Tablets and methods for improving their retronasal aroma

Abstract

To provide a tablet that can enhance retronasal aroma. [Solution] An oral or mouth-use tablet containing an ester-based fragrance and having a disintegration time of less than 9 minutes. The tablet is preferably a chewable tablet.

Description

Technical Field

[0001] The present invention relates to tablets and a method for improving their retronasal aroma.

Background Art

[0002] The aroma of foods and the like can be classified into those that can be felt only through the nose without putting them in the mouth (orthonasal aroma) and those that pass from the oral cavity to the nasal cavity when put in the mouth (retronasal aroma). Improving the retronasal aroma can lead to enhancing the product value of foods and the like.

[0003] On the other hand, some methods for improving the retronasal aroma have been proposed. For example, Patent Document 1 discloses an enhancer for retronasal aroma containing a specific dipeptide (γ-Glu-Abu, γ-glutamyl-2-aminobutyric acid). In Patent Document 2, it has been confirmed by sensory evaluation that adding rotundone, which is a citrus flavor enhancer, to a gum containing an orange flavor enhances the retronasal aroma.

[0004] On the other hand, as one form of foods, pharmaceuticals, and oral care products, preparations such as orally disintegrating tablets and chewable tablets are known. These preparations are tablets that are used by contacting with moisture and / or chewing in the oral cavity. Also, orally disintegrating tablets and chewable tablets containing a flavor component are known (see Patent Documents 3 and 4).

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

[0006] Research on retronasal aroma in foods and other products is still insufficient. For example, there are few studies reporting on the relationship between the composition and properties of food and its retronasal aroma. Furthermore, there have been no attempts to enhance the retronasal aroma of tablets, which are oral or oral preparations, in order to increase their value. No technologies or products focusing on retronasal aroma have been reported to date.

[0007] This invention has been made in view of the above circumstances, and the problem it aims to solve is to provide a tablet that can improve retronasal aroma. [Means for solving the problem]

[0008] The present invention relates, for example, to the following tablets. [1] An oral or oculum tablet containing an ester-based fragrance and having a disintegration time of less than 9 minutes. [2] The tablet according to [1], wherein the tablet is an orally disintegrating tablet or a chewable tablet.

[0009] [3] The tablet according to [1] or [2], wherein the amount of ester-based fragrance added is 0.05 to 1.8% by mass relative to the total mass of the added ingredients. [4] The tablet according to [1] or [2], further containing crystalline cellulose.

[0010] The present invention also includes a method for improving retronasal fragrance. [5] A method for improving the retronasal aroma of an oral or oral tablet containing an ester-based fragrance by adjusting the disintegration time to less than 9 minutes. [6] The method thereof, wherein the amount of ester-based fragrance added to the tablet is 0.05 to 1.8% by mass relative to the total mass of the added components. [7] The method according to [5] or [6], wherein the tablet contains crystalline cellulose. [Effects of the Invention]

[0011] The present invention provides a tablet that can enhance retronasal aroma. [Modes for carrying out the invention]

[0012] [1. About the tablets] First, the composition and properties of the tablets of the present invention will be described. The tablets of the present invention contain an ester-based fragrance and may further contain any other components.

[0013] [1-1.Fragrance] The tablets of the present invention contain an ester-based fragrance. The ester-based fragrance is not particularly limited as long as it is an ester, but examples include formic acid esters, aliphatic carboxylic acid esters, aromatic carboxylic acid esters, and cyclic esters. Examples of the above-mentioned formic acid esters include propyl formate, isobutyl formate, cis-3-hexenyl formate, and terpinyl formate.

