JP2014080410A - Deglutition function improving agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a deglutition function improving agent of which effective administration timing is identified, and which is extremely safe and therefore can be administered constantly every day.SOLUTION: A deglutition function improving agent of this invention includes Zingiber officinale in amounts of 0.5 mass% or more and 4.0 mass% or less in terms of dry mass, and is administered 10 or more minutes before a meal.

Description

  The present invention relates to a swallowing function improving agent that is very safe and can be taken constantly.

  With the arrival of a super-aging society, the increase in the number of elderly people with dysphagia due to Parkinson's disease, cerebrovascular disease, etc. has become a major problem. Therefore, food intake and medication support is provided by swallowing aids such as gel-like or concentrated liquid liquid wafers and liquid foods. However, liquid food can deprive people with dysphagia and enjoy the quality of life (QOL). In general, swallowing aids are difficult to apply to meals, and when they are applied, there are similar problems such as the type of food being limited and the taste of the meal being reduced. Therefore, if the swallowing function of a person with dysphagia can be improved directly, it can be said that it is very preferable as an improvement in the QOL.

  Substance P is known as a substance involved in the swallowing function. Substance P is a sensory neuron transmitter consisting of 11 amino acids and has various actions such as blood pressure lowering action, salivary secretion enhancing action, tearing action, and ileal contraction action in addition to being involved in the swallowing function.

  As substances that promote the secretion of substance P and improve the swallowing function, capsaicin contained in capsicum and the like (Patent Document 1) and gingerols contained in ginger and the like (Patent Document 2) are known.

  In addition, the inventors of the present invention prototyped a tablet containing ginger and its cured product, psoriasis, examined its physical properties, and evaluated the concentration of substance P in saliva after taking the tablet (non-contained) Patent Document 1).

International Publication No. 2004/058301 Pamphlet Japanese Patent Laid-Open No. 2008-5

The 132nd Annual Meeting of the Japanese Pharmaceutical Society 29E14-am14 (released February 1, 2012)

  As described above, the relationship between the swallowing function and substance P has been clarified, and substances that promote substance P secretion have also been studied. However, Patent Document 1 does not describe the timing of administration, and the technique of Patent Document 2 is aimed at addition to the diet. It is difficult to think that a drug that can improve the swallowing function can be smoothly swallowed by taking it with food. In addition, the present inventors have announced a tablet containing ginger and the like, but the research is mainly related to the physical properties of the tablet such as hardness and disintegration time, and further studies on its effects and the like were necessary. .

  Therefore, an object of the present invention is to provide an agent for improving swallowing function, in which an effective administration time is specified, and since it is extremely safe, it can be regularly administered daily.

  In order to solve the above-mentioned problems, the present inventors have measured in detail the changes over time in the amount of substance P in saliva after administration of a tablet containing a substance P secretagogue, and also have a sensory test for the tablet. And so on. As a result, the present inventors have completed the present invention by finding an appropriate component structure and the optimal administration time.

  The agent for improving swallowing function according to the present invention contains ginger (Zingiber officinale) in a dry mass of 0.5% by mass or more and 4.0% by mass or less, and is administered 10 minutes or more before a meal. And

  As the swallowing function improving agent of the present invention, those further containing mannitol or a combination of mannitol and sucrose are preferable. It has been clarified by actual sensory tests that the agent of the present invention containing these as excipients can rapidly disintegrate in the mouth to release the active ingredient and is easy to take for the elderly.

  The swallowing function improving agent of the present invention can increase the substance P concentration in saliva, and as a result, the swallowing function can be improved.

  The swallowing function improving agent of the present invention is preferably intended for elderly people 50 years or older. The swallowing function improving agent according to the present invention has been completed in consideration of easiness of taking by an elderly person based on the result of a sensory test for a subject over 50 years old.

  The agent for improving swallowing function according to the present invention is preferably administered 120 minutes or less before meals. It has been confirmed that the substance P amount in saliva is increased by the swallowing function improving agent of the present invention, and thereafter the amount is maintained at a high level for 120 minutes. Therefore, if the swallowing function improving agent of the present invention is taken 120 minutes or less before a meal, it can be enjoyed while the swallowing function is sufficiently improved.

