JP2021001155A - Solid composition containing processed eucommia ulmoides - Google Patents

Abstract

To provide a technique to impart sufficient tablet hardness to a formulation comprising processed Eucommia ulmoides.SOLUTION: A solid composition comprising processed Eucommia ulmoides as well as nattokinase is subjected to tableting, resulting in a tablet having sufficient hardness for distribution and the like.SELECTED DRAWING: None

Description

The present invention relates to a solid composition containing a processed Tochu product and capable of providing a sufficient tablet hardness.

Eucommia ulmoides, a deciduous plant native to China, is listed in Shennong Ben Cao Jing as a crude drug. Currently, Eucommia ulmoides, which is used as a crude drug, is mostly native or cultivated in mainland China. Adult trees about 20 years old are cut down, the bark is peeled off, and the obtained bark is used for medicinal purposes. It is used as a raw material. As for the medicinal effects of Tochu, the Chinese medicine dictionary and the Chinese People's Republic of Medicine have the effects of "supplementing the liver and kidneys, strengthening the ribs, and relaxing the womb, and have acid pain in the lower back and back, and weakness in the legs (knee paralysis). , Residual urine, abnormal bleeding in women, premature miscarriage, high blood pressure ", etc., and contains iridoid compounds such as pinoresinol di-O-β-D-glucoside and other lignan compounds as medicinal ingredients. It is reported that there is. Since Tochu is widely known for its effectiveness, it has traditionally been eaten by cooking crude drugs or roasting leaves to make tea. In addition, various oral compositions utilizing the characteristics of the processed Tochu product have also been proposed (see, for example, Patent Documents 1 and 2).

On the other hand, the oral composition containing the processed Tochu product may be provided as tablets for easy ingestion. When an oral composition containing a processed Tochu product is provided as a tablet, it is important to provide sufficient tablet hardness in order to suppress surface abrasion and cracking during distribution (transportation). However, in the prior art, studies focusing on tablet hardness have not been sufficiently conducted for tablets containing a processed Tochu product.

International Publication No. 02/76240

The present inventor conducted various studies on tablets containing the processed Tochu product, and found that even if the processed Tochu product was tableted by a usual method, it was not possible to provide sufficient tablet hardness. Therefore, an object of the present invention is to provide a formulation technique that overcomes the above-mentioned drawbacks, contains a processed product of Eucommia ulmoides, and has sufficient tablet hardness.

As a result of diligent studies to solve the above problems, the present inventor has obtained a tablet having sufficient hardness to withstand distribution, etc. by tableting and molding a solid composition containing nattokinase together with a Tochu processed product. Found to be obtained. 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. A solid composition containing (A) Tochu processed product and (B) Nattokinase.
Item 2. Item 2. The solid composition according to Item 1, wherein the component (A) is a processed product of Eucommia ulmoides leaf.
Item 3. Item 2. The solid composition according to Item 1 or 2, wherein the component (A) is an extract of Eucommia ulmoides leaf.
Item 4. Item 2. The solid composition according to any one of Items 1 to 3, which is in the form of powder or granules and is used as a raw material for tablet molding.
Item 5. Item 2. The solid composition according to any one of Items 1 to 3, which is in the form of tablets and is a food product or an internal medicine.
Item 6. It is a method to improve the hardness of tablets containing processed Tochu products.
A method for improving tablet hardness, in which nattokinase is contained in a tablet together with a processed Tochu product.
Item 7. A tablet hardness improver used to improve the hardness of tablets containing eucommia processed products containing nattokinase as an active ingredient.

According to the solid composition of the present invention, even though it contains a processed Tochu product, it can be provided with sufficient hardness when it is made into a tablet, so that the tablet containing the processed Tochu product can withstand distribution and the like. It can be provided with physical strength.

1. 1. Solid Composition The solid composition of the present invention is characterized by containing a processed Tochu product (sometimes referred to as component (A)) and nattokinase (sometimes referred to as component (B)). Hereinafter, the solid composition of the present invention will be described in detail.

[Tochu processed product]
The solid composition of the present invention contains a processed Tochu product. Eucommia ulmoides oliver is a processed material of Eucommia ulmoides oliver. Specifically, crushed eucommia ulmoides (including raw, dried and roasted eucommia ulmoides) and eucommia extract (extract powder, granules) Eucommia ulmoides, etc.) and the like.

