JP6823620B2 - I Ching compression molded product and its manufacturing method - Google Patents

Description

The present invention relates to an easily dispersible compression molded product that can be quickly dispersed in water while maintaining a certain hardness or higher, and a method for producing the same.

It is widely known that the hardness of a molded product obtained by compressing an organic powder containing chitin and chitosan depends on the pressure applied during compression. On the other hand, there is a need for a compression molded product (so-called easily dispersible compression molded product) that has contradictory characteristics such as rapid disintegration or dispersion under specific conditions while maintaining the hardness of the molded product above a certain level. There are also fields.

Tablets can be mentioned as a form in which the characteristics of the easily dispersible compression molded product can be utilized. Tablets obtained by molding powder containing an active ingredient into tablets are required to have a certain hardness or higher so as not to cause problems such as cracking, chipping, and abrasion in the packaging during transportation and storage. .. Furthermore, tablets are also required to have a disintegrating property that disintegrates in the digestive tract within an appropriate time after ingestion.

When the active ingredient having low moldability is tablet-molded, for example, an excipient is blended. Further, when the persistently disintegrating active ingredient is tablet-molded, for example, a disintegrant is blended. Further, in order to prevent locking obstacles such as binding and capping, a lubricant having an effect of reducing friction between particles may be blended. That is, tablets, which are easily dispersible compression molded products, are often produced by optimizing the compounding composition according to the characteristics of the active ingredient and the like. In other words, it is rare that only the active ingredient can be tableted to meet various required characteristics. As described above, the process of blending various kinds of raw materials and the granulation process lead to an increase in the number of manufacturing processes and an increase in cost. Therefore, it is necessary to develop a method for producing tablets satisfying various required characteristics by a simple process. Is requested.

Since the shape of many dietary fibers such as chitosan is fibrous, the powder fluidity is poor, and it is difficult to make tablets as they are. Further, since chitosan has a small bulk specific gravity, the filling amount of chitosan is limited, and the obtained tablets tend to be easily worn. Therefore, in order to mold tablets containing dietary fiber such as chitosan, a lubricant such as talc, magnesium stearate, sucrose fatty acid ester is usually added, or fluidity such as crystalline lactose and crystalline cellulose is added. Mix with a good excipient and tablet. However, when molded by mixing with other ingredients such as a lubricant, the content of dietary fiber is reduced, and it is necessary to enlarge the tablet in order to sufficiently ingest the active ingredient. However, since it may lead to a decrease in adherence of the person taking the drug, it is desired to develop a tablet capable of increasing the amount of dietary fiber in the tablet while increasing the fluidity.

Conventionally, it has been studied to produce a tablet having a certain degree of hardness and disintegration property by adjusting the blending balance between the active ingredient and an auxiliary ingredient such as a binder, a disintegrant, and an excipient. .. For example, a tablet in which a calcium material is blended as a molding aid to increase the hardness has been proposed (Patent Document 1). Further, a chitosan-containing tablet having improved hardness and disintegration, which is obtained by blending a calcium powder material and crystalline cellulose and tableting, has been proposed (Patent Document 2). Further, a chitosan-containing tablet having excellent disintegration property, which contains calcium carbonate, cellulose, and saponin in a predetermined ratio, has been proposed (Patent Document 3). Further, an orally disintegrating type tablet containing 30 to 90% by mass of N-acetylglucosamine (Patent Document 4) and a tablet containing chitosan, a calcium material, and an organic acid (Patent Document 5) have been proposed. Further, a tablet capable of disintegrating in the stomach, which is obtained by tableting chitosan powder with a large pressing force, has been proposed (Patent Document 6).

Japanese Patent No. 4132870 Japanese Unexamined Patent Publication No. 2004-262860 Japanese Patent No. 4824213 Japanese Patent No. 4403182 Japanese Patent No. 3737881 Japanese Patent No. 5969680

However, although the tablets proposed in Patent Documents 1 and 2 all have a certain degree of hardness, their disintegration property is still insufficient, and there is room for further improvement. Further, in order to produce these tablets, it is necessary to blend a specific ingredient other than the active ingredient as a molding aid, so that there is a problem that the content of the active ingredient tends to decrease relatively. Further, in Patent Document 3, the hardness of the obtained tablet is not examined at all. Further, in Patent Document 4, the disintegration time of the tablet at the time of chewing is examined, but the disintegration property in water is not examined at all. Further, since the tablet proposed in Patent Document 5 contains an organic acid and a calcium material as components other than chitosan, the content of chitosan is low. Furthermore, the tablets proposed in Patent Document 6 are still insufficient in hardness and dispersibility in water, and there is room for further improvement.

