JP7114227B2 - Tablets containing Seihaito extract powder - Google Patents

Description

TECHNICAL FIELD The present invention relates to a tablet containing Seihaito extract powder. More specifically, the present invention relates to a tablet containing Seihaito extract powder, which has sufficient hardness and a disintegrating property to disintegrate at an appropriate speed after administration.

Seihaito is a Chinese herbal medicine introduced in the Ming Dynasty's "Manbyo Kaishun", and is known to have the effect of suppressing inflammation of the throat and trachea, making it easier to remove phlegm, and soothing coughs. In modern times, its effects have been re-examined, mucolysis, promotion of airway fluid secretion, promotion of pulmonary surfactant secretion, lubrication of airway mucosa, suppression of inflammation of airway mucosa, recovery and activation of mucociliary transport ability, antibiotics The action of Seihaito, such as promotion of migration into sputum, has been further clarified (Non-Patent Documents 1 and 2). Today, Seihaito is also used for the purpose of relieving the adverse effects of exhaust gas, PM2.5, tobacco, etc., and cleaning the bronchi.

However, since Seihaito has a unique bitterness and acridness, it has the drawback of being difficult to take.

Conventionally, Kampo preparations are often formulated into tablets, granules, decoctions, capsules, etc. by making Kampo medicine into an extract powder, but among these, tablets have advantages such as ease of administration and masking of bitterness. Therefore, it can be said that it is the formulation form that is most easily accepted by consumers. Therefore, it is desired that the extract powder is formed into tablets to mask the bitterness and acridity of Seihaito, and that the preparation form be easy to take.

On the other hand, tablets containing Kampo extract powder have a large amount of active ingredient (Kampo extract powder) taken per day compared to general drugs, so the size of the tablet is large, and the number of tablets taken per dose is large. There is a drawback that it is difficult for consumers to take. Increasing the content of Kampo extract powder in the tablet is effective in overcoming such drawbacks. The content is reduced, and as a result, the hardness of the tablet is lowered, and it becomes impossible to provide hardness that can withstand packaging, transportation, and the like.

Conventionally, as a formulation method for increasing tablet hardness, it is known to add excipients such as lactose and crystalline cellulose, and binders such as hydroxypropylcellulose and hydroxypropylmethylcellulose. However, even if such a formulation method is applied to tablets containing Seihaito extract powder, the hardness is sometimes insufficient, and even if the hardness can be increased, the disintegration property is rather reduced. There's a problem.

Ken Miyata, Kampo Medicine, Vol. 12, No. 9, pp.234-244, 1988 Yasuo Tanno, Internal Medicine, Vol.67, No.4, pp.628-634, 1991

Tablets containing Seihaito extract powder must not only have a hardness that can withstand packaging and transportation, but also must disintegrate in an appropriate time after ingestion in order to fully demonstrate the physiological functions and pharmacological effects of herbal medicines in the body. must be absorbed by In fact, the 17th edition of the Japanese Pharmacopoeia also stipulates that tablets should fully disintegrate within 30 minutes in the disintegration test method. However, no technology has hitherto been found for making a tablet containing Seihaito extract powder have both sufficient hardness and excellent disintegration properties.

Accordingly, an object of the present invention is to provide a formulation technology that allows a tablet containing Seihaito extract powder to have sufficient hardness and a disintegrating property to disintegrate at an appropriate speed after administration.

As a result of intensive studies in order to solve the above problems, the present inventors found that specific disintegrants (carmellose, carmellose calcium, croscarmellose sodium, crospovidone, sodium starch glycolate and/or low-substituted hydroxypropyl cellulose ) and molding the Seihaito extract powder into tablets, it was found that not only excellent disintegration properties but also sufficient hardness can be obtained. The present invention has been completed through further studies based on such findings.

