Ciliary motility activator

Abstract

To provide an agent that can activate ciliary motility.SOLUTION: Sodium bicarbonate has the action that can activate ciliary motility and serves as, therefore, an active ingredient of a ciliary motility activator.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a ciliary motility activator.

Background Art

[0002] Pathogens such as viruses and bacteria cause infectious diseases by entering the body. The emergence of new pathogens causes new infectious diseases, and in the stage where effective treatment methods and vaccines have not been established, defense against pathogens is the best countermeasure.

[0003] In the defense against pathogens that cause lung infections, importance is attached to the functions of the mucosa and cilia that cover the inner wall of the airway (lower airway) from the pharynx to the lungs so that the pathogens inhaled from the mouth and nose do not reach the lungs. For this reason, as one approach to enhancing the defense ability, research has been conducted on components that activate ciliary motility in the airway mucosa.

[0004] In addition, cilia are present not only in the airway (lower airway) from the pharynx to the lungs but also in the nasal mucosa. Foreign substances that have invaded the nasal mucosa are transported by the function of cilia and excreted into the throat. In patients with sinusitis or allergic rhinitis, purulent nasal discharge becomes entangled with cilia, and the function of discharging foreign substances declines. In addition, Non-Patent Document 1 reports that a decrease in nasal mucociliary clearance is recognized as a characteristic of the elderly, and Non-Patent Document 2 reports that the nasal mucosal mucociliary transport function is lower in smokers than in non-smokers. Furthermore, pH is known as a factor that affects the function of nasal mucosal mucocilia, and Non-Patent Document 3 reports that the motility is most active at around pH 7.8, and in the range of pH 8.1 to 6.5, it generally continues to move actively, but outside this range, the attenuation of activity becomes faster. When the movement of nasal mucocilia declines, foreign substances are likely to stay in the nasal cavity for a long time, and pathogens are likely to proliferate. For this reason, nasal irrigation is recommended as another approach to enhancing the defense ability.

[0005] For example, as a method for removing foreign substances that have entered the nasal cavity, nasal irrigation with physiological saline is known. Non-Patent Document 4 reports that, using the saccharin test, the decreased nasal mucosal ciliary motility function in patients with chronic rhinosinusitis is improved by intranasal administration of physiological saline.

Prior Art Documents

Non-Patent Documents

[0006]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Summary of the Invention

Problems to be Solved by the Invention

[0007] The improvement of the nasal mucosal ciliary motility function by the nasal irrigation described in Non-Patent Document 4 is an incidental effect accompanying physical irrigation, namely, the entanglement of purulent nasal discharge with cilia is loosened and the cilia are released. That is, the nasal irrigation described in Non-Patent Document 4 does not physiologically activate the ciliary movement itself, so it is only effective for patients with chronic rhinosinusitis and cannot activate the ciliary movement when applied to the nasal cavity without the symptom of purulent nasal discharge.

[0008] Therefore, an object of the present invention is to provide an agent capable of activating ciliary movement.

Means for Solving the Problems

[0009] The present inventors intensively studied to solve the above problems, and found that sodium hydrogen carbonate has an effect of activating ciliary movement. The present invention was completed by further studies based on this finding.

[0010] That is, the present invention provides an invention in the following aspects. Item 1. A ciliary movement activator containing sodium hydrogen carbonate. Item 2. The ciliary movement activator according to Item 1, which is used in the form of an aqueous solution containing the sodium carbonate at the time of use. Item 3. The ciliary movement activator according to Item 2, wherein the pH of the aqueous solution is 8.2 to 9.1. Item 4. The ciliary movement activator according to any one of Items 1 to 3, which is applied to nasal mucus cilia. Item 5. The ciliary movement activator according to any one of Items 1 to 4, which is used for washing a nasal cavity presenting a stuffy feeling or a nasal cavity not presenting nasal symptoms.

Effects of the Invention

[0011] According to the present invention, an agent capable of activating ciliary movement is provided.

Modes for Carrying Out the Invention

[0012] The ciliary movement activator of the present invention is characterized by containing sodium hydrogen carbonate. The content of sodium hydrogen carbonate in the ciliary movement activator of the present invention is not particularly limited, and can be appropriately set according to the ciliary movement activating ability to be provided, or in addition thereto, the dosage form, and the necessity and dilution ratio at the time of use, etc.

[0013] In addition, when the cilia motility activator of the present invention is used in the form of an aqueous solution at the time of use, the content of sodium hydrogen carbonate can also be set based on the pH of sodium hydrogen carbonate at the time of use and the necessity and dilution ratio for dilution at the time of use.

[0014] In addition to the above-mentioned active ingredient, the cilia motility activator of the present invention may contain other bases and additives required for formulation and the like, as long as the effects of the present invention are not impaired. Such bases and additives are not particularly limited as long as they are pharmaceutically acceptable. Examples thereof include water, polyhydric alcohols, surfactants, pH adjusters, isotonic agents such as sodium chloride, and / or chelating agents such as sodium edetate. Among these base materials and additives, from the viewpoint of further enhancing the activating effect of cilia motility, polyhydric alcohols and surfactants are preferably mentioned.

