JP2022136301A - Solid preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a solid preparation that resists a change in color while containing ang-khak and/or a processed product thereof.

SOLUTION: The present invention discloses a method for preventing discoloration of a solid preparation containing (A) ang-khak and/or a processed product thereof. The solid preparation contains, in addition to the component (A), (B) an additive selected from the group consisting of cellulose and derivatives thereof, milk protein, oligosaccharides, sugar alcohols, edible processed oil and fat, thickening polysaccharides, and calcium stearate, so that it is possible to prevent discoloration of a solid preparation containing ang-khak and/or a processed product thereof.

SELECTED DRAWING: None

COPYRIGHT: (C)2022,JPO&INPIT

Description

TECHNICAL FIELD The present invention relates to a solid preparation containing monascus and/or a processed product thereof and having suppressed discoloration.

Monascus is a fermented rice malt obtained by inoculating and fermenting cereals with monascus, and has long been used as a food material or brewing material in China and other countries. In addition, it has been reported that monacolin K contained in red yeast rice exhibits a cholesterol-improving effect (Non-Patent Documents 1 and 2), and red yeast rice is used as a functional ingredient in formulations such as supplements. .

Preparations containing red yeast rice have been studied to improve their safety and functionality. For example, a technique for producing red yeast rice that does not co-produce the toxic substance citrinin (Patent Document 1
), a technique for producing red yeast rice with a high content of monacolin K (Patent Document 2), and a technique for obtaining an extract containing a high concentration of monacolin K from red yeast rice (Patent Document 3).

Fermentation Engineering Vol.64 No.6 1986 Japanese Journal of Clinical Nutrition Vol.22 No.3 2000

JP-A-07-274978 JP-A-2000-106835 JP-A-2002-27996

Since red yeast rice is easily soluble in the body, it is generally formulated as a solid preparation. However, solid formulations containing monascus have poor formulation stability and are prone to discoloration due to light and/or heat.

Accordingly, it is an object of the present invention to provide a solid preparation containing red yeast rice and/or a processed product thereof and having suppressed discoloration.

As a result of intensive studies, the present inventors found that discoloration of solid preparations containing red yeast rice and/or processed products thereof can be suppressed by adding predetermined additives to the solid preparations.

That is, the present invention provides inventions in the following aspects.
Section 1. From the group consisting of (A) red yeast rice and/or processed products thereof, and (B) cellulose and derivatives thereof, milk proteins and digests thereof, oligosaccharides, sugar alcohols, edible processed oils and fats, polysaccharide thickeners, and calcium stearate A solid formulation containing selected additives.
Section 2. Item 2. The solid preparation according to Item 1, wherein the amount of component (A) is 2% by weight or more.
Item 3. (A) A method for suppressing discoloration of a solid preparation containing monascus and/or a processed product thereof, wherein in the solid preparation, together with the component (A), (B) cellulose and its derivatives, milk protein, oligosaccharides , sugar alcohols, edible processed oils and fats, polysaccharide thickeners, and calcium stearate.

According to the present invention, there is provided a solid preparation containing red yeast rice and/or a processed product thereof and having suppressed discoloration.

1. Solid preparation The solid preparation of the present invention comprises (A) red yeast rice and/or its processed product (hereinafter also referred to as "(A) component"), and (B) cellulose and its derivatives, milk protein and its digestion. oligosaccharides, sugar alcohols, edible processed oils and fats, thickening polysaccharides, and additives selected from the group consisting of calcium stearate (hereinafter referred to as "(B) component" or "predetermined additive"
Also notated. ) and is characterized by containing. Discoloration is suppressed in the solid preparation of the present invention. The solid preparation of the present invention is described in detail below.

(A) Monascus and/or Processed Products Thereof The solid preparation of the present invention contains monascus and/or processed products thereof as component (A). Red yeast rice is a fermented rice malt made by adhering monascus to cereals.

The monascus used in the production of the monascus used in the present invention belongs to the Monascaceae family.
Any filamentous fungus belonging to e) may be used. Examples of filamentous fungi belonging to the Aspergillus family include:
Examples include filamentous fungi belonging to the genus Monascus and the genus Basipetospora, preferably the genus Monascus.