That is, the present invention provides inventions in the following aspects.
Section 1. Seihaito extract powder, and at least one disintegrant selected from the group consisting of carmellose, carmellose calcium, croscarmellose sodium, crospovidone, sodium starch glycolate, and low-substituted hydroxypropylcellulose, tablet.
Section 2. Item 2. The tablet according to Item 1, wherein the disintegrant is at least one selected from the group consisting of carmellose, carmellose calcium, and croscarmellose sodium.
Item 3. A method for improving the hardness and disintegration of a tablet containing Seihaito extract powder,
At least one disintegrant selected from the group consisting of carmellose, carmellose calcium, croscarmellose sodium, crospovidone, sodium starch glycolate, and low-substituted hydroxypropyl cellulose is added to a tablet containing Seihaito extract powder. The method for improving the hardness and disintegration property by containing.

The tablet of the present invention contains the Seihaito extract powder, has sufficient hardness to withstand packaging and transportation, and has a disintegrating property to disintegrate at an appropriate speed after administration.

1. Tablets The tablet of the present invention is at least one selected from the group consisting of Seihaito extract powder and carmellose, carmellose calcium, croscarmellose sodium, crospovidone, sodium starch glycolate, and low-substituted hydroxypropyl cellulose. It is characterized by containing a disintegrant of The tablet of the present invention is described in detail below.

Seihaito Extract Sueseihaito is a mixed crude drug containing Scutellaria root, Bellflower, Sohakuhi, Kyonin, Sanshishi, Tenmondo, Fritillaria, Chimpi, Taisou, Chikujo, Bukuryo, Radix, Bakumondo, Gomishi, Ginger and Glycyrrhiza. The Japanese Pharmacopoeia and Non-Japanese Pharmacopoeia Standards for crude drugs specify the standards and application sites for these crude drugs. Seihaito that can be used in the present invention can be prepared according to the following methods: "Guidelines for General Kampo Prescriptions" (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare, edited by Nichiyakuren Kampo Expert Committee, published by Yakugyo Jihosha) and "Revised General Kampo Prescriptions Guide" (supervised by the Japan Official Publications Association, edited by the Japan Kampo Herbal Medicines Association, published by Jiho Co., Ltd.).

The mixing ratio of each crude drug contained in Seihaito is not particularly limited, but usually the weight ratio is 2 to 2.5 of Scutellaria root, 2 to 2.5 of Bellflower, 2 to 2.5 of Sohakuhi, and 2 to 2 of Kyonin. .5, Sanshishi 2-2.5, Tenmondou 2-2.5, Bimo 2-2.5, Chimpi 2-2.5, Taiso 2-2.5, Chikujo 2-2.5, Bucuriho 3, Touki 3 , Bakumondou 3, Komishi 0.5 to 1, ginger 1, licorice 1.

The Seihaito extract powder used in the present invention is a dry powder obtained by drying the extract obtained by extracting Seihaito or its concentrate. The extraction and drying conditions for Seihaito will be described below.

The extraction solvent used for the extraction treatment of Seihaito is not particularly limited, but examples thereof include water, ethanol, acetic acid, and mixtures thereof.

The extraction conditions for Seihaito are not particularly limited. A method of heat brewing at 100° C. for 30 minutes to 2 hours can be mentioned.

The thus-obtained Seihaito extract is subjected to a drying treatment after removing solids by filtration or the like and, if necessary, concentrating. The method for drying the extract of Seihaito or its concentrate is not particularly limited, and examples thereof include spray drying, vacuum concentration drying, and freeze drying. Among these drying methods, the spray drying method is suitable.

When the Seihaito extract is subjected to a drying treatment (especially a drying treatment by spray drying), an excipient such as dextrin may be added to the Seihaito extract as necessary. By adding excipients in this manner, it is possible to shorten the drying time and reduce the hygroscopicity of the dried Seihaito extract powder. The types and amounts of excipients added during the drying treatment of the Seihaito extract are the same as in the case of producing general Kampo extract powder.

In addition, the content of Seihaito extract powder in the tablet of the present invention may be appropriately set according to the size of the tablet, the number of tablets to be taken per dose, etc. For example, it is 10 to 90% by weight, preferably 35 to 85% by weight, more preferably 45 to 85% by weight.

