JP6927763B2 - Tablets containing Seihaito extract powder - Google Patents

Description

The present invention relates to tablets containing Seihaito extract powder. More specifically, the present invention is a tablet containing Seihaito extract powder, which has sufficient hardness and disintegration property that disintegrates at an appropriate speed after administration, and is the same as Seihaito extract powder. Regarding tablets that can suppress discoloration.

Seihaito is a Chinese herbal medicine that was introduced in the Ming dynasty's "Man's Disease Rejuvenation" and is known to have the effect of suppressing inflammation of the throat and trachea, facilitating the removal of sputum, and relieving cough. In modern times, its effects have been re-examined, mucus dissolution, promotion of airway fluid secretion, promotion of lung surface active substance secretion, lubrication of airway mucosa, suppression of inflammation of airway mucosa, restoration and activation of mucosal hair transport ability, antibiotics The effects of Seihaito, such as promoting the transition to sputum, have been further clarified (Non-Patent Documents 1 and 2). Today, Seihaito is also used for the purpose of alleviating the adverse effects of exhaust gas, PM2.5, tobacco, etc., and purifying the bronchi.

However, Seihaito has a drawback that it is difficult to take because it has peculiar bitterness and harshness.

Conventionally, Chinese herbal preparations are often formulated into tablets, granules, decoctions, capsules, etc. using Chinese herbal medicine as an extract powder. Among these, tablets have advantages such as ease of administration and masking of bitterness. It can be said that this is the most acceptable form of formulation for consumers. Therefore, for Seihaito, it is desired to mold the extract powder into tablets to mask the bitterness and harshness and to make the pharmaceutical form easy to take.

On the other hand, tablets containing Chinese herbal extract powder take a larger amount of active ingredient (Chinese herb extract powder) per day than general drugs, so the tablets become larger and the number of tablets taken at one time is larger. It has the disadvantage that it is difficult for consumers to take it. In order to overcome such drawbacks, it is effective to increase the content of the Chinese herbal extract powder in the tablet, but when the content of the Chinese herbal extract powder in the tablet is increased, the excipients to be relatively blended The content is reduced, and as a result, the hardness of the tablet is reduced, and it becomes impossible to provide a hardness that can withstand packaging, transportation, and the like.

Conventionally, as a formulation method for increasing the hardness of tablets, it is known to add excipients such as lactose and crystalline cellulose and binders such as hydroxypropyl cellulose and hydroxypropyl methyl cellulose.

However, even if such a formulation method is applied to tablets containing Seihaito extract powder, the hardness is insufficient, or even if the hardness can be increased, the disintegration property is rather lowered. There's a problem.

In addition, Seihaito extract powder has a unique property that it is easily discolored by absorbing moisture, and when a disintegrant is added to a tablet containing Seihaito extract powder, discoloration is promoted by drawing in water by the disintegrant. There is also a problem. Unlike granules that are packaged separately, tablets are often packed together in bottles or bags, and have the property of easily absorbing moisture when the bottles or bags are opened each time they are taken. Therefore, for tablets containing Seihaito extract powder, it is necessary to design the formulation so that discoloration due to moisture absorption can be suppressed.

Conventionally, it has been reported that discoloration can be suppressed by blending polyvinyl acetate together with the Chinese herbal extract when formulating a Chinese herbal extract powder that is prone to discoloration due to moisture absorption (Patent Document 1). It has also been reported that discoloration of Chinese herbal extract powder can be suppressed by storing a pharmaceutical product containing Chinese herbal extract powder together with a desiccant (Non-Patent Document 3). However, such a method has drawbacks that a new manufacturing process is required and the packaging material cost is increased.

