JP2017125002A - Bitter taste suppressing method using mannitol powders - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide methods of suppressing bitter taste of bitter substances more effectively than conventional methods, for pharmaceuticals or various foods.SOLUTION: An obtained tablet by using, as a tablet raw material, mannitol powders of which 60% or more has a size of 75 μm or less and which has a specific surface area of 0.20 m/g or more to less than 0.64 m/g has a sweet taste starting properties, sweet taste sharpening properties, and sweet taste strength which are improved by the effect of a rapid dissolution rate, and can suppress the bitterness of a bitter substance taken together.SELECTED DRAWING: None

Description

  The present invention relates to a method for suppressing bitterness of a bitter substance using mannitol powder having a specific surface area and particle size as a raw material for tablets.

  Some drugs and foods have a bitter taste. Among the pharmaceutical ingredients, there are many substances having a bitter taste, and many of them give discomfort to the user. For this reason, various ideas have been made from the viewpoint of improving the QOL of the user, but there has been a demand for technical development for more effectively suppressing the bitterness of bitter substances. In addition, some foods have a bitter taste and do not like active eating because they contribute to health but have a bitter taste. Therefore, development of bitterness suppression technology not only for pharmaceuticals but also for various foods has been desired.

  Conventionally, as a method for suppressing bitterness, a fast-acting pharmaceutical preparation in which erythritol is blended as an essential component together with a bitter component has been invented (Patent Document 1), but the invention of Patent Document 1 describes the sweetness and bitterness of erythritol, a refreshing feeling, When erythritol could not be selected due to palatability, etc., it could not be applied.

  On the other hand, mannitol is widely used as a base for various foods and various pharmaceuticals, or an excipient for tablets and powders. Mannitol is a kind of sugar alcohol of hexose sugar, has excellent stability, is white crystalline powder, has no odor, has an appropriate sweetness and a refreshing feeling, and has excellent palatability. In addition, it has lower calories than sucrose and glucose, and has less reactivity with active ingredients such as pharmaceutical ingredients, so that it can be used for various drugs and is safe for the human body.

  In recent years, oral solid compositions of particles containing a bitter substance and particles containing a sweet substance have been developed, and a method for suppressing the unpleasant taste of medicinal ingredients and food ingredients has been disclosed (Patent Document 2). More specifically, among the particles containing an unpleasant taste component, the particle size of 150 μm or less is 7% or less of the entire composition, and the average particle size of the sweet substance is 150 μm or less to achieve the object. Is. As the sweet substance, mannitol is exemplified. However, in the invention of Patent Document 2, even when the average particle size of the mannitol powder is 150 μm or less, the bitterness suppressing effect may not be sufficient.

JP 2001-89396 A JP 2005-8640 A

  This invention is invented in view of this situation, and it aims at providing the method of suppressing the bitterness of a bitter substance more effectively than before.

  As a result of diligent research to solve the above problems, the present inventors established a method for suppressing the bitter taste of bitter substances using mannitol powder having a specific surface area and particle size as a raw material for tablets. It came to be completed.

More particularly, the present inventors is a 75μm or less of the particles more than 60%, a specific surface area using a mannitol powder is less than 0.20 m ² / g or more 0.64 m ² / g as tablet material, A method has been established that can improve bitterness more effectively than before by improving the sweetness rising method, sweetness sharpness, and sweetness intensity by the action of a high dissolution rate.

That is, the present invention is 75μm or less of the particles more than 60%, the specific surface area is bitterness suppression method using a mannitol powder is less than 0.20 m ² / g or more 0.64 m ² / g as tablet material .