The present invention has been made in view of the problems of the prior art, and the subject thereof is chitosan, which quickly disperses in a hydrophilic solvent containing water while maintaining a certain hardness or higher. It is an object of the present invention to provide an easily dispersible compression molded product containing insoluble dietary fiber as a main component, and a method for producing the same.

That is, according to the present invention, the easily dispersible compression molded product shown below is provided.
[1] It contains at least one of the powder components of chitin and chitosan, and the ratio of the powder component to the total solid content is 10% by mass or more, and the bulk density of the powder component is 0.15 to 0. It is 55 g / mL, and the particle size of the powder component is a particle size that passes through a mesh having a mesh size of 150 to 180 μm, and the ratio of the component that passes through the mesh having a mesh size of 45 μm in the powder component is 3 to 50 mass by mass. A easily dispersible compression molded product having a hardness of 8 to 30 kgf.
[2] The easily dispersible compression molded product according to the above [1], wherein the powder component is a powder of chitosan having a degree of deacetylation of 70% or more.
[3] The easily dispersible compression molded product according to the above [1] or [2], wherein the powder component further contains a cellulose powder.
[4] The easily dispersible compression molded product according to any one of [1] to [3] above, which further contains at least one of an excipient and a lubricant.
[5] The easy dispersion according to any one of [1] to [4] above, wherein the time from when the mixture is poured into water at 37 ° C. in a stirred state until the original shape cannot be visually observed is within 120 seconds. Sex compression molded product.
[6] Any of the above [1] to [5], which is a tablet, an orally disintegrating tablet, a chewable tablet, a dispersed tablet, a health food, an agricultural material, a livestock feed, a cosmetic, a flocculant, or a dust-reducing compounding material. Easily dispersible compression molded product described in Crab.

Further, according to the present invention, the following method for producing an easily dispersible compression molded product is provided.
[7] The method for producing an easily dispersible compression molded product according to any one of [1] to [6] above, wherein at least one powder of chitin and chitosan is mixed with water and the following formula (1) is used. In the step of obtaining a water-containing raw material having a water addition rate of 10 to 100% by mass represented by, and drying and classifying the obtained water-containing raw material, the water content is 15% by mass or less and the bulk density is 0.15-. A step of obtaining a powder component having a particle size of 0.55 g / mL, a particle size passing through a mesh having a mesh size of 150 to 180 μm, and a proportion of components passing through a mesh having a mesh size of 45 μm of 3 to 50% by mass, and the obtained powder. A method for producing an easily dispersible compression molded product, which comprises a step of compression molding a molding raw material containing a component to obtain an easily dispersible compression molded product.
Water addition rate (%) = (W / P) x 100 ... (1)
P: Amount of powder (g)
W: Amount of water to be added (g)

According to the present invention, there is provided an easily dispersible compression molded product containing insoluble dietary fiber such as chitosan as a main component, which quickly disperses in a hydrophilic solvent containing water while maintaining a certain hardness or higher, and a method for producing the same. can do.

<Easy dispersibility compression molded product>
Hereinafter, embodiments of the present invention will be described, but the present invention is not limited to the following embodiments. The easily dispersible compression molded product of the present invention (hereinafter, also simply referred to as “compression molded product”) contains at least one powder component of chitin and chitosan, and the ratio of the powder component to the total solid content is 10% by mass. % Or more. The details will be described below.