Ken Miyata, Kampo Medicine, Vol. 12, No. 9, pp.234-244, 1988 Yasuo Tanno, Internal Medicine, Vol. 67, No. 4, pp.628-634, 1991 Special Feature How to Use Chinese Medicine Using Extracts <General> Regarding the storage of extract preparations, clinical and drug treatment, No. 69, pp.278-282, 1992

Japanese Unexamined Patent Publication No. 2014-166994

Tablets containing Seihaito extract powder not only have a hardness that can be tolerated during packaging and transportation, but also disintegrate at an appropriate time after taking in order to fully exert the physiological functions and pharmacological effects of crude drugs in vivo. Need to be absorbed. In fact, the 17th revised Japanese Pharmacopoeia also stipulates that tablets can be sufficiently disintegrated within 30 minutes in the disintegration test method. However, conventionally, no technique has been found for making a tablet containing Seihaito extract powder have sufficient hardness and excellent disintegration property. Further, conventionally, in tablets containing Seihaito extract powder, discoloration due to moisture absorption has been a problem, but a formulation technique capable of suppressing the discoloration with sufficient hardness and excellent disintegration property has not been found. ..

Therefore, an object of the present invention is to provide a tablet containing Seihaito extract powder with sufficient hardness and disintegration property that disintegrates at an appropriate speed after administration, and discoloration of the Seihaito extract powder due to moisture absorption. It is to provide a formulation technology capable of suppressing.

As a result of diligent studies to solve the above problems, the present inventor has found that tablets containing Seihaito extract powder, disintegrant, and silicon dioxide and / or silicate have sufficient hardness and excellent disintegration property. In addition, it was found that discoloration due to moisture absorption of Seihaito extract powder can be suppressed. The present invention has been completed by further studies based on such findings.

That is, the present invention provides the inventions of the following aspects.
Item 1. Tablets containing Seihaito extract powder, disintegrant, and silicon dioxide and / or silicate.
Item 2. Item 2. The tablet according to Item 1, wherein the surface or a part of the Seihaito extract powder is tablet-molded using a granulated product coated with silicon dioxide and / or silicate.
Item 3. Item 1 or 2, wherein the disintegrant is at least one selected from the group consisting of carmellose, carmellose calcium, croscarmellose sodium, crospovidone, sodium starch glycolate, and low-degree-of-substitution hydroxypropyl cellulose. Tablets.
Item 4. Item 2. The tablet according to any one of Items 1 to 3, further comprising a lubricant.
Item 5. A method for producing a tablet, wherein a granulated product in which the surface or a part of the Seihaito extract powder is coated with silicon dioxide and / or a silicate, and a tableting mixed powder containing a disintegrant are tableted.
Item 6. Item 5. The production method according to Item 5, wherein the granulated product is granulated by Seihaito extract powder and a mixture of silicon dioxide and / or silicate by fluidized bed granulation.
Item 7. A method for improving the hardness and disintegration of tablets containing Seihaito extract powder.
The method for improving hardness and disintegration, wherein a tablet containing Seihaito extract powder contains a disintegrant and silicon dioxide and / or silicate.
Item 8. It is a method of suppressing discoloration due to moisture absorption of tablets containing Seihaito extract powder.
The method for suppressing discoloration, wherein a tablet containing Seihaito extract powder contains a disintegrant and silicon dioxide and / or silicate.

Although the tablet of the present invention contains Seihaito extract powder, it has sufficient hardness to withstand packaging, transportation, etc., and has a disintegrating property that disintegrates at an appropriate speed after administration. Furthermore, since the tablets of the present invention can suppress discoloration of Seihaito extract powder due to moisture absorption, even if they are packed together in a bottle or bag and provided, the discoloration due to unavoidable moisture absorption of the tablets that occurs during use or storage can be suppressed. It can be suppressed, and the appearance and properties of Seihaito extract powder and tablets can be stably maintained.

The results of observing the surface shape of the granulated product containing Seihaito extract powder and silicon dioxide with a scanning electron microscope when granulated by the stirring granulation method and when granulated by the fluidized bed granulation method are shown. It is a figure.

1. 1. Tablets The tablets of the present invention are characterized by containing Seihaito extract powder, a disintegrant, and silicon dioxide and / or silicate. Hereinafter, the tablet of the present invention will be described in detail.

