ltd.), Hammer crusher (manufactured by Hadano Sangyo Co., Ltd.), Impact type mill: Pulverizer (manufactured by Hosokawa Micron Co., Ltd.), Fine Impact Mill (manufactured by Hosokawa Micron Co., Ltd.), Supermicron Mill (made by Hosokawa Micron Corporation), Nomizer (manufactured by Hosokawa Micron Corporation), Fine Mill (manufactured by Nippon Pneumatic Industrial Co., Ltd.), CUM type centrifugal mill (manufactured by Mitsui Mining Co., Ltd.), Ixed Mill (manufactured by Kanno Sangyo Co., Ltd.), Ultraplex (manufactured by Sagano Sangyo Co., Ltd.) ), Contraplex (manufactured by Hadano Sangyo Co., Ltd.), Coroplex (manufactured by Hadano Sangyo Co., Ltd.), Sample Mill (manufactured by Seishin Co., Ltd.), Bantam Mill (manufactured by Seisin Co., Ltd.), Atomizer (manufactured by Seisin Co., Ltd.), Tornado Mill ( Nikkiso Co., Ltd.), Neamill (Dalton Co., Ltd.), HT type fine crusher (Horai Co., Ltd.), Free crusher (Nara Machinery Co., Ltd.), New Cosmizer (Nara Machinery Co., Ltd.), Turbo mill (Freund Sangyo Co., Ltd.), gather mill (Nishimura Machinery Co., Ltd.) Sakusho), Spar Powder Mill (manufactured by Nishimura Machinery Co., Ltd.), Blade Mill (manufactured by Nissin Engineering Co., Ltd.), Super Rotor (manufactured by Nisshin Engineering Co., Ltd.), Npa Crusher (manufactured by Sanjo Industry Co., Ltd.), Willet pulverizer (manufactured by Sanki Seisakusho Co., Ltd.), pulp pulverizer (manufactured by Ruiko Co., Ltd.), Jacobson fine pulverizer (manufactured by Shinko Pantech Co., Ltd.), universal mill (manufactured by Tokuju Kosakusho Co., Ltd.), airflow mill: CGS type Jet mill (Mitsui Mine Co., Ltd.), Micron Jet (Hosokawa Micron Co., Ltd.), Counter Jet Mill (Hosokawa Micron Co., Ltd.), Cross Jet Mill (Kurimoto Steel Works Co., Ltd.), Supersonic Jet Mill (Nippon Pneumatic) Industrial Co., Ltd.), Current Jet (Nisshin Engineering Co., Ltd.) ), Jet mill (manufactured by Sanjo Industry Co., Ltd.), Ebara Jet Micronizer (manufactured by Ebara Seisakusho Co., Ltd.), Ebara Triad Jet (manufactured by Ebara Seisakusho Co., Ltd.), selenium mirror (manufactured by Masuko Sangyo Co., Ltd.) New microsic mat (manufactured by Masuno Seisakusho Co., Ltd.), kryptron (manufactured by Kawasaki Heavy Industries, Ltd.), vertical roller mill: vertical roller mill (manufactured by Shinion Co., Ltd.), vertical roller mill (manufactured by Schaeffler Japan Co., Ltd.) And roller mills (manufactured by Kotobuki Giken Kogyo Co., Ltd.), VX mills (Kurimoto Steel Corporation), KVM type vertical mills (Earth Technica Co., Ltd.), IS mills (IHI Plant Engineering Co., Ltd.) and the like. Among these, jaw crusher (manufactured by Makino Co., Ltd.), pulverizer (manufactured by Hosokawa Micron Co., Ltd.), super micron mill (manufactured by Hosokawa Micron Co., Ltd.), tornado mill (manufactured by Nikkiso Co., Ltd.), free crusher (Manufactured by Nara Machinery Co., Ltd.), turbo mill (manufactured by Freund Sangyo Co., Ltd.), spar powder mill (manufactured by Nishimura Machinery Co., Ltd.), blade mill (manufactured by Nissin Engineering Co., Ltd.), supersonic jet mill (Nippon Pneumatic Industry) It is preferable to use a current jet (manufactured by Nissin Engineering Co., Ltd.).

  For the purpose of imparting functionality or improving functionality to the powdered cellulose in the present invention, the raw material of powdered cellulose and other organic and / or inorganic components may be mixed singly or in an arbitrary ratio of two or more types, and pulverized. Is possible. Moreover, it is possible to perform a chemical process in the range which does not impair the polymerization degree of the natural cellulose used for a raw material significantly.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the present application is, of course, not limited to such examples. The test method in the Example of this application is shown next.