  The dosage form of the swallowing function improving agent according to the present invention is preferably an orally disintegrating tablet. If it is an orally disintegrating tablet, it can rapidly disintegrate and release active ingredients into the mouth, increasing the amount of substance P in saliva and improving the swallowing function. Orally disintegrating tablets are easy to take for elderly people.

  Since the active ingredient of the swallowing function improving agent according to the present invention is ginger which is a food material and is extremely safe, it can even be taken for each meal. In addition, since the effective administration time has been specified and the swallowing function can be effectively improved, it is possible to re-enjoy meals for the elderly who have swallowed the function, and to increase the QOL. . Therefore, the swallowing function improving agent according to the present invention is industrially excellent as contributing to the problems associated with a super-aging society.

FIG. 1 shows the results of a sensory test on a control tablet containing no ginger and a tablet containing 1 to 5% by mass of ginger. FIG. 2 is a graph showing the result of taking a questionnaire about “which tablet should be taken every day” to the subject regarding a control tablet not containing ginger and a tablet containing 1 to 5% by mass of ginger. . FIG. 3 is a graph showing temporal changes in the concentration of substance P in saliva after administration of a control tablet not containing ginger and a tablet containing 1 to 5% by mass of ginger to a subject.

  The agent for improving swallowing function according to the present invention contains ginger (Zingiber officinale) in a dry mass of 0.5% by mass or more and 4.0% by mass or less, and is administered 10 minutes or more before a meal. And

  Ginger is a plant belonging to the order Ginger, Ginger family, and Ginger genus, and uses rhizomes as edibles, and mainly ginger such as Tosa University ginger, Tafuku ginger, Indian ginger, Omi ginger, etc. Medium ginger such as Boso ginger and camel ginger; small ginger such as gold ginger, platinum ginger, Sanshu ginger, Laos small ginger, and Yanaka ginger.

  Large ginger has a large yield per unit area, and its pungent taste is relatively weak, and is cultivated most in Japan. Medium ginger is smaller than large ginger and its pungent taste is relatively strong. Small ginger is smaller and has the strongest pungent taste.

  The kind of ginger used in the present invention is not particularly limited and may be appropriately selected. For example, large ginger is most easily available and inexpensive, and thus is suitably used when the cost should be suppressed. On the other hand, it is a pungent component that shows the effect of promoting the secretion of substance P. Since it is considered to be gingerols, shogaols and gingerones that bind to vanilloid receptors involved in the secretion of substance P, a smaller amount When it is desired to obtain a higher effect in the blending amount, medium ginger and further small ginger having a higher pungency and a higher concentration can be used.

  Further, so-called dry rice cake may be used. Inui is made by boiling raw ginger and drying it, and is used as a herbal medicine. In dried cocoon, a dehydration reaction or the like occurs with heat treatment, and for example, gingerols are converted into gingerols and the like. Therefore, although a preliminary experiment is necessary, for the purpose of improving the taste and enhancing the effect, dried ginger can be used.

  The form of ginger blended in the tablet of the present invention may be appropriately selected according to the dosage form and the like, and is not particularly limited. For example, the skin may be removed from the rhizome of ginger, coarsely cut, finely crushed and pulverized, or dried and further pulverized. Further, when the dosage form is a tablet, powder, granule or the like, a dry powder is suitable, and from the viewpoint that the substance P secretion promoting component can be quickly released in the mouth, it is preferable to make it as fine as possible.

  The swallowing function improving agent according to the present invention contains ginger in a dry mass of 0.5% by mass or more and 4.0% by mass or less. There exists a possibility that the improvement effect of a swallowing function may not fully be exhibited as the said mass is less than 0.5 mass%. On the other hand, if the mass exceeds 4.0% by mass, the unique pungent taste and irritation caused by ginger become strong, and the agent of the present invention is retained in the mouth, so that it may be difficult to take especially for the elderly. As the said mass, 1.0 mass% or more is more preferable, and 3.0 mass% or less is more preferable.

