WO2013081366A1 - Composition for cleaning nasal cavity containing mineral water - Google Patents
Composition for cleaning nasal cavity containing mineral water Download PDFInfo
- Publication number
- WO2013081366A1 WO2013081366A1 PCT/KR2012/010154 KR2012010154W WO2013081366A1 WO 2013081366 A1 WO2013081366 A1 WO 2013081366A1 KR 2012010154 W KR2012010154 W KR 2012010154W WO 2013081366 A1 WO2013081366 A1 WO 2013081366A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- mineral water
- composition
- present
- nasal
- rhinitis
- Prior art date
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- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
Definitions
- the present invention relates to a composition for washing the nasal cavity containing mineral water and a pharmaceutical composition capable of preventing or treating rhinitis and sinusitis.
- Rhinitis refers to inflammation occurring in the nasal mucosa inside the nose, which is the respiratory organ of the human body, and includes acute and chronic rhinitis, viral rhinitis due to cold, and allergic rhinitis. Symptoms include a runny nose (a benign nasal mucus) and a stuffy nose (nasal obstruction). In general, infection with rhinitis not only causes difficulty breathing, but also causes symptoms such as headache or attention deterioration, which causes greater discomfort, and is rarely cured despite long-term treatment. The disease recurs afterwards, making treatment difficult.
- allergic rhinitis or sinusitis causes chronic oxygen deficiency due to nasal congestion, which significantly reduces brain function. Therefore, children or adolescents with rhinitis or sinusitis often have chronic fatigue and learning disabilities, and even those with heavy workloads cause a lot of disruptions due to lower work efficiency.
- paranasal sinuses are located around the nose and filled with bone-filled air.
- the main paranasal sinuses are the frontal sinus located above both eyebrows, the maxillary sinus located on the face below both eyes, the ethmoid sinus located between both eyes, and the sphenoid sinus deep behind the nose. have.
- the paranasal sinuses are covered with the same type of mucosa as the nasal mucosa.
- the nasal and paranasal sinuses produce mucous secretions daily, from which the nasal secretions exit through the natural openings leading to the small sized pencil-holes in the nose.
- the obstruction of the sinus outlet may be caused by anatomical causes, irritants, or allergies in the nose, and sinus disease may occur frequently in the same family, and stress may be a cause of chronic sinus disease as well as nasal obstruction. May cause excessive breathing in the lungs and make asthma worse.
- antiallergic or antihistamines are prescribed for the treatment of nasal diseases including rhinitis.
- antihistamines have side effects of frequent relapses and drowsiness, and topical steroids sprayed on the nose also eliminate symptoms at the moment of use, but they can cause sinusitis if used for a long time.
- topical steroids sprayed on the nose also eliminate symptoms at the moment of use, but they can cause sinusitis if used for a long time.
- the nasal congestion is severe, there is a problem that the laser surgery is expensive, which is expensive.
- herbal medicine is acupuncture and aromatherapy, physiotherapy, drug therapy will be treated, these treatments also have a temporary symptomatic effect, it is not effective to cure rhinitis.
- the present invention comprises a nasal wash composition
- a nasal wash composition comprising the marine mineral water taken from the 1100m underground of the hot spring area of the coastal Dangu district 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, South Korea as an active ingredient to provide.
- the mineral water is a mineral component, potassium 200 ⁇ 230mg / L, sodium 7000 ⁇ 9500mg / L, calcium 1400 ⁇ 1700mg / L, magnesium 900 ⁇ 1100mg / L, zinc 3 ⁇ 9mg / L , Strontium 25 ⁇ 35mg / L, Selenium 200 ⁇ 500ug / L, Vanadium 65 ⁇ 75ug / L, Germanium 0.5 ⁇ 1.5ug / L, Manganese 10 ⁇ 40ug / L, Cobalt 1-3ug / L, Titanium 600 ⁇ 950ug / L , Copper 3 ⁇ 9ug / L, lithium 0.02 ⁇ 0.09mg / L, chlorine ion 16000 ⁇ 19500mg / L, fluorine ion 1.5 ⁇ 3.0mg / L, bromine ion 40 ⁇ 56mg / L, sulfate ion 3000 ⁇ 4
- the mineral water is a concentrate
- the concentrate may be contained in 0.5 to 50% (v / v) based on the total weight of the composition.
- the composition may be a liquid, paste, ointment, or spray formulation.
- the present invention provides a composition for the prevention or treatment of rhinitis or sinusitis, including the marine mineral water taken from the 1100m underground of the hot spring area of the waterfront district 92-1 Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, South Korea.
- the mineral water is a mineral component, potassium 200 ⁇ 230mg / L, sodium 7000 ⁇ 9500mg / L, calcium 1400 ⁇ 1700mg / L, magnesium 900 ⁇ 1100mg / L, zinc 3 ⁇ 9mg / L , Strontium 25 ⁇ 35mg / L, Selenium 200 ⁇ 500ug / L, Vanadium 65 ⁇ 75ug / L, Germanium 0.5 ⁇ 1.5ug / L, Manganese 10 ⁇ 40ug / L, Cobalt 1-3ug / L, Titanium 600 ⁇ 950ug / L , Copper 3 ⁇ 9ug / L, lithium 0.02 ⁇ 0.09mg / L, chlorine ion 16000 ⁇ 19500mg / L, fluorine ion 1.5 ⁇ 3.0mg / L, bromine ion 40 ⁇ 56mg / L, sulfate ion 3000 ⁇ 4
- the mineral water is the mineral water is a concentrate
- the concentrate may contain 0.5 to 50% (v / v) based on the total weight of the composition.
- the mineral water may be to reduce the swelling of the intranasal mucosa due to inflammation, and to reduce the expression of MUC5AC gene, a mucus hypersecretion-inducing factor.
- composition for nasal washing and the composition for the prevention or treatment of rhinitis or sinusitis caused by inflammation, etc. containing marine mineral water taken from 1100m underground of the hot spring area of 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, South Korea according to the present invention It has the effect of reducing the swelling and thickness of the nasal mucosa, and also improves the degree of inflammation, and also has an excellent effect of reducing the expression of substances that induce mucus hypersecretion, thereby improving, preventing and improving nasal disease symptoms such as sinusitis and rhinitis. There is an effect that can be widely used in the manufacture of treatable nasal washes and therapeutic agents and functional health foods.
- Figure 1 shows a microscopic view of the thickness of the nasal mucosa in rats induced by rhinosinusitis by LPS injection in the rat model, (a) is nothing treated, (b) saline solution Group treated with, (c) shows a group treated with LPS.
- FIG. 2 shows a photograph of the same mouse group as shown in FIG. 1 when observed with a microscope, and the arrow indicates the site of the increased PAS.
- Figure 3 shows the pictures observed by the Evans blue reagent staining effect on the vascular outflow due to inflammation in the same rat group as in Figure 1, the arrow shows the Evans blue staining with increased mucosal outflow.
- Figure 4 shows a photograph observed by Evans blue reagent staining effect of inflammation due to mineral water treatment according to the present invention
- A is a group not treated anything
- B is a group treated only saline
- C is LPS-treated group
- D treated with LPS and saline
- E treated with LPS and 25% mineral water
- F treated with LPS and 50% (v / v) mineral water
- One group, G represents the group treated with LPS and 100% (v / v) mineral water
- Figure 6 shows the result of observing the nasal mucosa thickness of the microscope through hematoxylene-eosin staining after separating the nasal mucosa tissue from each rat group of FIG.
- FIG. 7 shows the result of FIG. 6 as a bar graph.
- FIG. 8 is a mineral water according to the present invention in order to determine whether there is an effect of inhibiting the expression of the mucus hypersecretion inducing factor MUC5AC gene, after taking nasal tissue from each rat group of Figure 4, which can amplify the MUC5AC gene RT-PCR using the primers are shown.
- the present invention is characterized in that it provides a new nasal cleaning composition comprising mineral water excellent in nasal washing effect and particularly excellent in reducing nasal mucosal edema and mucus hypersecretion due to inflammation.
- Mineral water contained as an active ingredient in the nasal cleaning composition according to the present invention is characterized in that it is marine mineral water taken from the 1100m underground of the hot spring area of 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, South Korea.
- seawater In general, seawater is called deep seawater, which is distinguished from surface water, and deep sea water refers to seawater 200 meters or less from the surface of seawater. It contains many inorganic nutrients such as nitrogen, phosphorus, and silicic acid needed for plant growth because photosynthesis does not occur. It is known that it is not polluted by air or chemicals and contaminated with solar bacteria or general bacteria, and has a small number of benign bacteria, so that the physical cleanliness is excellent.
- nasal diseases caused by colds, sinusitis and allergic rhinitis cause headaches, sleep deprivation, coughing, stress, etc. in modern times, which greatly reduces the quality of life of the individual. It causes a loss of social costs.
- recent statistics show that about 15% of the total population has sinusitis and about 30% have allergies, costing about $ 2.4 billion and $ 3.4 billion in medical costs annually.
- research on nasal lavage that can increase the therapeutic effect is increasing.
- Nasal lavage is known to be a very effective way to improve mucus islet function, reduce swelling of the nasal mucosa, reduce the activity of inflammation-related factors and cleanse concentrated mucus (Tomooka LT et al., Clinical study and literature review of nasal irrigation. , Laryngoscope. 2000 Jul; 110 (7): 1189-93).
- the present inventors are developing a wash water that can wash the nasal cavity using marine mineral water, and marine mineral water, which is a deep seawater that is eluted from a rock bed of 1100m underground in the hot spring area, 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, Korea It was confirmed that the symptoms of the disease, mucosal edema, inflammatory factor activity and concentrated mucus removal effect is excellent, and that the mineral water is very suitable for use as a nasal cleaning composition.
- the vascular outflow due to the inflammatory flow path was stained with Evans blue dye, and as a result, nothing In comparison with the non-treated rats, LPS-induced rhinosinusitis significantly increased the outflow of Evans blue dye due to inflammation, and the outflow of Evans blue dye was reduced by the mineral water injection of the present invention.
- the group treated with 50% (v / v) and 100% (v / v) of the mineral water of the present invention has a higher outflow of Evans blue dye compared to the physiological saline treatment group used for nasal washing. It was found to be reduced (see FIGS. 3 and 4).
- the mineral water of the present invention has an effect of reducing nasal mucosa thickness, a symptom of nasal disease.
- the nasal mucosa was significantly thicker than that of normal rats in which the rhinosinusitis was induced by LPS, whereas the mineral water of the present invention was increased due to LPS.
- the nasal mucosa thickness was shown to be reduced and this decrease was proportional to the concentration of treated mineral water (see FIGS. 5 and 6).
