JP2006347981A - Tablet containing tricholoma matsutake sing. mycelium - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a tablet containing Tricholoma Matsutake Sing. mycelia, and having good collapsibility and stability. <P>SOLUTION: This tablet containing Tricholoma Matsutake Sing. mycelia is characterized by comprising Tricholoma Matsutake Sing. mycelia and a cellulosic polymer base material. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a matsutake mycelium-containing tablet having good disintegration and stability.

  Tricholoma matsutake (S. Ito & Imai) Sing. Is known to contain various physiologically active substances. For example, Patent Document 1 and Patent Document 2 contain matsutake. Various antitumor substances have been disclosed. In Patent Document 1, Emitanin-5-A, Emitanin-5-B, Emitanin-5, which are separated and purified from an extract obtained by extracting a liquid culture of matsutake mycelium with hot water or a dilute alkaline solution. It is disclosed that C and emitanin-5-D have an inhibitory effect on the growth of sarcoma 180 cells. Patent Document 2 discloses that a protein having a molecular weight of 20 to 210,000 (subunit molecular weight = 10 to 110,000) separated and purified from an aqueous extract of Matsutake fruit body has antitumor activity. Yes.

  Further, for example, Patent Document 3 discloses that matsutake mycelium itself is used as a pharmaceutical composition instead of the separated and purified product as described above. In Patent Document 3, matsutake (for example, mycelium, culture, or fruiting body), hot water extract of matsutake or dried product thereof, or alkaline solution extract of matsutake or dried product thereof, and pharmaceutically A pharmaceutical composition for promoting recovery from stress loading, comprising an acceptable carrier is disclosed. The dosage forms include powders, fine granules, granules, tablets, capsules, suspensions, emulsions, syrups, extracts, or pills, or injections, liquids for external use, and ointments. Non-oral agents such as suppositories, suppositories, topical creams, or eye drops are exemplified, and these oral agents include, for example, gelatin, sodium alginate, starch, corn starch, sucrose, lactose, glucose, mannitol, Excipients and binders such as carboxymethylcellulose, dextrin, polyvinylpyrrolidone, crystalline cellulose, soybean lecithin, sucrose, fatty acid ester, talc, magnesium stearate, polyethylene glycol, magnesium silicate, anhydrous silicic acid, or synthetic aluminum silicate , Disintegrant, surfactant, lubricant, fluidity promoter, diluent, preservative, coloring , Perfumes, flavoring agents, stabilizers, with humectants, preservatives, or antioxidants, etc., it is disclosed that can be produced by the usual method. However, in the example of Patent Document 3, the physiological activity is evaluated using a dried powder of a hot water extract of matsutake or a dried powder of an alkaline solution of matsutake. There is no description about the specific prescription and manufacturing method when using itself.

Japanese Patent Publication No.57-1230 Japanese Patent No. 2767521 International Publication No. 02/30440 Pamphlet

  So far, matsutake mycelium has generally been provided in the form of granular dry powder, but as an oral preparation, tableting is preferable from the viewpoint of ease of drinking and dose management. When the present inventor tried to tablet the matsutake mycelium itself, it was found that the disintegration was extremely poor when tableting was performed without adding other compounding agents. For example, if a matsutake mycelium tablet that does not contain a compounding agent is left in water, water immediately enters from the surface, but the surface part is in a gel state, so water cannot enter into the interior, and as a result, It was thought that the disintegration was inferior. In addition, a storage test was conducted on the tablets (that is, tablets obtained by tableting without adding other compounding agents) under conditions of 40 ° C./75% relative humidity (RH) and 25 ° C./60% RH. In this case, degradation over time and changes in color tone were observed.

  When a matsutake mycelium-containing tablet is taken orally, it is important to adopt a formulation or manufacturing method that allows the tablet to disintegrate properly in the stomach or digestive tract. Moreover, in order to ensure sufficient quality in the long-term distribution (at least 1 year, desirably 2 years, more desirably 3 years), it is necessary to have sufficient stability. However, it has not been easy to achieve both good disintegration and stability for the matsutake mycelium.