[0014] Examples of the above aliphatic carboxylic acid esters include benzyl lactate, ethyl acetate, isoamyl acetate, hexyl acetate, octyl acetate, nonyl acetate, decyl acetate, dodecyl acetate, dihydromyrcenyl acetate, linalyl acetate, citronellyl acetate, geranyl acetate, neryl acetate, tetrahydromugol acetate, lavandulyl acetate, nerolidol acetate, dihydrocuminyl acetate, terpinyl acetate, citriyl acetate, nopyl acetate, dihydroterpinyl acetate, trans-2-hexenyl acetate, 2,4-dimethyl-3-cyclohexenylmethyl acetate, miraldyl acetate, beticol acetate, butyl propionate, hexyl propionate, decenyl propionate, linalyl propionate, methyl butyrate, ethyl butyrate, amyl butyrate, Examples include isoamyl butyrate, hexyl butyrate, octyl butyrate, cinnamyl butyrate, isopropyl isobutyrate, octyl isobutyrate, linalyl isobutyrate, hexyl methylbutyrate, cis-3-hexenyl methylbutyrate, allyl 2-ethylbutyrate, ethyl 3-hydroxybutyrate, pentyl valerate, 2-methylpentyl 2-methylvalerate, ethyl hexanoate, 2-methylbutyl hexanoate, hexyl hexanoate, methyl 3-hydroxyhexanoate, methyl octanoate, ethyl octanoate, methyl nonanoate, ethyl nonanoate, ethyl decanoate, methyl undecylenate, isoprenyl angelicate, methyl geranate, triethyl citrate, ethyl acetoacetate, ethyl 2-hexylacetoacetate, and ethyl 2,4-decadienate.

[0015] Examples of the above aromatic carboxylic acid esters include linalyl benzoate, methyl salicylate, methyl cinnamate, ethyl benzylacetoate, methyl anthranilate, ethyl N-methylanthranilate, and ethyl methylphenylglycidate (such as ethyl 3-methyl-3-phenylglycidate). Examples of the above cyclic esters include sotolon, coumarin, jasmin lactone, and γ-jasmolactone.

[0016] The ester fragrance may be a synthetic fragrance, a naturally derived fragrance, a blended fragrance, a fragrance composition, an essential oil, etc. In the tablets of the present invention, the ester fragrance is preferably a C2-C14 ester.

[0017] In addition, the ester-based fragrance may be contained in tablets as a powder fragrance. If it is a powder fragrance, even a fragrance that is liquid (liquid state) at room temperature can be easily handled as a raw material for blending into tablets, and the storage stability and heat resistance of the fragrance can also be enhanced. The powder fragrance can be obtained by emulsifying the fragrance together with an excipient and then spray-drying it to powderize it, or by supporting the fragrance on a carrier. Examples of the excipient include dextrin, starch, gum arabic, gelatin, casein, etc. Examples of the carrier include powdered silica, powdered calcium silicate, cellulose particles, etc. The content ratio of the fragrance in the powder fragrance is usually 1 to 50% by mass, preferably 3 to 40% by mass, and particularly preferably 5 to 30% by mass.

[0018] The ester-based fragrance may be used alone or in combination of two or more.

[0019] The lower limit of the charging ratio of the ester-based fragrance in the tablet is preferably 0.05% by mass, more preferably 0.10% by mass, and particularly preferably 0.15% by mass with respect to the total mass of the charged components. On the other hand, the upper limit of the charging ratio of the ester-based fragrance in the tablet is preferably 1.8% by mass, more preferably 1.7% by mass, and particularly preferably 1.5% by mass with respect to the total mass of the charged components. When using a powder fragrance as the ester-based fragrance, the lower limit of the charging ratio of the powder fragrance in the tablet is preferably 0.6% by mass, more preferably 1.0% by mass, and particularly preferably 1.5% by mass with respect to the total mass of the charged components. On the other hand, the upper limit of the charging ratio of the powder fragrance in the tablet is preferably 19% by mass, more preferably 17% by mass, and particularly preferably 15% by mass with respect to the total mass of the charged components. By setting the charging ratio of the ester-based fragrance within such a range, a tablet having a good retronasal fragrance can be obtained. Since ester-based fragrances are generally hydrophobic, if the content ratio in the tablet is too high, the disintegration time tends to become long, and as a result, the retronasal fragrance also tends to decrease. The content ratio of the ester-based fragrance in the tablet can be measured by methods such as gas chromatography or gas chromatography-mass spectrometry after extraction using an organic solvent or the like.