  It is assumed that the mass is obtained by drying ginger. That is, when the ginger in the agent of the present invention is in a wet state, the ratio of ginger is measured after a sample is obtained and dried. In the present invention, the dry state in which the ginger content ratio is to be measured refers to a state in which the water content measured by a Karl Fischer moisture meter is 8% by mass or less, preferably 5% by mass or more.

  The agent for improving swallowing function according to the present invention is administered at least 10 minutes before a meal. When the agent of the present invention is administered, the active ingredient is released into the mouth, the substance P concentration in saliva is increased and the swallowing function is improved, but there is a time lag before the effect is exerted after administration. However, if administered 10 minutes or more before meals, the concentration of substance P in saliva is sufficiently increased, and meals can be enjoyed under an improved swallowing function. The administration time is preferably 12 minutes or more, more preferably 14 minutes or more, and particularly preferably 15 minutes or more.

  On the other hand, the upper limit of the administration time is not particularly limited, but is preferably 120 minutes or less before meals. According to the experimental findings by the present inventors, the substance P concentration in saliva is maintained at a sufficiently high level within 120 minutes from the administration of the agent of the present invention, and the effect of improving the swallowing function is sustained. . However, the substance P concentration becomes maximum within about 10 to 20 minutes by the administration of the agent of the present invention, and thereafter gradually decreases but gradually decreases. Therefore, it is more preferable to administer the substance P concentration 90 minutes or less before a meal. , More preferably 60 minutes or less, and particularly preferably 30 minutes or less.

  The dosage form of the swallowing function improving agent according to the present invention is not particularly limited as long as it can release an active ingredient in the mouth, and examples thereof include tablets, troches, powders, granules and the like. Further, it may be a liquid suspension containing ginger, or a powder or granule suspended in white hot water or the like. However, liquid agents and powders may be difficult to keep in the mouth, especially for elderly people. In addition, a large intake of water contained in a liquid suspension or the like may lead to aspiration of the elderly in particular. Furthermore, with a lozenge or the like, the active ingredient concentration in the mouth cannot be increased rapidly, and as a result, the substance P concentration in saliva may not be sufficiently increased. Therefore, as the dosage form, an orally disintegrating tablet capable of rapidly releasing the active ingredient is particularly preferable.

  For the swallowing function improving agent according to the present invention, a pharmaceutically acceptable additive may be used in accordance with the dosage form. Such additives include, for example, excipients, lubricants, disintegrants, stabilizers, preservatives, buffers, corrigents, suspending agents, emulsifiers, flavoring agents, solubilizers, colorants, viscosity agents. Examples thereof include a thickener.

  In particular, the swallowing function improving agent according to the present invention preferably contains mannitol or a combination of mannitol and sucrose. Since these not only serve as excipients but also act as sweeteners, they are effective in reducing the bitterness and irritation of ginger which is an active ingredient of the present invention.

  The blending amount of mannitol or a combination of mannitol and sucrose may be adjusted as appropriate, and is not particularly limited. For example, it can be about 50% by mass or more and 95% by mass or less with respect to the entire preparation. Further, when a combination of mannitol and sucrose is used, these ratios may be adjusted as appropriate, and are not particularly limited. For example, sucrose is 0.5 mass times or more and 1.5 mass times or less with respect to mannitol. Can do.

  The frequency and dose of administration are not particularly limited because the agent for improving swallowing function according to the present invention is extremely safe, and may be appropriately adjusted according to the age, sex, state, etc. of the user. For example, the mass of ginger converted to dry mass can be about 2 mg to 10 mg per time. The number of administrations is not particularly limited, but can be once before each meal, for example.

  The swallowing function improving agent according to the present invention can be released in the mouth to release ginger as an active ingredient, increase the substance P concentration in saliva, and improve the swallowing function. That is, in the present invention, since the substance P concentration in saliva needs to be increased, the swallowing function improving agent according to the present invention needs to remain in the mouth until the effect is sufficiently exhibited.