- the present inventors have found that the mineral water of the present invention can be used for nasal washing, which can prevent and improve nasal diseases caused by inflammation and allergy, and in particular, the mineral water of the present invention for nasal washing. It can be seen that when contained in more than 50% (v / v) based on the composition it can induce better efficacy.
- the present inventors investigated whether the mineral water of the present invention can affect the causative factors of nasal diseases such as rhinitis and sinusitis.
- MUC5AC is known to induce hypersecretion of mucus.
- the expression level of the factor was analyzed in the mouse models tested above. That is, after separating the nasal mucosa tissue from the group treated with physiological saline to LPS-induced rhinosinusitis-induced rhinosinusitis-treated rats and the rhinosinus-induced rats treated with mineral water of the present invention by concentration, RNA was extracted and the expression level of MUC5AC gene in each tissue was analyzed by RT-PCR using primers specific for MUC5AC gene.
- MUC5AC was used in the rat group that induced rhinosinusitis with LPS compared to the normal rat group that was not treated with anything. While the expression of the gene was increased by about three times or more, in the group treated with saline and mineral water of the present invention, the expression of the MUC5AC gene was found to be decreased compared to the rat group induced by rhinosinusitis with LPS, in particular physiological. Compared to the saline treatment group, the mineral water treatment group of the present invention was shown to more effectively reduce the expression of the MUC5AC gene. Was (see Fig. 6).
- the mucosal ciliary system serves as the primary defense mechanism for transporting inhaled particles or infectious agents out of the airways.
- the substances present in the airway sera are known to limit the toxicity of the particles and to inactivate infectious agents, and the physical mechanism of coughing is known to play a role in draining mucus from the airway passages.
- the mucosal ciliary system consists of ciliary epithelial cells, epithelial goblet cells, and serous and mucous cells located in the submucosal gland, and the cilia are active transport of chloride and passive transport of water across the epithelium through the lumen of the airway passage. It is surrounded by an aqueous layer (peripheral fluid) secreted by it and comes into contact with the floating mucus on the aqueous layer and provides for the movement of the mucus by a constant propulsion action.
- aqueous layer peripheral fluid
- mucus generally promotes removal of inhaled particles or infectious agents, but hypersecretion of mucus causes various diseases such as chronic bronchitis, acute asthma, cystic fibrosis, rhinitis, sinusitis and bronchiectasis.
- the mineral water of the present invention has an inhibitory effect on the expression of the MUC5AC gene that induces the production of mucus, thereby improving, preventing and treating the symptoms of nasal diseases such as rhinitis and sinusitis.
- the present invention can provide a nasal wash composition comprising the marine mineral water taken from the 1100m underground of the hot spring area of 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangneung-si, Gangwon-do, South Korea.
- the mineral water contained in the composition of the present invention as an active ingredient is a mineral component, potassium 200 ⁇ 230mg / L, sodium 7000 ⁇ 9500mg / L, calcium 1400 ⁇ 1700mg / L, magnesium 900 ⁇ 1100mg / L, zinc 3 ⁇ 9mg / L, Strontium 25 ⁇ 35mg / L, Selenium 200 ⁇ 500ug / L, Vanadium 65 ⁇ 75ug / L, Germanium 0.5 ⁇ 1.5ug / L, Manganese 10-40ug / L, Cobalt 1-3ug / L, Titanium 600 ⁇ 950ug / L, copper 3 ⁇ 9ug / L, lithium 0.02 ⁇ 0.09mg / L, chlorine ion 16000 ⁇ 19500mg / L, fluorine ion 1.5 ⁇ 3.0mg / L, bromine ion 40 ⁇ 56mg / L, sulfate ion 3000
- This component analysis is a result of the mineral component analysis of the mineral water according to the present invention commissioned by the Korea Institute of Science and Technology (KIST), the Korea Basic Science Institute (KBSI) and the Korea Institute of Geoscience and Mineral Resources (KIGAM). Mineral waters are new to date.
- KIST Korea Institute of Science and Technology
- KBSI Korea Basic Science Institute
- KIGAM Korea Institute of Geoscience and Mineral Resources
- the mineral water may use the marine mineral water itself taken from the 1100m underground of the hot spring area, 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangneung-si, Gangwon-do, South Korea, the mineral water is the total weight of the composition It can be used in an amount of 50% (v / v) to 100% (v / v) as a standard, or can be prepared and used as a concentrate, and when used as a concentrate, 0.5 to 50% based on the total weight of the composition It can be contained and used in the quantity of (v / v).
- the concentrate may be a solid obtained by evaporating, concentrating and drying the mineral water according to the present invention, or may be a concentrate obtained by evaporating the mineral water by natural drying or by artificially desalting and drying (or evaporating) the mineral water.
- the concentrate of the mineral water according to the present invention may be prepared by the following method.
- the filtration step may be subjected to a plurality of filtration steps, in the present invention was carried out a four-step filtration process. That is, the first stage filtration was removed by filtering the suspended matter more than 10um, and then removed by filtering the suspended matter more than 5um again as a second stage filtration, and then removed by filtering the suspended matter above 1um as a three-step filtration.
- the suspended solids filtered by 0.2um or more by a four-step filtration process.
- the desalination is not limited thereto, but may be used an electrodialysis machine.
- desalination powder is prepared through a drying step using natural drying or an artificial dryer.
- a vacuum freeze dryer was used for the drying.
- the desalted powder can be ground and packed.
- the preparation of the concentrate of the mineral water according to the present invention may be carried out first through the drying process after collecting the raw water, and then performing the filtration step.
- the nasal washing composition according to the present invention may further include a conventional therapeutic anti-allergic agent or anti-inflammatory agent suitable for improving nasal disease symptoms such as rhinitis and sinusitis, and also for flavoring, coloring, It may further include additives such as fungicides, antioxidants, preservatives, humectants, thickeners, inorganic salts, emulsifiers, synthetic polymer materials.
- the administration method of the nasal washing composition according to the present invention is not limited thereto, but a spray method, a squeeze method, or an administration method by an electric machine may be used, and may be used in any formulation form, but is convenient for washing. It is preferable to be a liquid so that it may be manufactured and used also in paste form, ointment, spray formulations, etc.
- the present invention can provide a composition for the prevention or treatment of rhinitis or sinusitis, which contains marine mineral water taken at 1100m underground from the hot spring area of 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, Korea.
- composition of the present invention can be used as a pharmaceutical composition for the prophylaxis or treatment of nasal diseases such as rhinitis or sinusitis, when the concentrated mineral water according to the present invention is used in a concentration of 0.5 to 50% by weight relative to the total weight of the composition can do.
- composition for the prophylaxis or treatment of rhinitis or sinusitis comprises a pharmaceutically effective amount of mineral water itself or mineral water concentrate according to the present invention alone or at least one pharmaceutically acceptable carrier, excipient or diluent It may include.
- the pharmaceutically effective amount herein refers to an amount sufficient to prevent, ameliorate or treat rhinitis or sinusitis.
- the pharmaceutically effective amount of mineral water concentrate according to the invention is 0.5-100 mg / day / kg body weight, preferably 0.5-5 mg / day / kg body weight.
- the pharmaceutically effective amount may be appropriately changed according to the degree of symptoms of the disease, the age, weight, health condition, sex, route of administration, and duration of treatment of the patient.
- pharmaceutically acceptable refers to a composition that is physiologically acceptable and does not normally cause an allergic reaction, such as gastrointestinal disorders, dizziness, or the like when administered to a human.
- carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil.
- fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers and preservatives may be further included.
- compositions for the prophylaxis and treatment of rhinitis or sinusitis of the present invention may be formulated using methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal.
- the formulations may be in the form of powders, granules, tablets, emulsions, syrups, aerosols, soft or hard gelatin capsules, sterile injectable solutions, sterile powders.
- composition according to the invention can be administered via several routes including oral, transdermal, subcutaneous, intravenous or intramuscular, the dosage of the active ingredient being determined by several factors such as the route of administration, the age, sex, weight and severity of the patient. It may be appropriately selected depending on.
- composition of the present invention can be administered in parallel with known compounds having the effect of preventing, improving or treating rhinitis or sinusitis.
- the present invention can provide a rhinitis or sinusitis medicament comprising a composition containing mineral water taken from 1100m underground in the hot spring area of Geumjin-ri Coastal Area.
- composition according to the present invention not only provides the excellent rhinitis or sinusitis inhibitory effect, but also is safer than conventional chemical preparations based on natural deep sea water, and does not have any toxic and side effects on the drug even when taken for a long time. Can be used with confidence.
- the composition of the present invention can be added to a food for the purpose of preventing or treating a disease caused by rhinitis or sinusitis, and thus can be used as a food composition for the prevention and improvement of disease symptoms caused by rhinitis or sinusitis. have.
- the "food” means a natural product or processed product containing one or more nutrients, and preferably means a state in which it can be directly eaten through a certain processing step, and a general meaning As used herein, it refers to food, food additives, functional foods and beverages.
- Foods to which the composition according to the present invention can be added include, for example, various foods, beverages, gums, teas, vitamin complexes, functional foods, and the like.
- food includes special nutritional products (e.g., formulated milk, young, infant food, etc.), processed meat products, fish products, tofu, jelly, noodles (e.g. ramen, noodles, etc.), bread, health supplements, seasonings.
- Foods e.g. soy sauce, miso, red pepper paste, mixed soy sauce
- sauces confectionery (e.g. snacks), candy, chocolates, gums, ice creams, dairy products (e.g.
- fermented milk, cheese, etc. other processed foods
- kimchi, Pickled foods various kimchi, pickles, etc.
- beverages e.g., fruit drinks, vegetable drinks, soy milk, fermented beverages, etc.
- natural seasonings e.g. ramen soup, etc.
- the food, beverage or food additives may be prepared by a conventional manufacturing method.
- the term "functional food” refers to the control of biological defense rhythms and disease prevention of food groups or food compositions that have added value to the food by using physical, biochemical, or biotechnological techniques to act and express the function of the food for a specific purpose. It means a food that is designed and processed to fully express the body's regulatory function regarding recovery and the like, and specifically, it may be a health functional food.
- the functional food may include food acceptable food additives, and may further include appropriate carriers, excipients and diluents commonly used in the manufacture of functional foods.
- the "beverage” refers to a generic term for drinking to quench thirst or to enjoy a taste and includes a functional drink.
- the beverage contains, as the essential ingredient, the composition for treating and preventing rhinitis or sinusitis according to the present invention as an essential ingredient, and there are no special limitations, and various flavors or natural carbohydrates are added as in the general beverage. It may contain as a component.