[0020] The tablet of the present invention may contain a fragrance other than the ester-based fragrance. The fragrance other than the ester-based fragrance is not particularly limited, and examples include alcohols (β-phenylethyl alcohol, geraniol, menthol, etc.), aldehydes (phenylacetaldehyde, etc.), phenols (vanillin, etc.), hydrocarbons (limonene, etc.), ketones, ethers, nitrogen-containing and / or sulfur-containing compounds, and acids. These fragrances may be either synthetic fragrances or those derived from natural products, and may be compounded fragrances, fragrance compositions, essential oils, etc.

[0021] [1-2. Other Components] The tablets of the present invention may contain, in addition to the above-mentioned fragrance, any other components to ensure the various properties of the tablets. Examples of any other components include excipients, binders, disintegrants, fluidizers, lubricants, effervescent components, useful components, oral medicinal components, stabilizers, flavoring agents, coating agents, and the like.

[0022] (Excipients) Any other excipient component is not particularly limited, but may be an inorganic or organic excipient. Examples of inorganic excipients include titanium dioxide, aluminum silicate, silicon dioxide, anhydrous sodium sulfate, anhydrous calcium hydrogen phosphate, sodium chloride, hydrated amorphous silicon dioxide, calcium silicate, light anhydrous silicic acid, heavy anhydrous silicic acid, calcium sulfate, calcium monohydrogen phosphate, calcium hydrogen phosphate, sodium hydrogen phosphate, potassium dihydrogen phosphate, calcium dihydrogen phosphate, sodium dihydrogen phosphate, magnesium oxide, and the like. Examples of organic excipients include crystalline cellulose, starch (corn starch, partially pregelatinized starch, etc.), fructose, caramel, agar, xylitol, paraffin, sucrose, fructose, maltose, lactose, sucrose, glucose, pullulan, polyoxyethylene hydrogenated castor oil, maltitol, reduced maltose syrup, reduced starch syrup, erythritol, xylitol, sorbitol, mannitol, lactitol, trehalose, reduced palatinose, maltose, etc.

[0023] Organic excipients are preferred as excipients in the tablets of the present invention. Excipients may be used alone or in combination of two or more.

[0024] (Binder) The binder, which is any other component, is not particularly limited, but examples include methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hypromellose, polyvinylpyrrolidone, reduced maltose syrup, starch (corn starch, partially pregelatinized starch, etc.), dextrin, pullulan, acacia gum, agar, acacia, tragacanth, sodium alginate, etc. The binder may be used alone or in combination of two or more.

[0025] (Disintegrant) Any other disintegrant component is not particularly limited, but examples include low-substituted hydroxypropylcellulose, carboxymethylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, starch (corn starch, partially pregelatinized starch, etc.), dietary fiber (agar, crystalline cellulose, etc.), croscarmellose sodium, sodium carboxymethyl starch, etc. The disintegrant may be used alone or in combination of two or more.

[0026] (Smoothing agent) Any other component, the fluidizing agent, is not particularly limited, but examples include calcium phosphate, calcium hydrogen phosphate, silicon dioxide, magnesium oxide, magnesium silicate, and calcium silicate. The fluidizing agent may be used alone or in combination of two or more types.

[0027] (lubricant) The lubricant, which is any other component, is not particularly limited, but examples include calcium stearate, magnesium stearate, stearic acid, sucrose fatty acid esters, talc, glycerin fatty acid esters, etc. The lubricant may be used alone or in combination of two or more types.

[0028] (Effervescent ingredients) The effervescent component in the tablet is not particularly limited, but it is preferable to include a combination of an acid and a carbonate. The acid may be an organic acid or an inorganic acid, but an organic acid is preferred. Examples of organic acids include citric acid, tartaric acid, malic acid, succinic acid, fumaric acid, and ascorbic acid, while an example of an inorganic acid is phosphoric acid. These acids may be used individually or in combination of two or more.