  Since the swallowing function improving agent according to the present invention has been completed based on the results of sensory tests on elderly subjects, it is easy to take and is particularly suitable for elderly people with dysphagia who are 50 years old or older. It can be said. Since the swallowing function declines with aging, the age of the recipient is preferably 60 years or older, more preferably 65 years or older, and even more preferably 70 years or older.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited by the following examples, but may be appropriately modified within a range that can meet the purpose described above and below. Of course, it is possible to implement them, and they are all included in the technical scope of the present invention.

Example 1 Production of Ginger-Containing Tablet (1) Preliminary Experiment Powders were mixed with the composition shown in Table 1 and inserted into a pressurizer (product name “Compact Press Manual Pump Type Model PCH-20” manufactured by NPA System). Thus, an orally disintegrating tablet having a weight of about 0.2 g and a thickness of about 3 mm was prepared.

  The hardness of the obtained tablet is the lowest in Formulation Example A containing mannitol, being slightly lower than 30N, the highest in Formulation Example C containing sucrose, being about 60N, and the hardness of Formulation Example B containing both mannitol and sucrose is It was in the middle. In addition, the disintegration time for water, disintegration test first liquid (pseudogastric fluid), disintegration test second liquid (pseudointestinal fluid) depends on the hardness, and the disintegration of formulation example A is the lowest, and disintegration of formulation example C The disintegrability of Formulation Example B was intermediate between these. The water absorption time showed the same tendency. Furthermore, the tableting pressure was also examined. The higher the tableting pressure, the lower the disintegration and the longer the water absorption time, and the lower the tableting pressure, the higher the disintegration and the shorter the water absorption time.

In addition, ten healthy males aged 25 to 60 years were used as subjects, and a sensory test of each orally disintegrating tablet was performed. Specifically, one tablet was placed on the tongue, and it was disintegrated while saliva was included and the tablets were licked. At that time, saliva was not swallowed, but collected in the mouth. The time when the tablet gradually disintegrated and the lump disappeared was regarded as the end of the oral disintegration. Next, an anonymous questionnaire was conducted according to the following criteria.
I. Sweetness-1: I don't feel at all, 2: I don't feel any strength, 3: Just right, 4: Somewhat strong, 5: Too strong II. Melting speed-1: fast 2: slightly fast 3: just right 4: slightly slow 5: slow III. Irritation-1: I don't feel at all, 2: I don't feel any strength, 3: Just right, 4: Somewhat strong, 5: Too strong IV. Roughness-1: I don't feel at all, 2: I don't feel at all, 3: I feel a little, 4: I feel V. Powdery-1: I don't feel at all, 2: I don't feel at all, 3: I feel a little, 4: I feel

  They were also asked to select which tablets would be better if they were taken every day. As a result, the dissolution rate was the fastest in Formulation Example A, the slowest in Formulation C, and just the Formulation B as well as the disintegration and water absorption time. As the most preferable tablets, 4 patients selected Formulation Example A, 6 patients selected Formulation Example B, and 0 patients selected Formulation Example C. From these results, it was determined that as an excipient for an orally disintegrating tablet containing ginger that is highly irritating, mannitol is preferable, and it is more preferable to include both mannitol and sucrose.

(2) Production of the tablet of the present invention The mixture of Formulation Example B in Table 1 is mixed with 1% by mass, 3% by mass or 5% by mass of ginger dry powder (manufactured by Asano Co., Ltd., product name “Ginger Powder”). And the orally disintegrating tablet was manufactured similarly to said (1). As a control, an orally disintegrating tablet of Formulation Example B containing no ginger dry powder was also produced. These tablets were subjected to a sensory test in the same manner as in the above (1) except that the “melting speed” in Evaluation Item II was changed to “bitterness”. The results of the evaluation items I to V are shown in FIG. 1, and the answer to the question “Which tablet should be taken every day?” Is shown in FIG.

  As shown in FIG. 1, the irritation increased according to the blending ratio of ginger dry powder. As for other evaluation items, no difference was recognized except that the 5% by mass ginger combination tablet had low sweetness and high bitterness. In addition, as shown in FIG. 2, in response to the question “Which tablet should be taken every day?”, One person selected 5% by weight ginger combination tablet, but six persons had 1% by weight ginger. A combination tablet was selected, and 3 persons selected a 3% by mass ginger combination tablet.