- foods containing the composition of the present invention include various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavoring agents, colorants and fillers (such as cheese and chocolate), and pectic acid. And salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like, which components may be independently or in combination Can be used.
- the amount of the composition according to the present invention may comprise from 0.001% to 90% by weight of the total food weight, preferably from 0.1% to 40% by weight.
- the amount of the composition according to the present invention may comprise from 0.001% to 90% by weight of the total food weight, preferably from 0.1% to 40% by weight.
- it may be included in a ratio of 0.001g to 2g, preferably 0.01g to 0.1g based on 100ml, in the case of long-term intake for health and hygiene purposes or health control purposes It may be less than the range, the active ingredient is not limited to the above range because it may be used in an amount above the range because there is no problem in terms of safety.
- the present invention can provide a health functional food for the prevention or improvement of rhinitis or sinusitis containing mineral water or mineral water concentrate according to the present invention as an active ingredient
- the form of the food is not limited thereto, powder, It may be in the form of granules, tablets, capsules or beverages.
- the present inventors collected the hot spring water taken from the 110m underground bedrock in the Geumjin-ri beach coastal area of Okgye-myeon, Gangneung-si, Gangneung-si, Gangwon-do, to collect mineral water that can be effectively used for nasal washing, and filtered by using a 0.25 micrometer line filter. After removing the contaminants, it was desalted using an electrodialysis machine (voltage: 5.5-7.5 V, electrode solution: 3% Na 2 SO 4, CJTTS-2-10 ED, Creative Techno). After the desalination process was filtered and dried using a vacuum freeze dryer (temperature: -40 ⁇ 30 °C, vacuum degree: 5mTorr), the mineral water concentrate of the present invention prepared by this process in the following experiment Used.
- Example 1 In order to determine whether the mineral water of the present invention according to Example 1 is suitable for use for nasal washing, and furthermore, it is possible to treat rhinitis diseases such as rhinosinusitis, a rat model in which rhinosinusitis is induced was produced. That is, 250 mg of healthy, respiratory disease-free Sprague Dawley rats, LPS, a factor inducing rhinosinusitis, was extracted from Pseudomonas aeruginosa (L-4524, Sigma, St. Louis, Mo, USA). / ml) and injected into the nose of the mouse in an amount of 0.1ml to produce a rat model in which rhinosinusitis was induced.
- rhinitis diseases such as rhinosinusitis
- mice were raised in an environment free of pathogens, and were allowed to freely ingest sterile standard rat food (Ralston Purina, St. Louis, MO) and water. Animal experiments were conducted with the approval of the clergy University Institutional Animal Care and Use Committee. At this time, the control was used to inject Saline (physiological saline) solution in the rat nose instead of LPS.
- Saline physiological saline
- the experimental rat group was divided as follows, and the following experiment was performed.
- the 25%, 50% and 100% mineral water means that the mineral water prepared in Example 1 diluted with physiological saline such that 25% (v / v), 50% (v / v), 100% refers to 100% mineral water concentrate, wherein LPS was prepared as described in Example 2, and the treatment group of A ⁇ G used the dose of 0.1ml in the amount of the nose of the rat. Injected into.
- the degree of plasma outflow was investigated in the rat group treated with each solution by using Evans blue reagent, which is measured by measuring the degree of staining because the plasma outflow increases when inflammation of the nasal cavity increases. It is used to analyze the degree of inflammation in the nasal cavity.
- the analysis of the degree of Evans blue effusion was first performed by injecting 1 ml of Evans blue solution (Sigma, 40 mg / ml in Salinee) into the external jugular vein of the mice, one minute after the injection, and a nasal tissue sample from each rat The samples were then immersed in 60 to 1 ml of formamide (Sigma, USA) for 24 hours.
- the sample was centrifuged for 30 seconds at 9,000 rpm and 20 ° C., and then the absorbance of the supernatant obtained by centrifugation using a microplate reader (model 680, Biorad, USA) was measured at 630 nm.
- Nasal mucosa was collected from each rat in each rat group (A-G) tested in Example 3, and the thickness of the mucosa was analyzed by hematoxylin-eosin staining.
- mucosal thickness was significantly increased compared to the rat group in which no rhinosinus was induced, and treated with LPS and saline.
- the thickness of the mucosa was found to be reduced compared to the group treated with LPS alone, and the decrease in the thickness of the mucosa was similar to the group treated with 50% of the mineral water of the present invention, and the mineral water of the present invention was 100%.
- the treated group was found to have a lower mucosal thickness than the normal saline treated group.
- the present inventors separated the nasal tissue from each rat group used in Example 3, extracted RNA from the tissue, and then extracted MUC5AC.
- the expression level of the MUC5AC gene was analyzed by performing RT-PCR using a primer capable of amplifying the gene.
- RNA was extracted using the extraction kit ((iNtRON Biotechnology, Inc., Gyeonggi-do, Korea) according to the user's proposed method, PCR reaction for MUC5AC was reacted for 15 minutes at 95 °C, 1 at 94 °C The reaction was repeated 32 times for 1 minute at 55 ° C. and 1 minute at 72 ° C.
- PCR reaction of glyceraldehyde 3-phosphate dehydrogenase was performed at 94 ° C. for 4 minutes, at 94 ° C. for 1 minute, and at 60 ° C. The reaction was repeated 35 times for 1 minute at 72 ° C.
- the primers used were designed by Gene Runner software (Hastings Software Inc., Las Vegas, Nev, USA) and purchased from GenBenk. The sequence of each primer is as follows.
- GAPDH forward primer 5'-GCTGGTGCTGAGTATGTCGT-3 '
- GAPDH reverse primer 3'-GAATGGGAGTTGCTGTTGAA-5 '
- the expression of the MUC5AC gene which functions as a mucus hypersecretion, is significantly more than three times higher in the LPS-induced rhinosinusitis than in the non-treated group and the PBS-only group.
- the expression of MUC5AC gene was decreased compared to the group treated with LPS alone, and the mineral water treated group of the present invention. was shown to decrease the expression of MUC5AC gene in proportion to mineral water concentration.
- the present inventors have an effect of reducing the swelling and thickness of the nasal mucosa caused by inflammation, etc., in the case of mineral water according to the present invention, and also improves the degree of inflammation, MUC5AC inducing mucus hypersecretion It is also excellent in reducing the expression of the gene, it can be seen that it can be used as a nasal disease treatment and nasal wash water, such as sinusitis and rhinitis.
- the inventors of the present invention to determine whether the mineral water according to the present invention can actually improve the symptoms of rhinitis and sinusitis patients, screening five patients for each experimental group three times a day determined by rhinitis and sinusitis at Catholic University St. Mary's Hospital (In morning weather, 2 pm, before bedtime) 10ml syringe was used to bow the head and the mineral water of the present invention was injected into the nasal cavity and waited for about 1 minute to let flow. This procedure was repeated for 10 days and the improved condition was evaluated on a 5 point scale on Day 5 and Day 10.
- the mineral water used was a solution containing 50% (v / v) of mineral water concentrate in water. The results are shown in Table 3 below. At this time, only the saline was used as a control group and saline used for nasal washing for improving the symptoms of conventional rhinitis.
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Abstract
The present invention relates to a composition for cleaning a nasal cavity containing mineral water as an active ingredient. More particularly, the present invention relates to a composition for cleaning a nasal cavity and to a composition for preventing or treating rhinitis or sinus infection, comprising, as a mineral component, 200 to 230mg/L of potassium, 7000 to 9500mg/L of sodium, 1400 to 1700mg/L of calcium, 900 to 1100mg/L of magnesium, 3 to 9mg/L of zinc, 25 to 35mg/L of strontium, 200 to 500ug/L of selenium, 65 to 75ug/L of vanadium, 0.5 to 1.5ug/L of germanium, 10 to 40ug/L of manganese, 1 to 3ug/L of cobalt, 600 to 950ug/L of titanium, 3 to 9ug/L of copper, 0.02 to 0.09mg/L of lithium, 16000 to 19500mg/L of chloride ion, 1.5 to 3.0mg/L of fluoride ion, 40 to 56mg/L of bromide ion, 3000 to 4500mg/L of sulfate ion, 0.8 to 1.2mg/L of boron and 0.5 to 15mg/L of silicon dioxide.
Description
본 발명은 광천수를 함유한 비강 세척용 조성물 및 비염과 축농증을 예방 또는 치료할 수 있는 약학적 조성물에 관한 것이다. The present invention relates to a composition for washing the nasal cavity containing mineral water and a pharmaceutical composition capable of preventing or treating rhinitis and sinusitis.
비염은 인체의 호흡기관인 코 내부의 비강점막에 생기는 염증을 일컫는 것으로서, 급성 및 만성 비염과 감기로 인한 바이러스성 비염 및 알레르기성 비염 등이 있다. 증상은 계속 흘러내리는 콧물(수양성 비루), 코막힘(비폐색) 등이 특징적인 질환이다. 일반적으로 비염에 감염되면 호흡하는데 어려움이 있을 뿐만 아니라, 그로 인하여 수반되는 두통이나 주의력 감퇴와 같은 증상이 수반되어 더욱 큰 불편을 초래하며, 장기간의 치료에도 불구하고 좀처럼 치료되지 않을 뿐 아니라, 치료된 후에도 재발되어 치료에 많은 어려움을 겪게 된다.Rhinitis refers to inflammation occurring in the nasal mucosa inside the nose, which is the respiratory organ of the human body, and includes acute and chronic rhinitis, viral rhinitis due to cold, and allergic rhinitis. Symptoms include a runny nose (a benign nasal mucus) and a stuffy nose (nasal obstruction). In general, infection with rhinitis not only causes difficulty breathing, but also causes symptoms such as headache or attention deterioration, which causes greater discomfort, and is rarely cured despite long-term treatment. The disease recurs afterwards, making treatment difficult.
특히, 알레르기성 비염이나 축농증은 코 막힘으로 만성적인 산소부족현상에 시달리게 되고 이는 뇌의 기능이 현저히 떨어뜨린다. 따라서 비염이나 축농증이 있는 어린이나 청소년들은 만성적인 피로와 학습장애를 호소하는 경우가 많으며 업무량이 많은 직장인들에게도 마찬가지로 업무효율의 저하로 인해 많은 차질을 야기 한다. In particular, allergic rhinitis or sinusitis causes chronic oxygen deficiency due to nasal congestion, which significantly reduces brain function. Therefore, children or adolescents with rhinitis or sinusitis often have chronic fatigue and learning disabilities, and even those with heavy workloads cause a lot of disruptions due to lower work efficiency.