(Powder component)
The powder component (powder) used in the compression molded product of the present invention is at least one of chitin and chitosan. Chitin is a basic polysaccharide (β- (1 → 4) -2-acetamido-2-deoxy-β-D-) having 2-acetamido-2-deoxy-D-glucose (N-acetylglucosamine) as a constituent unit. Glucose). Chitosan is a deacetylated product of chitin and is a basic polysaccharide (β- (1 → 4) -2-amino-2-" having 2-amino-2-deoxy-D-glucose (glucosamine) as a constituent unit. Deoxy-β-D-glucose). Further, the powder component used in the tablet of the present invention preferably further contains a cellulose powder. Chitin, chitosan, and cellulose are all industrially produced and various grades are available. In the present invention, using at least one of chitin and chitosan compresses various physiological activities such as fat absorption inhibitory effect, cholesterol lowering effect, blood pressure lowering effect, blood uric acid level lowering effect, and heavy metal adsorption ability. It is preferable because it can be imparted to.

Chitin and chitosan are active ingredients capable of exerting functions such as dietary fiber, LDL cholesterol level reduction, and uric acid level reduction, and are so-called insoluble dietary fibers. The weight average molecular weight of chitin and chitosan is not particularly limited. The weight average molecular weight of chitin and chitosan is preferably, for example, 7,000 to 3,000,000, and more preferably 10,000 to 2,000,000. However, in order to more effectively exert functions such as dietary fiber, LDL cholesterol level reduction, and uric acid level reduction, it is preferable that the molecular weights of chitin and chitosan are large. In particular, when adsorbing waste products, bile acids, uric acid and the like in the digestive tract to exert their functions, it is preferable to use chitin and chitosan having a molecular weight that is insoluble in water.

It is more preferable to use chitosan as the powder component. The degree of deacetylation of chitosan is preferably 70% or more, and more preferably 75 to 99%. When chitosan having a deacetylation degree of 70% or more is used, functions such as dietary fiber, LDL cholesterol level reduction, and uric acid level reduction can be more effectively exerted.

The degree of deacetylation of chitosan can be calculated from the titration amount obtained by performing colloidal titration. Specifically, a free amino group in the chitosan molecule is quantified by colloid titration with an aqueous solution of potassium polyvinyl sulfate using a toluidine blue solution as an indicator, and the degree of deacetylation of chitosan is determined. An example of a method for measuring the degree of deacetylation is shown below.

(1) Titration test Chitosan was added to a 0.5 mass% acetic acid aqueous solution so that the pure chitosan concentration was 0.5 mass%, and the chitosan was stirred and dissolved to make 100 g of 0.5 mass% chitosan / 0. Prepare a 5 mass% acetic acid aqueous solution. Next, 10 g of this solution and 90 g of ion-exchanged water are stirred and mixed to prepare a 0.05 mass% chitosan solution. Further, 50 mL of ion-exchanged water and about 0.2 mL of toluidin blue solution are added to 10 g of this 0.05 mass% chitosan solution to prepare a sample solution, which is titrated with a polyvinyl sulfate potassium solution (N / 400 PVSK). The titration rate is 2 to 5 ml / min, and the point at which the sample solution is held for 30 seconds or longer after the color changes from blue to magenta is defined as the titration amount at the end point. The pure chitosan content means the mass of chitosan in the raw material chitosan sample. Specifically, it is the solid content mass obtained by drying the raw material chitosan sample at 105 ° C. for 2 hours.

(2) Blank test A similar titration test is performed using ion-exchanged water instead of the 0.5% by mass chitosan / 0.5% by mass acetic acid aqueous solution used in the above titration test.

(3) Calculation of degree of acetylation X = 1/400 × 161 × f × (VB) / 1000
= 0.4025 × f × (VB) / 1000
Y = 0.5 / 100-X
X: Mass of free amino group in chitosan (corresponding to mass of glucosamine residue)
Y: Mass of bound amino groups in chitosan (corresponding to mass of N-acetylglucosamine residue)
f: Titer of N / 400 PVSK V: Titration of sample solution (mL)
B: Blank test titration (mL)
Deacetylation degree (%)
= (Free amino group) / {(Free amino group) + (Binding amino group)} × 100
= (X / 161) / (X / 161 + Y / 203) × 100
In addition, "161" is the molecular weight of the glucosamine residue, and "203" is the molecular weight of the N-acetylglucosamine residue.

The ratio of the powder component to the total solid content contained in the compression molded product of the present invention is 10% by mass or more, preferably 30% by mass or more, and more preferably 60% by mass or more. When the ratio of the powder component to the total solid content is less than 10% by mass, the amount of the active ingredient such as chitosan in the tablet is small. The upper limit of the ratio of the powder component such as chitosan to the total solid content in the tablet is not particularly limited, and may be 100% by mass (that is, all the solid content is the chitosan powder component).