  Accordingly, an object of the present invention is to provide a matsutake mycelium-containing tablet having good disintegration and stability.

The above-mentioned problem can be solved by a matsutake mycelia-containing tablet characterized by comprising a matsutake mycelium and a cellulosic polymer base material according to the present invention.
According to a preferred embodiment of the tablet of the present invention, the cellulosic polymer base material contains one or both of crystalline cellulose and powdered cellulose.

  The tablet of the present invention has good disintegration and stability. More specifically, in the disintegration test based on the Japanese Pharmacopoeia disintegration test method, it disintegrates within 30 minutes. Therefore, when the tablet of the present invention is taken orally, the tablet disintegrates completely in the stomach. In addition, since it is stable for at least 6 months or more in a storage test at 40 ° C./75% RH, the tablet of the present invention can guarantee quality sufficient for distribution as food.

  When the present inventor examined various disintegrants, the content of the matsutake mycelium, which is an active ingredient, is higher when the cellulosic polymer base material is used as a carrier than when other disintegrants are used. It was found that even when it exceeds 45% by weight, good disintegration is exhibited. This result shows that even when the content of the carrier is relatively lowered, the disintegrating action can be sufficiently exerted when the cellulosic polymer base material is used as compared with other disintegrants. ing. Such knowledge is completely unexpected even if the cellulosic polymer base material itself is well known as a disintegrating agent or even a person skilled in the art, and the present invention is based on such knowledge.

Hereinafter, the present invention will be described in detail.
The tablet of the present invention contains matsutake mycelium as an active ingredient, and further contains at least a cellulosic polymer substrate as a carrier that imparts good disintegration and stability.

  Examples of matsutake mycelium that can be used as an active ingredient in the tablet of the present invention include natural mycelia of matsutake, or mycelia obtained by culture (that is, cultured mycelium). Matsutake mycelium has various physiological activities such as antitumor activity (Japanese Patent Publication No. 57-1230, Japanese Patent No. 2776721), immune enhancement activity (International Publication No. 01/49308 pamphlet), or stress load recovery promotion. It is known to have activity (WO 03/070264 pamphlet) and the like.

  When natural matsutake mycelium is used, for example, natural mycelium can be used as it is, or mycelia obtained by removing water from natural mycelium by an appropriate means (for example, freeze-drying). It can also be used in the form of a dried product, and can also be used in the state of a dried mycelium powder obtained by pulverizing the dried mycelium. When the cultured mycelium is used, for example, the mycelium obtained by culturing and the medium (Broth) may be used in a state in which the medium is removed by an appropriate removal means (for example, filtration). Alternatively, the mycelium after removing the medium can be used in the form of a dried mycelium from which water has been removed by an appropriate means (for example, freeze-drying). Can be used in the state of a pulverized mycelium dry product powder. Especially, it is preferable to use the mycelium of the state which pulverized the dried mycelium from the point of ensuring the workability at tablet molding and uniformity.

  The content (as dry weight) of the matsutake mycelium contained in the tablet of the present invention is not particularly limited as long as desired disintegration and stability are obtained, but is usually 5 to 80% by weight. , Preferably 5 to 65% by weight, more preferably 5 to 50% by weight.

  Examples of the cellulose-based polymer base material that can be used as a carrier in the tablet of the present invention include crystalline cellulose, powdered cellulose, carmellose or a salt thereof (for example, carmellose calcium, carmellose sodium), a cellulose derivative (for example, hydroxy Propylmethylcellulose, methylcellulose, and ethylcellulose), and crystalline cellulose or powdered cellulose is preferred, and crystalline cellulose and powdered cellulose are more preferably used in combination in terms of obtaining good disintegration.