또한, 부비동은 코 주위에 위치하며 뼈로 둘러싸인 공기가 차 있는 방을 말하며, 주요한 부비동은 양 눈썹 위에 위치한 전두동, 양 눈 아래의 안면부에 위치한 상악동, 양 눈 사이에 위치한 사골동, 코 뒤에 깊숙이 위치한 접형동이 있다. 부비동은 비강점막과 같은 종류의 점막으로 덮혀 있어, 비강과 부비동은 매일 점액성 분비물을 생산하며, 부비동에서 분비물은 콧속으로 연필심 크기의 작은 구멍으로 연결되는 자연개구부를 통하며 빠져 나오게 되고, 비강을 통과하면서 먼지 입자, 세균, 공해물질을 여과하는 기능을 갖고 있으며, 이 점액은 비강을 덮고 있는 수백만개의 섬모라고 하는 구조에 의해 목 뒤로 넘어가 무의식중에 삼키게 되어 위에서 삼켜진 유해물질이나 세균이 산성물질에 의해 녹거나 죽게 된다. 이것은 우리 몸의 정상기능이기 때문에 보통 사람은 그 과정을 느끼지 못한다. 부비동의 배출구가 막히면 점액이 고이고 2차적인 세균 감염에 의하여 농(고름)이 발생하게 된다. In addition, the paranasal sinuses are located around the nose and filled with bone-filled air.The main paranasal sinuses are the frontal sinus located above both eyebrows, the maxillary sinus located on the face below both eyes, the ethmoid sinus located between both eyes, and the sphenoid sinus deep behind the nose. have. The paranasal sinuses are covered with the same type of mucosa as the nasal mucosa.The nasal and paranasal sinuses produce mucous secretions daily, from which the nasal secretions exit through the natural openings leading to the small sized pencil-holes in the nose. As it passes through, it has the function of filtering dust particles, bacteria and pollutants, and this mucus goes over the neck by a structure called millions of cilia that cover the nasal passages, and it is unconsciously swallowed by harmful substances or bacteria swallowed from above. It melts or dies. Since this is a normal function of our bodies, the average person does not feel the process. If the sinus outlet is blocked, mucus will accumulate and pus will develop due to secondary bacterial infection.
따라서 이러한 부비동 배출구의 폐쇄는 콧속의 해부학적 원인이나 자극물질, 알레르기 등에 의해 일어날 수 있고, 부비동 질환은 같은 가족 내에서 흔히 발병할 수 있으며, 스트레스도 만성 부비동 질환의 원인이 될 수 있을 뿐 아니라 비폐색은 폐에 과다호흡을 일으켜 천식을 악화시키기도 한다.Therefore, the obstruction of the sinus outlet may be caused by anatomical causes, irritants, or allergies in the nose, and sinus disease may occur frequently in the same family, and stress may be a cause of chronic sinus disease as well as nasal obstruction. May cause excessive breathing in the lungs and make asthma worse.
따라서 이러한 비염을 포함하는 코 질환의 치료를 위해 항알레르기제나 항히스타민제를 처방하고 있다. 그러나 항히스타민제는 재발이 잦고 졸음이 오는 부작용이 있으며, 코에 뿌리는 국소용 스테로이드 역시 사용하는 순간에는 증세를 없애지만 오래 사용하면 오히려 축농증을 유발할 수 있기 때문에 2주 이상 사용해선 안 되는 문제점이 있다. 또한, 코막힘이 심할 경우에는 레이저 수술을 하기도 하기만 이는 수술비용이 많이 든다는 문제점이 있다. Therefore, antiallergic or antihistamines are prescribed for the treatment of nasal diseases including rhinitis. However, antihistamines have side effects of frequent relapses and drowsiness, and topical steroids sprayed on the nose also eliminate symptoms at the moment of use, but they can cause sinusitis if used for a long time. . In addition, when the nasal congestion is severe, there is a problem that the laser surgery is expensive, which is expensive.
또한, 한방에서는 전기침과 향기요법, 물리요법, 약물요법으로 치료를 하게 되는데, 이러한 치료법 또한 일시적인 증상 완화 효과를 가져다 줄 뿐, 비염을 완치할 수 있는 효과를 거두지 못하고 있다.In addition, herbal medicine is acupuncture and aromatherapy, physiotherapy, drug therapy will be treated, these treatments also have a temporary symptomatic effect, it is not effective to cure rhinitis.
최근에는 비강 세척제로서 천연추출물을 사용한 대한민국 등록특허 제614,679호 한국산 겨우살이 추출물을 유효성분으로 함유하는 점막면역 증진용 세척제 조성물 기술이 개발된 바 있지만, 유효성분의 수득이 용이하지 못하고 비용도 많이 든다는 문제점이 있다. Recently, a mucosal immunity-promoting detergent composition technology containing a Korean mistletoe extract using natural extract as a nasal cleanser has been developed, but it is not easy to obtain an active ingredient and it is expensive. There is this.
따라서 이와 같은 각종 비염이나 부비동염을 효과적으로 치료하기 위해서는 보조적으로 효과가 있으며 비용 절감 효과도 있는 비강세척제를 이용하여 비강을 적절히 세척할 필요성이 있으며, 나아가 보다 효과적이며 체내 안정적인 새로운 비강 세척제 및 코 질환 치료제의 개발이 시급한 실정이다.Therefore, in order to effectively treat such various kinds of rhinitis or sinusitis, it is necessary to properly wash the nasal cavity with a nasal cleanser that is auxiliary and cost effective. Development is urgent.
본 발명의 목적은 광천수를 함유하는 비강 세척용 조성물을 제공하는 것이다. It is an object of the present invention to provide a composition for nasal washing, containing mineral water.
또한, 본 발명의 목적은 광천수를 함유하는 비염 또는 축농증 예방 또는 치료용 조성물을 제공하는 것이다.It is also an object of the present invention to provide a composition for preventing or treating rhinitis or sinusitis containing mineral water.
상기와 같은 본 발명의 목적을 달성하기 위해서, 본 발명은 대한민국 강원도 강릉시 옥계면 금진3리 92-1번지 해안단구 지역 온천지의 지하 1100m 지점에서 취수한 해양성 광천수를 유효성분으로 포함하는 비강 세척용 조성물을 제공한다.In order to achieve the object of the present invention as described above, the present invention comprises a nasal wash composition comprising the marine mineral water taken from the 1100m underground of the hot spring area of the coastal Dangu district 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, South Korea as an active ingredient to provide.
본 발명의 일실시예에 있어서, 상기 광천수는 미네랄 성분으로서, 칼륨 200~230mg/L, 나트륨 7000~9500mg/L, 칼슘 1400~1700mg/L, 마그네슘 900~1100mg/L, 아연 3~9mg/L, 스트론튬 25~35mg/L, 셀레늄 200~500ug/L, 바나듐 65~75ug/L, 게르마늄 0.5~1.5ug/L, 망간 10~40ug/L, 코발트 1~3ug/L, 티탄 600~950ug/L, 구리 3~9ug/L, 리튬 0.02~0.09mg/L, 염소이온 16000~19500mg/L, 불소이온 1.5~3.0mg/L, 브롬이온 40~56mg/L, 황산이온 3000~4500mg/L, 보론 0.8~1.2mg/L 및 이산화규소 0.5~15mg/L를 함유할 수 있다. In one embodiment of the present invention, the mineral water is a mineral component, potassium 200 ~ 230mg / L, sodium 7000 ~ 9500mg / L, calcium 1400 ~ 1700mg / L, magnesium 900 ~ 1100mg / L, zinc 3 ~ 9mg / L , Strontium 25 ~ 35mg / L, Selenium 200 ~ 500ug / L, Vanadium 65 ~ 75ug / L, Germanium 0.5 ~ 1.5ug / L, Manganese 10 ~ 40ug / L, Cobalt 1-3ug / L, Titanium 600 ~ 950ug / L , Copper 3 ~ 9ug / L, lithium 0.02 ~ 0.09mg / L, chlorine ion 16000 ~ 19500mg / L, fluorine ion 1.5 ~ 3.0mg / L, bromine ion 40 ~ 56mg / L, sulfate ion 3000 ~ 4500mg / L, boron It may contain 0.8-1.2 mg / L and silicon dioxide 0.5-15 mg / L.
본 발명의 일실시예에 있어서, 상기 광천수는 농축물이고, 상기 농축물은 조성물 총 중량을 기준으로 0.5~50%(v/v)로 함유할 수 있다. In one embodiment of the present invention, the mineral water is a concentrate, the concentrate may be contained in 0.5 to 50% (v / v) based on the total weight of the composition.
본 발명의 일실시예에 있어서, 상기 조성물은 액상, 페이스트상, 연고, 또는 스프레이용 제제일 수 있다. In one embodiment of the present invention, the composition may be a liquid, paste, ointment, or spray formulation.
또한, 본 발명은 대한민국 강원도 강릉시 옥계면 금진3리 92-1번지 해안단구 지역 온천지의 지하 1100m 지점에서 취수한 해양성 광천수를 유효성분으로 포함하는 비염 또는 축농증의 예방 또는 치료용 조성물을 제공한다.In addition, the present invention provides a composition for the prevention or treatment of rhinitis or sinusitis, including the marine mineral water taken from the 1100m underground of the hot spring area of the waterfront district 92-1 Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, South Korea.
본 발명의 일실시예에 있어서, 상기 광천수는 미네랄 성분으로서, 칼륨 200~230mg/L, 나트륨 7000~9500mg/L, 칼슘 1400~1700mg/L, 마그네슘 900~1100mg/L, 아연 3~9mg/L, 스트론튬 25~35mg/L, 셀레늄 200~500ug/L, 바나듐 65~75ug/L, 게르마늄 0.5~1.5ug/L, 망간 10~40ug/L, 코발트 1~3ug/L, 티탄 600~950ug/L, 구리 3~9ug/L, 리튬 0.02~0.09mg/L, 염소이온 16000~19500mg/L, 불소이온 1.5~3.0mg/L, 브롬이온 40~56mg/L, 황산이온 3000~4500mg/L, 보론 0.8~1.2mg/L 및 이산화규소 0.5~15mg/L를 함유할 수 있다. In one embodiment of the present invention, the mineral water is a mineral component, potassium 200 ~ 230mg / L, sodium 7000 ~ 9500mg / L, calcium 1400 ~ 1700mg / L, magnesium 900 ~ 1100mg / L, zinc 3 ~ 9mg / L , Strontium 25 ~ 35mg / L, Selenium 200 ~ 500ug / L, Vanadium 65 ~ 75ug / L, Germanium 0.5 ~ 1.5ug / L, Manganese 10 ~ 40ug / L, Cobalt 1-3ug / L, Titanium 600 ~ 950ug / L , Copper 3 ~ 9ug / L, lithium 0.02 ~ 0.09mg / L, chlorine ion 16000 ~ 19500mg / L, fluorine ion 1.5 ~ 3.0mg / L, bromine ion 40 ~ 56mg / L, sulfate ion 3000 ~ 4500mg / L, boron It may contain 0.8-1.2 mg / L and silicon dioxide 0.5-15 mg / L.