In the processed Tochu product, the site where Tochu is used is not particularly limited, and examples thereof include leaves, bark, fruits, seeds, petioles, xylem, roots, and rhizomes. These parts may be used alone or in combination of two or more. Among these, leaves are preferably mentioned. Hereinafter, the crushed product and extract powder of Eucommia leaf (sometimes referred to as Eucommia tea leaf) will be described.

The crushed product of Eucommia ulmoides leaves can be obtained by subjecting Eucommia ulmoides leaves to treatments such as steaming, kneading, drying, and roasting, if necessary, and then crushing the leaves.

The extract of Eucommia leaf can be obtained by subjecting Eucommia leaf to an extraction treatment to obtain an extract and then drying the extract.

The eucommia leaf used as an extraction raw material may be in a raw state as it is, or may be subjected to pretreatment such as crushing, cutting, steaming, kneading, drying, and roasting, if necessary. ..

The extraction treatment may be any general extraction method used for producing plant extracts, and examples thereof include solvent extraction treatment, supercritical extraction treatment, and steam distillation treatment. Among these, solvent extraction treatment is preferable.

Examples of the extraction solvent used in the solvent extraction treatment include water; lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol, n-propanol, isopropanol and n-butanol; and many alcohols such as propylene glycol and 1,3-butylene glycol. Valuable alcohols; ketones such as acetone; chain and cyclic ethers such as tetrahydrofuran and diethyl ether; polyethers such as polyethylene glycol; and mixtures thereof. Among these extraction solvents, water, a lower alcohol, and a mixture thereof, more preferably water, ethanol, and a mixture thereof, still more preferably water.

The solvent extraction treatment may be carried out by immersing or refluxing the Tochu leaf in the extraction solvent. For example, about 1 to 50 parts by weight of the extraction solvent is used per 1 part by weight of the Tochu leaf for about 5 minutes to several hours. It may be preferably carried out for about 10 to 90 minutes. The temperature conditions during the solvent extraction treatment may be, for example, room temperature (25 ° C.) to about 100 ° C., preferably about 60 to 100 ° C.

By removing the solid matter by solid-liquid separation after the extraction treatment, an extract of Eucommia ulmoides leaves can be obtained. The extract obtained by the extraction treatment is filtered as necessary; various chromatographies using a column packed with a carrier such as polystyrene gel (polystyrene / divinylbenzene copolymer, etc.), ion exchange resin, activated charcoal, etc. Extract powder is obtained by subjecting to the purification treatment of the above and then drying treatment. The drying treatment can be performed by, for example, spray drying, concentrated drying under reduced pressure, freeze drying and the like. In addition, the obtained extract powder may be molded into granules if necessary.

In the solid composition of the present invention, the content of the processed Tochu product is not particularly limited, and examples thereof include 5 to 90% by weight. More specifically, when the processed product of Eucommia ulmoides is a crushed product of Eucommia leaf, the content of the crushed Eucommia leaf is 7 to 90% by weight, preferably 10 to 90% by weight, more preferably 15. ~ 90% by weight can be mentioned. When the processed Eucommia leaf is an extract of Eucommia leaf, the content of the extract of Eucommia leaf is 5 to 90% by weight, preferably 10 to 90% by weight, and more preferably 15 to 90% by weight. ..

[(B) Nattokinase]
The solid composition of the present invention contains nattokinase. In this way, by using the Tochu processed product and nattokinase in combination, it is possible to provide sufficient hardness when made into tablets.

The nattokinase used in the present invention can be obtained by a known production method. Specific methods for producing nattokinase include a method of culturing Bacillus natto, a method of obtaining from a transformant incorporating a gene encoding nattokinase, a method of synthesizing by chemical synthesis, and the like. The nattokinase used in the present invention may be obtained by any production method, but from the viewpoint of reducing the production cost, the nattokinase obtained by culturing Bacillus natto is preferable.