The bulk density of the powder component is 0.15 to 0.55 g / mL, preferably 0.15 to 0.35 g / mL, and more preferably 0.15 to 0.25 g / mL. When the bulk density is less than 0.15 g / mL, the degree of entanglement of the fibers between the powder components becomes large, and the dispersibility of the molded product obtained by compression molding in water is lowered. In addition, since it becomes bulky when it is filled into a constant volume, workability is also reduced. Further, preparing a powder component having a bulk density of more than 0.55 g / mL is not suitable as a manufacturing process because it involves miniaturization due to high energy.

The bulk density of the powder component is measured using an apparent bulk density measuring device according to a measuring method conforming to JIS K 5101. Specifically, using a bulk density measuring device for pigments (JIS K 5101 type, manufactured by Tsutsui Rikagaku Kikai Co., Ltd., etc.), the powder component to be measured is naturally dropped from above the 30 mL container into the container. .. Then, the bulk density of the powder component can be calculated from the mass of the contents of the container obtained by scraping off the overflowing powder component.

The particle size of the powder component is a particle size that passes through a mesh having a mesh size of 150 to 180 μm. If the particle size of the powder component does not pass through the mesh having an opening of 180 μm, the hardness of the obtained compression molded product decreases. The proportion of the powder component that passes through the mesh having a mesh size of 45 μm is 3 to 50% by mass, preferably 5 to 45% by mass. If the proportion of the powder component that passes through the mesh having a mesh size of 45 μm is more than 50% by mass, the content ratio of fine particles (dust) increases, which makes compression molding difficult. The particle size of the powder component can be appropriately adjusted by sieving using a vibrating sieve machine provided with a mesh having a specific opening.

(Other ingredients)
The compression molded product of the present invention may contain components (other components) other than the above powder components. Other ingredients include common ingredients such as excipients, lubricants, binders, disintegrants, colorants, flavoring agents, flavoring agents, deodorants, emulsifiers, dispersants, preservatives, etc. it can.

Excipients include, for example, crystalline cellulose, purulan, glucose, guar gum, xanthan gum, sorbitol, mannitol, starch, dextrin, lactose, reduced maltose, erythritol, xylitol, sodium alginate, methyl cellulose, ethyl cellulose, arabic gum, hydroxypropyl methyl cellulose phthalate. And so on. Further, a pulverized chitin product or a crushed chitosan product before being mixed with water can be used as an excipient. When crushed chitosan or the like is compression-molded, the hardness becomes very high due to the entanglement of fibers. Therefore, by taking advantage of such characteristics, a pulverized chitosan product or the like can be used as an excipient. Specifically, the balance between the hardness of the obtained compression molded product and the dispersibility in water can be controlled by mixing the chitosan-treated product that has been dried after the water addition step and the chitosan pulverized product that has not undergone the water addition step. ..

Examples of the lubricant include eggshell powder, sucrose fatty acid ester, stearic acid, magnesium stearate, aluminum stearate, calcium stearate, talc, polyvinylpyrrolidone, and hydrogenated plant oil.

Furthermore, in addition to the above components, water-soluble vitamins (vitamins B1, B2, B6, B12, C, etc.), fat-soluble vitamins (vitamins A, D, E, etc.), collagen, ginkgo biloba extract, oligosaccharides, if necessary. , Acerola extract, aloe extract, royal jelly, acetaminophen, acetylsalicylic acid, ibuprofen, tramadol, benzbromalon, probenecid, sulfinpyrazone, bucolome, rosartan, balsartan, thermisartan, olmesartan, irbesartan, azilsartan, mefenamic acid, candesartan, etc. Can also be blended.

Further, after compression molding, it may be coated with a coating agent such as shellac to obtain a coated molded product. The amount of the coating agent is not particularly limited, but is preferably 0.1 to 2.0% by mass with respect to the compression molded product. Examples of the coating method include a method of spraying a coating agent on a compression molded product and drying it, and a method of using a sugar coating machine or the like.

