JP3113580B2 - Method for producing collapsible composition and method for producing collapsible molded article using the composition - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a tablet, granule, etc., which can be obtained by mixing a food material or a pharmaceutically active ingredient.
The present invention also relates to a method for producing a disintegrable composition which disintegrates in a short time when water is added, and a method for producing a disintegrable molded article using the composition.

[0002]

2. Description of the Related Art Heretofore, tablets or granules have been prepared by mixing fillers with physiologically active food materials such as chlorella and royal jelly or mixing excipients with pharmaceutically active ingredients and compressing or granulating. Molding has been performed.

Hitherto, lactose, cellulose, starch, rice flour and the like have been used as such fillers or excipients. The bulking agent or excipient is required to be able to be tableted or granulated in a state where a food material or a pharmaceutically active ingredient is mixed, and it is desired that the filler or excipient be rapidly disintegrated in the body when ingested orally. Sometimes.

[0004] However, the extenders or excipients used hitherto have moldability but insufficient disintegration, or have difficulty in moldability even if they are excellent in disintegration. There were many of them, and few had both moldability and disintegration. In addition, especially when wet granulation was performed, the disintegration properties were often poor.

[0005] On the other hand, there has been proposed a so-called effervescent tablet in which a effervescent agent and a neutralizing agent are blended so that the tablet disintegrates due to the generation of carbon dioxide due to neutralization when poured into water. Was not suitable for use in foods and pharmaceuticals that were orally ingested and broken down in the body.

Japanese Patent Publication No. 5-75373 discloses that (1) 10 to 50 parts by weight of aspartame, and (2) at least one kind selected from carboxymethyl starch, carboxymethyl cellulose and derivatives thereof. 2 parts by weight or agar 5
And (3) 30 to 85 parts by weight of lactose and tableting to a tablet hardness of 0.5 to 2 kg. I have.

[0007]

The above Japanese Patent Publication No. 5-75373 discloses carboxymethyl starch,
It is disclosed that one or more selected from carboxymethylcellulose, derivatives thereof, guar gum, powdered agar, crystalline cellulose, and starch are added. The above-mentioned disintegrant is added in powder form to a certain aspartame and lactose as a bulking agent, and tableting is performed by a dry method.

However, according to experiments by the present inventors, even if agar powder, cellulose, or the like is used as a disintegrant, if they are mixed as they are in a powder state and tablet-formed by a dry method, it is difficult to obtain a tablet at room temperature. Disintegration in water is not sufficiently obtained,
Therefore, it was found that the disintegration property in the body upon oral ingestion could not be sufficiently expected.

[0009] Accordingly, an object of the present invention is to provide, when added to a food material or a pharmaceutically active ingredient, moldability for making a tablet or a granule and impart excellent disintegration to the obtained molded product. It is an object of the present invention to provide a method for producing a disintegrable composition, and a method for producing a disintegrable molded article using the composition.

[0010]

Means for Solving the Problems The first object of the present invention to achieve the above object is to provide agar powder and 1 to 5 times by weight of insoluble dietary fiber and / or yeast based on the agar powder. , Water or an ethyl alcohol aqueous solution having an alcohol concentration of less than 50% by volume.

A second aspect of the present invention is a method for producing a disintegrable composition, wherein the mixture is further dried.

A third aspect of the present invention is that the insoluble dietary fiber comprises
This is a method for producing a disintegratable composition which is at least one selected from cellulose, wheat fiber, corn fiber, beet fiber, and alginic acid.

A fourth aspect of the present invention is that the insoluble dietary fiber comprises:
This is a method for producing a disintegrable composition that is crystalline cellulose.

A fifth aspect of the present invention is (A) agar powder, 1 to 5 times by weight of insoluble dietary fiber and / or yeast, and ethyl alcohol having a water or alcohol concentration of less than 50% by volume. Disintegrating composition obtained by mixing with an aqueous solution, or disintegrating composition obtained by further drying the composition and (B) a food material or a pharmaceutically active ingredient, and tableting or granulating. A method for producing a disintegrable molded article, characterized in that:

According to the first method for producing a disintegrable composition of the present invention, agar powder, insoluble dietary fiber and / or yeast, and water or an aqueous ethyl alcohol solution having an alcohol concentration of less than 50% by volume are mixed. As a result, the agar powder swells with water or an aqueous ethyl alcohol solution to obtain a composition containing insoluble dietary fiber and / or yeast. This composition can impart good moldability when added to a food material or a pharmaceutically active ingredient, and can impart excellent disintegration to the obtained molded article.

