JP2022169855A - Frequent urination improver - Google Patents

Abstract

To provide a technique that extends a urination interval without depending on the amount of urine in a bladder and without being affected mentally.SOLUTION: A frequent urination improver is characterized by containing Alpinia zerumbet essential oil and/or vanilla essential oil as active ingredients, which is for nasal administration. The Alpinia zerumbet essential oil contains p-Cymene, β-terpinene, α-pinene, camphene, and 1,8-cineole, and the vanilla essential oil contains ethyl vanillin, vanillin, linalool, and coumarin.SELECTED DRAWING: Figure 1

Description

There is an application for exception to loss of novelty

TECHNICAL FIELD The present invention relates to a frequent urination improving agent capable of prolonging micturition intervals.

The micturition interval not only depends on the amount of urine in the bladder, but is also subject to psychological influences. When you are nervous, you may feel the urge to urinate even if there is not much urine in your bladder, which may cause frequent urination.

When this condition is pathologically exacerbated, it is called psychogenic pollakiuria or neurogenic pollakiuria, and it is difficult to treat it with ordinary drugs for treating pollakiuria (Non-Patent Document 1). In addition, urinary incontinence occurs when a person does not make it to the toilet in time, regardless of the distance to the toilet after remembering the urge to urinate, just before taking off the underwear in the toilet. In this way, the desire to urinate is susceptible to psychological influences.

Edited by Kimio Sugaya, "Illustrated Practical Treatment of Dysuria Neurogenic Bladder/Nervous Frequent Urination", p66-67, Yogakusha, Kobe, 2019

Accordingly, an object of the present invention is to provide a technique for extending the micturition interval without depending on the amount of urine in the bladder and without being affected mentally.

As a result of intensive research to solve the above problems, the present inventors have found that the essential oil of a specific plant prolongs the urinary interval, and completed the present invention.

That is, the present invention is an agent for improving frequent urination, characterized by containing Alpinia speciosa essential oil and/or vanilla essential oil as active ingredients.

Since the agent for improving frequent urination of the present invention is a plant-derived essential oil that has been used conventionally, it can be used safely.

FIG. 1 shows the results of measurement of intravesical pressure with physiological saline in lightly anesthetized rats in the shell ginger aroma group or the control group of Example 1. FIG. FIG. 2 shows the results of measuring the plasma monoamine concentration in the shell ginger aroma group or the control group of Example 1. FIG. FIG. 3 shows the results of measurement of intravesical pressure in lightly anesthetized rats with normal saline saline and 0.25% acetic acid saline (0.25% acetic acid) in the Alpinia alpinia group or the control group in Example 1. FIG. FIG. 4 shows the results of measurement of micturition interval and intravesical pressure with physiological saline in lightly anesthetized rats before and after inhalation of vanilla essential oil in Example 2. FIG. FIG. 5 shows the results of measurement of micturition interval and intravesical pressure with physiological saline in lightly anesthetized rats before and after inhalation of the sequasa essential oil in Example 2. FIG. FIG. 6 shows the results of measuring plasma monoamine concentrations in the vanilla group or control group of Example 2. FIG.

The agent for improving frequent urination of the present invention contains Alpinia speciosa essential oil and/or vanilla essential oil as active ingredients.

Examples of the shell ginger essential oil include those obtained from leaves, stems, flowers, etc. of shell ginger (scientific name: Alpinia zerumbet) according to conventional methods such as steam distillation and hot water distillation. As this shell ginger essential oil, commercially available products can also be used, and examples of such commercial products include shell ginger essential oil (manufactured by Nippon Getto Co., Ltd.), Daito Getto (Incent Co., Ltd.), and the like. be done. The shell ginger essential oil contains, for example, p-cymene, β-terpinene, α-pinene, camphene, 1,8-cineole, and the like. For the agent for improving frequent urination of the present invention, Alpinia speciosa essential oil may be used as it is, or it may be appropriately concentrated or diluted according to the strength of the odor of the essential oil.