The Kiyoshihaiyu extract powder Kiyoshihaiyu, a mixed crude drug containing Scutellaria, bellflower, mulberry bark, apricot kernel, Sanshishi, Tenmondou, Fritillaria, citrus unshiu peel, gymnastics, Chikujo, Bukuryou, angelica, Bakumondou, Gomishi, ginger, liquorice. The standards and sites of use of these crude drugs are stipulated in the Japanese Pharmacopoeia and the Japanese Pharmacopoeia Non-Japanese Pharmacopoeia Standards. The preparation of Seihaito that can be used in the present invention includes "Guide for General Chinese Medicine Prescription" (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare, edited by the Japan Yakuren Chinese Medicine Expert Committee, published by Yakuhin Jihosha) and "Revised General Chinese Medicine Prescription". It can be done according to "Guide" (supervised by Japan Official Standards Association, edited by Japan Chinese Herbal Medicine Association, published by Jiho Co., Ltd.).

The mixing ratio of each crude drug contained in Seihaito is not particularly limited, but usually, in terms of weight ratio, licorice 2 to 2.5, licorice 2 to 2.5, licorice 2 to 2.5, and apricot kernel 2 to 2 .5, Licorice 2-2.5, Tenmondou 2-2.5, Crude drug 2-2.5, Chinpi 2-2.5, Taiso 2-2.5, Chikujo 2-2.5, Schisandra chinensis 3, Touki 3 , Bakumondou 3, Garbage 0.5 to 1, Ginger 1, and Licorice 1.

The Seihaito extract powder used in the present invention is a dry powder obtained by subjecting an extract obtained by extracting Seihaito or a concentrated solution thereof to a drying treatment. The extraction and drying conditions of Seihaito will be described below.

The extraction solvent used in the extraction treatment of Seihaito is not particularly limited, and examples thereof include water, ethanol, acetic acid, and a mixed solution thereof.

The extraction conditions for Seihaito are not particularly limited, but for example, 5 to 25 times, preferably 10 to 20 times, the amount of the extraction solvent is added to the total weight (dry weight) of the crude drug, and usually 70 to 70 to 20 times. A method of heating and brewing at 100 ° C. for 30 minutes to 2 hours can be mentioned.

The Seihaito extract thus obtained is subjected to a drying treatment after the solid content is removed by filtration or the like, and if necessary, it is concentrated. The method for drying the extract of Seihaito or the concentrated solution thereof is not particularly limited, and examples thereof include spray drying, concentrated drying under reduced pressure, and freeze drying. Among these drying methods, the spray drying method is preferable.

When the Seihaito extract is subjected to a drying treatment (particularly, a drying treatment by spray drying), an excipient such as dextrin may be added to the Seihaito extract, if necessary. By adding the excipient in this way, it becomes possible to shorten the drying time. The types and amounts of excipients added during the drying process of Seihaito extract are the same as in the case of producing general Chinese herbal extract powder.

The content of Seihaito extract powder in the tablets of the present invention may be appropriately set according to the size of the tablets, the number of tablets to be taken at one time, and the like, and is, for example, 10 to 90% by weight, preferably 10 to 90% by weight. 35 to 85% by weight, more preferably 45 to 85% by weight.

Disintegrant The tablets of the present invention contain a disintegrant. By including the disintegrant, it becomes possible to impart excellent disintegration property while increasing the hardness.

The disintegrant used in the present invention is not particularly limited as long as it is a component capable of promoting the disintegration of tablets by permeation and swelling of water, and is not particularly limited, for example, carmellose, carmellose calcium, croscarmellose sodium, and cloth. Examples thereof include povidone, sodium starch glycolate, low-degree-of-substitution hydroxypropyl cellulose, pregelatinized starch, and partially pregelatinized starch.

