Composition for preventing or treating nasal mucosa diseases, containing high concentration of oxygen

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating nasal mucosa diseases, containing a high concentration of oxygen. Specifically, when administered in the form of a nasal drop solution, aerosol spray, ointment, or gel, the composition of the present invention can continuously deliver high-concentration oxygen directly to the nasal mucosa and enhance ciliary movement. In addition, the composition exhibits an effect of promoting wound healing or inhibiting inflammation through improvement of ciliary motion of the nasal mucosa, and thus can be widely used for preventing or treating burns, infections, inflammations, and nasal mucosa diseases that may occur after nasal surgery.

Description

Composition for the prevention or treatment of non-mucosal diseases containing high concentration of oxygen

[0001] The present invention relates to a pharmaceutical composition for preventing or treating nasal mucous membrane diseases, which contains high concentrations of oxygen, and more specifically, to a composition that continuously delivers high concentrations of oxygen to the nasal mucous membrane to improve nasal mucous membrane ciliary movement, thereby promoting nasal mucous membrane wound healing and alleviating inflammation.

[0002] The nose is exposed to the external environment and is easily injured by infection, inflammation, trauma, or surgery. Therefore, to protect against these threats, the nose possesses various defense mechanisms, including nasal hairs, cilia, nasal mucus, and antibodies. Nasal hairs function as a primary filter, filtering out inhaled foreign substances larger than a certain size. Smaller foreign substances and microorganisms are transported and filtered through the mucus contained in nasal mucus by the movement of cilia.

[0003] Cilia are tiny, hair-like structures found in the cells of the nose. They move rapidly, at a rate of 5-20 times per second, to remove foreign substances and microorganisms from the outside world. If ciliary activity is disrupted and prevents proper defense, inflammation and infection can occur, leading to conditions like rhinitis and sinusitis. Therefore, proper ciliary activity is essential for maintaining this defense and proper nasal function.

[0004] Conventional techniques for increasing ciliary activity include saline irrigation and oxygen capsule-based methods. However, saline irrigation has limitations: it only physically removes foreign substances to increase ciliary activity, making it difficult to increase ciliary activity itself. Furthermore, the oxygen capsule-based method suffers from structural limitations in providing high-pressure oxygen. Consequently, technologies capable of actually increasing ciliary activity are limited.

[0005] Against this backdrop, the present invention confirmed that when nasal mucous membrane tissue is cultured in a solution containing a high concentration of oxygen, ciliary movement increases and wound healing is promoted, thereby confirming the possibility that providing a high concentration of oxygen to the nasal mucous membrane can contribute to the prevention and treatment of postoperative trauma, infection, and inflammation.

[0006] [Prior Art Literature]

[0007] [Patent Document]

[0008] (Patent Document 0001) Republic of Korea Publication Patent Document No. 10-2017-0141870 (December 28, 2017)

[0009] The purpose of the present invention is to provide a composition capable of treating high concentrations of oxygen to improve symptoms of non-mucosal diseases.

[0010] To achieve the above purpose, the present invention provides a pharmaceutical composition for preventing or treating non-mucosal diseases, which comprises high concentration oxygen.

[0011] The present invention also provides a composition for nasal washing, comprising high concentration oxygen.

[0012] When using a pharmaceutical composition containing high-concentration oxygen according to the present invention, it has the effect of promoting wound healing or alleviating inflammation through improving ciliary movement of the nasal mucosa by directly treating the nasal mucosa with high-concentration oxygen of 25 to 80 DO (Dissolved Oxygen), so it can be widely used for treating trauma or infection after surgery or for preventing or treating nasal mucosa diseases.

[0013] Figure 1a shows the results of confirming the effect of promoting wound healing in the BEAS-2B cell line when the oxygen concentration (DO; Dissolved Oxygen) is 15 to 21 DO.