The nattokinase used in the present invention may be a refined product, but may be in an unpurified state as long as it can be blended in foods and pharmaceuticals for internal use. For example, when nattokinase obtained by culturing Bacillus natto is used, it may be an extract of a culture of Bacillus natto. Further, the culture of Bacillus natto may be subjected to ion exchange chromatography, gel filtration chromatography, hydrophobic chromatography or the like to purify nattokinase, and the culture of Bacillus natto may be used as needed. It may be a product obtained by removing water or drying after being subjected to a crude purification treatment such as solid-liquid separation.

In addition, nattokinase is commercially available as a powder product, a crude product, a refined product, etc. to which an excipient or the like is added, and in the present invention, these commercially available products can also be used as the nattokinase.

Examples of the content of nattokinase in the solid composition of the present invention include 1 to 60,000 FU / g. From the viewpoint of further improving the hardness when formed into tablets, the content of nattokinase in the solid composition of the present invention is preferably 100 to 35,000 FU / g, more preferably 150 to 35,000 FU / g.

Further, in the solid composition of the present invention, the ratio of the eucommia processed product to the nattokinase may be within the range according to the content of each of the above-mentioned components. The ratio is as follows. From the viewpoint of further improving the hardness when made into tablets, nattokinase is preferably 3000 to 300,000 FU, and more preferably 4000 to 200,000 FU per 1 g of the Tochu processed product.

In the present invention, "FU" indicating the activity of nattokinase is a fibrin-degrading activity unit according to the standard of Bacillus subtilis culture extract food announced on January 15, 2003 by the Japan Health and Nutrition Food Association. ..

[lubricant]
The solid composition of the present invention preferably contains a lubricant in order to improve moldability into tablets. Specific examples of the lubricant include calcium stearate, magnesium stearate, talc, and hydrogenated vegetable oil. These lubricants may be used alone or in combination of two or more.

When the solid composition of the present invention contains a lubricant, the content thereof is not particularly limited, but is, for example, 0.5 to 10% by weight, preferably 0.5 to 8% by weight, more preferably 1. ~ 5% by weight can be mentioned.

[Other ingredients]
The solid composition of the present invention may contain other nutritional components and pharmacological components in addition to the above-mentioned components. Such nutritional components and pharmacological components are not particularly limited as long as they can be used in foods and medicines for internal use. For example, vitamins, amino acids, minerals, sugars, vegetable fats and oils, vegetable fats and oils, fatty acids, etc. Examples include fragrances, seasonings, vegetable extracts (other than black ginger extracts), antioxidants, hypoglycemic agents, anticholesterol agents, immunostimulators and the like. These components may be used alone or in combination of two or more.

Further, the solid composition of the present invention may further contain a base, additives and the like in addition to the above-mentioned components, if necessary. Such bases and additives are not particularly limited as long as they can be used in foods and pharmaceuticals, and for example, water, lower alcohols, higher alcohols, water-soluble polymers, surfactants, polyhydric alcohols, etc. Examples thereof include pH adjusters, buffers, antioxidants, preservatives, thickeners, chelating agents and the like. These may be used individually by 1 type, and may be used in combination of 2 or more type.

[Dosage form / form]
Dosage forms of the solid composition of the present invention include powders, granules, tablets and the like.

When the solid composition of the present invention is a powder or granule, it is used, for example, as a raw material for tablet molding. When the solid composition of the present invention is granulated, it can be carried out by a known method such as city wet granulation.

The solid composition of the present invention in the form of tablets can be obtained by tableting the solid composition of the present invention in the form of powder or granules. Further, the tablets may be coated as needed to be coated tablets. When the solid composition of the present invention is a tablet, it may be used as a supplement for general foods and drinks, foods for specified health uses, dietary supplements, functional foods, foods for the sick, and the like. It may be used as an internal medicine.

The tableting conditions when the solid composition of the present invention is made into tablets are not particularly limited, but for example, the tableting pressure may be set to about 8 to 15 kN, preferably about 8 to 13 kN.

When the solid composition of the present invention is a tablet, the tablet hardness thereof is specifically 100 N or more, preferably 100 to 300 N, and more preferably 100 to 200 N. In the present invention, the tablet hardness is a value measured by a load cell type tablet hardness meter (test speed of breaking terminal 0.5 mm / sec).