These disintegrants may be used alone or in combination of two or more. Among these disintegrants, carmellose, carmellose calcium, croscarmellose sodium, crospovidone, sodium starch glycolate, and low are preferable from the viewpoint of more preferably combining sufficient hardness and appropriate disintegration property. Degree of Substitution Hydroxypropyl Cellulose, more preferably Carmellose, Carmellose Calcium, and Croscarmellose Sodium.

These disintegrants are commercially available, and commercially available disintegrants can be used in the present invention. For example, the product name "NS-300" manufactured by Nichirin Chemical Industry Co., Ltd. as carmelose, the product name "ECG505" manufactured by Nichirin Chemical Industry Co., Ltd. as carmelose sodium, and Nichirin Chemical Co., Ltd. as croscarmellose sodium. The trade name "Kiccolate ND-2HS" manufactured by Kogyo Co., Ltd. can be used.

The content of the disintegrant in the tablet of the present invention is not particularly limited, and examples thereof include 1 to 30% by weight. From the viewpoint of more preferably combining sufficient hardness and appropriate disintegration property, the content of the disintegrant in the tablet of the present invention is preferably 5 to 20% by weight, more preferably 5 to 10% by weight. ..

In the tablet of the present invention, the ratio of the Seihaito extract powder to the disintegrant is determined according to the contents of both components described above. For example, 1 to 100 parts by weight of the Seihaito extract powder per 100 parts by weight of the disintegrant. 100 parts by weight can be mentioned. From the viewpoint of more preferably combining sufficient hardness and appropriate disintegration property, the disintegrant is preferably 5 to 50 parts by weight, more preferably 5 to 20 parts by weight, per 100 parts by weight of the Seihaito extract powder. Can be mentioned.

Silicon Dioxide and / or Silicates The tablets of the present invention further contain silicon dioxide and / or silicates. By containing silicon oxide and / or silicate together with the disintegrant, the hardness is improved while maintaining the excellent disintegration property imparted by the disintegrant, and the discoloration of the Seihaito extract powder due to moisture absorption is suppressed. Becomes possible.

The type of silicon dioxide used in the present invention is not particularly limited, and examples thereof include light anhydrous silicic acid and hydrous silicon dioxide.

The type of silicate used in the present invention is also not particularly limited, and for example, aluminum silicate, magnesium aluminate silicate, magnesium aluminometasilicate, calcium silicate, magnesium silicate, magnesium silicate. Examples include aluminum.

In the tablet of the present invention, one of these silicon dioxide and silicate may be used alone, or two or more thereof may be used in combination. Among silicon dioxide and silicate, silicon dioxide is preferable, and further, from the viewpoint of more effectively combining sufficient hardness, excellent disintegration property, and discoloration suppressing effect due to moisture absorption of Seihaito extract powder. Light anhydrous silicic acid and hydrous silicon dioxide are preferable, and light anhydrous silicic acid is more preferable.

Silicon dioxide and silicates are commercially available, and commercially available silicon dioxide and / or silicates can be used in the present invention. For example, the trade name "Adsolider 101" manufactured by Fuji Silysia Chemical Ltd. can be used as the light anhydrous silicic acid, and the trade name "Carplex # 80" manufactured by DSL Japan Co., Ltd. can be used as the hydrous silicon dioxide.

The content of silicon dioxide and / or silicate in the tablet of the present invention is not particularly limited, and examples thereof include 1 to 40% by weight in total. It is preferable as the content of silicon dioxide and / or silicate from the viewpoint of more effectively combining sufficient hardness, excellent disintegration property, and discoloration suppressing action due to moisture absorption of Seihaito extract powder. Is 5 to 30% by weight, more preferably 5 to 25% by weight.

In the tablet of the present invention, the ratio of Seihaito extract powder to silicon dioxide and / or silicate is determined according to the contents of both components described above. For example, per 100 parts by weight of Seihaito extract powder. , Silicon dioxide and / or silicates totaling 1-100 parts by weight. From the viewpoint of more effectively combining sufficient hardness, excellent disintegration property, and discoloration suppressing action due to moisture absorption of Seihaito extract powder, the total amount of silicon dioxide and / or silicate is preferably 5. ~ 50 parts by weight, more preferably 5 to 30 parts by weight.