<Manufacturing method of easily dispersible compression molded product>
Next, the method for producing the above-mentioned compression molded product will be described. In the method for producing a compression-molded product of the present invention, at least one powder of chitin and chitosan is mixed with water to obtain a water-containing raw material having a water content of 10 to 100% by mass represented by the following formula (1). In the step (step (1)), the obtained water-containing raw material was dried and classified to form a mesh having a water content of 15% by mass or less, a bulk density of 0.15 to 0.55 g / mL, and a mesh size of 150 to 180 μm. The step of obtaining a powder component (step (2)) in which the proportion of the component passing through the mesh having a particle size of passing and a mesh opening of 45 μm is 3 to 50% by mass, and the molding raw material containing the obtained powder component are compression-molded. It has a step (step (3)) of obtaining an easily dispersible compression molded product. The details will be described below.
Water addition rate (%) = (W / P) x 100 ... (1)
P: Amount of powder (g)
W: Amount of water to be added (g)

(Step (1))
In the step (1), at least one powder of chitosan and chitin is mixed with water to obtain a water-containing raw material having a water addition rate of 10 to 100% by mass. By mixing the above powder and water, the particle surface of the powder (chitosan particles, chitin particles) can be treated. As a result, the dispersibility of the finally obtained compression molded product in water can be improved. Further, if the powder component obtained by pulverizing the crude material of chitin or chitosan with a cutter mill, a jet mill or the like without carrying out the step (1) or the step (2) described later is used as it is, compression molding is performed. The obtained compression molded product is less likely to be dispersed in water, and the dispersion time becomes longer.

The water content of the water-containing raw material obtained by mixing the powder and water is 10 to 100% by mass, preferably 10 to 80% by mass, and more preferably 10 to 60% by mass. When the water addition rate of the water-containing raw material exceeds 100% by mass, the mixture containing the powder and water tends to be grouped together, so that the proportion of the components that do not pass through the mesh having an opening of 180 μm increases, and the yield decreases. In addition, the hardness of the obtained compression molded product is reduced.

A mixer can be used to mix the powder and water. The type of the mixer is not particularly limited, and for example, a kneader, a cylindrical mixer, a V-type mixer, a screw-type mixer, or the like can be used.

After mixing the powder and water, it is preferable to stir under heating conditions to obtain a water-containing raw material. The heating temperature is not particularly limited, but is preferably 80 ° C. or lower. When a mixture containing powder and water is stirred under heating conditions, it retains a constant hardness during compression molding and imparts the property of rapidly dispersing in water in a short time as compared with the case where it is stirred under non-heating conditions. It is possible to do.

(Step (2))
In the step (2), the hydrous raw material obtained in the step (1) is dried and classified to obtain a powder component. The water content of the powder component is 15% by mass or less, preferably 12% by mass or less, and more preferably 10% by mass or less. When the water content of the powder component obtained by drying the water-containing raw material is more than 15% by mass, coloring and a molecular weight reduction reaction due to a Maillard reaction or the like are likely to occur during long-term storage.

The water-containing raw material may be dried under heating conditions or under reduced pressure conditions. Further, it may be dried while mixing, or it may be taken out from the mixer and dried in a stationary state. Drying the water-containing raw material under heating conditions is preferable because the drying time can be shortened as compared with the case where the water-containing raw material is dried under non-heating conditions.

(Step (3))
In the step (3), the molding raw material containing the powder component obtained in the step (2) is compression molded. Thereby, the compression molded product of the present invention can be obtained. Only the powder component may be used as the molding raw material, or the dry powder and other components may be mixed to prepare the molding raw material. Other ingredients include excipients, lubricants, binders, disintegrants, colorants, flavoring agents, flavoring agents, deodorants, emulsifiers, dispersants, auxiliaries, preservatives, buffers, etc. Ingredients can be used. Further, the compression molded product can be produced by a general compression molding method using a tablet molding machine such as a tablet press.

(Physical characteristics of compression molded products)
The hardness of the compression molded product of the present invention produced by the above production method is 8 to 30 kgf, preferably 10 kgf or more. That is, since the compression molded product produced by the production method of the present invention has sufficiently high hardness, defects such as cracking, chipping, and abrasion are less likely to occur in the package during transportation and storage. The hardness of the compression-molded product in the present specification is defined when the compression-molded product is compression-broken in the horizontal direction using a tablet hardness tester (for example, trade name “Monsanto Tablet Hardness Tester B Type”, manufactured by Fuji Rika Kogyo Co., Ltd.). It is the required load (unit: kgf). The average value measured 5 times for each formulation was taken as the hardness of the compression molded product.