Examples of filamentous fungi belonging to the genus Monascus include M. pilosus
), Monascus purpureus (M. purpureus), Monascus pubigeru (M. pubigeru
s), M. anka, M. serorubescens
), M. rubellus, M. kaoliang
, Monascus rubiginosus (M. rubiginosus), Monascus major (M. major)
, Monascus ruber (M. ruber), Monascus paxii (M. paxii), Monascus ruber
M. fuliginosus, M. vitreus, M. barkeri, Monascus sp., and variants or mutants thereof. Monascus used in the present invention may be produced using one type of Monascus, or may be produced by combining two or more types of Monascus. Among these monascus, Monascus pyrosus is preferred.

The type of cereal used as a raw material for red yeast rice used in the present invention is not particularly limited as long as it is edible and can be fermented by red yeast rice. Wheat, barley, rye, oats and other barley, soybeans (white soybeans, black soybeans, green soybeans, etc.)
, these defatted soybeans, and beans such as these hypocotyls. The monascus used in the present invention may be produced using one type of grain, or may be produced by combining two or more types of grains. Among these grains, rice is preferred, and polished rice is more preferred.

Monascus can be produced by a conventional method using monascus and cereals. Specifically, monascus can be produced by inoculating monascus in steamed (cooked or steamed) cereals and statically culturing under aerobic conditions of about 20 to 40°C. In addition, grains used as raw materials may be subjected to chopping or pulverization before or after steaming, if necessary.

In the present invention, the fermented red yeast rice may be used as it is, or the fermented red yeast rice may be heated and
A processed product of red yeast rice that has been subjected to one or more treatments such as drying, crushing, crushing, grinding, and extraction may be used.

Examples of processed products of monascus include dried monascus, powder of dried monascus, fine granules of dried monascus, and dried monascus extract powder; paste of monascus; including concentrated extracts) and the like. Among these processed products of monascus, preferably dried products, more preferably dried monascus powder, dried monascus granules, and even more preferably dried monascus powder are mentioned. In addition, the monascus and enzymes contained in the processed product of monascus may be viable or in an active state, or may be inactivated by heat treatment or the like.

A commercially available product of red yeast rice can also be used. For example, powdered dried rice red yeast rice is sold under the trade names "V. Red yeast rice 3P-D" and "V. Red yeast rice 3P-D20" (both manufactured by Kobayashi Value Support Co., Ltd.). These commercially available products can be used.

In the solid preparation of the present invention, the content of component (A) is, for example, 2% by weight or more, more specifically 5 to 30% by weight, preferably 10 to 20% by weight.
Alternatively, the content of component (A) in the solid preparation of the present invention may be, for example, 40-99% by weight or 45-95% by weight.

(B) Predetermined Additives The solid preparation of the present invention contains, as components (B), cellulose and its derivatives, milk protein and its digest, oligosaccharides, sugar alcohols, edible processed oils and fats, thickening polysaccharides, and calcium stearate. Contains additives selected from the group consisting of Discoloration of the solid preparation containing component (A) is suppressed by including these predetermined additives.

Cellulose and its derivative cellulose are not limited as long as they play a role as an excipient in solid preparations, and various celluloses described in the Japanese Pharmacopoeia can be used. Moreover, what is used as a food additive can also be used. The form of cellulose is not particularly limited, and for example, crystalline cellulose (including microcrystalline cellulose) can also be used. The cellulose may also be used in the form of a mixture with other components, such as crystalline cellulose/carmellose sodium (a mixture of crystalline cellulose and carmellose sodium).

Cellulose derivatives include alkyl derivatives of cellulose such as methyl cellulose, ethyl cellulose and methyl ethyl cellulose; hydroxypropyl cellulose (HPC);
Hydroxypropyl derivatives such as hydroxypropylmethylcellulose (HPMC); carboxymethylcellulose (CMC, carmellose), and its calcium salts (carmellose calcium), potassium salts (carmellose potassium), sodium salts (carmellose sodium) and the like.

One of these celluloses and derivatives thereof may be used alone, or two or more of them may be used in combination. Among these cellulose and derivatives thereof, crystalline cellulose and hydroxypropyl derivatives of cellulose are preferred from the viewpoint of further improving the effect of suppressing discoloration.