본 발명의 일실시예에 있어서, 상기 광천수는 상기 광천수는 농축물이고, 상기 농축물은 조성물 총 중량을 기준으로 0.5~50%(v/v)로 함유할 수 있다. In one embodiment of the present invention, the mineral water is the mineral water is a concentrate, the concentrate may contain 0.5 to 50% (v / v) based on the total weight of the composition.
본 발명의 일실시예에 있어서, 상기 광천수는 염증으로 인한 비강 내 점막의 부종을 감소시키고, 점액 과분비 유발 인자인 MUC5AC 유전자의 발현을 감소시키는 효과를 갖는 것일 수 있다. In one embodiment of the present invention, the mineral water may be to reduce the swelling of the intranasal mucosa due to inflammation, and to reduce the expression of MUC5AC gene, a mucus hypersecretion-inducing factor.
본 발명에 따른 대한민국 강원도 강릉시 옥계면 금진3리 92-1번지 해안단구 지역 온천지의 지하 1100m 지점에서 취수한 해양성 광천수를 함유한 비강 세척용 조성물 및 비염 또는 축농증의 예방 또는 치료용 조성물은 염증 등으로 유발되는 코 점막의 부종 및 두께를 감소시키는 효과가 있고, 염증 정도도 개선시키는 효과가 있으며, 점액 과분비를 유도하는 물질의 발현 감소 효과도 우수하여, 축농증 및 비염 등과 같은 코 질환 증상을 개선, 예방 및 치료할 수 있는 비강 세척수 및 치료제와 기능성 건강식품의 제조에 널리 사용할 수 있는 효과가 있다.The composition for nasal washing and the composition for the prevention or treatment of rhinitis or sinusitis caused by inflammation, etc., containing marine mineral water taken from 1100m underground of the hot spring area of 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, South Korea according to the present invention It has the effect of reducing the swelling and thickness of the nasal mucosa, and also improves the degree of inflammation, and also has an excellent effect of reducing the expression of substances that induce mucus hypersecretion, thereby improving, preventing and improving nasal disease symptoms such as sinusitis and rhinitis. There is an effect that can be widely used in the manufacture of treatable nasal washes and therapeutic agents and functional health foods.
도 1은 쥐 모델을 대상으로 LPS 주입에 의해 비부비동염을 유발시킨 쥐 내 비강 점막의 두께를 현미경을 통해 관찰한 사진을 나타낸 것으로서, (a)는 아무것도 처리하지 않은 군, (b)는 생리식염수를 처리한 군, (c)는 LPS를 처리한 군을 나타낸 것이다.Figure 1 shows a microscopic view of the thickness of the nasal mucosa in rats induced by rhinosinusitis by LPS injection in the rat model, (a) is nothing treated, (b) saline solution Group treated with, (c) shows a group treated with LPS.
도 2는 도 1과 동일한 쥐 군들에 대해 PAS로 염색한 결과를 현미경을 통해 관찰한 사진을 나타낸 것이며, 화살표는 증가된 PAS의 부위를 표시한 것이다.FIG. 2 shows a photograph of the same mouse group as shown in FIG. 1 when observed with a microscope, and the arrow indicates the site of the increased PAS.
도 3은 도 1과 동일한 쥐 군들에 대해 염증으로 인한 혈관 유출 감소 효과를 Evans blue 시약 염색법으로 관찰한 사진을 나타낸 것이며, 화살표는 점막 유출이 증가된 Evans blue 염색을 나타낸 것이다. Figure 3 shows the pictures observed by the Evans blue reagent staining effect on the vascular outflow due to inflammation in the same rat group as in Figure 1, the arrow shows the Evans blue staining with increased mucosal outflow.
도 4은 본 발명에 따른 광천수 처리에 따른 염증으로 인한 혈관 유출 감소 효과를 Evans blue 시약 염색법으로 관찰한 사진을 나타낸 것으로서, A는 아무것도 처리하지 않은 군, B는 생리식염수만을 처리한 군, C는 LPS만을 처리한 군, D는 LPS와 생리식염수를 처리한 군, E는 LPS와 25%(v/v)의 광천수를 처리한 군, F는 LPS와 50%(v/v)의 광천수를 처리한 군 , G는 LPS와 100%(v/v)의 광천수를 처리한 군을 나타낸 것이며,Figure 4 shows a photograph observed by Evans blue reagent staining effect of inflammation due to mineral water treatment according to the present invention, A is a group not treated anything, B is a group treated only saline, C is LPS-treated group, D treated with LPS and saline, E treated with LPS and 25% mineral water, F treated with LPS and 50% (v / v) mineral water. One group, G, represents the group treated with LPS and 100% (v / v) mineral water,
도 5는 도 4의 각 실험군에 따른 Evans blue 시약의 유출정도를 흡광도로 측정하여 나타낸 결과이다.5 is a result of measuring the degree of leakage of the Evans blue reagent according to each experimental group of Figure 4 measured by the absorbance.
도 6는 도 4의 각 쥐 군으로부터 코 점막 조직을 분리한 후, 헤마토크실렌-에오신 염색을 통해 코 점막 두께 정도를 현미경으로 관찰한 결과를 나타낸 것이다.Figure 6 shows the result of observing the nasal mucosa thickness of the microscope through hematoxylene-eosin staining after separating the nasal mucosa tissue from each rat group of FIG.
도 7은 도 6의 결과를 수치화하여 막대 그래프로 나타낸 것이다.FIG. 7 shows the result of FIG. 6 as a bar graph.
도 8은 본 발명에 따른 광천수가 점액 과분비 유도 인자인 MUC5AC 유전자의 발현을 억제하는 효과가 있는지 확인하기 위해, 상기 도 4의 각 쥐 군으로부터 비강 조직을 채취한 후, MUC5AC 유전자를 증폭할 수 있는 프라이머를 사용하여 RT-PCR을 수행한 결과를 나타낸 것이다. 8 is a mineral water according to the present invention in order to determine whether there is an effect of inhibiting the expression of the mucus hypersecretion inducing factor MUC5AC gene, after taking nasal tissue from each rat group of Figure 4, which can amplify the MUC5AC gene RT-PCR using the primers are shown.
본 발명은 비강 세척 효과가 우수하고 특히 염증으로 인한 코 점막내 부종 감소효과와 점액 과분비를 감소시키는 효과가 우수한 광천수를 유효성분으로 하는 새로운 비강 세척용 조성물을 제공함에 그 특징이 있으며, 본 발명에 따른 비강 세척용 조성물에 유효성분으로 함유된 광천수는 대한민국 강원도 강릉시 옥계면 금진3리 92-1번지 해안단구 지역 온천지의 지하 1100m 지점에서 취수한 해양성 광천수라는 점에 특징이 있다. The present invention is characterized in that it provides a new nasal cleaning composition comprising mineral water excellent in nasal washing effect and particularly excellent in reducing nasal mucosal edema and mucus hypersecretion due to inflammation. Mineral water contained as an active ingredient in the nasal cleaning composition according to the present invention is characterized in that it is marine mineral water taken from the 1100m underground of the hot spring area of 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, South Korea.
일반적으로 해수는 표층수와 구별하여 해양 심층수라고 불리우고 있는데, 해양 심층수라는 것은 해수 표면으로부터 200미터 이하의 해수를 일컫는 것으로서, 광합성이 일어나지 않아 식물성장에 필요한 질소, 인, 규산 등의 무기영양소를 많이 포함하고 있으며, 대기나 화학물질에 의한 오염 및 태양균이나 일반세균에 오염되지 않고, 양성 세균수도 적어 물리적 청정성도 매우 뛰어난 것으로 알려져 있다. In general, seawater is called deep seawater, which is distinguished from surface water, and deep sea water refers to seawater 200 meters or less from the surface of seawater. It contains many inorganic nutrients such as nitrogen, phosphorus, and silicic acid needed for plant growth because photosynthesis does not occur. It is known that it is not polluted by air or chemicals and contaminated with solar bacteria or general bacteria, and has a small number of benign bacteria, so that the physical cleanliness is excellent.
또한, 일년 내내 저온으로 그 변화가 적고 안정된 낮은 수온성을 갖으며, 필수 미량원소나 다양한 미네랄 성분이 균형있게 포함되어 있어 용존되어 있는 금속이온들의 작용으로 활성 산소에 대한 탁월한 소거작용 효과 등 체내 유용한 특성을 가지고 있다. In addition, its temperature is low all year round, its stability is low, and its water temperature is stable. It contains essential trace elements and various mineral components in a balanced manner, and it is useful in the body such as excellent scavenging effect on active oxygen due to the action of dissolved metal ions. Has characteristics.
따라서 해양 오염이 심각한 현재의 상태에서 표층수는 식음료 등 인체에 사용하기에 적합하지 않으나, 해양심층수는 표면층에 비하여 생균수가 그다지 많지 않을뿐더러 병원성 생물이 거의 포함되어 있지 않기 때문에 의료용 및 식음료로 선택하는 경우에 안전성이 지극히 높다고 할 수 있다. Therefore, in the current state of serious marine pollution, surface water is not suitable for use in the human body such as food and beverage, but since deep sea water is not much more viable than the surface layer and contains little pathogenic organisms, it is selected as medical and food and beverage. The safety is extremely high.
한편, 감기, 축농증, 알레르기 비염 등으로 인한 코 질환은 현대에서 두통, 수면부족, 기침, 스트레스 등을 유발하여 개인의 삶의 질을 크게 떨어뜨리는 원인이 되며, 이로 인한 집중력 저하 등으로 인해 경제적 및 사회적 비용 손실을 초래한다. 미국의 경우 최근 통계치에 의하면, 전체 인구의 약 15%가 축농증을 앓고 있고 약 30%가 알레르기를 앓고 있어 매년 약 24억 달러 및 34억 달러의 막대한 의료비용이 지출되고 있어, 이를 효과적으로 치료하기 위한 치료제 개발과 함께 치료 효과를 상승시킬 수 있는 비강 세척에 대한 연구가 증가하고 있다.On the other hand, nasal diseases caused by colds, sinusitis and allergic rhinitis cause headaches, sleep deprivation, coughing, stress, etc. in modern times, which greatly reduces the quality of life of the individual. It causes a loss of social costs. In the United States, recent statistics show that about 15% of the total population has sinusitis and about 30% have allergies, costing about $ 2.4 billion and $ 3.4 billion in medical costs annually. With the development of therapeutics, research on nasal lavage that can increase the therapeutic effect is increasing.