According to the second method for producing a disintegrable composition of the present invention, after mixing agar powder, water or an ethyl alcohol aqueous solution having an alcohol concentration of less than 50% by volume, and insoluble dietary fiber and / or yeast. By drying, an insoluble dietary fiber and / or yeast is encapsulated in agar, and a dried composition can be obtained. This composition is added to a food material or a pharmaceutically active ingredient, and imparts good moldability even when compressed or granulated by a wet method or a dry method, and the obtained molded product is obtained. Excellent disintegration can be provided.

As shown in the examples described below, even when agar powder and microcrystalline cellulose are used in combination as disintegrants, the agar powder is added to a food material or a pharmaceutically active ingredient in a powdered state without swelling. When formed by a dry method, sufficient disintegration cannot be obtained.

According to the third method for producing a disintegrable composition of the present invention, the use of at least one selected from the group consisting of cellulose, wheat fiber, corn fiber, beet fiber and alginic acid as insoluble dietary fiber enables The effect of the invention can be enhanced.

According to the fourth method for producing a disintegratable composition of the present invention, the effect of the present invention can be maximized by using crystalline cellulose as the insoluble dietary fiber.

According to the fifth method for producing a disintegrable molded product of the present invention, agar powder, water or an ethyl alcohol aqueous solution having an alcohol concentration of less than 50% by volume, and insoluble dietary fiber and / or yeast are mixed. Thereafter, the disintegratable composition of the present invention obtained by further drying if necessary, and a food material or a pharmaceutically active ingredient are mixed, and tableting or granulation is performed, so that disintegration in water is excellent, Therefore, it is possible to obtain tablets or granular foods or pharmaceuticals which are expected to have excellent digestibility and absorption in the body.

[0021]

BEST MODE FOR CARRYING OUT THE INVENTION The disintegratable composition of the present invention comprises agar powder, 1 to 5 times by weight of insoluble dietary fiber and / or yeast based on the agar powder, and a water or alcohol concentration of less than 50% by volume. With an aqueous solution of ethyl alcohol, and then, if necessary, further drying the mixture.

The powder agar has a particle size of 50 to 200 μm.
And those having a jelly strength of 500 to 800 g / cm ² are preferable. As powder agar satisfying such conditions, for example, “KT
Type "(trade name, manufactured by Ina Agar Co., Ltd.) or the like.

Examples of the insoluble dietary fiber include cellulose, wheat fiber, corn fiber, beet fiber,
It is preferable to use at least one selected from alginic acid and the like, and among these, crystalline cellulose is most preferable. The particle size of the insoluble dietary fiber is preferably from 10 to 200 μm, and may be used after being pulverized if necessary. As the crystalline cellulose, for example, "Avicel" (trade name, manufactured by Asahi Kasei Corporation) or the like can be used.

In the present invention, yeasts such as live yeasts, dried yeasts, and crushed products thereof can be used instead of or together with the insoluble dietary fiber. The type of yeast is not particularly limited as long as it is generally used for foods, and may be any of brewer's yeast, alcoholic yeast, baker's yeast, sake yeast, wine yeast, and the like.

In the present invention, the mixing ratio of insoluble dietary fiber and / or yeast is 1 to 5 times the weight of powdered agar. If the compounding ratio is less than 1 part by weight with respect to the powder agar, there is a problem that moldability and fluidity are disadvantageous, and if it exceeds 5 parts by weight, there is a problem that disintegration and dispersibility are easily delayed. It is not preferable.

In the present invention, when water or an ethyl alcohol aqueous solution having an alcohol concentration of less than 50% by volume swells powder agar and mixes it with insoluble dietary fiber and / or yeast, the insoluble dietary fiber and / or yeast becomes agar. Used to be encapsulated in. The added amount of water or an aqueous solution of ethyl alcohol is preferably such that the powder agar can be sufficiently swollen, and is 1 to 2 times the weight of the total of the powder agar and the insoluble dietary fiber and / or yeast. It is preferable to set the degree.

