JP6532765B2 - Tablet containing quick acting ingredient and sustained ingredient - Google Patents

Description

  The present invention relates to a tablet comprising an immediate acting ingredient and a sustained ingredient.

An oral preparation containing a physiologically active ingredient dissolves in the stomach and is designed to absorb the active ingredient in the small intestine. In addition, in the case of a preparation containing a plurality of active ingredients, in which a component requiring immediate action and a component requiring persistence co-exist, the immediate action component exerts its action more rapidly, so that the action is sustained. The ingredients that need to be coated are coated with a water-insoluble substance such as shellac, and the ingredients that require immediate action are formulated to be rapidly disintegrated in the stomach and absorbed in the small intestine.
In addition, many capillaries are distributed in the oral cavity mucous membrane, and they are absorbed quickly by using a sublingual or buccal dosage form, and are transported by the bloodstream systemically without undergoing liver metabolism. It is known that the bioavailability is high. Many drugs have been proposed as immediate-acting tablets utilizing this mechanism.
Patent Document 1 discloses a technique for orally administering a sugar alcohol-coated drug granule as a fast disintegrating tablet. Patent Document 2 describes an orally disintegrating tablet having an inner core and an outer layer structure.
However, buccal administration is not very popular due to the unpleasant taste and irritation of the drug.

Japanese Patent Application Publication No. 2013-544230 WO 2010/087462

  An object of the present invention is to provide a tablet comprising an immediate acting ingredient and a sustained ingredient.

  The present inventor raises the body temperature of a subject who has been administered by oral administration during the course of research on a formulation containing a plurality of ingredients effective for dieting, and then administers various diet active ingredients to achieve the desired diet effect. Found a phenomenon that is sustained. And as a result of further examination, the present invention was made.

The main components of the present invention are as follows.
(1) A tablet comprising a water-soluble coating layer and an inner core, wherein the water-soluble coating layer contains a black ginger extract, and the inner core is one or more selected from gymnema, mulberry leaf extract, green tea extract, kidney bean extract tablets characterized that you containing substances.
(2) The tablet according to (1), wherein the water-soluble coating layer is a hydroxypropyl methylcellulose (HPMC) layer.
(3) The tablet according to ( 1) or (2), wherein the inner core is shellac coated for the purpose of imparting enteric properties.

  According to the present invention, a tablet comprising an immediate release ingredient and a sustained ingredient is provided.

It is a schematic diagram which shows the structure of the tablet of an Example. 1 shows the results of the taste test of Example 1. 7 shows the results of the taste test of Example 2. It is the result of the taste test of Comparative Example 1. It is the result of the taste test of Comparative Example 2. It is a result of a heat generation effect test. It is a result of the temperature change measurement over time by the thermometer of the forefinger tip performed in Experiment 4. FIG.

The present invention is a tablet comprising a water-soluble coating layer and an inner core, wherein the water-soluble coating layer contains a component which is required to exhibit immediate effect, and the inner core contains a component which acts continuously. The pill is characterized by
When the tablet of the present invention is blended with a component for dieting, the water-soluble coating layer is blended with a component having a temperature rising effect, the inner core is blended with a diet component acting continuously, and the component of the coating layer raises the body temperature. And promote energy consumption by the components of the inner core and exert a diet effect. The immediate acting component can be released in the oral cavity before being released in the stomach to obtain a faster effect.
The ingredient to be mixed in the coating layer of the diet preparation is any one or more ingredients of a black ginger extract, a ginger extract and a hihatsu extract, which have a temperature raising action.
The ingredient having a long-lasting effect, which is incorporated into the inner core of the diet preparation, is one or more substances selected from gymnema, persimmon leaf extract, green tea extract, chitosan and kidney bean extract.

  As the water-soluble coating layer, water-soluble polymer polysaccharides and cellulose derivatives can be used. Examples of high molecular weight polysaccharides include alginic acid, alginate, mannan and chitosans. As a cellulose derivative, hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) can be exemplified. HPMC is particularly preferred as a component of the water-soluble coating layer used in the present invention. Among the HPMCs, low viscosity products are particularly desirable. For example, TC-5 (Shin-Etsu Chemical Co., Ltd.) Metroles SE-06 (Shin-Etsu Chemical Co., Ltd.) can be exemplified. HPMC is a cellulose ether in which 2-hydroxypropyl group is introduced into methylcellulose (MC), and is the same as sodium carboxymethylcellulose (CMC-Na) and carboxymethylcellulose calcium (CMC-Ca) listed in the Food Additives Standard It is a derivative of cellulose (cellulose ethers) in the category and, like methylcellulose, widely used as a capsule base for general food additives or dietary supplements in Europe and the United States, a binder for tablets, or a coating agent There is. For general food use, for example, used as edible film, frozen pizza (prevention of moisture transfer from topping to dough, shape retention of topping), nut product (antioxidant effect), meat product (water retention, prevention of discoloration) ), Fried potatoes (preventing oil absorption), etc.