  The tablet of the present invention can further contain a carrier other than the cellulosic polymer base material as a carrier. Examples of the carrier include a carrier capable of imparting good disintegration property, such as starch base material (for example, corn starch, potato starch), lactose, or appropriate binding property and / or good fluidity. Carriers that can be applied, such as pregelatinized starch, glycerin fatty acid ester, starch syrup (eg reduced maltose starch syrup), sucrose fatty acid ester, propylene glycolate, citrate, calcium citrate, calcium phosphate Can be mentioned. The tablet of the present invention can contain one or more carriers other than the cellulosic polymer base material as long as desired disintegration and stability are obtained.

The content of the carrier contained in the tablet of the present invention is not particularly limited as long as desired disintegration and stability can be obtained, but is usually 20 to 95% by weight, preferably 35 to 95% by weight. %, More preferably 50 to 95% by weight.
The content of the cellulosic polymer base material contained in the tablet of the present invention is not particularly limited as long as desired disintegration and stability can be obtained. % By weight, preferably 10 to 80% by weight.

In the tablet of the present invention, when crystalline cellulose is used as the cellulosic polymer substrate, the content is not particularly limited as long as desired disintegration and stability are obtained, but with respect to the tablet weight. The amount is usually 5 to 90% by weight, preferably 10 to 80% by weight.
In the tablet of the present invention, when powdered cellulose is used as the cellulosic polymer substrate, the content is not particularly limited as long as desired disintegration and stability are obtained, but the tablet weight is Usually, it is 1 to 50% by weight, preferably 2 to 30% by weight.
In the tablet of the present invention, when crystalline cellulose and powdered cellulose are used in combination as the cellulosic polymer base material, the total content thereof is not particularly limited as long as desired disintegration and stability are obtained. The amount is usually 5 to 90% by weight, preferably 10 to 80% by weight, based on the tablet weight.

In the tablet of the present invention, when starch syrup (for example, reduced maltose starch syrup) is used as a carrier other than the cellulosic polymer base material, the content is particularly limited as long as desired disintegration and stability are obtained. However, it is usually 5 to 90% by weight, preferably 10 to 80% by weight, based on the tablet weight.
In the tablet of the present invention, when pregelatinized starch is used as a carrier other than the cellulosic polymer base material, its content is not particularly limited as long as desired disintegration and stability are obtained. It is 0.1-20 weight% normally with respect to a weight, Preferably it is 0.1-1 weight%.

  The tablet of the present invention can be prepared according to an ordinary formulation method, except that matsutake mycelium is used as an active ingredient and a cellulosic polymer base material is used as a carrier. For example, as the granulation method, a known granulation method such as a fluidized bed granulation method, an agitation granulation method, or an extrusion granulation method can be used. The fluidized bed granulation method is preferable in that the disintegration property of the tablet after tableting molding can be maintained well.

  When using the fluidized bed granulation method, for example, an appropriate amount of matsutake mycelium, which is an active ingredient, and an appropriate amount of carrier are put into a fluidized bed granulator, mixed, and then sprayed with water or a binder solution. The tablet of the present invention can be prepared by using a granule which has been granulated and then dried, and then compressed with a tableting machine. When using a plurality of carriers, an appropriate amount of matsutake mycelium as an active ingredient and an appropriate amount of carrier (a part of the plurality of carriers) are put into a fluid bed granulator, mixed, and then mixed with water. Alternatively, the binder solution is sprayed and granulated, and the dried granules are mixed with an appropriate amount of carrier (a carrier other than the carrier previously added) and mixed, and then tableted with a tableting machine. Tablets can be prepared. In this case, after charging into the fluidized bed granulator, a part of the plurality of carriers can be sprayed as an aqueous solution into the fluidized bed granulator.

  More specifically, for example, when using crystalline cellulose, powdered cellulose, powdered reduced maltose starch syrup, pregelatinized starch, and glycerin fatty acid ester as a plurality of carriers, an appropriate amount of matsutake mycelium as an active ingredient, and powder reduction After putting maltose starch syrup and crystalline cellulose into the fluidized bed granulator, granulate while spraying the pregelatinized starch aqueous solution (for example, 1% pregelatinized starch aqueous solution) into the fluidized bed granulator, The powdery cellulose and glycerin fatty acid ester are added and mixed, and then tableted by a tableting machine to prepare the tablet of the present invention.