In the case of using an ethyl alcohol aqueous solution, if the alcohol concentration is 50% by volume or more, the disintegrable composition obtained has poor fluidity. It becomes difficult to mold when making the agent.

Further, simply mixing the agar powder with the insoluble dietary fiber and / or yeast in a dry state without swelling the agar powder with water or an ethyl alcohol aqueous solution imparts sufficient disintegration to the molded product. I can't.

In the present invention, the method of mixing agar powder, insoluble dietary fiber and / or yeast, and an aqueous solution of ethyl alcohol having a water or alcohol concentration of less than 50% by volume is carried out by adding a water or alcohol concentration of 50 or less to the agar powder. After adding a volume% of ethyl alcohol aqueous solution to swell the agar, insoluble dietary fiber and / or yeast may be added and mixed, or agar powder and insoluble dietary fiber and / or yeast may be mixed. Water or alcohol concentration 50% by volume in the mixture
Less than less ethyl alcohol aqueous solution may be added and mixed. In addition, after mixing these, it is preferable that they are sufficiently stirred and kneaded.

The disintegratable composition of the present invention is prepared as a mixture in a wet state in which agar powder, insoluble dietary fiber and / or yeast, and an aqueous solution of ethyl alcohol having a water or alcohol concentration of less than 50% by volume are mixed. Alternatively, the mixture can be further dried to prepare a dry powder. In the case of a mixture in a wet state, it is necessary to simultaneously add and mix food ingredients and pharmaceutically active ingredients and perform tableting or granulation. In this case, it can be stored in that state and transported to a food factory or a pharmaceutical factory for use, and can be commercialized as a disintegrable composition itself.

The mixture of agar powder, insoluble dietary fiber and / or yeast, and water or an aqueous solution of ethyl alcohol may be dried by any method such as freeze-drying and hot-air drying. It is preferable to dry uniformly using a machine or the like. It is preferable that the dried collapsible composition is prepared so that the particle size is smaller than 30 mesh, from the viewpoint of easy handling.

In the method for producing the disintegratable composition of the present invention, other components such as starches may be added as long as the effects of the present invention are not impaired.

The disintegrable molded article of the present invention is prepared by mixing the disintegratable composition produced as described above with a food material or a pharmaceutically active ingredient, tableting or granulating the mixture to form tablets or granules. It is manufactured by molding.

As described above, the disintegratable composition is a mixture of agar powder, insoluble dietary fiber and / or yeast, and an aqueous solution of ethyl alcohol having a water or alcohol concentration of less than 50% by volume. Alternatively, these mixtures may be dried. In addition, when mixing the dried disintegrable composition and a food material or a pharmaceutically active ingredient, dry mixing may be performed as it is, and tableting or granulation may be performed by a dry method, or water may be added. Tableting or granulation may be performed by a wet method.

As described above, when the agar powder and the crystalline cellulose are mixed with a food material or a pharmaceutically active ingredient as a dry powder and compressed or granulated by a dry method, sufficient disintegration is obtained. Is not obtained, the agar powder is swollen with water or an aqueous ethyl alcohol solution, and after incorporation of insoluble dietary fiber and / or yeast, and then using the disintegratable composition of the present invention obtained by drying, A molded product excellent in disintegration property can be obtained even by tableting or granulation molding by a dry method.

In the present invention, as the food material, those having a physiological activity such as chondroitin, royal jelly, chlorella, gymnema, garcinia, bovine bone, nucleic acid, mushrooms, collagen and propolis or those rich in nutrients which are apt to be lacking are preferable. Used. As the pharmaceutically active ingredient, various substances that can be commercialized as tablets or granules can be used.

When a molded product is prepared by mixing a food material or a pharmaceutically active ingredient with the disintegratable composition of the present invention, the amount of the disintegrable composition to be added is 3% by weight or more in terms of solid content in the product. It is preferable that 3% by weight of disintegrable composition
If it is less than 3, disintegration cannot be sufficiently imparted to the obtained molded article. The upper limit of the amount of the disintegrable composition need not be particularly limited, but if it exceeds 30% by weight, the disintegration of the molded product is too fast or the tablet thickness increases.