The water-soluble coating layer is preferably 0.5 to 10% by mass, preferably 1.0 to 5.0% by mass with respect to the tablet weight. In the water-soluble coating layer, in addition to the functional components, a plasticizer such as glycerin, a high sensitivity sweetener, or a masking agent such as lecithin may be blended, if necessary. The compounding amount of the masking agent may be set to an appropriate amount according to the characteristics of the functional component to be compounded.
The coating operation can be carried out by a known gelation coating method for producing enteric tablets. Moreover, the method used for coating a sugar-coated tablet may be used.

It is preferable to apply a water-insoluble coating such as shellac or zein as needed between the water-soluble coating layer and the coated inner core tablet. Since the water-soluble coating layer has low moisture absorption preventing and masking effects, it is necessary to protect and mask it by the non-water-soluble coating layer when the inner core is compounded with highly hygroscopic components and components with bitterness and astringency. is there. Particularly in the case of tablets for diet and incorporating substances that have absorption inhibitory effects, they should be coated with a water-insoluble coating with shellac to prevent these substances from being released in the oral cavity and causing discomfort. It is preferable to form a water-soluble coating layer.
In particular, in the case where the inner core is blended with gymnema, it is more preferable to coat the inner core with shellac in order to suppress the influence of the gymnema on taste.

  The components in the water-soluble coating layer that require immediate action can be selected appropriately in designing the formulation. When the preparation of the present invention is used as a diet, a substance having a temperature increasing action is blended. As a substance having a body temperature increasing action, any one or more of a black ginger extract, a ginger extract and a hihatsu extract is blended.

  Black ginger (black ginger) is a plant of the ginger family Banturus genus, and a scientific name is Kaempferia parviflora. It is distributed in Southeast Asia such as Thailand and is easily available from this area. In addition, since a black ginger extract is commercially available from Maruzen Pharmaceutical Co., Ltd., an extract extracted using water, a hydrophilic organic solvent, or a mixed solvent thereof may be used.

  Ginger is a ginger-like plant of the ginger family, and the spicy component Shogaol or (6) -shogaol is produced when ginger is dried or heated. Shogaol is known to have a blood flow improving effect, and a ginger extract containing shogaol is commercially available from Ikeda Saccharification Industry Co., Ltd., and may be used.

  Hihatsu (Piper longum) is an evergreen vine that is distributed in Southeast Asia, which belongs to the genus Pepper. The spikelets are thick and cylindrical, and are used as spices. The use site of Hihatsu used in the present invention is most preferably a fruit ear, but a root, a leaf, a stem, a flower or a mixture of these may also be used. As the extract of Hihatsu, an extract extracted using water, a hydrophilic organic solvent, or a mixed solvent thereof is commercially available from Maruzen Pharmaceutical Co., Ltd., and may be used.

Gymnema refers to an extract of the plant Gymnema sylvestre, which belongs to the family Galactica, and the main component is gymnemic acid. Gymnema is native to India, Southeast Asia, China, etc., and water or alcohol extract of its leaf is known to have sweetness suppressing effect and sugar absorption suppressing effect by the intestinal tract. The Gymnema-Sylvesta extract has an astringent bitter taste and suppresses the sensation of sugar and other sweet substances, and after taking it, it loses its sweetness for a while, so the taste of other foods is Lose.
Gymnema extract is commercially available from Dainippon Meiji Sugar Co., Ltd., and when it is used as a tablet for diet in the present invention, it is blended in the inner core.

As described above, in the case of a tablet in which gymnema is incorporated into the inner core, the inner core is coated with shellac.
Shellac is an exudate of the black scale insect, which is a natural material that is insoluble in water but soluble in organic solvents such as ethanol. Shellac is suitable as an enteric coating material because it is insoluble in acidic conditions but becomes soluble at pH above pH 6.5.
Coating with shellac is carried out by dissolving shellac in ethanol or a suitable organic solvent and spraying this onto the surface of the inner core tablet, or surface coating using a sugar-coated tablet coating apparatus. The coating amount of shellac is preferably 0.2 to 2.0% by mass, preferably 0.3 to 1.0% by mass with respect to the tablet weight.