Lubricants The tablets of the present invention may further contain a lubricant. The type of lubricant used in the present invention is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include stearate such as magnesium stearate, talc, and hydrogenated vegetable oil. ..

These lubricants may be used alone or in combination of two or more.

Among these lubricants, magnesium stearate has an effect of improving the discoloration suppressing effect of Seihaito extract powder due to moisture absorption, and is preferably used.

When the lubricant is contained in the tablet of the present invention, the content thereof is not particularly limited, but for example, 0.01 to 10% by weight, preferably 0.05 to 5% by weight, more preferably 0. 1 to 5% by weight, particularly preferably 0.5 to 2% by weight. Further, when magnesium stearate is used as a lubricant and the content is satisfied, discoloration of Seihaito extract powder can be suppressed more effectively.

When the tablet of the present invention contains a lubricant, the ratio of the Seihaito extract powder to the lubricant is determined according to the contents of both components described above. For example, Seihaito extract powder 100 Per part by weight, the lubricant is 0.1 to 10 parts by weight, preferably 0.5 to 5 parts by weight, and more preferably 0.5 to 3 parts by weight. When magnesium stearate is used as a lubricant and the above ratio is satisfied, discoloration of Seihaito extract powder can be suppressed even more effectively.

Other Ingredients In addition to the above ingredients, the tablets of the present invention may contain other nutritional ingredients and pharmacological ingredients depending on the intended use. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmaceutically acceptable, but for example, antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, and astringents. Agents, antiemetics, antitussives, sputum, anti-inflammatory enzyme agents, sedative hypnotics, antihistamines, caffeines, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, crude drug extract powders, vitamins, Mentors and the like can be mentioned. These nutritional components and pharmacological components may be used alone or in combination of two or more. Further, the content of these components is appropriately set according to the type of the component to be used and the like.

In addition to the above-mentioned components, the tablet of the present invention may contain other additives required for formulation into tablets, if necessary. Such additives are not particularly limited as long as they are pharmaceutically acceptable, and include, for example, water, excipients (other than silicon dioxide and / or silicates), binders, antioxidants, and preservatives. Examples thereof include agents, fragrances, flavoring agents, thickeners, pigments, pH adjusters, buffers, chelating agents and the like. These additives may be used alone or in combination of two or more. Further, the content of these additives is appropriately set according to the type of the additive to be used and the like.

Physical characteristics of the product The tablet of the present invention can have an appropriate hardness that does not break during packaging, transportation, or the like. The hardness of the tablet of the present invention may be such that it does not break during packaging, transportation, etc., but specific examples thereof include 80 N or more, preferably 90 to 500 N. In the present invention, the hardness of a tablet refers to a value measured by a load cell type tablet hardness tester.

In addition, the tablet of the present invention has a disintegrating property that disintegrates at an appropriate speed after ingestion. The disintegration property of the tablet of the present invention may be such that it disintegrates at an appropriate speed after administration. Specifically, in the disintegration test method shown below, the disintegration time is 5 to 30 minutes, preferably 10. Those that satisfy ~ 20 minutes can be mentioned. In the present invention, the disintegration time of a tablet refers to a value measured according to the disintegration test method specified in the 17th revised Japanese Pharmacopoeia.

Formulation form The tablet of the present invention may be coated with a sugar coating base, a water-soluble film coating base, or the like, if necessary. Further, the tablet of the present invention can be suitably used as a gastric-soluble tablet (normal tablet) or an enteric-coated tablet.

The weight of the tablet of the present invention per tablet may be appropriately set according to the number of tablets taken at one time, the content of Seihaito extract powder, and the like, and examples thereof include about 200 to 500 mg. ..

Production Method The tablet of the present invention can be obtained according to a known production method. Specifically, it can be produced by subjecting a mixture of raw material components to tableting molding. Further, the mixture of the raw material components to be subjected to tableting molding may be a granulated product in which all or a part of the raw material components are granulated.