  When using the stirring granulation method, for example, an appropriate amount of matsutake mycelium, which is an active ingredient, and an appropriate amount of carrier are put into an agitation granulator, and granulated by spraying water or a binder solution. The tablet of this invention can be prepared by tableting the granule obtained by drying this with a tableting machine.

  When the extrusion granulation method is used, for example, after mixing an appropriate amount of matsutake mycelium, which is an active ingredient, with an appropriate amount of carrier, adding water or a binder solution and kneading, this is then extruded granulation. The tablet of the present invention can be prepared by putting the granules into the machine and granulating them, and then drying the resulting granulated product and compressing the granules obtained with a tableting machine.

  The disintegration property of the tablet of the present invention can be evaluated by, for example, a disintegration test based on the Japanese Pharmacopoeia Disintegration Test Method (14th revised Japanese Pharmacopoeia Manual, General Test Method, 58, Disintegration Test Method). For example, the disintegration tester specified in the Japanese Pharmacopoeia Disintegration Test Method can be used, and water can be used as a test solution, and evaluation can be performed according to the section of the tablet of the Japanese Pharmacopoeia Disintegration Test Method.

  The stability of the tablet of the present invention is determined, for example, by the “Stability Test Guideline” (http: The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) (http: Based on: //www.nihs.go.jp/dig/ich/quality/q1a/q1a_jp.html), for example, long-term storage test (temperature: 25 ° C., humidity: 60% RH), acceleration test ( Temperature: 40 ° C., humidity: 75% RH). When evaluating the stability in a shorter period of time, it is also possible to evaluate it under conditions of higher temperature (for example, 50 ° C. or 60 ° C.) and / or high humidity (for example, 90% RH).

  EXAMPLES Hereinafter, the present invention will be specifically described by way of examples, but these do not limit the scope of the present invention.

Example 1: Manufacture of tablets
In this example, tablets having the formulation shown in Table 1 were prepared according to the following procedure.
As the matsutake mycelium, Matsutake FERM BP-7304 strain described in International Publication WO02 / 30440 was used in a dry powder state. The Matsutake Ferm BP-7304 strain is the National Institute of Advanced Industrial Science and Technology, Patent Biological Depositary Center (formerly the National Institute of Biotechnology, Institute of Biotechnology, 1-chome, Tsukuba, Ibaraki, Japan It has been deposited since September 14, 2000 at No. 1 Central No. 6)].

  The matsutake mycelium, powdered reduced maltose starch syrup, and crystalline cellulose were weighed and then put into a fluidized bed granulator and sprayed with a 1% pregelatinized starch aqueous solution for granulation. Powdered cellulose and glycerin fatty acid ester were added to the obtained granules and mixed, and then tableted by a tableting machine to obtain tablets.

<< Example 2: Evaluation of tablets >>
(1) Disintegration test About the tablet of this invention prepared in Example 1, when disintegration property in water was investigated by the Japanese Pharmacopoeia disintegration test method, the time required for disintegration was 16.5 minutes to 17.7 minutes. (Average: 17.3 minutes).

(2) Stability test The tablet of the present invention prepared in Example 1 was bottle-packaged, and an accelerated test (40 ° C / 75% RH) for 6 months was performed. When the tablet weight, disintegration test, properties, tablet hardness, loss on drying (1 g, 105 ° C., 6 hours), pH, and nutritional components were evaluated, it was confirmed to be stable.

  The matsutake mycelium-containing tablet of the present invention can be applied to medicines or foods using various physiological activities of the matsutake mycelium.

Claims (2)

  A matsutake mycelia-containing tablet comprising a matsutake mycelium and a cellulose polymer base material.   The matsutake mycelium-containing tablet according to claim 1, wherein the cellulose-based polymer base material contains one or both of crystalline cellulose and powdered cellulose.