<Average particle size measurement>
Measurement was performed using a Microtrac particle size analyzer (Nikkiso Co., Ltd.). As a measurement principle, a laser scattering method is used, and the particle size distribution is expressed as an accumulation distribution, and a value at which the accumulation distribution is 50% is defined as an average particle diameter.

<Degree of polymerization>
The cellulose polymerization degree was calculated | required by the viscosity measuring method using the copper ethylenediamine of the 16th revision Japanese Pharmacopoeia commentary and the crystalline cellulose confirmation test (2) description.

<Crystallinity>
The crystallinity was determined by measuring the X-ray diffraction of the sample. For the measurement of X-ray diffraction, an appropriate amount of sample was placed on a glass cell, and an X-ray diffraction measurement apparatus (RAD-2C system, manufactured by Rigaku Corporation) was used. The crystallinity is calculated by the method of Segal et al. (L. Segal, JJ Greery, et al, Text. Res. J., 29, 786, 1959) and the method of Kamide et al. (K. Kamide et al. , Polymer J., 17, 909, 1985), and using the diffraction intensity of 2θ = 4 ° to 32 ° of the diffraction diagram obtained from the X-ray diffraction measurement as a baseline, the diffraction intensity of the 002 plane and 2θ = 1 From the diffraction intensity of the amorphous portion at 18.5 °, the following formula was used.
Xc = (I _002C -Ia) / I _002C × 100
Xc: degree of crystallinity of cellulose (%)
I _002C : 2θ = 22.6 °, 002 plane diffraction intensity Ia: 2θ = 18.5 °, diffraction intensity of amorphous part

<Powder falling speed>
A 5 g sample was vibrated and dropped using a powder tester (PT-N type, manufactured by Hosokawa Micron Corporation), and the time required for the whole powder to fall was measured. A larger value means better powder flowability.

<Whiteness>
In accordance with JIS P8148, the whiteness was measured using a Hunter whiteness meter.

<Tablet breaking strength>
Using a KBr tablet press, 100 mg of a sample was compressed at 300 kg / cm ² for 1 minute to produce a tablet having a diameter of 1 cm. The breaking strength of the obtained tablets was measured with a FUDO rheometer. It means that tablet strength is so high that this value is large.

<Example 1>
A bleached wood pulp sheet (LBKP, Nippon Paper Industries Co., Ltd., average polymerization degree 1800) was used as a raw material and reacted at 95 ° C. for 2 hours at a pulp concentration of 3.5% and a hydrochloric acid concentration of 0.5N. After the reaction is completed, the mixture is neutralized with sodium hydroxide, sufficiently washed with water, then air-dried for about 1 day under the temperature condition of 60 ° C., and the dried sample is subjected to a tornado mill (manufactured by Nikkiso Co., Ltd.). Using this, mechanically pulverized to obtain powdered cellulose.

The obtained powder had an average particle size of 33.9 μm, an average degree of polymerization of 800, a degree of crystallinity of 83.7%, a powder falling speed of 0.29 g / sec, a whiteness of 88.9%, a tablet The breaking strength was 82.9 kg / cm ² .

<Example 2>
A bleached wood pulp sheet (LBSP, manufactured by Nippon Paper Industries Co., Ltd., average polymerization degree 1450) was used as a raw material and reacted at 95 ° C. for 2 hours at a pulp concentration of 3.5% and a hydrochloric acid concentration of 0.1 N. After the reaction is completed, the mixture is neutralized with sodium hydroxide, sufficiently washed with water, then air-dried for about 1 day under the temperature condition of 60 ° C., and the dried sample is subjected to a tornado mill (manufactured by Nikkiso Co., Ltd.). Using this, mechanically pulverized to obtain powdered cellulose.

The obtained powder had an average particle size of 43.7 μm, an average degree of polymerization of 750, a crystallinity of 83.9%, a powder drop rate of 0.15 g / sec, a whiteness of 92.3%, a tablet The breaking strength was 90.4 kg / cm ² .

<Example 3>
A bleached wood pulp sheet (LBSP, manufactured by Nippon Paper Industries Co., Ltd., average polymerization degree 1450) was used as a raw material and reacted at 95 ° C. for 2 hours at a pulp concentration of 3.5% and a hydrochloric acid concentration of 0.4 N. After the reaction is completed, the mixture is neutralized with sodium hydroxide, sufficiently washed with water, then air-dried for about 1 day under the temperature condition of 60 ° C., and the dried sample is subjected to a tornado mill (manufactured by Nikkiso Co., Ltd.). Using this, mechanically pulverized to obtain powdered cellulose.