Disintegrant The tablet of the present invention contains at least one disintegrant selected from the group consisting of carmellose, carmellose calcium, croscarmellose sodium, crospovidone, sodium starch glycolate, and low-substituted hydroxypropylcellulose. . By selecting and including a specific disintegrant in this way, it is possible to provide tablets containing Seihaito extract powder with not only excellent disintegration properties but also sufficient hardness to withstand packaging and transportation. become.

In the tablet of the present invention, these disintegrants may be used singly or in combination of two or more. Among these disintegrants, carmellose, carmellose calcium, and croscarmellose sodium are preferred from the viewpoint of more preferably combining sufficient hardness and moderate disintegration.

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

The content of the specific disintegrant in the tablet of the present invention is not particularly limited, but may be, for example, 1 to 30% by weight. From the viewpoint of more preferably combining sufficient hardness and moderate disintegration, the content of the specific disintegrant in the tablet of the present invention is preferably 5 to 20% by weight, more preferably 5 to 10% by weight. is mentioned.

In the tablet of the present invention, the ratio of the Seihaito extract powder and the specific disintegrant is determined according to the content of both components described above. 1 to 100 parts by weight of the disintegrant. From the viewpoint of more preferably combining sufficient hardness and moderate disintegration, the specific disintegrant is preferably 5 to 50 parts by weight, more preferably 5 to 20 parts by weight, per 100 parts by weight of Seihaito extract powder. parts by weight.

Silicon Dioxide and/or Silicate The tablet of the present invention may further contain silicon dioxide and/or silicate. By containing silicon oxide and/or silicate, it is possible to improve the hardness while maintaining the disintegration property, and also to suppress discoloration due to moisture absorption, which is a problem specific to the Seihaito extract powder. .

The type of silicon dioxide used in the present invention is not particularly limited, but 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, but examples include aluminum silicate, magnesium aluminosilicate, magnesium aluminometasilicate, calcium silicate, magnesium silicate, and magnesium silicate. Aluminum etc. are mentioned.

In the tablet of the present invention, one of these silicon dioxides and silicates may be used alone, or two or more thereof may be used in combination. Among silicon dioxide and silicates, silicon dioxide is preferable, and light anhydrous silicic acid and hydrated silicon dioxide are more preferable from the viewpoint of more effectively improving hardness and suppressing discoloration of Seihaito extract powder. and more preferably light anhydrous silicic acid.

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

In the tablet of the present invention, when containing silicon dioxide and / or silicate, the content is not particularly limited, for example, the total amount of silicon dioxide and / or silicate is 1 to 40% by weight. be done. From the viewpoint of more effectively improving hardness and suppressing discoloration of Seihaito extract powder, the content of silicon dioxide and/or silicate is preferably 5 to 30% by weight, more preferably 10% by weight. ~25% by weight.

In the tablet of the present invention, when containing silicon dioxide and / or silicate, the ratio of Seihaito extract powder and silicon dioxide and / or silicate is determined according to the content of both components described above However, for example, the total amount of silicon dioxide and/or silicate is 1 to 100 parts by weight per 100 parts by weight of Seihaito extract powder. From the viewpoint of more effectively improving the hardness and suppressing the discoloration of the Seihaito extract powder, the total amount of silicon dioxide and/or silicate is preferably 5 to 50 parts by weight, more preferably 5 to 50 parts by weight. 30 parts by weight.

Lubricant The tablet 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. Examples include stearates such as magnesium stearate, talc, and hydrogenated vegetable oils. .

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

Among these lubricants, magnesium stearate is preferably used because it can effectively suppress discoloration due to moisture absorption, which is a problem peculiar to Seihaito extract powder.

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

When the tablet of the present invention contains a lubricant, the ratio between the Seihaito extract powder and the lubricant is determined according to the content of both components described above. The amount of 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 the Seihaito extract powder can be more effectively suppressed.

Other Ingredients In addition to the above ingredients, the tablet of the present invention may contain other nutritional ingredients and pharmacological ingredients depending on its use. Such nutritional ingredients and pharmacological ingredients are not particularly limited as long as they are pharmaceutically acceptable. antiemetics, antitussives, expectorants, anti-inflammatory enzymes, sedatives, hypnotics, antihistamines, caffeines, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal extract powder, vitamins, menthol and the like. These nutritional ingredients and pharmacological ingredients may be used singly or in combination of two or more. Moreover, the contents of these components are appropriately set according to the types of components used.