[0015] As the polyhydric alcohol, from the viewpoint of further enhancing the activating effect of cilia motility, a dihydric alcohol is preferably mentioned, and propylene glycol is more preferably mentioned. When the cilia motility activator of the present invention contains a polyhydric alcohol, the ratio of sodium hydrogen carbonate to the polyhydric alcohol is not particularly limited. For example, the content of the polyhydric alcohol with respect to 1 part by weight of sodium hydrogen carbonate is, for example, 0.05 to 3 parts by weight, preferably 0.1 to 1.5 parts by weight, more preferably 0.15 to 1 part by weight, and still more preferably 0.2 to 0.5 parts by weight.

[0016] As the surfactant, from the viewpoint of further enhancing the activating effect of cilia motility, a nonionic surfactant is preferably mentioned, polyoxyethylene sorbitan fatty acid ester is more preferably mentioned, and polyoxyethylene sorbitan monooleate (polysorbate 80) having an average added mole number of ethylene oxide (EO) of 20 is even more preferably mentioned.

[0017] In addition to the above components, the cilia motility activator of the present invention may contain other pharmacological components such as antibacterial agents as necessary, as long as the effects of the present invention are not impaired. The antibacterial agent is not particularly limited, but from the viewpoint of further enhancing the activation effect of cilia motility, preferably a quaternary ammonium salt, and from the viewpoint of further enhancing the activation effect of cilia motility, preferably benzalkonium chloride. When the cilia motility activator of the present invention contains an antibacterial agent, the ratio of sodium hydrogen carbonate to the antibacterial agent is not particularly limited. For example, the content of the antibacterial agent relative to the parts by weight of sodium hydrogen carbonate is, for example, 0.001 to 0.1 parts by weight, preferably 0.002 to 0.02 parts by weight, more preferably 0.003 to 0.01 parts by weight.

[0018] [Dosage form and product form] Examples of the dosage form of the cilia motility activator of the present invention include powders, granules, tablets, liquid preparations (aqueous liquid preparations), and the like. Among these, a liquid preparation (aqueous liquid preparation) is preferred because the cilia motility activator can be used as it is at the time of use or can be easily diluted at the time of use. These dosage forms of the cilia motility activator can be prepared by generally known methods.

[0019] In addition, the cilia motility activator of the present invention may be prepared so as to be used as it is without being diluted at the time of use, or may be prepared so as to be diluted at the time of use and used in the form of an aqueous liquid preparation. Note that dilution includes both dissolving powders, granules, and tablets in a liquid base and mixing a liquid preparation (that is, a concentrated liquid preparation) with a liquid base. A preferred dosage form of the cilia motility activator of the present invention is a concentrated liquid preparation prepared so as to be diluted at the time of use and used in the form of an aqueous liquid preparation.

[0020] The concentration of sodium hydrogen carbonate when using the ciliary motility activator of the present invention is not particularly limited, and for example, 0.2% by weight or more can be mentioned. From the viewpoint of further enhancing the activation effect of ciliary motility, the concentration of sodium hydrogen carbonate when using the ciliary motility activator of the present invention is preferably 0.3 to 2.0% by weight, more preferably 0.45 to 1.5% by weight, still more preferably 0.6 to 1.3% by weight, and even more preferably 0.75 to 0.9% by weight or 0.75 to 0.85% by weight.

[0021] The pH when using the ciliary motility activator of the present invention is not particularly limited. However, since the ciliary motility activator of the present invention is excellent in the activation effect of ciliary motility, it can effectively activate ciliary motility even at a pH at which it has been reported that the activity of ciliary motility decreases. From such a viewpoint, the preferable pH (25 °C) when using the ciliary motility activator of the present invention is 8.2 to 9.1, more preferably 8.3 to 8.8, and still more preferably 8.4 to 8.6.

[0022] The osmotic pressure when using the ciliary motility activator of the present invention is not particularly limited and can be appropriately set in consideration of the irritation to the tissue at the application site. For example, the closer the osmotic pressure is to the osmotic pressure when using the ciliary motility activator of the present invention, the more preferable it is. Specifically, the osmotic pressure at 25 °C is 250 to 350 mOsm / kg, preferably 270 to 2300 mOsm / kg, and more preferably 280 to 290 mOsm / kg.

[0023] When the ciliary motility activator of the present invention is prepared to be diluted and used during use, the dilution ratio during use is not particularly limited. For example, in the case of a concentrated liquid preparation, for example, 2 to 100 times, preferably 3 to 50 times, and more preferably 4 to 20 times can be mentioned. Further, the liquid base used for dilution is preferably water.

[0024] [Use] The ciliary motility activator of the present invention is used for the purpose of activating ciliary motility. By activating ciliary motility, the ability to expel foreign substances such as viruses can be enhanced, so it can be used for the purpose of preventing infectious diseases.