The obtained powder had an average particle size of 31.6 μm, an average degree of polymerization of 400, a degree of crystallinity of 85.6%, a powder falling speed of 0.34 g / sec, a whiteness of 91.8%, a tablet The breaking strength was 71.3 kg / cm ² .

<Comparative Example 1>
A bleached wood pulp sheet (LBKP, manufactured by Nippon Paper Industries Co., Ltd., average polymerization degree 1800) was used as a raw material and reacted at 95 ° C. for 2 hours at a pulp concentration of 3.5% and a hydrochloric acid concentration of 0.4 N. After the reaction is completed, the mixture is neutralized with sodium hydroxide, sufficiently washed with water, then air-dried for about 1 day at a temperature condition of 60 ° C., and the dried sample is subjected to super rotor blade mill (Nisshin Engineering Co., Ltd.). The powdered cellulose was obtained by mechanically pulverizing the product.

The obtained powder had an average particle size of 45.3 μm, an average degree of polymerization of 1000, a degree of crystallinity of 82.6%, a powder falling speed of 0.06 g / sec, a whiteness of 86.9%, a tablet The breaking strength was 106.5 kg / cm ² .

<Comparative example 2>
An exposed wood pulp sheet (LBKP, manufactured by Nippon Paper Industries Co., Ltd., average polymerization degree 1800) was used as a raw material and reacted at 95 ° C. for 2 hours at a pulp concentration of 3.5% and a hydrochloric acid concentration of 1.2 N. After the reaction is completed, the mixture is neutralized with sodium hydroxide, sufficiently washed with water, then air-dried for about 1 day at a temperature condition of 60 ° C., and the dried sample is subjected to super rotor blade mill (Nisshin Engineering Co., Ltd.). The powdered cellulose was obtained by mechanically pulverizing the product.

The obtained powder had an average particle size of 26.2 μm, an average degree of polymerization of 550, a crystallinity of 84.3%, a powder drop rate of 0.32 g / sec, a whiteness of 75.3%, and a tablet The breaking strength was 67.3 kg / cm ² .

<Comparative Example 3>
A bleached wood pulp sheet (LBSP, manufactured by Nippon Paper Industries Co., Ltd., average polymerization degree 1450) was used as a raw material and reacted at 95 ° C. for 2 hours at a pulp concentration of 3.5% and a hydrochloric acid concentration of 0.9 N. After the reaction is completed, the mixture is neutralized with sodium hydroxide, sufficiently washed with water, then air-dried for about 1 day at a temperature condition of 60 ° C., and the dried sample is subjected to super rotor blade mill (Nisshin Engineering Co., Ltd.). The powdered cellulose was obtained by mechanically pulverizing the product.

The obtained powder had an average particle size of 30.5 μm, an average degree of polymerization of 230, a degree of crystallinity of 86.8%, a powder falling speed of 0.31 g / sec, a whiteness of 90.4%, a tablet The breaking strength was 57.1 kg / cm ² .

<Comparative example 4>
A commercially available powdered cellulose, “KC Flock W-50GK” (manufactured by Nippon Paper Industries Co., Ltd.) has an average particle diameter of 43.9 μm, an average degree of polymerization of 1400, a degree of crystallinity of 65.7%, and a powder falling speed. Was 0.05 g / sec, whiteness was 91.9%, and tablet breaking strength was 58.3 kg / cm ² .

<Comparative Example 5>
Using a bleached wood pulp sheet (LBSP, Nippon Paper Industries Co., Ltd., average polymerization degree 1450) as a raw material, using a vertical roller mill (manufactured by Shinion Co., Ltd.), raw material charging amount 100 kg, production rate 30 kg / hr To obtain powdery cellulose.

The obtained powder had an average particle size of 26.3 μm, an average degree of polymerization of 1300, a degree of crystallinity of 55.2%, a powder falling speed of 0.33 g / sec, a whiteness of 92.8%, and a tablet The breaking strength was 41.5 kg / cm ² .

Claims (3)

In powdered cellulose obtained by pulverizing pulp hydrolyzed with mineral acid, the average particle size of the powdered cellulose is 30 to 45 μm, the degree of polymerization is 300 to 1300, and the degree of crystallinity is 75 to 90%. Powdered cellulose for tablets, characterized in that The powdery cellulose for tablets according to claim 1, wherein the whiteness of the powder or more cellulose is 80% or more. The powdery cellulose for tablets according to claim 1 or 2, wherein the pulp is a pulp derived from wood.