A cylindrical shape having a diameter of 8 mm and 200 mg, which is obtained by compression molding a compression molded product of the present invention produced by the above production method (for example, a molding raw material containing a powder component at a compression pressure of 2 tf using a compressor). The dispersion time of the compression molded product) in water at 37 ° C. is preferably 120 seconds or less, more preferably 60 seconds or less, and particularly preferably 30 seconds or less. That is, the compression molded product produced by the production method of the present invention is excellent in dispersibility so that it can be quickly dispersed in water while maintaining a certain hardness or higher. Therefore, the compression molded product of the present invention is less likely to cause problems such as cracking, chipping, and abrasion in the package during transportation and storage, and has good dispersibility in water. Therefore, for example, tablets and oral cavity. It is suitable as a disintegrating tablet, chewable tablet, dispersed tablet, health food, agricultural material, livestock feed, cosmetics, flocculant, dust reduction compounding material and the like. The dispersion time of the compression molded product is a value (unit: seconds) measured according to the procedure shown below.
[Measurement of dispersion time]
About 80 mL of water at 37 ° C. is put in a 100 mL beaker, and the compression molded product is charged from a height of 2 cm above the water surface while stirring at a rotation speed of 400 rpm with a 2 cm magnetic stirrer. The time from when the compression molded product comes into contact with water until it swells and disperses and the original shape of the compression molded product cannot be visually confirmed is measured 5 times, and the average value is defined as the dispersion time (unit: seconds). Even when a liquid medium other than water (for example, a hydrophilic solvent containing water) is used, the dispersion time can be measured under the same conditions.

Next, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited to these Examples. Hereinafter, the terms "part" and "%" are based on mass unless otherwise specified.

<Measuring method of bulk density of powder components>
Using a bulk density measuring instrument for pigments (JIS K 5101 type, manufactured by Tsutsui Rikagaku Kikai Co., Ltd.), the powder component was naturally dropped from above into a 30 mL container, the overflowing powder was scraped off, and the powder was removed from the weight of the contents. The bulk density of the components was calculated.

<Preparation of powder components>
(Manufacturing Example 1)
A crude chitosan having a weight average molecular weight of 1 million (deacetylation degree 85%) is pulverized with a jet mill, and a chitosan powder having a particle size (moisture content 5%, bulk density 0.14 g / mL) passing through a mesh having an opening of 150 μm is used. An opening of 45 μm pass 30%) was obtained.

(Manufacturing Example 2)
A crude chitosan having a weight average molecular weight of 1.5 million (deacetylation degree 91%) is crushed with a cutter mill, and a chitosan powder having a particle size (moisture content 11%, bulk density 0.28 g / mL) that passes through a mesh with an opening of 180 μm, An opening of 45 μm pass 55%) was obtained.

(Manufacturing Example 3)
A crude chitosan having a weight average molecular weight of 1.5 million (deacetylation degree 91%) is crushed with a cutter mill and passed through a mesh with a mesh size of 250 μm, but a chitosan powder having a particle size (moisture content of 8) that does not pass through a mesh with a mesh size of 180 μm. %, Bulk density 0.19 g / mL, Opening 45 μm pass 1%).

(Manufacturing Example 4)
A crude chitin having a weight average molecular weight of 1.5 million (deacetylation degree 5%) is pulverized with a jet mill, and a chitin powder having a particle size (moisture content 6%, bulk density 0.27 g / mL) passing through a mesh having a mesh size of 180 μm is used. An opening of 45 μm pass 53%) was obtained.

(Manufacturing Example 5)
A coarse cellulose having a weight average molecular weight of 1 million was pulverized with a cutter mill to obtain a cellulose powder having a particle size that passed through a mesh having a mesh size of 150 μm. 100 parts of the obtained cellulose powder and 100 parts of water were put into a kneader to obtain a water-containing raw material having a water addition rate of 100%. After heating to 80 ° C. with the lid of the kneader and stirring for 1 hour, the mixture was taken out into an enamel dish and allowed to stand in an incubator. After heating to 80 ° C. and drying, the mixture was classified with a mesh having an opening of 150 μm to obtain a cellulose powder (moisture content 5%, bulk density 0.27 g / mL, opening 45 μm pass 35%).