비강 세척은 점액 섬수 기능을 향상시키고 코 점막의 부종을 감소시키며, 염증 관여 인자의 활성 감소와 농축된 점액을 청소하는데 매우 효과적인 방법으로 알려져 있다(Tomooka LT 등, Clinical study and literature review of nasal irrigation., Laryngoscope. 2000 Jul;110(7): 1189~93). Nasal lavage is known to be a very effective way to improve mucus islet function, reduce swelling of the nasal mucosa, reduce the activity of inflammation-related factors and cleanse concentrated mucus (Tomooka LT et al., Clinical study and literature review of nasal irrigation. , Laryngoscope. 2000 Jul; 110 (7): 1189-93).
이에 본 발명자들은 해양 광천수를 이용하여 비강을 세척할 수 있는 세척수를 개발하던 중, 대한민국 강원도 강릉시 옥계면 금진3리 92-1번지 해안단구 지역 온천지의 지하 1100m 암반층에서 용출되는 해양 심층수인 해양성 광천수가 코 질환의 증상인 점막 부종, 염증인자활성 및 농축된 점액 제거 효과가 우수하다는 것을 확인하고, 상기 광천수를 비강 세척용 조성물로 사용하기에 아주 적절하다는 사실을 확인하였다. Therefore, the present inventors are developing a wash water that can wash the nasal cavity using marine mineral water, and marine mineral water, which is a deep seawater that is eluted from a rock bed of 1100m underground in the hot spring area, 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, Korea It was confirmed that the symptoms of the disease, mucosal edema, inflammatory factor activity and concentrated mucus removal effect is excellent, and that the mineral water is very suitable for use as a nasal cleaning composition.
즉, 본 발명의 일실시예에 따르면, LPS로 비부비동염을 유발시킨 쥐를 대상으로 본 발명의 광천수를 쥐 코에 주입시킨 후, 염증 유로 인한 혈관 유출을 Evans blue dye로 염색하여 확인한 결과, 아무것도 처리하지 않은 정상 쥐 군에 비해 LPS로 비부비동염을 유발시킨 쥐군은 염증 유발로 인해 Evans blue dye의 유출이 현저히 증가한 것으로 나타났으며, 이러한 Evans blue dye의 유출은 본 발명의 광천수 주입으로 인해 감소되는 것으로 나타났고, 특히 본 발명의 광천수를 50%(v/v) 및 100%(v/v)로 처리한 군은 종래 비강 세척용으로 사용되던 생리식염수 처리 군에 비해 Evans blue dye의 유출이 더 감소된 것으로 나타났다(도 3 및 도 4 참조).That is, according to one embodiment of the present invention, after injecting the mineral water of the present invention into the rat nose in rats induced sinusitis with LPS, the vascular outflow due to the inflammatory flow path was stained with Evans blue dye, and as a result, nothing In comparison with the non-treated rats, LPS-induced rhinosinusitis significantly increased the outflow of Evans blue dye due to inflammation, and the outflow of Evans blue dye was reduced by the mineral water injection of the present invention. In particular, the group treated with 50% (v / v) and 100% (v / v) of the mineral water of the present invention has a higher outflow of Evans blue dye compared to the physiological saline treatment group used for nasal washing. It was found to be reduced (see FIGS. 3 and 4).
또한, 본 발명의 다른 일실시예에서는 본 발명의 광천수가 코 질환의 증상인 코 점막 두께를 감소시킬 수 있는 효과가 있는지 확인하였는데, 앞서 실험한 것과 동일한 실험 쥐들을 사용하여 코 점막 조직을 헤마토크실렌-에오신 염색을 통해 두께를 관찰한 결과, LPS로 비부비동염을 유발시킨 쥐군은 코 점막이 정상 쥐에 비해 현저하게 두꺼워진 것으로 나타난 반면, 본 발명의 광천수를 주입한 군에서는 LPS로 인해 증가된 코 점막 두께가 감소된 것으로 나타났고, 이러한 감소는 처리한 광천수의 농도에 비례하는 것으로 나타났다(도 5 및 도 6 참조).In another embodiment of the present invention, it was confirmed that the mineral water of the present invention has an effect of reducing nasal mucosa thickness, a symptom of nasal disease. As a result of thickness measurement through xylene-eosin staining, the nasal mucosa was significantly thicker than that of normal rats in which the rhinosinusitis was induced by LPS, whereas the mineral water of the present invention was increased due to LPS. The nasal mucosa thickness was shown to be reduced and this decrease was proportional to the concentration of treated mineral water (see FIGS. 5 and 6).
따라서 이러한 결과를 통해 본 발명자들은 본 발명의 광천수가 염증 및 알레르기 등으로 유발되는 코 질환을 예방 및 개선할 수 있는 비강 세척용으로 사용할 수 있음을 알 수 있었고, 특히 본 발명의 광천수를 비강 세척용 조성물 기준으로 50%(v/v) 이상으로 함유할 경우 더 우수한 효능을 유도할 수 있음을 알 수 있었다. Therefore, through these results, the present inventors have found that the mineral water of the present invention can be used for nasal washing, which can prevent and improve nasal diseases caused by inflammation and allergy, and in particular, the mineral water of the present invention for nasal washing. It can be seen that when contained in more than 50% (v / v) based on the composition it can induce better efficacy.
나아가, 본 발명자들은 본 발명의 광천수가 비염 및 축농증 등 코 질환의 원인인자에 영향을 줄 수 있는지를 조사하였는데, 본 발명의 일실시예에 따르면, 점액의 과분비를 유도하는 작용을 하는 것으로 알려진 MUC5AC 인자의 발현 수준을 상기 실험한 쥐 모델들을 대상으로 분석하였다. 즉, LPS로 비부비동염을 유발시킨 쥐군, 비부비동염 유발 쥐군에 생리식염수를 처리한 군 및 비부비동염을 유발시킨 쥐군에 본 발명의 광천수를 농도별로 처리한 군으로부터 코 점막 조직을 분리한 후, 총 RNA를 추출하고 MUC5AC 유전자에 특이적인 프라이머를 사용한 RT-PCR을 통해 각 조직내 MUC5AC 유전자의 발현 정도를 분석하였는데, 그 결과, 아무것도 처리하지 않은 정상 쥐군에 비해 LPS로 비부비동염을 유발시킨 쥐군은 MUC5AC 유전자의 발현이 약 3배 이상으로 증가한 것으로 나타난 반면, 생리식염수 및 본 발명의 광천수를 처리한 군에서는 MUC5AC 유전자의 발현이 LPS로 비부비동염을 유발시킨 쥐 군에 비해 감소된 것으로 나타났고, 특히 생리식염수 처리 군에 비해 본 발명의 광천수 처리 군이 MUC5AC 유전자의 발현을 더 효과적으로 감소시키는 것으로 나타났다(도 6 참조).Furthermore, the present inventors investigated whether the mineral water of the present invention can affect the causative factors of nasal diseases such as rhinitis and sinusitis. According to one embodiment of the present invention, MUC5AC is known to induce hypersecretion of mucus. The expression level of the factor was analyzed in the mouse models tested above. That is, after separating the nasal mucosa tissue from the group treated with physiological saline to LPS-induced rhinosinusitis-induced rhinosinusitis-treated rats and the rhinosinus-induced rats treated with mineral water of the present invention by concentration, RNA was extracted and the expression level of MUC5AC gene in each tissue was analyzed by RT-PCR using primers specific for MUC5AC gene. As a result, MUC5AC was used in the rat group that induced rhinosinusitis with LPS compared to the normal rat group that was not treated with anything. While the expression of the gene was increased by about three times or more, in the group treated with saline and mineral water of the present invention, the expression of the MUC5AC gene was found to be decreased compared to the rat group induced by rhinosinusitis with LPS, in particular physiological. Compared to the saline treatment group, the mineral water treatment group of the present invention was shown to more effectively reduce the expression of the MUC5AC gene. Was (see Fig. 6).
일반적으로 호흡계의 전도 기도내에서, 점막섬모계는 흡입된 입자 또는 감염인자를 기도 밖으로 운반하는 일차적 방어기작으로서 역할을 한다. 또한, 기도 장액에 존재하는 물질은 입자의 독성을 제한하고 감염인자를 불활성화하는 역할을 하며, 기침의 물리적 기작은 기도 통로로부터 점액을 배출하는 역할을 하는 것으로 알려져 있다. 또한, 점막섬모계는 점막밑샘에 위치한 섬모성 상피세포, 상피 배상세포, 및 장액성 및 점액성 세포로 구성되어 있으며, 섬모는 기도통로의 관강으로 상피를 가로질러 염화물의 능동수송 및 물의 수동적 운반에 의하여 분비되는 수성층(섬모주위 체액)으로 둘러싸여 있고 수성층 상에 떠다니는 점액과 접촉하고, 일정방향 추진 동작에 의하여 점액의 이동을 제공한다. In general, within the conduction airways of the respiratory system, the mucosal ciliary system serves as the primary defense mechanism for transporting inhaled particles or infectious agents out of the airways. In addition, the substances present in the airway sera are known to limit the toxicity of the particles and to inactivate infectious agents, and the physical mechanism of coughing is known to play a role in draining mucus from the airway passages. In addition, the mucosal ciliary system consists of ciliary epithelial cells, epithelial goblet cells, and serous and mucous cells located in the submucosal gland, and the cilia are active transport of chloride and passive transport of water across the epithelium through the lumen of the airway passage. It is surrounded by an aqueous layer (peripheral fluid) secreted by it and comes into contact with the floating mucus on the aqueous layer and provides for the movement of the mucus by a constant propulsion action.
한편, 점액은 일반적으로 흡입된 입자 또는 감염인자의 제거를 촉진하지만, 점액의 과분비는 만성 기관지염, 급성 천식, 낭성섬유증, 비염, 축농증 및 기관지확장증 같은 각종의 질병의 원인이 된다. On the other hand, mucus generally promotes removal of inhaled particles or infectious agents, but hypersecretion of mucus causes various diseases such as chronic bronchitis, acute asthma, cystic fibrosis, rhinitis, sinusitis and bronchiectasis.