Further, in the production of tablets of the present invention, granulated products in which a part or all of the surface of Seihaito extract powder is coated with silicon dioxide and / or silicate (hereinafter referred to as "coated granulated products"). In some cases), the coated granules and other raw materials are mixed and tableted to obtain tablets that can more effectively suppress discoloration due to moisture absorption of Seihaito extract powder. Can be done.

The method for producing the coated granulated product is not particularly limited, and for example, a method of subjecting a mixture of Seihaito extract powder and silicon dioxide and / or silicate to a fluidized bed granulator for granulation. Can be mentioned.

The coverage of silicon dioxide and / or silicate in the coated granulated product is not particularly limited, but is, for example, 70% or more, preferably 80% or more, more preferably 90% or more, and particularly preferably 100. %. Here, for the "coating ratio of silicon dioxide and / or silicate", the granulated product is observed with a scanning electron microscope (SEM), and the coating ratio of each granulated product is calculated by the following formula. It is a value obtained by calculating the average value of the coverage obtained from the granulated material of one or more pieces. Such a coverage can be adjusted by appropriately setting the amount of Seihaito extract powder used as a raw material, the amount of silicon dioxide and / or silicate, the conditions for granulating the fluidized bed, and the like.

Further, the coated granulated product may be produced by using all of Seihaito extract powder and silicon dioxide and / or silicate to be blended in the tablet, but the coated granulated product may be produced by using a part of them. Granules may be produced, and the remaining Seihaito extract powder and / or silicon dioxide and / or silicate may be mixed with the obtained coated granules and subjected to tableting.

The locking molding can be performed using an apparatus such as a single-shot locking machine, a rotary locking machine, or a high-speed rotary locking machine. The tableting pressure at the time of tableting is not particularly limited as long as the tablet can be molded, but it may be ^{usually set to about 250 to 4000 kg / cm 2.}

2. Method for improving hardness and disintegration of tablets-Method for suppressing discoloration due to moisture absorption of tablets The present invention provides a method for improving the hardness and disintegration of tablets containing Seihaito extract powder. Specifically, the improvement method is characterized in that a tablet containing Seihaito extract powder contains a disintegrant and silicon dioxide and / or silicate. The types and amounts of the components used in the improvement method, the method for molding tablets, and the like are as described in the column of "1. Tablets".

The present invention also provides a method for suppressing discoloration of tablets containing Seihaito extract powder due to moisture absorption. Specifically, the suppression method is characterized in that a tablet containing Seihaito extract powder contains a disintegrant and silicon dioxide and / or silicate. The types and amounts of the components used in the suppression method, the tablet molding method, and the like are as described in the above-mentioned "1. Tablet" column.

Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited to these Examples.

The sources of the main ingredients used in the following test examples and prescription examples are as follows.
Silicon dioxide: Light anhydrous silicic acid, trade name "Adsolider 101" manufactured by Fuji Silysia Chemical Ltd., and hydrous silicon dioxide, trade name "Carplex # 80" manufactured by DSL Japan Co., Ltd. Carmelose: Trade name "NS-300", Nichirin Carmelose Sodium manufactured by Kagaku Kogyo Co., Ltd .: "ECG505", Croscarmellose Sodium manufactured by Nichirin Chemical Industry Co., Ltd .: "Kiccolate ND-2HS", Magnesium stearate manufactured by Nichirin Kagaku Kogyo Co., Ltd .: "Magnetic stearate plant""Sex", manufactured by Taihei Kagaku Sangyo Co., Ltd.