  Although there is no restriction | limiting in particular as a bitter substance used as the object of this invention, A pharmaceutical component, a foodstuff, those combinations, etc. with a bitter taste are mentioned. For example, in the case of pharmaceutical ingredients, nourishing tonics, antipyretic analgesics, antipsychotics, anxiolytics, antidepressants, hypnotic sedatives, antispasmodics, central nervous system agonists, brain metabolism improvers, cerebral circulation improvers Antiepileptics, sympathomimetics, gastrointestinal drugs, antacids, anti-ulcers, antitussive expectorants, antiemetics, respiratory stimulants, bronchodilators, antiallergic drugs, dental and oral drugs, antihistamines, cardiotonics, arrhythmias Agents, diuretics, antihypertensive agents, vasoconstrictors, coronary vasodilators, peripheral vasodilators, hyperlipidemia agents, diuretics, antibiotics, chemotherapeutic agents, diabetics, osteoporosis Drugs, antirheumatic drugs, skeletal muscle relaxants, antispasmodic drugs, hormone drugs, alkaloid narcotics, sulfa drugs, gout drugs, anticoagulants, antineoplastic drugs, Alzheimer's disease drugs, etc. It is done. In addition, as for foods, food supplements called nutritional supplements, foods for specified health use, health functional foods such as nutritional functional foods, health foods and the like can be mentioned.

  Here, the bitter taste in the present invention refers to the bitter taste of the bitter taste that is felt until 10 seconds have elapsed after ingesting the bitter substance in the oral cavity, and the content of the bitter taste that is felt until 25 seconds have elapsed after 10 seconds have elapsed since ingestion. Say. As a method for ingesting a bitter substance, the bitter substance may be ingested as it is, or a bitter substance contained in a tablet or the like may be ingested.

The mannitol powder in the present invention, it is 75μm or less particles of 60% or more, as long as the specific surface area is less than 0.20 m ² / g or more 0.64 m ² / g, can be used without limitation More preferably, particles having a particle size of 50 μm or less are 80% or more. The specific surface area is a value measured using a specific surface area measuring apparatus, and specifically, is measured by a BET method by nitrogen gas adsorption using an automatic specific surface area measuring apparatus (Gemini 2375: manufactured by SHIMADZU). The particle size is a cumulative value in a volume-based distribution measured using a laser diffraction particle size distribution measuring device, and specifically, a laser diffraction particle size distribution measuring device (MICROTRAC MT3000: manufactured by Microtrack Bell) is used. To measure. In order to obtain the specific surface area and particle size in the mannitol powder of the present invention, for example, the raw material mannitol powder may be pulverized and classified as necessary.

  Furthermore, the mannitol powder according to the present invention can be granulated and granulated to be used as a raw material for tablets. The granulation method and granulation conditions in the step of preparing the granule are not particularly limited, but purified water, ethanol aqueous solution, aqueous solutions of various sugar alcohols such as mannitol, maltitol, xylitol, sorbitol, erythritol, hydroxypropylcellulose, methylcellulose, etc. Wet granulation using a binder selected from these binders is preferred. For example, a general fluidized bed granulator, stirring granulator, extrusion granulator, rolling fluidized bed granulator or the like can be used. . After granulation, if necessary, sieving and drying can be performed, and particle size can also be selected.

  Next, the manufacturing method of the tablet which concerns on this invention is demonstrated. For the tablet production method, a commonly used compression molding machine such as a single-shot tableting machine or a rotary tableting machine can be used. The raw materials for tablets of the present invention are used by mixing as appropriate, and are formed into tablets. The shape of the tablet is not particularly limited, and can be exemplified by round tablets, flat tablets, ordinary R tablets, Sumi square tablets, Sumi round tablets, sugar-coated tablets, two-stage R tablets, You can also In addition, although the mannitol powder in this invention can also be used as it is for the raw material for tablets, it is preferable to use it as a granule because it is easier to use. That is, by using it as a granule, it is possible to prevent the occurrence of tableting troubles such as capping phenomenon and sticking phenomenon that occur when tablets are obtained.

  In addition, the raw material for tablets according to the present invention can be included together with the mannitol powder of the present invention without limitation as long as it is a component that is usually used in foods and pharmaceuticals. For example, various acidulants such as ascorbic acid, citric acid and malic acid, high sweeteners such as acesulfame K, sucralose and aspartame, various sugar alcohols such as maltitol, xylitol, sorbitol and erythritol, mint, vanilla, grapefruit, matcha And other flavors and flavors, lubricants, disintegrants, disintegration aids, water-conducting agents, foaming agents, colorants, and other bases and food materials as well as pharmaceuticals Is possible. In particular, the addition of various flavors and flavors is preferable because the flavor of the mannitol powder is improved without being hindered by the rise of sweetness associated with the good mouthfeel.

  According to the present invention, by using mannitol powder having a specific specific surface area and particle size as a raw material for tablets, the bitterness of bitter substances can be suppressed more effectively than before.

  Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the following examples.

  In the examples, quinine sulfate, which is a bitter substance, was a product of Wako Pure Chemical Industries, Ltd., and caffeine was a product of Shiratori Pharmaceutical Co., Ltd. called caffeine (extract).

  In the examples, Kollidon CL-F, a disintegrating agent, is a product of BASF Japan, Magnesium stearate, a lubricant, is a product of Wako Pure Chemical Industries, and Grapefruit flavor, which is a flavor, is a dry-coated grapefruit. A product of Takada Incense Co., Ltd. called Flavor # 3261 was used.

  Furthermore, in the examples, the hydroxypropyl cellulose used as a binder was a product of Nippon Soda Co., Ltd. called HPC-SSL. Further, as the mannitol powder, products manufactured by Mitsubishi Corporation Food Tech Co., Ltd., Mannit K, Mannit P and Mannit S were used. Table 1 shows the measured values of average particle size, particle size, and specific surface area. In addition, an average particle diameter is the value of the median diameter in the volume reference | standard distribution measured using the laser diffraction type particle size distribution analyzer (MICROTRAC MT3000: Microtrac Bell make).

  Various mannitol powder materials listed in Table 1 were granulated with a fluidized bed granulator ("FLO-1" manufactured by Freund Sangyo Co., Ltd.) while spraying a hydroxypropyl cellulose solution having a concentration of 8% by weight as a binder. Mannitol granules were obtained. The granulation conditions were as follows: charged amount 500 g, set temperature: intake air 60 to 80 ° C., exhaust gas 30 to 35 ° C., binder solution 94 g, spray rate: 8 g / min (continuous spray). About the obtained mannitol granules, 180 mg of the mixed powder shown in the powder blending ratio table shown in Table 2 was prepared and used as a raw material for tablets. The quinine sulfate was mixed in advance with various mannitol granules. In tableting, the raw material for tablets is prepared by a small high-speed rotary tablet machine VIRGO (manufactured by Kikusui Seisakusho Co., Ltd.). Under these conditions, tableting was performed by the direct tableting method so that the tablet hardness was 5 kgf, and tablets were formed. Furthermore, sensory evaluation was performed about the obtained tablet.

  In the sensory evaluation, various mannitol tablets were evaluated using the Mannit S tablet as a reference product. Evaluation was performed using a panel of 8 persons for each mannitol tablet.

  The sensory evaluation of the tablets was performed as follows.

  The “bitterness” of the sample was evaluated with a score of 7 levels from very strong (−3 points) to the standard product to the same (0 points) to very weak (+3 points) as the standard product. Asked. In addition, the “grapefruit flavor” of the sample was evaluated based on a 7-point score that was very bad (−3 points) to the same as the reference product (0 points) to very good (+3 points). The value was determined. The results are shown in Table 3.

  From the sensory evaluation results, it was confirmed that both the Mannit C tablet and the Mannit P tablet were evaluated to be less bitter than the reference product.

  About the mannitol granule obtained in Example 1, 180 mg of the mixed powder shown in the powder blending ratio table shown in Table 4 was prepared and used as a raw material for tablets. Tableting was performed in the same manner as in Example 1. Furthermore, sensory evaluation was performed about the obtained tablet.

  In the sensory evaluation, an evaluation was made on what was simultaneously ingested 0.001 g of caffeine and various mannitol tablets, based on what was simultaneously ingested 0.001 g of caffeine and Mannitol S tablets. Evaluation was performed using a panel of 8 persons for each mannitol tablet.

  The sensory evaluation of the tablets was performed as follows.

  About the "bitterness" of the sample, it was evaluated by 7-point score from very strong (-3 points) to the standard (same as 0 points) to very weak (+3 points), and an average value was obtained. . The results are shown in Table 5.

  From the sensory evaluation results, it was confirmed that both the Mannit C tablet and the Mannit P tablet were evaluated to be less bitter than the standard.

  As described above, the method according to the present invention can more effectively suppress the bitterness of the bitter substance than before.

Claims (1)

And a 75μm or less particles of 60% or more, bitterness suppression method using a mannitol powder specific surface area is less than 0.20 m ² / g or more 0.64 m ² / g as tablet material.