The present invention will be described in detail below by showing test examples of tablets for diet and comparative examples.
[Example]
1. Production of Inner Core Tablet Each raw material weighed based on the formulation described in Table 1 below was mixed by a V-type mixer to obtain a tableted powder.
The tablets were produced on a rotary tableting machine (HATA AP-38). Tablets having a tablet weight of 250 mg and a hardness of about 10 kgf were obtained at a tableting speed of 30 rpm and a batting pressure of 1.3 t.

2. Shellac Coating Based on the formulation in Table 2 below, both Example 1 and Example 2 were coated with 1 mg (0.4%) shellac per tablet using Rack Glaze 10E (10% strength shellac solution) in the inner core did. As a coating machine, Powrex made Doria Coater DRC-500 for Example 1 and Powrex made Doria Coater DRC-1400 for Example 2 were used.

3. HPMC Layer Coating Based on the formulation in Table 2 above, all the ingredients other than Rack Glaze 10E were weighed, each ingredient was mixed, and the coating solution was prepared. In order to dissolve the black ginger extract uniformly in the coating solution, it is necessary to use water-containing ethanol as a solvent. Ethanol of 30% concentration was used as the solvent of the coating solution. As a coating machine, Example 1 used Powrex made Doria Coater DRC-500, and Example 2 used Powrex made Doria Coater DRC-1400.
The tablets of Example 1 and Example 2 obtained by the above-described operation have the structure shown in the schematic view of FIG.

4. Preparation of Tablet of Comparative Example Each raw material weighed based on the formulation of Comparative Example 1 and Comparative Example 2 described in Table 1 was mixed by a V-type mixer to obtain a tableted powder. The tablets were produced on a rotary tableting machine (HATA AP-38). Tablets having a tablet weight of 250 mg and a hardness of about 10 kgf were obtained at a tableting speed of 30 rpm and a battering pressure of 1.3 t.
Comparative Example 1 was finished as uncoated tablets, and Comparative Example 2 was coated with 1 mg shellac per tablet. A Powrex Doria Coater DRC-500 was used for coating.

5. Test Example 1
The tablets of Examples 1 and 2 and Comparative Examples 1 and 2 are tablets having the configuration of Table 3 below.

A taste test was conducted to evaluate the intraoral action of the tablet having the above constitution.
<Taste test (oral dissolution test)>
In each of the examples and comparative examples, a sensory evaluation test was conducted by five subjects for each formulation. Four tablets were licked in the oral cavity for 20 seconds and then swallowed with water. The taste of Black Ginger and Gymnema was evaluated in three ways: "feel", "slightly feel", and "not feel". Based on the design of the present invention, in the tablets of Examples 1 and 2, only the immediate-acting ingredient Black Ginger should be released in the oral cavity, and only the taste of Black Ginger should be felt.
The evaluation results of each preparation are shown in FIGS.
In the preparations of Examples 1 and 2, the taste of black ginger was strongly evaluated as "feel", and the taste of gymnema was evaluated as "slightly feel" or "not feel" (Fig. 2, Fig. 3).
On the other hand, the tablet of Comparative Example 1 (uncoated tablet) was evaluated as "feel" for both Black Ginger and Gymnema. Further, Comparative Example 2 (only shellac coating) resulted in "slightly feeling" or "not feeling" the taste of black ginger, and almost no black ginger was released. On the other hand, Gymnema divided evaluation from "feel" to "not feel" (Fig. 4, Fig. 5).
In Comparative Examples, both Black Ginger and Gymnema were released in the oral cavity, or Black Ginger was not released, but in Examples 1 and 2, it can be seen that only Black Ginger was released in the oral cavity. That is, it shows that only the component requiring immediate action was selectively released.

6. Test example 2
Heat generation test
The immediate efficacy of the tablets was tested.
Four tablets of Example 1 and Comparative Example 2 were licked in the oral cavity for 20 seconds and then consumed with water. The temperature between the left thumb and forefinger was measured at regular intervals after drinking. The temperature measurement used the thermometer (made by FLIR Systems). The measurement results are shown in FIG. 6 as the results of averaging the temperature increase values of five persons.
With the tablet of Example 1 (black ginger 5 mg incorporated in the water-soluble coating layer), a temperature rise was observed 5 minutes after dosing, and a maximum of 1.9 ° C. was observed. No significant temperature rise was observed in Comparative Example 2 (shellac coating).
From the results of Test Example 1 and Test Example 2 above, it is confirmed that in the tablet of the present invention, the components required to exhibit immediate action are absorbed in the oral cavity and acted systemically quickly to increase the body temperature. It was done.