Moreover, the tablet of the present invention may contain, if necessary, other additives required for formulation into a tablet, in addition to the components described above. Such additives are not particularly limited as long as they are pharmaceutically acceptable. Examples include water, excipients (other than silicon dioxide and/or silicate), binders, disintegrants ( disintegrants), antioxidants, preservatives, perfumes, corrigents, thickeners, pigments, pH adjusters, buffers, chelating agents and the like. These additives may be used singly or in combination of two or more. Moreover, the content of these additives is appropriately set according to the type of additive used.

Formulation physical properties The tablet of the present invention can be provided with appropriate hardness so that it will not break during packaging, transportation, or the like. The hardness of the tablet of the present invention is sufficient as long as it does not break during packaging or transportation. In the present invention, tablet hardness refers to a value measured by a load cell type tablet hardness tester.

In addition, the tablet of the present invention has disintegration properties such that it disintegrates at an appropriate speed after administration. Regarding the disintegration property of the tablet of the present invention, it is sufficient that it disintegrates at an appropriate speed after administration. Those satisfying ~20 minutes can be mentioned. In the present invention, the tablet disintegration time refers to a value measured according to the disintegration test method specified in the Japanese Pharmacopoeia 17th Edition.

Form of Formulation 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. Moreover, the tablet of the present invention can be suitably used as a gastric-soluble tablet (usually a tablet) or an enteric-coated tablet.

Further, the weight per tablet of the tablet of the present invention may be appropriately set according to the number of tablets per dose, the content of the Seihaito extract powder, etc., and for example, it is about 200 to 500 mg. .

Manufacturing Method The tablet of the present invention can be obtained according to a known manufacturing method. Specifically, it can be produced by subjecting a mixture of raw ingredients to tablet molding. Moreover, the mixture of the raw material components subjected to tablet molding may be a granule obtained by granulating all or part of the raw material components.

Tableting and molding can be performed using an apparatus such as a single-punch tableting machine, a rotary tableting machine, or a high-speed rotary tableting machine. In addition, the tableting pressure for tableting is not particularly limited as long as the tablets can be molded, but it is usually set to about 250 to 4000 kg/cm ² .

2. Method for Improving Tablet Hardness and Disintegration The present invention provides a method for improving the hardness and disintegration of tablets containing Seihaito extract powder. Specifically, the improvement method includes adding a tablet containing Seihaito extract powder to carmellose, carmellose calcium, croscarmellose sodium, crospovidone, sodium starch glycolate, and low-substituted hydroxypropyl cellulose. It is characterized by containing at least one selected disintegrant. In the improvement method, the types and blending amounts of the components used, the method of forming tablets, and the like are as described in the section "1. Tablets" above.

EXAMPLES The present invention will be specifically described below by way of examples, but the present invention is not limited to these examples.

The major components used in the following test examples and formulation examples are obtained from the following sources.
Silicon dioxide: light anhydrous silicic acid, trade name "Adsolider 101" Carmellose manufactured by Fuji Silysia Chemical Co., Ltd.: trade name "NS-300", carmellose sodium manufactured by Nichirin Chemical Industry Co., Ltd.: "ECG505", Nichirin Chemical Croscarmellose sodium manufactured by Kogyo Co., Ltd.: "Kikkolate ND-2HS", Magnesium stearate manufactured by Nichirin Chemical Industry Co., Ltd.: "Magnesium stearate vegetable", manufactured by Taihei Chemical Industry Co., Ltd.