2. 2. Method for Improving Tablet Hardness / Agent for Improving Tablet Hardness The method for improving tablet hardness of the present invention is a method for improving the hardness of a tablet containing a Tochu processed product, in which the tablet contains nuttokinase together with the Tochu processed product. It is a feature.

Further, the tablet hardness improving agent of the present invention is an agent used for improving the hardness of tablets containing a Tochu processed product, and is characterized by containing nattokinase as an active ingredient.

The types and amounts of the components used in these tablet hardness improving methods and tablet hardness improving agents, specific embodiments, etc. are as described in the column of "1. Solid composition" above.

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

Production Example: Preparation of Eucommia leaf extract powder The "Eucommia leaf extract powder" used in the examples, comparative examples, and formulation examples shown below was produced by the following method.

5 kg of fresh leaves of Tochu were steamed at 110 ° C. for 90 seconds with a band steamer for producing Japanese tea. Fresh leaves were put into the machine from the inlet of the band steamer, steam was applied from the upper and lower steam supply devices while moving on the conveyor, and steamed at 110 ° C. for 90 seconds. Next, the steamed eucommia leaves were kneaded for 30 minutes using a kneading machine, and then the kneaded material was dried at 80 ° C. for 5 hours with a water content of 5% or less using a drier. Then, it was roasted at 110 ° C. for 30 minutes using a leaf roasting machine (IR-10SP type: Terada Seisakusho). 1 kg of roasted Tochu tea leaves was put into 15 kg of hot water at 90 ° C. and extracted at 90 ° C. for 30 minutes to obtain 14 kg. Then, the mixture was filtered using a 150 mesh filter, and the filtrate was cooled to 5 ° C. and left overnight. The supernatant was taken out, and the filtrate was concentrated under reduced pressure at 50 ° C. to obtain 1 kg. The concentrate is treated with a centrifuge manufactured by Kubota Co., Ltd., the precipitate is removed by centrifugation at a rotation speed of 1800 rpm, and the obtained supernatant is heat-sterilized (85 ° C., 2 hours) to extract Tochu leaf water. Obtained an extract. The concentrated extract solution was dried by a spray-drying method to obtain Tochu leaf extract powder (300 g).

Test Example 1
Tablets having the compositions shown in Table 1 were produced. The specific manufacturing method is as shown below. First, a predetermined amount of Tochu tea extract powder, nattokinase, and calcium stearate were mixed to prepare a solid composition. Next, the obtained solid composition was tableted at a tableting pressure of 10 kN using a tableting machine (20 kN table press TB-20H, manufactured by NPa System Co., Ltd.), and tablets (diameter: about 8 mm, thickness: about 4 mm). Got

For each of the obtained tablets, the hardness of the tablets was measured using a load cell type tablet hardness meter PC-30 (Okada Seiko Co., Ltd.) at a test speed of a breaking terminal of 0.5 mm / sec.

The results obtained are shown in Table 1. In the solid composition containing Tochu tea extract powder and a lubricant, when tableted into tablets, the tablet hardness was about 70 N, and it was not possible to provide a hardness that could withstand distribution (Comparative Example 1). Further, even in the solid composition containing nattokinase powder and a lubricant, the tablet hardness after tableting was insufficient (Comparative Example 2). On the other hand, when a solid composition containing nattokinase powder and a lubricant was tableted together with Tochu tea extract powder, the tablet hardness was remarkably high and had sufficient hardness to withstand distribution (Examples 1 to 1). 3).

Claims (7)

A solid composition containing (A) Tochu processed product and (B) Nattokinase. The solid composition according to claim 1, wherein the component (A) is a processed product of Eucommia ulmoides leaf. The solid composition according to claim 1 or 2, wherein the component (A) is an extract of Eucommia ulmoides leaf. The solid composition according to any one of claims 1 to 3, which is in the form of powder or granules and is used as a raw material for tablet molding. The solid composition according to any one of claims 1 to 3, which is in the form of tablets and is a food product or an internal medicine. It is a method to improve the hardness of tablets containing processed Tochu products.
A method for improving tablet hardness, in which nattokinase is contained in a tablet together with a processed Tochu product. A tablet hardness improver used to improve the hardness of tablets containing eucommia processed products containing nattokinase as an active ingredient.