[0025] The cilia activated by the ciliary motility activator of the present invention are not particularly limited, and examples include cilia present in the upper respiratory tract and cilia present in the lower respiratory tract. Preferably, cilia present in the upper respiratory tract are included, and more preferably, nasal cavity mucus cilia are included.

[0026] When the ciliary motility activator of the present invention is applied to nasal cavity mucus cilia, the state of the nasal cavity in contact with the ciliary motility activator of the present invention is not particularly limited. For example, it may be any of a nasal cavity presenting purulent nasal discharge or nasal congestion due to it such as sinusitis, a nasal cavity presenting a stuffy feeling, and a nasal cavity not presenting nasal symptoms (such as nasal discharge, stuffy feeling, etc.).

[0027] Since the ciliary motility activator of the present invention is considered to be able to physiologically activate the motility function of cilia itself, it can effectively activate ciliary motility even for cilia without factors that physically restrict ciliary motility such as purulent nasal discharge. From such a viewpoint, preferred examples of the nasal cavity in contact with the ciliary motility activator of the present invention include a nasal cavity not accompanied by purulent nasal discharge or nasal congestion caused by it. Specifically, a nasal cavity presenting a stuffy feeling (for example, a nasal cavity accompanied by rhinitis due to allergic rhinitis, vasomotor rhinitis, etc.), and a nasal cavity not presenting nasal symptoms, etc. are included. In addition, the ciliary motility activator of the present invention is preferably applied to a subject with a reduced nasal cavity mucus ciliary motility function. Examples of such application subjects include smokers and elderly people (specifically, 65 years old or older), etc.

[0028] The method for applying the ciliary motility activator of the present invention to cilia is not particularly limited, and examples include washing (rinsing), and aerosol spraying or aerosol inhalation. From the viewpoint of further enhancing the activation effect of ciliary motility, the method for applying the ciliary motility activator of the present invention to cilia preferably includes washing (rinsing), and specifically includes nasal cavity washing.

[0029] In addition, since the ciliary motility activator of the present invention has an immediate effect, it can be used before the cilia are exposed to an environment where they can come into contact with foreign substances, for example, before meeting others or going out, more specifically, 10 to 30 minutes before meeting others or going out, etc.

Examples

[0030] Examples are shown below to more specifically explain the present invention, but the present invention is not limited thereto.

[0031] Test Example A nasal irrigation solution with the formulation and properties shown in Table 1 was prepared and 25 ml was contained in a discharge container. In addition, as subjects, those with or without allergic symptoms and nasal symptoms as shown in Table 2 were selected.

[0032] (1) Regarding the nasal irrigation solution (physiological saline) of Comparative Example 1, nasal irrigation (nasal douching) was performed by using a discharge container to flow the entire liquid flow of the nasal irrigation solution (physiological saline) into the nasal cavity. (2) The subjects were acclimatized in a sitting position for 20 minutes. (3) After blowing the nose, a saccharin granule with a diameter of 1 mm was attached to one inferior turbinate. The attachment site was 8 mm deep from the front end of the inferior turbinate. (4) After attachment, the time until the taste was felt was measured. This time was defined as the nasal clearance time (NCT). At this time, swallowing was performed once every 30 seconds to confirm whether the taste was felt. (5) After 3 hours, the same operations as (1) to (4) were performed using the nasal irrigation solution (ciliary motility activator) of Example 1. (6) The value (difference) obtained by subtracting the NCT according to Example 1 from the NCT according to Comparative Example 1 was derived. The results are shown in Table 2. (7) On another day, the same operations as (1) to (6) were performed except that the nasal irrigation solution (ciliary motility activator) of Example 2 or 3 was used.

[0033]

Table 1

[0034]

Table 2

[0035] As is clear from Table 2, in all subjects, it was confirmed that the NCT was shortened. In addition, the shortening effect of NCT was observed not only in subjects A and B with nasal symptoms of nasal congestion (subjects in whom the movement of cilia might have been physically restricted due to purulent nasal discharge), but also in subject C with a feeling of stuffiness without purulent nasal discharge symptoms, and subjects D, E, and F without nasal symptoms (none of them had factors physically restricting the movement of cilia). Therefore, it is considered that the ciliary movement was physiologically activated.

[0036] In addition, for Example 2 and Example 3 as well, in all subjects, the NCT was shortened and the activation effect of ciliary movement was confirmed. The degree of shortening of NCT was the greatest in Example 1.

Claims

1. A ciliary motility activator containing sodium hydrogen carbonate.

2. The ciliary motility activator according to claim 1, which is used in the form of an aqueous solution containing the sodium carbonate at the time of use.

3. The ciliary motility activator according to claim 2, wherein the pH of the aqueous solution is 8.2 to 9.

1.

4. The ciliary motility activator according to any one of claims 1 to 3, which is applied to nasal mucus cilia.

5. The ciliary motility activator according to any one of claims 1 to 4, which is used for washing a nasal cavity presenting a stuffy feeling or a nasal cavity not presenting nasal symptoms.

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