(Manufacturing Example 6)
100 parts of chitosan powder and 50 parts of water obtained in Production Example 1 were put into a kneader to obtain a water-containing raw material having a water addition rate of 50%. After heating to 80 ° C. with the lid of the kneader and stirring for 1 hour, the mixture was taken out into an enamel dish and allowed to stand in an incubator. After heating to 80 ° C. and drying, the mixture was classified with a mesh having an opening of 150 μm to obtain chitosan powder (moisture content: 7%, bulk density: 0.22 g / mL, opening: 45 μm pass: 21%).

(Manufacturing Example 7)
100 parts of chitosan powder and 25 parts of water obtained in Production Example 2 were put into a kneader to obtain a water-containing raw material having a water addition rate of 25%. After heating to 80 ° C. with the lid of the kneader and stirring for 1 hour, the lid was opened and the mixture was dried while continuing heating and stirring at 80 ° C. Then, the mixture was classified with a mesh having an opening of 180 μm to obtain chitosan powder (moisture content: 4%, bulk density: 0.40 g / mL, opening: 45 μm pass: 35%).

(Manufacturing Example 8)
100 parts of chitosan powder and 100 parts of water obtained in Production Example 2 were put into a kneader to obtain a water-containing raw material having a water addition rate of 100%. After stirring for 1 hour without heating with the lid of the kneader, the mixture was taken out into an enamel dish. After drying under reduced pressure using a vacuum dryer, the mixture was classified with a mesh having an opening of 180 μm to obtain chitosan powder (moisture content 6%, bulk density 0.45 g / mL, opening 45 μm pass 15%).

(Manufacturing Example 9)
100 parts of the chitin powder and 50 parts of water obtained in Production Example 4 were placed in a plastic bag to obtain a water-containing raw material having a water addition rate of 50%. After closing the mouth of the plastic bag and shaking it up, down, left and right for 15 minutes to mix the contents, it was taken out to a enamel dish and allowed to stand in an incubator. After heating to 80 ° C. and drying, the mixture was classified with a mesh having an opening of 150 μm to obtain chitosan powder (moisture content 8%, bulk density 0.43 g / mL, opening 45 μm pass 9%).

(Manufacturing Example 10)
100 parts of chitosan powder and 200 parts of water obtained in Production Example 2 were placed in a plastic bag to obtain a water-containing raw material having a water addition rate of 200%. After closing the mouth of the plastic bag and shaking it up, down, left and right for 15 minutes to mix the contents, it was taken out to a enamel dish and allowed to stand in an incubator. After heating to 80 ° C. and drying, the mixture was classified with a mesh having an opening of 180 μm to obtain chitosan powder (moisture content 9%, bulk density 0.44 g / mL, opening 45 μm pass 2%).

<Manufacturing of compression molded products>
(Example 1)
Using a tableting machine (trade name "HANDTAB-100", manufactured by Ichihashi Seiki Co., Ltd., diameter of mortar: 8 mm), 200 mg of chitosan powder obtained in Production Example 6 is compressed by applying a compression pressure of 2 tf to obtain a compression molded product. Got

(Examples 2 to 8 and Comparative Examples 1 to 6)
The types and amounts of chitosan powder, chitin powder, cellulose powder, crystalline cellulose (trade name "Comprecel" (manufactured by Fushimi Pharmaceutical Co., Ltd.), food additives) and sucrose fatty acid esters shown in Tables 1-1 and 1-2. A compression molded product was obtained in the same manner as in Example 1 except that the trade names “DK ester” (manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd.) and food additives were used.

(Measurement of hardness)
Using a tablet hardness tester (trade name "Monsanto Tablet Hardness Tester B type", manufactured by Fuji Rika Kogyo Co., Ltd.), the load (unit: kgf) required for compression fracture in the horizontal direction of the compression molded product was measured. The average value of the loads measured 5 times for each formulation was defined as the hardness. The results are shown in Tables 1-1 and 1-2.