7. Test Example 3
<Taste test (oral dissolution test) part 2>
In each of the examples and comparative examples, a sensory evaluation test was conducted by five subjects for each formulation. Four tablets were licked in the oral cavity for 20 seconds and then swallowed with water. While licking the tablet, the taste of the black ginger and the gymnema was evaluated in two ways, "feel" and "do not feel", and it was evaluated whether the body felt warm after taking the tablet. Furthermore, in order to evaluate the inhibitory effect on dysgeusia by gymnema, a 4% sucrose aqueous solution was taken after taking the tablet, and it was evaluated whether sweetness was not felt or not. Based on the design of the present invention, in the tablets of Examples 1 and 2, only the immediate-acting ingredient Black Ginger should be released in the oral cavity, and only the taste of Black Ginger should be felt.
The evaluation results of each preparation are shown in Table 4 below.

As shown in Table 4, in the preparations of Examples 1 and 2, the taste of black ginger was evaluated as "feel", and the taste of gymnema was evaluated as "not feel". On the other hand, although the preparations of Comparative Examples 1 and 2 did not feel the taste of black ginger, they were evaluated as "feeling" the bitter taste of gymnema, and the taste of gymnema could not be masked.
The rate at which the body felt warm after taking the tablet was the highest in Example 1, followed by the high in Example 2, and the lowest in the tablets of Comparative Example 1 and Comparative Example 2.
The occurrence of taste disorder due to gymnema occurred only in Comparative Example 1 in which the tablet was not provided with a coating layer, and did not occur in Examples 1, 2 and 2 in which Shellac Coat was applied.
From the above results, in Comparative Examples 1 and 2, while the sensational effect of Black Ginger is low, and problems such as the occurrence of dysgeusia due to Gymnema are observed, in the tablets of Examples 1 and 2, only Black Ginger is in the oral cavity. The effect of Black Ginger is exerted immediately. That is, the formulations of the examples show that only the components requiring immediate action were selectively released.

8. Test Example 4
Heat generation test 2
Further tests were conducted to confirm the immediate effect of the tablets. Tests were carried out in the case where four tablets of Example 1 and Comparative Example 2 were ingested as test groups and in the case where nothing was ingested as a control.
Immediately after drinking the tablet in the oral cavity for 20 seconds in a room at a room temperature of about 23 ° C. for 20 seconds and drinking with water, the left hand was immersed in water at 15 ° C. for 1 minute. The temperature of the left forefinger was measured at regular intervals to measure the degree of recovery of the left-hand temperature cooled with cold water. When measuring the temperature, a photograph of the left hand was taken using a thermometer "i5" (manufactured by FLIR Systems), and the temperature of the forefinger was determined using an analysis software "FLIR tools" (manufactured by FLIR Systems). The measurement results are shown in FIG. 7 as the results of averaging the temperature rise values of five people.
In any of the test groups, the temperature of the forefinger, which was 30 ° C. to 34 ° C. immediately before cold water loading, dropped to 20 ° C. to 21 ° C. immediately after cold water loading, and returned to the temperature before cold water loading after 10 minutes. The temperature change of Comparative Example 2 (only shellac coating) was the same as in the case of not taking anything, and returned to the original temperature in 10 minutes, while the tablet of Example 1 (5 mg of black ginger in the water-soluble coating layer) When the formulation was ingested, it showed a higher temperature than the other test groups from 2 minutes after cold water loading, and returned to almost the original temperature after 6 minutes.
It has been confirmed that Black Ginger, which is an immediate-acting component of the present invention, is rapidly absorbed and has an effect on the periphery (fingertips).

Claims (3)

A tablet comprising a water-soluble coating layer and an inner core, wherein the water-soluble coating layer contains black ginger extract, and the inner core comprises one or more substances selected from gymnema, mulberry leaf extract, green tea extract, kidney bean extract tablets characterized that you contained.   The tablet according to claim 1, wherein the water-soluble coating layer is a hydroxypropyl methylcellulose (HPMC) layer. The tablet according to claim 1 or 2, wherein the inner core is shellac coated for the purpose of imparting enteric properties.