[0029] The carbonates that make up the effervescent components are not particularly limited, but examples include sodium carbonate, potassium carbonate, calcium carbonate, magnesium carbonate, sodium bicarbonate, potassium bicarbonate, and sodium sesquicarbonate. These carbonates may be used individually or in combination of two or more.

[0030] (Useful ingredients) Any other active ingredients are not particularly limited as long as they exhibit a suitable effect on humans (e.g., clinical efficacy) when taken orally. Examples of active ingredients include hypnotics, psychotropic drugs, antiepileptic drugs, Parkinson's syndrome treatments, analgesics, Alzheimer's disease treatments, antiallergic drugs, cardiac stimulants, antiarrhythmic drugs, antianginic drugs, antihypertensive drugs, antihyperlipidemic drugs, diuretics, expectorants, antiasthmatic drugs, antacids, peptic ulcer treatments, antithrombotic drugs, thrombolytic drugs, anti-inflammatory drugs, gout treatments, osteoporosis treatments, chronic rheumatoid arthritis treatments, diabetes treatments, anticancer drugs, antibiotics, antifungal drugs, immunosuppressants, and other disease treatments; as well as cinnamon, peony, apricot kernel, peach kernel, licorice, and Phellodendron bark. Examples of useful ingredients include crude drugs such as dried tangerine peel, spruce, senega, clove, angelica, gentian, gentian, swertia, rehmannia, digitalis, valerian, balloon flower, aloe, pinellia, turmeric, and ginger; herbal medicines such as kakkonto, anchusan, goreisan, shoseiryuto, tokishakuyakusan, and maoto; nutritional components such as vitamins, minerals, and amino acids; and health-promoting components such as polyphenols, collagen, coenzyme Q10, lutein, zeaxanthin, indigestible dextrin, inulin, lactic acid bacteria, bifidobacteria, and cannabidiol. In addition, fragrances, including ester-based fragrances, can also be useful ingredients. These useful ingredients may be used individually or in combination of two or more.

[0031] (Oral medicinal ingredients) Any other oral medicinal ingredients are not particularly limited as long as they exhibit some desirable effect in the oral cavity. Examples of oral medicinal ingredients include: breath freshening ingredients such as sodium copper chlorophyllin, sodium iron chlorophyllin, isopropylmethylphenol, hinokitiol, licorice, cinnamon, clove, fennel, flavonoids, champignon extract, perilla extract, oolong tea extract, and hencha extract; antibacterial agents such as cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, decalinium chloride, chlorhexidines, and triclosan; anti-inflammatory agents such as azulene, azulene sulfonate, glycyrrhetinic acid, lysozyme chloride, Phellodendron amurense extract, Angelica acutiloba extract, and epsilon-aminocaproic acid; blood circulation promoters such as tocopherols; fluorine compounds such as sodium monofluorophosphate, potassium monofluorophosphate, and sodium fluoride; and enzymes such as dextranase, mutanase, lysozyme, amylase, protease, and lytic enzymes. Furthermore, fragrances, including ester-based fragrances, can also be used as oral medicinal ingredients. These oral medicinal ingredients may be used individually or in combination of two or more.

[0032] The tablets of the present invention can further utilize other components that have been conventionally used as components of tablets, depending on the purpose.

[0033] The tablets of the present invention preferably contain crystalline cellulose. By containing crystalline cellulose, it is possible to obtain tablets with a good retronasal aroma and excellent performance in various aspects. Furthermore, by containing an effervescent component, the retronasal aroma derived from ester-based fragrances can be enhanced in the tablets of the present invention.