(Measurement of dispersion time)
About 80 mL of water at 37 ° C. was placed in a 100 mL beaker, and the mixture was stirred at a rotation speed of 400 rpm using a 2 cm magnetic stirrer. Next, the compression molded product was put in from a height of 2 cm from the water surface, and the time from when the compression molded product came into contact with water until it swelled and dispersed and the original shape of the compression molded product could not be visually confirmed was measured 5 times. The average value was used as the dispersion time (unit: seconds). The results are shown in Tables 1-1 and 1-2.

(Example 9)
10 parts of chitosan powder obtained in Production Example 6 and 10 parts of chitosan powder obtained in Production Example 10 are mixed so as to be uniform and powder components (chitosan powder; moisture content 8%, 0.33 g / mL, opening 45 μm). Pass 12%) was obtained. A compression molded product was obtained in the same manner as in Example 1 except that the obtained powder component was used. The hardness of the obtained compression molded product was 8.1 kgf, and the dispersion time was 8 seconds.

<Measurement of dispersion time using the first solution of the disintegration test>
7.0 mL of HCl and water were added to 2.0 g of NaCl, and NaCl was dissolved to prepare 1,000 mL of the first solution of the disintegration test of pH 1.2. The dispersion time of the compression molded product of Example 1 measured using the prepared first liquid of the disintegration test was 110 seconds. On the other hand, when an attempt was made to measure the dispersion time of the compression molded product of Comparative Example 6 using the prepared first liquid of the disintegration test, the surface of the compression molded product became a gel state. The measurement was continued for a few more minutes, but the original shape of the compression molded product could not be visually confirmed.

<Evaluation (2)>
The compression molded product produced in Example 1 was placed on the tongue and lightly pressed against the upper jaw. The time required for the compression molded product to completely disperse in the mouth was measured and found to be 15 seconds. Further, the compression molded product produced in Example 8 was placed on the tongue and lightly pressed against the upper jaw. The time required for the compression molded product to completely disperse in the mouth was measured and found to be 20 seconds.

The easily dispersible compression molded product of the present invention is useful as, for example, an orally disintegrating tablet.

Claims (7)

It contains at least one of the powder components of chitin and chitosan, and the ratio of the powder component to the total solid content is 10% by mass or more.
The bulk density of the powder component is 0.15 to 0.55 g / mL.
The particle size of the powder component is a particle size that passes through a mesh having an opening of 150 to 180 μm.
The ratio of the component that passes through the mesh having a mesh size of 45 μm in the powder component is 3 to 50% by mass.
An easily dispersible compression molded product having a hardness of 8 to 30 kgf. The easily dispersible compression molded product according to claim 1, wherein the powder component is a powder of chitosan having a degree of deacetylation of 70% or more. The easily dispersible compression molded product according to claim 1 or 2, wherein the powder component further contains a cellulose powder. The easily dispersible compression molded product according to any one of claims 1 to 3, further containing at least one of an excipient and a lubricant. The easily dispersible compression molded product according to any one of claims 1 to 4, wherein the time from when the product is put into water at 37 ° C. in a stirred state until the original shape cannot be visually observed is within 120 seconds. .. The invention according to any one of claims 1 to 5, which is a tablet, an orally disintegrating tablet, a chewable tablet, a dispersed tablet, a health food, an agricultural material, a livestock feed, a cosmetic, a flocculant, or a dust-reducing compounding material. Easy-dispersible compression molded product. The method for producing an easily dispersible compression molded product according to any one of claims 1 to 6.
A step of mixing at least one powder of chitin and chitosan with water to obtain a water-containing raw material having a water content of 10 to 100% by mass represented by the following formula (1).
The obtained water-containing raw material is dried and classified, and has a water content of 15% by mass or less, a bulk density of 0.15 to 0.55 g / mL, a particle size that passes through a mesh having a mesh size of 150 to 180 μm, and a mesh size of 45 μm. In the process of obtaining a powder component in which the proportion of the component passing through the mesh is 3 to 50% by mass,
A step of compression-molding the obtained molding raw material containing the powder component to obtain an easily dispersible compression-molded product,
A method for producing an easily dispersible compression molded product having.
Water addition rate (%) = (W / P) x 100 ... (1)
P: Amount of powder (g)
W: Amount of water to be added (g)