The disintegrable molded article of the present invention may contain, for example, a lubricant, a binder, a dispersant, an emulsifier, a sweetener, a flavoring agent, etc., usually in the form of tablets or granules, as long as the effects of the present invention are not impaired. Can be added.

[0039]

【Example】

Example 1 "KT Type" (trade name, manufactured by Ina Agar Co., Ltd.) 100, which is a powder agar having a jelly strength of 730 g / cm ² and an average particle size of 100 μm
Add 300 parts by weight of water to 300 parts by weight of water, stir the powdered agar to stir, and add 200 parts by weight of “Avicel” (trade name, manufactured by Asahi Kasei Kogyo Co., Ltd.) which is crystalline cellulose with an average particle size of 40 μm. Then, the mixture was stirred and kneaded to obtain a mixture.

Next, this mixture was placed in a fluidized bed dryer and dried with hot air to obtain a disintegratable composition as a powder of 30 mesh pass.

Example 2 Instead of water, an aqueous solution of ethyl alcohol having an alcohol concentration of 33% by volume (hereinafter referred to as "33% alcohol") or an aqueous solution of ethyl alcohol having an alcohol concentration of 50% by volume (hereinafter referred to as "55% alcohol") was used.
% Alcohol ") and anhydrous ethyl alcohol (hereinafter referred to as" anhydroalcohol ").
In the same manner as in the above, disintegrating compositions using various concentrations of ethyl alcohol aqueous solutions or ethyl alcohol as solvents were obtained.

Test Example 1 For the various disintegrable compositions obtained in Examples 1 and 2,
The appearance, fluidity, tableting properties (moldability), and disintegration properties were tested, and the suitability of the solvent was evaluated. Fluidity measured the angle of repose. The tableting property was determined by compressing the tablet at a constant pressure and measuring the hardness of the tablet. In addition, the disintegration
According to the disintegration test method of the general test method of "12 Pharmacopoeia Law, revised by 12 stations," it was poured into water at 37 ° C and the time until disintegration was measured.

Table 1 shows the results. In Table 1, each evaluation of appearance, fluidity, tableting property (moldability), and disintegration is good based on the above measurement results.
Somewhat poor ... △, poor… ×.

[0044]

[Table 1]

From the results shown in Table 1, when water or 33% alcohol is used as a solvent, a composition excellent in all of appearance, fluidity, tableting property (moldability) and disintegration is obtained. It can be seen that when 50% alcohol is used, the fluidity deteriorates, and when anhydrous alcohol is used, the fluidity deteriorates, and the tableting and disintegration properties also deteriorate slightly. Therefore, it is understood that water or an ethyl alcohol aqueous solution having an alcohol concentration of less than 50% by volume is suitable as a solvent for producing the disintegratable composition.

Comparative Example 1 The same agar powder as in Example 1 and crystalline cellulose were dry-blended without using water to obtain a powder mixture.

Example 3 300 parts by weight of water was added to 100 parts by weight of the same powder agar as in Example 1, and the mixture was stirred to swell the powder agar. 200 parts by weight (manufactured by Beer Co., Ltd.) were added, and the mixture was stirred and kneaded to obtain a mixture.

Next, this mixture was placed in a fluidized-bed dryer and dried with hot air to obtain a disintegratable composition as a powder of 30 mesh pass.

Comparative Example 2 The same agar powder as in Example 3 and brewer's yeast were dry-blended without using water to obtain a powder mixture.

Test Example 2 Garcinia and sucrose fatty acid ester as a lubricant
The disintegratable composition obtained in Example 1 or the powder mixture obtained in Comparative Example 1 was mixed at a mixing ratio shown in Table 2, and a wet method in which an appropriate amount of water was added, and a dry method in which water was not added. Is a 8.5 mm diameter triangular punch with a weight of 250 mg / tablet and a hardness of about 5 kg
To obtain tablets. The tablets obtained by the wet method are Nos. 1 to 5, and the tablets obtained by the dry method are Nos. 6 to 10.

The tablets Nos. 1 to 10 thus obtained were subjected to a disintegration test in the same manner as in Test Example 1. Table 2 shows the results.

[0052]

[Table 2] (In the table,% of composition represents% by weight.)

From the results shown in Table 2, when tableting was performed by the wet method, No. 2 containing the disintegrable composition or powder mixture was used.
It can be seen that the tablets of Nos. 3, 4, and 5 have a significantly shorter disintegration time than the tablet of No. 1 in which neither the disintegrating composition nor the powder mixture is blended.