[0034] [1-3. Collapse Time] The tablets of the present invention have a disintegration time of less than 9 minutes. A disintegration time of less than 9 minutes allows for the production of tablets with a good retronasal aroma. The disintegration time refers to the measurement taken using an auxiliary disc and water as the test solution, in accordance with the disintegration test method described in the 18th edition of the Japanese Pharmacopoeia. The upper limit of the disintegration time of the tablets of the present invention is preferably 8 minutes 30 seconds or less, more preferably 8 minutes or less, and particularly preferably 7 minutes 30 seconds or less. On the other hand, the lower limit of the disintegration time is preferably 1 minute or more, more preferably 1 minute 30 seconds or more, and particularly preferably 2 minutes or more. If the disintegration time is too short, the tablets disintegrate too quickly in the oral cavity, which may reduce the retronasal aroma.

[0035] The disintegration time of a tablet can be controlled, for example, by adjusting the type and amount of disintegrant, the amount of ester-based flavoring, and the compression pressure.

[0036] [1-4. Uses of Tablets] The tablets of the present invention are for oral or nasal use. Oral use refers to a mode of use in which the user (or eater) consumes the tablet by chewing and / or coming into contact with saliva, allowing the tablet to disintegrate and / or dissolve in the mouth, with the aim of oral intake of the active ingredient. In this case, the user can taste the retronasal fragrance of the fragrance contained in the tablet, and if the fragrance is also an active ingredient, at least a portion of it can be absorbed nasally. As a result, compared to oral intake of all active ingredients, the absorption rate can be improved (for example, bioavailability can be increased); and in some cases, the effects can be more effectively exerted by combining drug absorption from the digestive system via the mouth with drug absorption from the respiratory system via the nose.

[0037] On the other hand, "oral use" refers to a method of use in which tablets containing oral medicinal ingredients are placed in the mouth with water as needed and / or chewed, dissolving in the mouth through contact with moisture, and then finally swallowed or spat out. In this case as well, the user can enjoy the retronasal fragrance of the flavoring contained in the tablet.

[0038] Given this mode of use, the tablets of the present invention may be orally disintegrating tablets or chewable tablets.

[0039] In one embodiment, the tablets of the present invention are used (consumed) to taste a retronasal aroma. In another embodiment, the tablets of the present invention are used to deliver at least a portion of the active ingredients via the nose.

[0040] [2. Method for manufacturing oral tablets] The method for manufacturing tablets of the present invention can employ methods known in the pharmaceutical field. Known methods for manufacturing tablets can be broadly classified into two types: a method in which each component is granulated into granules and a mixture of these granules and other components is compressed into tablets (indirect tableting method); and a method in which a mixed powder of each component is directly compressed into tablets without granulating each component (direct tableting method). Granulation methods in the indirect tableting method can be broadly classified into wet methods and dry methods. Granulation methods also include fluidized bed granulation and agitated granulation.

[0041] The tableting process can be carried out using a tablet press, and various types of tablet presses, such as single-shot presses and rotary presses, can be used. Furthermore, the oral tablets of the present invention may be coated tablets by subjecting the uncoated tablets obtained by tableting to various coating treatments as needed.

[0042] The tablets of the present invention are preferably obtained by compressing a mixture containing an ester-based fragrance, but the ester-based fragrance may also be included in the coating of coated tablets.

[0043] [3. Methods to improve the retronasal aroma of tablets] The present invention relates to a method for improving the retronasal aroma of tablets. The method includes adjusting the disintegration time of a tablet containing an ester-based flavoring to less than 9 minutes. The method for adjusting the disintegration time to less than 9 minutes is not particularly limited, but examples include adjusting the type and content of the disintegrant, the content of the ester-based flavoring, and the compression pressure.

[0044] In this specification, "improvement of retronasal fragrance" means an increase in the area under the sensor intensity curve measured by the method described in the examples. As one embodiment, in the process of developing a tablet containing an ester-based fragrance to be a product, the type and amount of disintegrant, the amount of ester-based fragrance, the tableting pressure, etc. are adjusted so that the disintegration time is within a predetermined range, and as a result, the retronasal fragrance is improved compared to before the adjustment.