Test Example 1
1. 1. Tablet manufacturing
1-1. Prepare dry weight of powder Kiyoshihaiyu extract, scutellaria root 2 parts by weight, Campanulaceae 2 parts by weight, mulberry bark 2 parts by weight, apricot kernel 2 parts by weight, Sanshishi 2 parts by weight, Tenmondou 2 parts by weight, Fritillaria 2 parts by weight, citrus unshiu peel 2wt 2 parts by weight of Taisou, 2 parts by weight of Chikujo, 3 parts by weight of Bukuryo, 3 parts by weight of Touki, 3 parts by weight of Bakumondou, 0.5 parts by weight of garbage, 1 part by weight of Shokyo, and 1 part by weight of Kanzo. Extraction treatment was carried out at about 95 ° C. for 1 hour using 5 times the total amount (dry weight of the raw material) of water, and centrifugation was performed to obtain an extract. Seihaito extract was obtained by filtering the obtained extract (150 mesh). The obtained Seihaito extract was concentrated under a reduced pressure of 60 ° C. or lower according to a conventional method, and dried using a spray-drying method to prepare Seihaito extract powder.

1-2. Preparation of Tablets Tablets having the compositions shown in Table 1 were produced. Specifically, the components shown in Table 1 are mixed in a predetermined amount, and the obtained mixed powder is tableted with a hydraulic tableting machine (TB-20N, NPA System Co., Ltd.) with a pressing force of 10 kN. A tablet of 200 mg (disk-shaped with a diameter of 8 mm) was obtained per tablet.

2. Evaluation of Hardness For each of the obtained tablets, the hardness of 10 tablets was measured with a load cell type tablet hardness tester (PC-30, Okada Seiko Co., Ltd.), and the average value was calculated. The relative value of the hardness of each tablet was calculated with the hardness of the tablets of Comparative Example 1 as 100%.

3. 3. Evaluation of disintegration For each tablet obtained, the disintegration time was measured using a disintegration tester (NT-1HM, Toyama Sangyo Co., Ltd.) according to the disintegration test method specified in the 17th revised Japanese Pharmacopoeia. bottom.

4. Evaluation of Discoloration Suppressing Effect Each tablet immediately after production was stored in an open state at 25 ° C. and 60% RH for 12 hours. The L value, a value, and b value of the tablets immediately after production and after 12 hours of storage were measured using a color difference meter (spectrocolorimeter CLR-7100F, Shimadzu Corporation). The color difference (ΔE * ab) before and after storage of each tablet was determined according to the following calculation formula.

Using the color difference (ΔE * ab) calculated for each tablet, the discoloration suppression rate (%) was determined according to the following calculation formula.

5. Results The results obtained are shown in Table 1. Tablets containing Seihaito extract powder and a disintegrant and not silicon dioxide had excellent disintegration properties, but could not suppress discoloration of Seihaito extract powder (Comparative Example 1). On the other hand, tablets containing Seihaito extract powder, disintegrant, and silicon dioxide have excellent disintegration properties and improved hardness compared to those without silicon dioxide, and during packaging and transportation. It was able to sufficiently withstand the above, and further, the discoloration of the Seihaito extract powder could be suppressed (Examples 1 to 5).

Test Example 2
1. 1. Tablet manufacturing
1-1. Preparation of Seihaito extract powder Seihaito extract powder was prepared under the conditions shown in Test Example 1 above.

1-2. Tablet manufacturing
Example 6
The components shown in Table 2 are mixed in a predetermined amount, and the obtained mixed powder is tableted with a single-shot tableting machine (CRUX, Kikusui Seisakusho Co., Ltd.) at a pressure of 15 kN, and 440 mg per tablet (diameter 9. A 5 mm disk-shaped tablet was obtained.

Examples 7-10
Seihaito extract powder and silicon dioxide were mixed in a predetermined amount shown in Table 2 and granulated using a stirring granulator (VG-05, Paulec Co., Ltd.) to obtain granulated products. A predetermined amount of the obtained granulated product and other raw materials are mixed, and the mixture is tableted with a single-shot tableting machine (CRUX, Kikusui Seisakusho Co., Ltd.) at a pressure of 15 kN as a mixing powder for tableting. A 440 mg (disk-shaped 9.5 mm diameter) tablet was obtained.