[0014] Figure 1b shows the results of confirming the effect of promoting wound healing in the BEAS-2B cell line when the oxygen concentration (DO; Dissolved Oxygen) was 22 to 24 DO.

[0015] Figure 2 shows the results of confirming the effect of promoting wound healing when low-concentration oxygen water was repeatedly treated to the BEAS-2B cell line.

[0016] Figure 3a shows the results of confirming the effect of promoting wound healing in the BEAS-2B cell line when the oxygen concentration is 25 to 27 DO.

[0017] Figure 3b shows the results of confirming the effect of promoting wound healing in the BEAS-2B cell line when the oxygen concentration is 26 to 30 DO.

[0018] Figure 4a shows the results of confirming the effect of promoting wound healing in the BEAS-2B cell line when the oxygen concentration is 50 to 76 DO.

[0019] Figure 4b shows the results of confirming the effect of promoting wound healing in the BEAS-2B cell line when the oxygen concentration was 77 to 80 DO.

[0020] Figure 5a shows the results of confirming the effect of promoting wound healing in the BEAS-2B cell line when the oxygen concentration was 81 to 84 DO.

[0021] Figure 5b shows the results of confirming the effect of promoting wound healing in the BEAS-2B cell line when the oxygen concentration is 85 to 100 DO.

[0022] Figure 6a shows the results of confirming the effect of improving ciliary movement when the oxygen concentration is 24 to 25 DO.

[0023] Figure 6b shows the results of confirming the effect of improving ciliary movement when the oxygen concentration is 50 to 81 DO.

[0024] Figure 7 shows the results of confirming the effect of suppressing the expression of inflammatory cytokines at oxygen concentrations of 25, 50, and 80 DO.

[0025] Figure 8 shows the results of comparing the degree of active oxygen production when the oxygen concentration is 70, 80, 90, and 100 DO.

[0026] Hereinafter, the present invention will be described in detail.

[0027] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Generally, the nomenclature used herein is well known and commonly used in the art.

[0028] When the present invention says that a component or a step "includes", this does not mean that other components or other steps are excluded, but rather that other components or other steps may be further included, unless specifically stated otherwise.

[0029] As used herein, the term "administration" means a method of causing at least partial localization to a desired site of an individual or placing a given substance into an individual. Administration may be carried out by any method known in the art.

[0030] In the present invention, the term "prevention" may include, without limitation, any act that can block, suppress or delay symptoms caused by a non-mucosal disease by using the composition of the present invention.

[0031] In the present invention, the term "treatment" may include, without limitation, any act that can improve or benefit symptoms caused by a non-mucosal disease by using the composition of the present invention.

[0032] In the present invention, the term "nasal mucous membrane" refers to the epithelium and subepithelial connective tissue covering the nasal cavity.

[0033] In the present invention, the term "upper airway mucous membrane" refers to the epithelial and subepithelial connective tissue covering the upper respiratory tract, i.e., the nasal cavity, paranasal sinuses, nasopharynx, pharynx, and larynx, which are composed of the same cells and tissues.

[0034] The present invention provides a pharmaceutical composition for preventing or treating non-mucosal diseases, which comprises high concentration oxygen.

[0035] The above composition can improve ciliary movement of the non-mucosal membrane, thereby having an effect of promoting wound healing or alleviating inflammation, but is not limited thereto.

[0036] The above non-mucosal disease may be at least one selected from the group consisting of nasal polyps, septal deviation, rhinitis, sinusitis, rhinorrhea, posterior nasal drip syndrome, nasal obstruction, nasal and paranasal cavity cancer, mucosal edema, inflammation, hyposmia, nasopharyngitis, pharyngitis, laryngitis, and anosmia, but is not limited thereto.

[0037] The concentration of the above oxygen may be, but is not limited to, 25 to 80 DO.

[0038] According to one embodiment of the present invention, when the oxygen concentration is less than 25 DO or more than 80 DO, the effects of promoting wound healing and ciliary movement may be inhibited.