The above-mentioned vanilla essential oil is vanilla essential oil obtained from vanilla (scientific name: Vanilla planifolia) seed pods containing vanilla (scientific name: vanilla planifolia) seeds, which is repeatedly fermented and dried, according to a conventional method such as steam distillation or hot water distillation. In addition, fragrances containing artificially synthesized main components of vanilla essential oil, such as ethyl vanillin, vanillin, linalool, and coumarin, may also be used. As the vanilla essential oil and vanilla flavor, commercially available products can also be used. ), Karis Essential Oil Vanilla Extract (Karis Seijo Co., Ltd.), and the like. Vanilla essential oil may be used as it is for the frequent urination improving agent of the present invention, or it may be appropriately concentrated or diluted according to the strength of the odor of the essential oil.

In addition to Alpinia speciosa essential oil and/or vanilla essential oil, the agent for improving pollakiuria of the present invention may be combined with other essential oils such as lavender essential oil and Tyrin alpinia essential oil, solvents such as ethanol, and the like.

The dosage form of the frequent urination improving agent of the present invention is not particularly limited. Ointments, creams, patches, liquids for external use, sprays, cosmetics, sachets, etc. may be used.

Since the agent for improving pollakiuria of the present invention exerts its effects when taken into the body, the method of ingestion is not particularly limited, but nasal administration is preferred.

Examples of methods for nasally ingesting the agent for improving frequent urination of the present invention include aroma oils, room fragrances, aroma candles, perfumes, fragrances, nasal drops, and scents containing Alpinia alba essential oil and/or vanilla essential oil as active ingredients. A method of inhaling through the nose using a bag or the like can be mentioned.

In particular, the aroma oil and room fragrance are soaked, applied, or sprayed on filter paper or the like, or by using an aroma diffuser, and extracting Alpinia speciosa essential oil and/or vanilla essential oil, which are the active ingredients of the agent for improving frequent urination of the present invention. Volatilization into space is preferable. When the shell ginger essential oil and/or vanilla essential oil are volatilized in this space, the concentration is not particularly limited, but for example, it may be within the range of the scent concentration that humans feel comfortable.

In addition, the usage time of the agent for improving pollakiuria of the present invention is not particularly limited. Furthermore, the timing of use of the agent for improving frequent urination of the present invention is not particularly limited. while you are

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

Example 1
The action of getto essential oil to improve frequent urination:
<animal>
Test 1) SD female rats (10 animals: body weight about 207-240 g)
1. Control group (5 animals)
2. Getto group (5 animals)
Test 2) 10 SD female rats (weight about 279-293 g)
1. Control group (5 animals)
2. Shell ginger aroma group (5 animals)
<Essential oil>
Getto essential oil (getto essential oil: manufactured by Nippon Getto Co., Ltd.) (p-cymene 23%, β-terpinene 18.9%, α-pinene 13.3%, camphene 6.7%, 1,8 cineol 5. 6%, β-pinene 3.7%, etc.)

<Test method>
Urethane light anesthesia (0.6 g/kg: 0.2 g/kg intraperitoneal administration, 0.4 g/kg subcutaneous administration) was performed under isoflurane inhalation anesthesia. After about 40 minutes, a catheter (PE50) was inserted urethrally into the bladder under restraint (NAIGAI-CFK-1P; NMS, Tokyo), and physiological saline was continuously infused into the bladder at a rate of 3 ml/h. Cystometry was performed. Urination was allowed around the catheter. Aroma diffusers (Sensor Aroma Fan, ADF36-SAF, Radonna Co., Ltd., Tokyo) were prepared at a ratio of one per three cows in the getto aroma group. In both test 1) and test 2), the shell ginger aroma group was divided into 2 groups of 3, each 3 was covered with vinyl at a height of 20 cm, and one of the 4 directions of the vinyl was covered, and the bottom was about 1 cm. Opened 3 cm. An aroma diffuser impregnated with Alpinia speciosa essential oil (3 drops) was placed in the center of the three animals, and continuous intracystic pressure measurement was performed for about 1.5 hours while allowing the rats to smell the aroma of Alpinia speciosa essential oil. The control group underwent continuous cystometry for approximately 1.5 hours without aromatherapy. From about 1 hour after the continuous cystometrometry, the bladder contraction interval, baseline bladder pressure and maximum bladder contraction pressure were determined, and the residual urine volume after the final bladder contraction was measured.