Example 11
Seihaito extract powder and silicon dioxide were mixed in a predetermined amount shown in Table 2 and granulated using a fluidized bed granulator (MP-01, Paulec Co., Ltd.) to obtain granulated products. A predetermined amount of the obtained granulated product and other raw materials are mixed, and the mixture is tableted with a single-shot tableting machine (CRUX, Kikusui Seisakusho Co., Ltd.) at a pressure of 15 kN as a mixing powder for tableting. A 440 mg (disk-shaped 9.5 mm diameter) tablet was obtained.

2. Evaluation of Tablets and Results Each of the obtained tablets was evaluated for hardness, disintegration property, and discoloration suppressing effect in the same manner as in Test Example 1.

Table 2 shows the evaluation results of hardness and disintegration. The hardness of the tablet is a measured value. As a result, all the tablets had high hardness and excellent disintegration property. Further, the disintegration property of the tablet (Example 11) using the granulated product granulated by the fluidized bed granulator as a raw material is the tablet using the granulated product granulated by the stirring granulator as a raw material (Example 11). It was superior to 7-10).

Regarding the discoloration suppressing effect, the tablets using the granulated product granulated by the fluidized layer granulator as a raw material (Example 11) were tablets that were tableted without granulation (Example 6), and stirring. Compared with the tablets (Examples 7 to 10) using the granulated product granulated by the granulator as a raw material, the discoloration suppressing effect was remarkably improved.

When the properties of the granulated product granulated by the stirring granulation method and the granulated product granulated by the fluidized bed granulation method were photographed with an electron microscope, the granulated product granulated by the fluidized bed granulation method was not found. It was confirmed that the surface of the Seito-to extract powder was coated with silicon dioxide. In addition, FIG. 1 shows an example of the results of observing these granulated products with a scanning electron microscope at a magnification of 2000. The silicon dioxide coverage of the granulated product granulated by the fluidized bed granulation method was calculated to be 90% or more by the above-mentioned method. By tableting silicon dioxide using a granulated product whose surface is coated with the Seihaito extract powder, water absorption of the Seihaito extract powder is more effectively suppressed, and as a result, in the tablet of Example 11. In addition to exhibiting a high discoloration suppressing effect, stickiness due to water absorption was also suppressed, which was considered to have led to a reduction in disintegration time.

Formulation Examples Tablets having the compositions shown in Table 3 (440 mg per tablet) were produced in the same manner as in Examples 7 and 11. The obtained tablets had a hardness sufficient to withstand during packaging, transportation, etc., had excellent disintegration properties, and had an excellent discoloration suppressing effect.

Claims (8)

Kiyoshihaiyu extract powder, disintegrants, and contains silicon dioxide, tablets. Kiyoshihaiyu some or all parts of extract powder of surfaces are tabletted using granules which are thus coated on silicon dioxide The tablet of claim 1. The disintegrant is at least one selected from the group consisting of carmellose, carmellose calcium, croscarmellose sodium, crospovidone, sodium starch glycolate, and low-degree-of-substitution hydroxypropyl cellulose, according to claim 1 or 2. The listed tablets. The tablet according to any one of claims 1 to 3, further comprising a lubricant. Granulation some or all parts of Kiyoshihaiyu extract powder surface is thus coated with silicon dioxide, and the mixed powder for tableting comprising a disintegrant, molded tablet manufacturing method of tablets. The granules, Kiyoshihaiyu extract powder, and the mixture is granulated dioxide silicon by fluidized bed granulation process according to claim 5. A method for improving the hardness and disintegration of tablets containing Seihaito extract powder.
Tablets containing Kiyoshihaiyu extract powder, disintegrants, and the inclusion of silicon dioxide, the hardness and disintegration method for improving. It is a method of suppressing discoloration due to moisture absorption of tablets containing Seihaito extract powder.
Tablets containing Kiyoshihaiyu extract powder, disintegrants, and the inclusion of silicon dioxide, method of suppressing the discoloration.

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