[0039] The pharmaceutical composition of the present invention may further include suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.

[0040] The pharmaceutical dosage form of the composition according to the present invention can be used in the form of their pharmaceutically acceptable salts, and can also be used alone or in combination with other pharmaceutically active compounds as well as in an appropriate combination.

[0041] The pharmaceutical composition according to the present invention can be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, sterile injection solutions, nasal drops, nasal aerosol sprays, ointments, or gel preparations, respectively, according to conventional methods, and preferably, can be formulated and used in the form of nasal drops, nasal aerosol sprays, ointments, or gel preparations, but is not limited thereto.

[0042] The above pharmaceutical composition may be used in a form applied to or impregnated with a sponge, cotton, gauze, patch, or dressing, but is not limited thereto. The application refers to applying or allowing the pharmaceutical composition to be absorbed onto the sponge, cotton, gauze, patch, or dressing, and the impregnation refers to allowing the pharmaceutical composition to penetrate into the sponge, cotton, gauze, patch, or dressing so that the properties of the composition are applied according to the intended use of the present invention.

[0043] Carriers, excipients and diluents that may be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate mixtures, and the like.

[0044] Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations can be manufactured by mixing at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc., with the pharmaceutical composition. In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, syrups, etc., and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, suspending agents, emulsions, lyophilized preparations, preservatives, etc. can be included.

[0045] Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solutions and suspensions can include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases include witepsol, macrogol, Tween 61, cacao butter, laurin butter, and glycerogelatin.

[0046] The preferred dosage of the composition of the present invention varies depending on the patient's condition and weight, the degree of disease, the drug form, the route of administration, and the period of administration, but can be appropriately selected by a person skilled in the art.

[0047] The present invention also provides a composition for nasal washing comprising high concentration oxygen.

[0048] The above nasal washing composition may be, but is not limited to, a liquid or spray formulation.

[0049] The above composition may further include an appropriate conventional therapeutic anti-allergic agent or anti-inflammatory agent for improving symptoms of non-mucosal diseases, and may further include additives such as fragrances, pigments, bactericides, antioxidants, preservatives, moisturizers, thickeners, inorganic salts, emulsifiers, and synthetic polymers for improving physical properties.

[0050]

[0051] Hereinafter, the present invention will be described in more detail through examples. These examples are intended solely to illustrate the present invention more specifically, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples, in accordance with the gist of the present invention.

[0052]

[0053] Example 1. Experimental materials and methods

[0054] To determine the minimum and maximum concentrations of oxygen water for enhancing ciliary motility and promoting wound healing in BEAS-2B cells, a non-mucosal and airway epithelial cell line, experiments were conducted using respiratory mucosal cell lines and human nasal mucosal cells. For the oxygen water generator, equipment capable of producing solutions containing high concentrations of oxygen was manufactured, and actual dissolved oxygen levels (DO) were measured. Experiments were conducted with oxygen water concentrations ranging from 10 to 100 DO.

[0055]

[0056] Example 2. Effect of promoting wound healing

[0057] To confirm the wound healing effect of a solution containing high concentration of oxygen, wounds were made on airway epithelial cell lines, and the degree of recovery was observed under a microscope and compared with the control group.

[0058] As a result of the experiment, compared to the control group (N) with an oxygen concentration (DO; Dissolved Oxygen) of about 7 to 8, there was no difference in the overall wound healing rate from the control group in the DO 15 to 24 range (Fig. 1), and even when DO 15 and DO 20 were repeatedly administered at 0, 2, 4, 24, and 28 hours, the wound healing effect was hardly observed (Fig. 2).

[0059] In the DO range of 25 to 80, rapid wound healing was observed for the first 24 hours, and a tendency for the wound area to steadily decrease for up to 48 hours was confirmed (Figs. 3 and 4). However, at concentrations of DO 80 or higher, wound healing tended to slow down, and at DO 100, there was no difference or wound healing was actually inhibited (Fig. 5). The above results show that DO 25 to 80 has the effect of promoting wound healing, but at low concentrations of DO less than 25 or high concentrations of DO 81 or higher, wound healing slowed down.