In test 1), plasma monoamine was measured by collecting blood after measuring intravesical pressure.
In test 2), after measuring the cystometrogram with physiological saline, the 0.25% saline solution with acetic acid was changed and continuously infused into the bladder at a rate of 3 ml/h, and continuous cystometrometry was performed for about 1 hour. The contraction interval, bladder baseline pressure and maximum bladder contraction pressure were determined, and the residual urine volume after the final bladder contraction was measured.
Statistical processing: Values are expressed as mean ± standard error, t-test (two-sided test) was used, and p<0.05 was considered significant.

<Results>
Test 1) In the shell ginger aroma group, the urination interval was significantly longer than in the control group (Fig. 1, Table 1). On the other hand, there was no difference between the two groups in bladder baseline pressure, micturition threshold pressure and maximum bladder contraction pressure. In both groups, there was no residual urine. Regarding plasma monoamines, serotonin levels were significantly higher in the shell ginger aroma group than in the control group (Fig. 2, Table 2). However, adrenaline, noradrenaline and dopamine levels did not differ between the two groups.

Test 2) The rats in Test 2 were several weeks older than the rats in Test 1 and weighed more. In the control group, the urinary interval was extended, probably because the bladder was larger than that of the rats in Test 1 as measured by intracystometry with physiological saline. Even so, the getto aroma group had a significantly longer urination interval than the control group (Fig. 3, Table 3).

When 0.25% saline acetic acid was injected into the bladder, the acetic acid stimulation significantly shortened the micturition interval in both groups. It was significantly longer than the bladder contraction interval with 0.25% acetic acid saline in the control group, and was at the level of the voiding interval with saline in the control group (Fig. 3, Table 3). Although there was no difference in the bladder baseline pressure between the two groups, the maximum bladder contraction pressure with 0.25% acetic acid saline in the control group was higher than the maximum bladder contraction pressure with saline in the control group and 0.25 in the getto group. It was significantly higher than the maximal bladder contraction pressure with % acetic acid saline.

<Conclusion>
The scent of shell ginger essential oil increased the blood serotonin concentration and extended the interval between urination. Even when the bladder was stimulated with acetic acid to cause frequent urination, the scent of shell ginger essential oil extended the micturition interval. This suggests that aromatherapy using shell ginger essential oil may have therapeutic effects for frequent urination.

Example 2
The effect of vanilla essential oil on frequent urination:
<animal>
Test 3) SD female rats (12 animals: body weight about 195-220 g)
1. Vanilla essential oil group (7 animals)
2. Shikwasa essential oil group (5 animals)
Test 4) SD female rats (12 animals: body weight about 195-220 g)
1. Vanilla essential oil group (6 animals)
2. Control group (6 animals)
<Essential oil>
Vanilla essential oil (Aroma Essence Blue Label Vanilla (registered trademark): manufactured by Global Product Planning Co., Ltd.) (60% ethanol, 25% dipropylene glycol, 10% ethyl vanillin, 2% vanillin, 2% linalool, 1% coumarin )
Shikuwasa essential oil (Shikuwasa essential oil: manufactured by Okinawa Research Center)

<Test method>
Test 3) 12 rats were anesthetized with urethane (0.6 g/kg subcutaneously, half the dose normally used for anesthesia). One hour later, rats were individually placed in restraint cages (NAIGAICFK-1P; NMS, Tokyo, Japan). A polyethylene catheter (PE50; Clay Adams, NJ, USA) was inserted transurethrally into the bladder. This catheter was connected to an infusion pump and pressure transducer via polyethylene tubing to deliver saline into the bladder at a rate of 0.05 mL/min. Continuous cystometry was performed for 80 minutes to record baseline bladder activity. Then, 7 rats inhaled vanilla essential oil and 5 rats inhaled sequarsa essential oil for the next 60 minutes following cystometry. This experiment was performed during the daytime, during the sleeping period of rats, from 10:00 am to 2:00 pm. Cystometry parameters before and during inhalation, and postvoid volume at the end of the residual experiment were compared between groups.