The milk protein and digested milk protein thereof are not particularly limited as long as they are proteins derived from milk. There are no particular restrictions on the organisms from which milk is derived, and examples of milk include cow's milk and goat's milk. Specific examples of milk proteins include whey protein and casein.

The milk protein digest is not particularly limited as long as it is obtained by digesting the above milk protein with an endo-type protease. Endo-type proteases include, for example, bromelain, papain, alcalase, trypsin and the like. The hydrolysis rate of the milk protein digest (hydrolysis rate (%) is derived from (formol nitrogen content/total nitrogen content) x 100) is not particularly limited, but may be, for example, 5 to 10%. be done.

One of these milk proteins and digests thereof may be used alone, or two or more of them may be used in combination.

The oligosaccharide is not particularly limited as long as it has 2 to 20 monosaccharide bonds. Specific examples of oligosaccharides include sucrose, lactose, maltose, trehalose, turanose, cellobiose, malto-oligosaccharides, iso-malto-oligosaccharides, gentio-oligosaccharides, chitin-oligosaccharides, chitosan-oligosaccharides, straight-chain oligosaccharides, branched-chain oligosaccharides, raffinose, and galacto-oligosaccharides. sugar, fructooligosaccharide, milk oligosaccharide, soybean oligosaccharide, beet oligosaccharide, agar oligosaccharide (
agarooligosaccharide), sialyloligosaccharide, palatinose oligosaccharide, xylooligosaccharide, inulooligosaccharide, coupling sugar, nigerooligosaccharide, panose oligosaccharide, cellooligosaccharide,
pectin oligosaccharide, levan oligosaccharide, mannooligosaccharide, cyclic oligosaccharide (cyclodextrin), galactosyl lactose and the like.

One of these oligosaccharides may be used alone, or two or more of them may be used in combination. Among these oligosaccharides, agarooligosaccharides and cyclic oligosaccharides are preferred from the viewpoint of further improving the effect of suppressing discoloration.

Sugar alcohol The sugar alcohol is not particularly limited, but examples thereof include reduced starch sugar, reduced maltose and the like.

These sugar alcohols may be used individually by 1 type, and may be used in combination of multiple types. Among these sugar alcohols, from the viewpoint of further improving the effect of suppressing discoloration,
Preferred is reduced maltose.

Edible processed oil The edible processed oil is not particularly limited as long as it is a hardened oil. Hydrogenated oil is an edible processed fat that is solid at room temperature and produced by a method of hydrogenating fat. Oils and fats used as materials for such edible processed oils and fats may be either vegetable oils or animal oils and fats. Vegetable oils include soybean oil, rapeseed oil, palm oil, coconut oil, palm kernel oil, etc. Animal oils include whale oil,
fish oil, beef tallow, lard and the like.

These edible processed fats and oils may be used singly or in combination of multiple types. Among these edible processed oils and fats, from the viewpoint of further improving the effect of suppressing discoloration,
Hydrogenated rapeseed oil is preferred.

Polysaccharide thickener Polysaccharide thickener is not particularly limited, but examples include gum arabic, xanthan gum, carrageenan (e.g., kappa-type carrageenan, iota-type carrageenan, lambda-type carrageenan, etc.)
, galactomannans (e.g., locust bean gum, tara gum, guar gum, etc.), alginic acids (e.g., alginic acid, alginates (e.g., sodium alginate, potassium alginate, calcium alginate, etc.), alginate esters (e.g., propylene glycol alginate, etc.), etc. ), pectin (e.g., low methoxyl (LM) pectin, high methoxyl (HM) pectin), gellan gum (e.g., deacylated gellan gum, native gellan gum, etc.), agar, gelatin, tamarind seed gum, glucomannan,
Welan gum, psyllium seed gum, karaya gum, curdlan, pullulan, starch, furcelleran and the like.

These polysaccharide thickeners may be used singly or in combination of multiple types. Among these thickening polysaccharides, gum arabic, gellan gum, and pullulan are preferred from the viewpoint of further improving the effect of suppressing discoloration.

Calcium stearate As the calcium stearate, those listed in the Official Code of Food Additives can be preferably used.