  Many elderly people and dementia patients have impaired swallowing function, and highly irritating preparations may be rejected. On the other hand, since meals are daily, preparations for improving swallowing function require constant intake. Therefore, it was concluded that the amount of ginger to be blended with the agent of the present invention was too much at 5% by mass in dry mass, and about 1 to 3% by mass was good.

Example 2
The 1 mass%, 3 mass%, or 5 mass% ginger combination tablet prepared in Example 1 (2) above and the control tablet (formulation example B tablet) were tested for effects on the amount of substance P in saliva. Specifically, 5 adult men in their 20s or 30s and 5 adult men in their 50s were subjects, and only control tablets were administered to subjects in their 20s or 30s, while all tablets were administered to subjects in their 50s Was administered.
Each tablet was placed on the tongue until it disintegrated spontaneously. Immediately before tablet administration (0 hours), 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes, and 120 minutes after tablet administration, saliva collection tubes (Salstat, Salivet (registered) Saliva was collected using (trademark) cotton). The collected saliva was centrifuged at 3000 rpm, 4 ° C. for 15 minutes, and after the amount of the obtained saliva was measured, it was diluted 20 volumes with physiological saline or a dedicated diluent attached to the measurement kit described later. The diluted saliva was stored at −20 ° C. or lower until used for measurement. The substance P concentration in the diluted saliva was measured using a substance P assay kit (manufactured by R & D Systems, Parameter (registered trademark)). The diluted saliva was added to a microplate coated with sheep anti-mouse polyclonal antibody, and further, the Substance P Conjugate of the kit was added, and reacted at room temperature for 3 hours while stirring. Next, after the plate was sufficiently washed with a detergent-containing washing solution, a substrate solution was added and reacted at room temperature for 30 minutes. After stopping the reaction by adding a reaction stop solution, the absorbance (measurement wavelength: 450 nm, correction wavelength: 540 to 570 nm) was measured. A calibration curve prepared from the results obtained from the substance P standard solution was compared with the measurement data, and the substance P amount in saliva was calculated. The results are shown in FIG. In Table 2, “*” indicates a case where there is a significant difference at p <0.05 with respect to the control (50 generations) in the significance test (Dunnett's-test).

  As shown in the results of FIG. 3 and Table 2, in subjects in their 20s or 30s, the substance P in the saliva was increased simply by including the control tablet in the mouth, and it can be said that preparations for swallowing were ready. On the other hand, in subjects in their 50s, the amount of substance P in saliva was not so high even when the control tablet was included in the mouth, and it immediately decreased, and the change was very small. In addition, when 5 mass% ginger combination tablet was administered, the amount of substance P in saliva increased rapidly, but then decreased immediately, and as a result, the AUC of substance P in saliva throughout the test decreased.

  On the other hand, when 1% by mass ginger combination tablet or 3% by mass ginger combination tablet was administered, the amount of substance P in saliva did not increase as quickly as in the case of 5% by mass ginger combination tablet, but reached the maximum concentration after 15 minutes. In addition, the decrease in the amount of substance P in saliva once increased was gradual, and the AUC of substance P in saliva throughout the test was large.

  From the above results, it was concluded that the amount of ginger to be blended with the agent of the present invention is preferably about 1 to 3% by mass in dry mass, and is preferably taken about 10 to 20 minutes before meals.

Claims (6)

  A swallowing function improving agent characterized by comprising ginger (Zingiber officinale) in a dry mass of 0.5% by mass or more and 4.0% by mass or less and administered 10 minutes or more before a meal.   Furthermore, the swallowing function improving agent of Claim 1 containing the combination of a mannitol or a mannitol and sucrose.   The agent for improving swallowing function according to claim 1 or 2, which increases the substance P concentration in saliva.   The swallowing function improving agent according to any one of claims 1 to 3, which is intended for an elderly person 50 years or older.   The swallowing function improving agent according to any one of claims 1 to 4, which is administered 120 minutes or less before a meal.   It is an orally disintegrating tablet, The swallowing function improving agent in any one of Claims 1-5.