[0045] Another embodiment involves ensuring that the disintegration time of the product (tablets containing ester-based fragrance) is within a predetermined range, and that the retronasal fragrance can be enjoyed in the product's instructions, packaging, and introduction. Yet another embodiment involves inspecting the production process of the product (tablets containing ester-based fragrance) to ensure that the disintegration time is within a predetermined range and that the retronasal fragrance meets predetermined standards. [Examples]

[0046] The present invention will be described more specifically below with reference to examples. However, the present invention is not limited to the following examples.

[0047] [A. Tablet Manufacturing] Tablets with the compositions shown in Examples 1-3, Comparative Example 1, and Reference Examples 1-3 in Table 1 were manufactured using a rotary tablet press by direct compression. A 15 mm diameter die was used, and the compression pressure was approximately 6000 N. Tablets with a thickness of 6.4 mm were produced in this manner. In Examples 1-3, Comparative Example 1, and Reference Examples 1-3, the unit of the numerical values ​​representing the amount of each component is mg.

[0048] The following are the ingredients used as flavorings in the manufacture of the tablets. • Powdered ethyl butyrate: A fragrance powdered with dextrin containing 9.3% by mass of ethyl butyrate. • Powdered limonene: A fragrance powdered with dextrin containing 8.3% by mass of limonene.

[0049] [B. Evaluation of Retronasal Aroma] The retronasal aroma of the obtained tablets was evaluated. Specifically, a Lunmai nasal cannula (manufactured by TM Trading Co., Ltd.) was attached to the nose of each subject, and a portable odor sensor XP-329IIIR (manufactured by Shin-Cosmos Electric Co., Ltd.) was connected to its end.

[0050] Seventeen subjects evaluated the retronasal aroma by chewing each tablet. Each subject was free to chew the tablets themselves, but the number of chews ranged from 30 to 40. During this time, the retronasal aroma was measured in real time using an odor sensor. Data sampling during the measurement was performed at 2 Hz.

[0051] The area under the sensor intensity curve was calculated from the intensity curve obtained by measurement with an odor sensor. Table 1 shows the area under the sensor intensity curve. The calculated area under the sensor intensity curve was standardized according to the amount of fragrance contained in the tablet. The average area under the curve was calculated for each tablet, and these results are shown in Table 1.

[0052] [C. Measurement of decay time] The disintegration time of the obtained tablets was measured using a disintegration test machine in accordance with the disintegration test method described in the 18th edition of the Japanese Pharmacopoeia. An auxiliary plate was used, and water was used as the test solution. For each of Examples 1-3, Comparative Example 1, and Reference Examples 1-3, the disintegration time of six tablets was measured, and the average value was calculated. The measurement results are shown in Table 1.

[0053] [Table 1]

[0054] As can be seen from the comparison between Comparative Example 1 and Examples 1 and 2, in tablets containing ethyl butyrate, an ester-based fragrance, the area under the strength curve is significantly improved when the disintegration time is less than 9 minutes.

[0055] On the other hand, as can be seen from Reference Examples 1-3, in tablets containing limonene, a hydrocarbon-based fragrance, no clear correlation was observed between disintegration time and area under the intensity curve. Rather, it appears that the area under the intensity curve improves when the disintegration time exceeds 6 minutes.

[0056] The improvement in retronasal aroma when the disintegration time is less than 9 minutes is thought to be a characteristic of tablets containing ester-based fragrances.

Claims

1. An oral or oculum tablet containing an ester-based fragrance and having a disintegration time of less than 9 minutes.

2. The tablet according to claim 1, wherein the tablet is an orally disintegrating tablet or a chewable tablet.

3. The tablet according to claim 1 or 2, wherein the amount of ester-based fragrance added is 0.05 to 1.8% by mass relative to the total mass of the added components.

4. The tablet according to claim 1 or 2, further containing crystalline cellulose.

5. A method for improving the retronasal aroma of an oral or oral tablet containing an ester-based fragrance by adjusting the disintegration time to less than 9 minutes.

6. The method according to claim 5, wherein the amount of the ester-based fragrance added to the tablet is 0.05 to 1.8% by mass relative to the total mass of the added components.

7. The method according to claim 5 or 6, wherein the tablet contains crystalline cellulose.

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