In the solid preparation of the present invention, the total content of component (B) is, for example, 0.1% by weight or more, preferably 1 to 70% by weight, more preferably 1.5 to 60% by weight. ,
More preferably 10 to 50% by weight is mentioned.

In the solid preparation of the present invention, the ratio of the components (A) and (B) is determined according to the above content of each component. The content of component (B) per 1 part by weight is preferably 0.05 to 7 parts by weight, more preferably 0.1 to 5 parts by weight, still more preferably 0.2 to 4 parts by weight, still more preferably 0.2 parts by weight. 5~
3 parts by weight.

Other Ingredients The solid preparation of the present invention may contain, if necessary, other nutritional ingredients and/or pharmacological ingredients in addition to the components (A) and (B). Such nutritional ingredients and pharmacological ingredients are not particularly limited as long as they can be used in foods and/or pharmaceuticals. , seasonings, plant extracts (
components other than the above component (A)), antioxidants (other than the above component (A)), and the like. These components may be used singly or in combination of two or more. In addition, the content of these components is appropriately set according to the types of nutritional components and/or pharmacological components to be used, the application of the oral composition, and the like.

Furthermore, the solid preparation of the present invention may contain bases and/or additives, etc., if necessary, in order to prepare a desired dosage form. Such bases and additives are not particularly limited as long as they can be used in foods and/or pharmaceuticals. Examples include excipients, disintegrants,
Binders, lubricants and the like (both of which are other than the above component (B)). These components may be used singly or in combination of two or more. In addition, the content of these components is appropriately set according to the type of base and/or additive used, the application of the solid preparation, and the like.

Dosage Form/Formulation Form The dosage form of the solid preparation of the present invention is not particularly limited, but examples thereof include granules, fine granules, powders, tablets, capsules (hard capsules) and the like. Since the solid preparation of the present invention is excellent in the effect of suppressing discoloration, a suitable example in the case of a capsule is a capsule contained in a translucent capsule.

The solid preparation of the present invention can be appropriately accommodated in any container. Since the solid preparation of the present invention has an excellent effect of suppressing discoloration, suitable examples of the container include translucent containers and containers that are not individual packages that can be freely opened and closed (that is, opening and closing of the container inevitably causes the stored solid preparation to become unavoidable). type that is frequently exposed to the environment outside the container).

Specific examples of the form of the solid preparation of the present invention include foods and beverages and drugs for internal use (including quasi-drugs for internal use).

When the solid preparation of the present invention is to be in the form of a food preparation, the above components (A) and (B) may be prepared as they are or in combination with other food materials or additives into a desired form. Examples of such foods include general foods, foods for specified health uses, dietary supplements, foods with function claims, foods for the sick, and the like. The form of these foods and drinks is not particularly limited, but specific examples include supplements such as granules, fine granules, powders, tablets and capsules.

When the solid preparation of the present invention is made into a pharmaceutical formulation for internal use, the above components (A) and (B)
The ingredients may be formulated into the desired form either as such or in combination with other added ingredients. Specific examples of such medicines for internal use include granules, fine granules, powders, tablets, capsules and the like.

2. Method for Suppressing Discoloration As described above, component (B) can suppress discoloration of solid preparations containing component (A). More specifically, component (B) has the ability to suppress discoloration of a solid preparation containing component (A) due to at least one of heat and light. Therefore, the present invention further provides (A) a method for suppressing discoloration of a solid preparation containing red yeast rice and/or a processed product thereof, wherein in the solid preparation, (B) cellulose and There is also provided a method for suppressing discoloration by blending an additive selected from the group consisting of derivatives thereof, milk proteins, oligosaccharides, sugar alcohols, edible processed oils and fats, thickening polysaccharides, and calcium stearate.

In the method for suppressing discoloration of the present invention, details such as the types and amounts of components used are as shown in the section "1. Solid formulation" above.

EXAMPLES The present invention will be described in more detail below with reference to Examples, but the present invention is not limited to these Examples.

Solid preparations having the compositions shown in Tables 1 and 2 of Test Examples were prepared. Details of the components (A) and (B) shown in each table are as follows.