따라서 이러한 점을 고려할 때, 본 발명의 광천수는 점액물질의 생산을 유도하는 MUC5AC 유전자의 발현 억제 효과를 가지고 있어 비염 및 축농증 등 코 질환의 증상을 개선, 예방 및 치료할 수 있다는 사실을 알 수 있었다. Therefore, in consideration of this, it was found that the mineral water of the present invention has an inhibitory effect on the expression of the MUC5AC gene that induces the production of mucus, thereby improving, preventing and treating the symptoms of nasal diseases such as rhinitis and sinusitis.
그러므로 본 발명은 대한민국 강원도 강릉시 옥계면 금진3리 92-1번지 해안단구 지역 온천지의 지하 1100m 지점에서 취수한 해양성 광천수를 유효성분으로 포함하는 비강 세척용 조성물을 제공할 수 있다.Therefore, the present invention can provide a nasal wash composition comprising the marine mineral water taken from the 1100m underground of the hot spring area of 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangneung-si, Gangwon-do, South Korea.
또한, 본 발명의 조성물에 유효성분으로 포함되는 상기 광천수는 미네랄 성분으로서, 칼륨 200~230mg/L, 나트륨 7000~9500mg/L, 칼슘 1400~1700mg/L, 마그네슘 900~1100mg/L, 아연 3~9mg/L, 스트론튬 25~35mg/L, 셀레늄 200~500ug/L, 바나듐 65~75ug/L, 게르마늄 0.5~1.5ug/L, 망간 10~40ug/L, 코발트 1~3ug/L, 티탄 600~950ug/L, 구리 3~9ug/L, 리튬 0.02~0.09mg/L, 염소이온 16000~19500mg/L, 불소이온 1.5~3.0mg/L, 브롬이온 40~56mg/L, 황산이온 3000~4500mg/L, 보론 0.8~1.2mg/L 및 이산화규소 0.5~15mg/L를 함유한다.In addition, the mineral water contained in the composition of the present invention as an active ingredient is a mineral component, potassium 200 ~ 230mg / L, sodium 7000 ~ 9500mg / L, calcium 1400 ~ 1700mg / L, magnesium 900 ~ 1100mg / L, zinc 3 ~ 9mg / L, Strontium 25 ~ 35mg / L, Selenium 200 ~ 500ug / L, Vanadium 65 ~ 75ug / L, Germanium 0.5 ~ 1.5ug / L, Manganese 10-40ug / L, Cobalt 1-3ug / L, Titanium 600 ~ 950ug / L, copper 3 ~ 9ug / L, lithium 0.02 ~ 0.09mg / L, chlorine ion 16000 ~ 19500mg / L, fluorine ion 1.5 ~ 3.0mg / L, bromine ion 40 ~ 56mg / L, sulfate ion 3000 ~ 4500mg / L, 0.8-1.2 mg / L boron and 0.5-15 mg / L silicon dioxide.
이러한 성분 분석은 한국과학기술연구원(KIST), 한국기초과학지원연구원(KBSI) 및 한국지질자원연구원(KIGAM)에 의뢰한 본 발명에 따른 광천수의 미네랄 성분 분석 결과로서, 이러한 상기 미네랄 성분 구성을 지닌 광천수는 지금까지 알려진 바 없는 신규한 것이다.This component analysis is a result of the mineral component analysis of the mineral water according to the present invention commissioned by the Korea Institute of Science and Technology (KIST), the Korea Basic Science Institute (KBSI) and the Korea Institute of Geoscience and Mineral Resources (KIGAM). Mineral waters are new to date.
또한, 본 발명에서 상기 광천수는 대한민국 강원도 강릉시 옥계면 금진3리 92-1번지 해안단구 지역 온천지의 지하 1100m 지점에서 취수한 해양성 광천수 자체를 사용할 수 있고, 광천수 자체를 사용할 경우 상기 광천수는 조성물 총 중량을 기준으로 50%(v/v)~100%(v/v)의 양으로 사용할 수 있으며, 또는 농축물로 제조하여 사용할 수 있고, 농축물로 사용할 경우에는 조성물 총 중량을 기준으로 0.5~50%(v/v)의 양으로 함유하여 사용할 수 있다. In addition, in the present invention, the mineral water may use the marine mineral water itself taken from the 1100m underground of the hot spring area, 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangneung-si, Gangwon-do, South Korea, the mineral water is the total weight of the composition It can be used in an amount of 50% (v / v) to 100% (v / v) as a standard, or can be prepared and used as a concentrate, and when used as a concentrate, 0.5 to 50% based on the total weight of the composition It can be contained and used in the quantity of (v / v).
상기 농축물은 본 발명에 따른 광천수를 증발, 농축 및 건조시켜 얻은 고형분일 수 있고, 또는 상기 광천수를 자연건조로 증발시키거나, 인공적으로 탈염 및 건조(또는 증발)시켜 얻은 농축액일 수도 있다. The concentrate may be a solid obtained by evaporating, concentrating and drying the mineral water according to the present invention, or may be a concentrate obtained by evaporating the mineral water by natural drying or by artificially desalting and drying (or evaporating) the mineral water.
구체적으로 본 발명의 따른 상기 광천수의 농축물은 하기와 같은 방법으로 제조될 수 있다. 우선 원수(原水)를 채수한 후, 필터링하는 여과 단계를 거친다. 이때 상기 여과단계는 여러 차례의 여과 단계를 거칠 수 있는데, 본 발명에서는 4단계의 여과 과정을 수행하였다. 즉, 1단계 여과는 10um 이상의 부유물을 필터링하여 제거하였고, 이후 2단계 여과로서 다시 5um 이상의 부유물을 필터링하여 제거한 다음, 3단계 여과로서 1um 이상의 부유물을 필터링하여 제거하였다. 이후 UV를 통해 살균 처리한 다음, 4단계 여과과정으로 0.2um 이상의 부유물을 필터링하여 제거하였다. 이렇게 여과 과정을 거쳐 수득한 수득물은 탈염 단계 및 건조 과정을 수행할 수 있으며, 탈염은 이에 제한되는 것은 아니나 전기투석기를 이용할 수 있다. Specifically, the concentrate of the mineral water according to the present invention may be prepared by the following method. First, raw water is collected and then filtered. At this time, the filtration step may be subjected to a plurality of filtration steps, in the present invention was carried out a four-step filtration process. That is, the first stage filtration was removed by filtering the suspended matter more than 10um, and then removed by filtering the suspended matter more than 5um again as a second stage filtration, and then removed by filtering the suspended matter above 1um as a three-step filtration. After sterilization through UV, the suspended solids filtered by 0.2um or more by a four-step filtration process. Thus obtained product obtained by the filtration process can be carried out a desalting step and drying process, the desalination is not limited thereto, but may be used an electrodialysis machine.
이후, 자연건조나 인공건조기를 이용한 건조단계를 거쳐 탈염 파우더를 제조한다. 본 발명의 일실시예에서는 상기 건조를 위해 진공동결 건조기를 사용하였다. 마지막 단계에서는 탈염 파우더를 분쇄하여 포장할 수 있다.Thereafter, desalination powder is prepared through a drying step using natural drying or an artificial dryer. In one embodiment of the present invention, a vacuum freeze dryer was used for the drying. In the final step, the desalted powder can be ground and packed.
또한, 본 발명에 따른 광천수의 농축물의 제조는 원수를 채수한 후 건조과정을 통해 먼저 농축과정을 수행할 수 있고, 이후 여과 단계를 수행할 수 있다. In addition, the preparation of the concentrate of the mineral water according to the present invention may be carried out first through the drying process after collecting the raw water, and then performing the filtration step.
본 발명에 따른 비강 세척용 조성물은, 비염 및 축농증 등과 같은 코 질환 증상 개선을 위하여 적당한 통상의 치료용 항알레르기제, 또는 항염증 제제를 더 포함할 수도 있으며, 또한 물성 개선을 위하여 향료, 색소, 살균제, 산화방지제, 방부제, 보습제, 점증제, 무기염류, 유화제, 합성 고분자 물질 등의 첨가제를 더 포함할 수도 있다.The nasal washing composition according to the present invention may further include a conventional therapeutic anti-allergic agent or anti-inflammatory agent suitable for improving nasal disease symptoms such as rhinitis and sinusitis, and also for flavoring, coloring, It may further include additives such as fungicides, antioxidants, preservatives, humectants, thickeners, inorganic salts, emulsifiers, synthetic polymer materials.
나아가 본 발명에 따른 비강 세척용 조성물의 투여 방식은, 이에 제한되는 것은 아니지만, 스프레이 방식, 스퀴즈 방식, 또는 전동식 기계 등에 의한 투여 방식이 사용될 수 있고, 임의의 제제 형태로 사용 가능하지만, 세척에 편리하도록 액상인 것이 바람직하며, 페이스트상, 연고, 스프레이용 제제 등으로도 제조하여 사용할 수 있다.Furthermore, the administration method of the nasal washing composition according to the present invention is not limited thereto, but a spray method, a squeeze method, or an administration method by an electric machine may be used, and may be used in any formulation form, but is convenient for washing. It is preferable to be a liquid so that it may be manufactured and used also in paste form, ointment, spray formulations, etc.
나아가 본 발명은 대한민국 강원도 강릉시 옥계면 금진3리 92-1번지 해안단구 지역 온천지의 지하 1100m 지점에서 취수한 해양성 광천수를 유효성분으로 포함하는 비염 또는 축농증의 예방 또는 치료용 조성물을 제공할 수 있다.Furthermore, the present invention can provide a composition for the prevention or treatment of rhinitis or sinusitis, which contains marine mineral water taken at 1100m underground from the hot spring area of 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, Korea.
본 발명의 조성물은 비염 또는 축농증과 같은 코 질환의 예방 또는 치료를 위한 약학적 조성물로 사용될 수 있으며, 본 발명에 따른 광천수를 농축하여 사용할 경우, 상기 조성물 총 중량에 대하여 0.5~50중량%로 포함할 수 있다. The composition of the present invention can be used as a pharmaceutical composition for the prophylaxis or treatment of nasal diseases such as rhinitis or sinusitis, when the concentrated mineral water according to the present invention is used in a concentration of 0.5 to 50% by weight relative to the total weight of the composition can do.