Inhalation of vanilla essential oil and shiikuasa essential oil was performed as follows. First, a paper disc (2.5 x 3.0 cm, 1 mm thick) was impregnated with essential oil and placed on a hot plate diffuser positioned 20 cm from the rat's nose. Each rat and hot plate diffuser were placed in a cardboard box (approximately 80 x 60 x 60 cm) with two-thirds of one side of the box covered with clear vinyl and the rest left open. Inhalation was performed for 60 minutes under continuous cystometry.

Test 4) 12 rats were anesthetized with urethane (0.6 g/kg subcutaneously). After 1 hour, the rats were placed individually in restraint cages (NAIGAI-CFK-1P; NMS, Tokyo, Japan). Cystometry was not performed in this group. Six rats inhaled vanilla essential oil for 60 minutes as above, and the remaining six rats did not inhale anything. Blood was then collected from the inferior vena cava under temporary isoflurane anesthesia, and serum was obtained by centrifugation for measurement of monoamine concentration (BML, Tokyo, Japan). Serum monoamine levels were compared between the two groups. Results were reported as mean±standard error of the mean (SEM). Groups were compared using Student's paired or unpaired t-test. P<0.05 was considered to indicate statistical significance.

<Results>
Study 3) The interval between bladder contractions (14.5±1.8 min; P=0.012) was lengthened by inhalation of vanilla essential oil (20.0±1.9 min). (Fig. 4). However, bladder pressure, maximal bladder contraction pressure, and residual volume (<0.1 mL) did not change from baseline. On the other hand, each rat's body movement increased during inhalation of Shikuwasa essential oil. However, interval between bladder contractions, baseline bladder pressure, maximum bladder contraction pressure and residual volume (<0.1 mL) did not change before and during inhalation (Fig. 5).

Test 4) Serum concentrations of adrenaline (8.8±1.2 ng/mL vs 19.7±3.5 ng/mL, P=0.016), noradrenaline (2.2±0.5 ng/mL vs 4.3±0.7 ng /mL, P = 0.017) and dopamine (0.10 ± 0.03 ng/mL vs. 0.23 ± 0.04 ng/mL, P = 0.014) in vanilla essential oil inhaled rats. (Fig. 6). There were no significant differences in serum serotonin levels between these groups.

<Conclusion>
It has been suggested that the scent of vanilla essential oil may suppress urinary intention and reduce urinary frequency and nocturia. On the other hand, it was suggested that Shikuwasa essential oil, which is known to have a refreshing effect, does not suppress the intention to urinate, so it does not have the potential to reduce nocturia.

Example 3
Human study 1:
Getto essential oil (getto essential oil: manufactured by Nippon Getto Co., Ltd.) was impregnated into cotton put in a commercially available sachets. When this was used in a tense situation in a case of psychogenic pollakiuria, it suppressed pollakiuria.

Example 4
Human study 2:
Vanilla essential oil (Aroma Essence Blue Label Vanilla (registered trademark): manufactured by Global Product Planning Co., Ltd.) was impregnated with cotton put in a commercially available sachet. When this was used in a tense situation in a case of psychogenic pollakiuria, it suppressed pollakiuria.

The agent for improving pollakiuria of the present invention can be used to prolong the micturition interval.

Claims (4)

An agent for improving frequent urination, characterized by containing Alpinia speciosa essential oil and/or vanilla essential oil as an active ingredient. The agent for improving frequent urination according to claim 1, which is for intranasal use. The agent for improving frequent urination according to claim 1 or 2, wherein the shell ginger essential oil contains p-cymene, β-terpinene, α-pinene, camphene, and 1,8-cineol. 3. The frequent urination improving agent according to claim 1, wherein the vanilla essential oil contains ethyl vanillin, vanillin, linalool and coumarin.

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