Further, when tableting was performed by the dry method, compared with the tablet of No. 6 in which neither the disintegrating composition nor the powder mixture was blended,
The tablets of Nos. 7 and 9 in which the disintegrable composition was blended were significantly reduced in disintegration time, but the tablets of Nos.
It can be seen that the effect of shortening the disintegration time is not so much observed for the 10 tablets. Further, in both of the wet method and the dry method, it can be seen that the larger the proportion of the disintegrable composition or powder mixture, the greater the effect of shortening the disintegration time.

Incidentally, Garcinia, a lubricant and Comparative Example 1
To the agar powder and the powder mixture of crystalline cellulose obtained in
The tablets of Nos. 3 and 5, which were formed by adding water to the wet process and wet-molded, had the agar powder swelled and wetted with microcrystalline cellulose during wet-molding. Applicable to molded products. That is, No. 2, 3, 4, 5,
The tablets of Nos. 7 and 9 are examples of the present invention, and the tablets of Nos. 8 and 10 are comparative examples corresponding to Japanese Patent Publication No. 5-75373.
Tablets 1 and 6 are controls.

That is, as compared with the control tablets Nos. 1 and 6, the tablets Nos. 2, 3, 4, 5, 7, and 9 of Example 3 had significantly reduced disintegration time, No. of Comparative Example 3
It can be seen that the tablets of Nos. 8 and 10 have little effect on shortening the disintegration time.

Test Example 3 Chlorella, a sucrose fatty acid ester as a lubricant, and the disintegratable composition obtained in Example 3 or the powder mixture obtained in Comparative Example 2 were mixed as shown in Table 3. The mixture was mixed at a ratio of 200 mg / kg with a round punch with a diameter of 8.0 mm by dry direct hitting.
One tablet was tableted to a hardness of about 4 kg to obtain a tablet. These tablets are designated Nos. 11-15. The tablets of Nos. 12 and 14 are examples of the present invention, the tablets of Nos. 13 and 15 are comparative examples, and the tablet of No. 11 is a control.

The tablets Nos. 11 to 15 were subjected to a disintegration test in the same manner as in Test Example 1. Table 3 shows the results.

[0059]

[Table 3]

From the results in Table 3, when tableting was performed by the dry method,
Compared with the control No. 11 tablet containing neither the disintegrable composition nor the powder mixture, the tablets of Nos. 12 and 14, which are the examples of the present invention in which the disintegrable composition was added, had a long disintegration time. It can be seen that the tablets of Comparative Examples Nos. 13 and 15 in which the powder mixture was blended had little effect of shortening the disintegration time. Also, it can be seen that the greater the proportion of the disintegrable composition or powder mixture, the greater the effect of shortening the disintegration time.

Test Example 4 A lyophilized product of royal jelly, a sucrose fatty acid ester as a lubricant, and the disintegratable composition obtained in Example 1 or the powder mixture obtained in Comparative Example 1 were prepared in the form of a table. The tablets were mixed at the compounding ratio shown in Fig. 4 and pressed by a dry method with a triangular punch having a diameter of 8.5 mm to a weight of 250 mg / 1 tablet and a hardness of about 5 kg to obtain tablets. These tablets are designated Nos. 16-20. No.
The tablets of Nos. 17 and 19 are examples of the present invention, the tablets of Nos. 18 and 20 are comparative examples, and the tablet of No. 16 is a control.

The tablets of Nos. 16 to 20 were subjected to a disintegration test in the same manner as in Test Example 1. Table 4 shows these results.
Shown in

[0063]

[Table 4]

From the results in Table 4, when tableting was performed by the dry method,
As compared to the control No. 16 tablet containing neither the disintegrable composition nor the powder mixture, the tablets of Nos. 17 and 19, which are the examples of the present invention in which the disintegrable composition was added, had a significantly longer disintegration time. However, it can be seen that the tablets of Nos. 18 and 20 of Comparative Examples in which the powder mixture was blended had little effect of shortening the disintegration time. Also, it can be seen that the greater the proportion of the disintegrable composition or powder mixture, the greater the effect of shortening the disintegration time.