Test example 1
1. manufacture of tablets
1-1. 2 parts by weight of Scutellaria root, 2 parts by weight of Bellflower, 2 parts by weight of Souhakuhi , 2 parts by weight of Kyonin, 2 parts by weight of Sanshishi, 2 parts by weight of Tenmondo, 2 parts by weight of Vimo, 2 parts by weight of Chimpi part, 2 parts by weight of taisou, 2 parts by weight of chikujo, 3 parts by weight of bukuryo, 3 parts by weight of Toki, 3 parts by weight of Bakumondo, 0.5 parts by weight of garbage, 1 part by weight of ginger, and 1 part by weight of licorice. Extraction treatment was performed at about 95° C. for 1 hour using 5 times as much water as the total amount (raw material dry weight), followed by centrifugation to obtain an extract. The obtained extract was filtered (150 mesh) to obtain a Seihaito extract. The obtained Seihaito extract was concentrated under reduced pressure at 60° C. or less according to a conventional method, and dried using a spray drying method to prepare Seihaito extract powder.

1-2. Manufacture of tablets Tablets having the composition shown in Table 1 were manufactured. Specifically, the components shown in Table 1 are mixed in predetermined amounts, and the resulting mixed powder is tableted with a hydraulic tableting machine (TB-20N, NPA System Co., Ltd.) at a pressure of 10 kN, Tablets of 200 mg per tablet (disk-shaped with a diameter of 8 mm) were obtained.

2. Evaluation of Hardness For each obtained tablet, 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. Taking the hardness of the tablet of Comparative Example 1 as 100%, the relative hardness of each tablet was calculated.

3. Disintegration evaluation For each obtained tablet, using a disintegration tester (NT-1HM, Toyama Sangyo Co., Ltd.), disintegration time is measured according to the disintegration test method specified in the 17th revision of the Japanese Pharmacopoeia. did.

4. Results The results obtained are shown in Table 1. When carmellose, carmellose calcium, or croscarmellose sodium was not contained, the hardness of the tablet was not sufficient and the disintegration time was extremely long (Comparative Example 1). On the other hand, when carmellose, carmellose calcium, or croscarmellose sodium is contained, the hardness of the tablet is improved to the extent that it can withstand packaging, transportation, etc., and the disintegration time is 20 minutes. within, and had excellent disintegration properties.

Reference test example 1
Using shakuyakukanzoto extract powder and bofutsushosan extract powder, tablets having the composition shown in Table 2 were produced. The specific manufacturing conditions are the same as in Test Example 1, except that the extract powder was used instead of the Seihaito extract powder. The shakuyakukanzoto extract powder and Bofutsushosan extract powder used were those listed in the Japanese Pharmacopoeia.

Each obtained tablet was measured for tablet hardness and disintegration under the same conditions as in Test Example 1 above. Regarding the tablet hardness, the relative value of Reference Example 1 was calculated with the hardness of Reference Example 2 as 100%, and the relative value of Reference Example 3 was calculated with the hardness of Reference Example 4 as 100%.

Table 2 shows the results obtained. As a result, when shakuyakukanzoto extract powder and bofutsushosan extract powder were used, tableting with croscarmellose sodium reduced the disintegration time, but increased hardness. I didn't. That is, the improvement in hardness and disintegration demonstrated in Examples 1 to 3 of Test Example 1 is a unique effect based on the combination of Seihaito extract powder and a specific disintegrant. rice field.

Formulation Example Tablets having the composition shown in Table 3 were produced. Specifically, Seihaito extract powder and silicon dioxide were mixed in predetermined amounts shown in Table 3, and granulated using a stirring granulator (VG-05, Powrex Co., Ltd.) to obtain granules. The obtained granules and other raw materials are mixed in predetermined amounts, and tableted as a mixed powder for tableting with a single-shot tableting machine (CRUX, Kikusui Seisakusho Co., Ltd.) at a pressure of 15 kN. Tablets of 440 mg (9.5 mm diameter discs) were produced. The tablets thus obtained had sufficient hardness to withstand packaging, transportation, and the like, and had excellent disintegration properties.

Claims (2)

A tablet comprising Seihaito extract powder and at least one disintegrant selected from the group consisting of carmellose, carmellose calcium and croscarmellose sodium . A method for improving the hardness and disintegration of a tablet containing Seihaito extract powder,
The method for improving hardness and disintegration, comprising adding at least one disintegrant selected from the group consisting of carmellose, carmellose calcium, and croscarmellose sodium to the tablet containing Seihaito extract powder.