[0060]

[0061] Example 3. Effect of improving ciliary beating frequency (CBF)

[0062] To determine the effect of a solution containing high concentrations of oxygen on improving ciliary motility, human nasal mucosa was collected, administered the solution, and observed under a microscope. Moving cilia were photographed with a high-speed digital camera, and sections with clear image quality were selected, recorded, and stored on a computer. The recorded images were then analyzed using an image analysis program to measure the frequency of ciliary motility.

[0063] As a result of the experiment, in the DO range below 25, the number of ciliary movements was no different from that of the control group, and 24 hours after administration of the DO 24 solution, the ciliary movement value decreased to about 84% (Fig. 6a), whereas in the DO range of 25 to 80, ciliary movement tended to be continuously activated after solution administration (Fig. 6b). However, when the DO 81 and DO 84 solutions were administered, the effect of ciliary movement was reduced, and a pattern of decreasing ciliary movement frequency over time was observed. Through the above results, it can be seen that when the DO range is 25 to 80, it has the effect of activating ciliary movement, but when the DO is a low concentration below 25 or a high concentration above 81, ciliary movement is reduced.

[0064]

[0065] Example 4. Anti-inflammatory effect

[0066] Experiments were conducted using BEAS-2B cell lines, and both the control and experimental groups were cultured in a medium supplemented with cytokines including TNF-α, IL-8M IL-1b, and GM-CSF after inducing inflammation with LPS (lipopolysaccharide). The anti-inflammatory effect of oxygen water was confirmed by RT-PCR. The experimental results showed that the expression of inflammatory cytokines was suppressed when the oxygen concentration was 25, 50, and 80 (Fig. 7).

[0067]

[0068] Example 5. Effect of generating reactive oxygen species (ROS)

[0069] After administering oxygen water to BEAS-2B cells for 24 hours, the amount of reactive oxygen species (ROS) generated was compared according to the oxygen water concentration. When the oxygen water concentration was 70 or 80, there was no significant difference from the control group, but when the oxygen water concentration was 90 or 100, the amount of reactive oxygen species increased (Fig. 8). Therefore, it can be seen that when the oxygen water concentration is 90 or higher, harmful results are produced due to the generation of reactive oxygen species, and therefore, it can be seen that the composition according to the invention should contain an oxygen water concentration less than 90.

Claims

1. A pharmaceutical composition containing high concentration oxygen for the prevention or treatment of nasal mucous membrane diseases.

2. A pharmaceutical composition according to claim 1, characterized in that the composition improves ciliary movement of the non-mucosal membrane.

3. A pharmaceutical composition according to claim 1, characterized in that the composition is a nasal drop, nasal aerosol spray, ointment, or gel formulation.

4. A pharmaceutical composition according to claim 1, characterized in that the composition is used in a form applied to or impregnated with a sponge, cotton, gauze, patch, or dressing.

5. A pharmaceutical composition according to claim 1, wherein the non-mucosal disease is at least one selected from the group consisting of nasal polyps, septal deviation, rhinitis, sinusitis, rhinorrhea, posterior nasal drip syndrome, nasal obstruction, nasal and paranasal cavity cancer, mucosal edema, inflammation, hyposmia, nasopharyngitis, pharyngitis, laryngitis, and anosmia.

6. A pharmaceutical composition according to claim 1, wherein the concentration of oxygen is 25 to 80 DO (Dissolved Oxygen).

7. A composition for nasal washing containing high concentration oxygen.

8. A nasal washing composition according to claim 7, wherein the nasal washing composition is a liquid or spray formulation.

9. A composition for nasal washing, wherein the oxygen concentration in the 7th paragraph is 25 to 80 DO.

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