Test Example 5 Gymnema, lactose, crystalline cellulose, the disintegrating composition obtained in Example 1 or the powder mixture obtained in Comparative Example 1 were mixed at the mixing ratio shown in Table 5. Then, water was added, and the mixture was extruded and granulated with a basket having a screen of 1 mm, and dried at 50 ° C. to obtain a granular material having an 18 mesh pass. These granules are designated as Nos. 21-23.

Since granulation was carried out by adding water, the mixture containing the powder mixture obtained in Comparative Example 1 also falls under the Examples of the present invention. For example, No. 21 granules containing microcrystalline cellulose are the control.

For the granules Nos. 21 to 23, granulation properties
The granule strength was measured, and a disintegration test was performed in the same manner as in Test Example 1. The granulation property was determined by measuring the calorific value and the granulation pressure at the time of granulation, and the granule strength was evaluated by a friability test using a fly aviator and evaluated according to the evaluation criteria shown in Table 5. Table 6 shows the test results.

[0068]

[Table 5]

[0069]

[Table 6]

From the results in Table 6, it can be seen that, compared to the control No. 21 granule in which microcrystalline cellulose was added without using agar powder, the No. 1 example of the present invention in which agar powder and microcrystalline cellulose were used in combination was used. It can be seen that the granules of .22 and 23 have significantly reduced disintegration time. In addition, the control granules No. 21 have excellent granule strength, but have poor granulation properties, whereas the granules Nos. 22 and 23 of the examples have granulation properties and granules. It turns out that it is excellent in all of the strength.

Test Example 6 Bovine bone, lactose and crystalline cellulose, the disintegratable composition obtained in Example 1 or the powder mixture obtained in Comparative Example 1 were
After mixing at the mixing ratio shown in Table 6, water was added, and the mixture was extruded and granulated with a basket having a screen of 1 mm, dried at 50 ° C,
A granular material having an 18 mesh pass was obtained. These granules
No. 24 to 26.

Since the granulation was carried out by adding water, the mixture containing the powder mixture obtained in Comparative Example 1 is also an example of the present invention. , No.
24 granules are controls.

With respect to the granules Nos. 24 to 26, Test Example 5
The granulation property and the granule strength were measured in the same manner as in Example 1, and the disintegration test was performed in the same manner as in Test Example 1. Table 7 shows the results.

[0074]

[Table 7]

From the results in Table 7, it can be seen that, compared to the control granule No. 24 to which microcrystalline cellulose was added without using agar powder, the No. 24 example of the present invention in which agar powder and microcrystalline cellulose were used in combination was used. It can be seen that the granules of .25 and 26 have significantly reduced disintegration time.

[0076]

As described above, according to the present invention,
When tableting or granulating a food material or a pharmaceutically active ingredient, a disintegratable composition obtained by encapsulating insoluble dietary fiber and / or yeast with an agar powder swollen with water or an aqueous ethyl alcohol solution. By adding the compound, a molded product excellent in disintegration can be obtained without impairing the moldability.

Continuation of the front page (58) Field surveyed (Int.Cl. ⁷ , DB name) A61K 47/36 A61K 9/16 A61K 9/20

Claims (5)

(57) [Claims] An agar powder and 1 to 1 agar powder.
A method for producing a disintegratable composition, comprising mixing 5 times by weight of insoluble dietary fiber and / or yeast with water or an ethyl alcohol aqueous solution having an alcohol concentration of less than 50% by volume. 2. The method for producing a disintegrable composition according to claim 1, wherein the mixture is further dried. 3. The method according to claim 1, wherein the insoluble dietary fiber is cellulose, wheat fiber, corn fiber, beet fiber,
The at least one kind selected from alginic acid.
Or the method for producing the disintegrable composition according to 2. 4. The method for producing a disintegrable composition according to claim 3, wherein the insoluble dietary fiber is crystalline cellulose. 5. A mixture of agar powder, an insoluble dietary fiber and / or yeast which is 1 to 5 times the weight of this agar powder, and an aqueous ethyl alcohol solution having a water or alcohol concentration of less than 50% by volume. A disintegratable composition obtained by drying the composition, or a disintegrable composition obtained by further drying the composition, and (B) a food material or a pharmaceutically active ingredient, and tableting or granulating. A method for producing a disintegrable molded article.