(A) Ingredient Red yeast rice: Powdered dried rice red yeast rice (trade name “3P-D20”, manufactured by Kobayashi Value Support Co., Ltd. This dry rice red yeast powder is made by fermenting white rice with Monascus pilosus. It is a dry powder of koji, and red yeast mold and enzymes are inactivated by heat treatment.)

(B) Component HPMC: Metrose 60SH-4001, Shin-Etsu Chemical Co., Ltd. HPC: NISSO HPC (HPC-SSL), Nippon Soda Co., Ltd. Crystalline cellulose: Crystalline cellulose FD-302, Asahi Kasei Co., Ltd. Whey protein: Wheyco W81 Instant, Nippon Shinyaku Co., Ltd. Agaro-oligosaccharide: Shionogiagaoligo, Shionogi Healthcare Co., Ltd. Reduced maltose: Amalty MR-51, Mitsubishi Corporation Life Sciences Co., Ltd. Hydrogenated rapeseed oil: Lovely wax-102, Kawaken Fine Chemicals Co., Ltd. Gum arabic: Instantgum, Nexira
Pullulan: Food additive pullulan, Hayashibara Co., Ltd. Calcium stearate: Aura Bright CA-66, NOF Corporation Calcium carbonate: Scallop powder, N.C. Corporation

Each component was bagged and mixed well and sieved through a 100 mesh screen. A solid formulation (powder) was obtained by placing the mixture in a bag and mixing again. The following discoloration suppression test was performed on the obtained solid preparation.

<Discoloration suppression test>
30 g of the solid formulation was divided into three test groups of 10 g each (control, temperature test group and light test group). For controls, a transparent bag (Seinichi Co., Ltd., Unipack [
E-4]), and then put it in an aluminum outer bag (Seinichi Co., Ltd., Lamizip [AL-1
8]), heat-sealed, and stored at 4°C for 1 week. The temperature test group was placed in the above transparent bag, further placed in the above aluminum outer bag, heat-sealed, and stored at 40° C. for one week. For the light test group, put the solid formulation in the above transparent bag, stretch it evenly, and store it in a place exposed to sunlight for 1 week (March 18, 2022 to March 25, 2022, Ibaraki City, Osaka Prefecture). did.

For each test group, using a color difference meter, the amount of color change between the control and the temperature test group (
Color change was quantitatively confirmed by measuring ΔE (temperature)) and the amount of color change (ΔE (light)) between control and light test groups. The results are shown in Tables 1 and 2.

As shown in Table 1, discoloration due to heat was confirmed in the solid preparation consisting of component (A) (Comparative Example 1). Discoloration of solid preparations due to heat was suppressed (each example). In addition, in the solid preparations consisting of component (B), the degree of discoloration due to heat was found to be greater, the same, or less than that of the solid preparations consisting of (A) (reference examples). In view of the degree of , the effect of suppressing discoloration due to heat in each example was remarkable. In view of the fact that when calcium carbonate, which is used as an excipient in solid preparations as well as the component (B), was used, the effect of suppressing discoloration due to heat was not observed and was significantly deteriorated (Comparative Example 11-1). , The effect of suppressing discoloration due to heat confirmed in each example is recognized as a unique effect by blending the component (B).

As shown in Table 2, discoloration due to light was confirmed in the solid preparation consisting of component (A) (Comparative Example 1). Discoloration of solid preparations due to light was suppressed (each example). In addition, the degree of discoloration due to light in the solid preparations consisting of component (B) was found to be greater, the same, or less than that of the solid preparations consisting of (A) (reference examples). In view of the degree of , the effect of suppressing discoloration due to light in each example was remarkable. Considering that when calcium carbonate, which is used as an excipient in solid preparations as well as component (B), was used, the effect of suppressing discoloration due to light was not observed and was significantly deteriorated (Comparative Example 11-1). , The effect of suppressing discoloration due to light, which was confirmed in each example, is recognized to be a unique effect by blending the component (B).

Claims (3)

A solid preparation comprising (A) red yeast rice and/or a processed product thereof and (B) calcium stearate, wherein the amount of component (B) is 0.1% by weight or more. The solid preparation according to claim 1, wherein the content of component (B) is 0.05 to 7 parts by weight per 1 part by weight of component (A). 3. The solid preparation according to claim 1, wherein the amount of component (A) is 2% by weight or more.