또한, 본 발명에 따른 상기 비염 또는 축농증의 예방 또는 치료용 조성물은 약학적으로 유효한 양의 본 발명에 따른 광천수 자체 또는 광천수 농축물을 단독으로 포함하거나 하나 이상의 약학적으로 허용되는 담체, 부형제 또는 희석제를 포함할 수 있다. 상기에서 약학적으로 유효한 양이란 비염 또는 축농증을 예방, 개선 또는 치료하기에 충분한 양을 말한다. 예컨대, 본 발명에 따른 광천수 농축물의 약학적으로 유효한 양은 0.5~100 mg/day/체중kg, 바람직하게는 0.5~5 mg/day/체중kg이다. 그러나 상기 약학적으로 유효한 양은 질환의 증상 정도, 환자의 연령, 체중, 건강상태, 성별, 투여 경로 및 치료기간 등에 따라 적절히 변화될 수 있다.In addition, the composition for the prophylaxis or treatment of rhinitis or sinusitis according to the present invention comprises a pharmaceutically effective amount of mineral water itself or mineral water concentrate according to the present invention alone or at least one pharmaceutically acceptable carrier, excipient or diluent It may include. The pharmaceutically effective amount herein refers to an amount sufficient to prevent, ameliorate or treat rhinitis or sinusitis. For example, the pharmaceutically effective amount of mineral water concentrate according to the invention is 0.5-100 mg / day / kg body weight, preferably 0.5-5 mg / day / kg body weight. However, the pharmaceutically effective amount may be appropriately changed according to the degree of symptoms of the disease, the age, weight, health condition, sex, route of administration, and duration of treatment of the patient.
또한, 상기에서 "약학적으로 허용되는"이란 생리학적으로 허용되고 인간에게 투여될 때, 통상적으로 위장 장애, 현기증과 같은 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 조성물을 말한다. 상기 담체, 부형제 및 희석제의 예로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필 하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 또한, 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제 및 방부제 등을 추가로 포함할 수 있다.In addition, "pharmaceutically acceptable" as used herein refers to a composition that is physiologically acceptable and does not normally cause an allergic reaction, such as gastrointestinal disorders, dizziness, or the like when administered to a human. Examples of such carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil. In addition, fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers and preservatives may be further included.
또한, 본 발명의 비염 또는 축농증의 예방 및 치료용 조성물은 포유동물에 투여된 후 활성 성분의 신속, 지속 또는 지연된 방출을 제공할 수 있도록 당업계에 공지된 방법을 사용하여 제형화될 수있다. 제형은 분말, 과립, 정제, 에멀젼, 시럽, 에어로졸, 연질 또는 경질 젤라틴캅셀, 멸균 주사용액, 멸균 분말의 형태일 수 있다.In addition, compositions for the prophylaxis and treatment of rhinitis or sinusitis of the present invention may be formulated using methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. The formulations may be in the form of powders, granules, tablets, emulsions, syrups, aerosols, soft or hard gelatin capsules, sterile injectable solutions, sterile powders.
본 발명에 따른 조성물은 경구, 경피, 피하, 정맥 또는 근육을 포함한 여러 경로를 통해 투여될 수 있으며, 활성 성분의 투여량은 투여 경로, 환자의 연령, 성별, 체중 및 환자의 중증도 등의 여러 인자에 따라 적절히 선택될 수 있다. The composition according to the invention can be administered via several routes including oral, transdermal, subcutaneous, intravenous or intramuscular, the dosage of the active ingredient being determined by several factors such as the route of administration, the age, sex, weight and severity of the patient. It may be appropriately selected depending on.
또한, 본 발명의 조성물은 비염 또는 축농증을 예방, 개선 또는 치료하는 효과를 가지는 공지의 화합물과 병행하여 투여할 수 있다.In addition, the composition of the present invention can be administered in parallel with known compounds having the effect of preventing, improving or treating rhinitis or sinusitis.
따라서 본 발명은 금진리 해안단구 지역 온천지의 지하 1100m 지점에서 취수한 광천수를 유효성분으로 함유하는 조성물을 포함하는 비염 또는 축농증 약제를 제공할 수 있다.Therefore, the present invention can provide a rhinitis or sinusitis medicament comprising a composition containing mineral water taken from 1100m underground in the hot spring area of Geumjin-ri Coastal Area.
나아가 본 발명에 따른 조성물은 상기 우수한 비염 또는 축농증 억제 효과를 제공할 뿐만 아니라, 천연 해양 심층수를 원료로 하는 바 기존의 화학적 제제보다 안전성이 높아, 약물에 대한 별다른 독성 및 부작용도 없어 장기간 복용시에도 안심하고 사용할 수 있다.Furthermore, the composition according to the present invention not only provides the excellent rhinitis or sinusitis inhibitory effect, but also is safer than conventional chemical preparations based on natural deep sea water, and does not have any toxic and side effects on the drug even when taken for a long time. Can be used with confidence.
따라서 본 발명의 조성물은 비염 또는 축농증에 의해 발생하는 질환의 예방 또는 치료를 목적으로 하는 식품에 첨가할 수 있으므로, 비염 또는 축농증으로 인해 발생하는 질환 증상의 예방 및 개선을 위한 식품용 조성물로 사용할 수 있다. Therefore, the composition of the present invention can be added to a food for the purpose of preventing or treating a disease caused by rhinitis or sinusitis, and thus can be used as a food composition for the prevention and improvement of disease symptoms caused by rhinitis or sinusitis. have.
또한 비염 또는 축농증으로 인해 발생하는 질환 증상의 예방 및 개선에 효과가 있는 식품, 예컨대, 식품의 주원료, 부원료, 식품 첨가제, 기능성 식품 또는 음료로 용이하게 활용할 수 있다.In addition, it can be easily utilized as foods, such as the main ingredients, secondary ingredients, food additives, functional foods or beverages that are effective in preventing and improving disease symptoms caused by rhinitis or sinusitis.
본 발명에서 상기 "식품"이란, 영양소를 한 가지 또는 그 이상 함유하고 있는 천연물 또는 가공품을 의미하며, 바람직하게는 어느 정도의 가공 공정을 거쳐 직접 먹을 수 있는 상태가 된 것을 의미하며, 통상적인 의미로서, 식품, 식품 첨가제, 기능성 식품 및 음료를 모두 포함하는 것을 말한다.In the present invention, the "food" means a natural product or processed product containing one or more nutrients, and preferably means a state in which it can be directly eaten through a certain processing step, and a general meaning As used herein, it refers to food, food additives, functional foods and beverages.
본 발명에 따른 조성물을 첨가할 수 있는 식품으로는 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 기능성 식품 등이 있다. 추가로, 본원발명에서 식품에는 특수영양식품(예, 조제유류, 영,유아식 등), 식육가공품, 어육제품, 두부류, 묵류, 면류(예, 라면류, 국수류 등), 빵류, 건강보조식품, 조미식품(예, 간장, 된장, 고추장, 혼합장 등), 소스류, 과자류(예, 스넥류), 캔디류, 쵸코렛류, 껌류, 아이스크림류, 유가공품(예, 발효유, 치즈 등), 기타 가공식품, 김치, 절임식품(각종 김치류, 장아찌 등), 음료(예, 과실 음료, 채소류 음료, 두유류, 발효음료류 등), 천연조미료(예, 라면 스프 등)을 포함하나 이에 한정되지 않는다. 상기 식품, 음료 또는 식품첨가제는 통상의 제조방법으로 제조될 수 있다.Foods to which the composition according to the present invention can be added include, for example, various foods, beverages, gums, teas, vitamin complexes, functional foods, and the like. In addition, in the present invention, food includes special nutritional products (e.g., formulated milk, young, infant food, etc.), processed meat products, fish products, tofu, jelly, noodles (e.g. ramen, noodles, etc.), bread, health supplements, seasonings. Foods (e.g. soy sauce, miso, red pepper paste, mixed soy sauce), sauces, confectionery (e.g. snacks), candy, chocolates, gums, ice creams, dairy products (e.g. fermented milk, cheese, etc.), other processed foods, kimchi, Pickled foods (various kimchi, pickles, etc.), beverages (e.g., fruit drinks, vegetable drinks, soy milk, fermented beverages, etc.), natural seasonings (e.g. ramen soup, etc.) are not limited thereto. The food, beverage or food additives may be prepared by a conventional manufacturing method.
또한, 상기 "기능성 식품"이란 식품에 물리적, 생화학적, 생물 공학적 수법 등을 이용하여 해당 식품의 기능을 특정 목적에 작용, 발현하도록 부가가치를 부여한 식품군이나 식품 조성이 갖는 생체방어리듬조절, 질병방지와 회복 등에 관한 체내조절기능을 생체에 대하여 충분히 발현하도록 설계하여 가공한 식품을 의미하며, 구체적으로는 건강 기능성 식품일 수 있다. 상기 기능성 식품에는 식품학적으로 허용 가능한 식품 보조 첨가제를 포함할 수 있으며, 기능성 식품의 제조에 통상적으로 사용되는 적절한 담체, 부형제 및 희석제를 더욱 포함할 수 있다.In addition, the term "functional food" refers to the control of biological defense rhythms and disease prevention of food groups or food compositions that have added value to the food by using physical, biochemical, or biotechnological techniques to act and express the function of the food for a specific purpose. It means a food that is designed and processed to fully express the body's regulatory function regarding recovery and the like, and specifically, it may be a health functional food. The functional food may include food acceptable food additives, and may further include appropriate carriers, excipients and diluents commonly used in the manufacture of functional foods.
또한, 본원발명에서 상기 "음료"란 갈증을 해소하거나 맛을 즐기기 위하여 마시는 것의 총칭을 의미하며 기능성 음료를 포함한다. 상기 음료는 지시된 비율로 필수 성분으로서 본 발명에 따른 상기 비염 또는 축농증 치료 및 예방용 조성물을 포함하는 것 외에 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다.In addition, in the present invention, the "beverage" refers to a generic term for drinking to quench thirst or to enjoy a taste and includes a functional drink. The beverage contains, as the essential ingredient, the composition for treating and preventing rhinitis or sinusitis according to the present invention as an essential ingredient, and there are no special limitations, and various flavors or natural carbohydrates are added as in the general beverage. It may contain as a component.
나아가 상기 기술한 것 이외에 본원발명의 조성물을 함유하는 식품은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 충진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있으며, 상기 성분은 독립적으로 또는 조합하여 사용할 수 있다.Furthermore, foods containing the composition of the present invention, in addition to those described above, include various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavoring agents, colorants and fillers (such as cheese and chocolate), and pectic acid. And salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like, which components may be independently or in combination Can be used.
본원발명의 조성물을 함유하는 식품에 있어서, 상기 본 발명에 따른 조성물의 양은 전체 식품 중량의 0.001중량% 내지 90중량%로 포함할 수 있으며, 바람직하게는 0.1중량% 내지 40중량%로 포함할 수 있고, 음료의 경우, 100ml를 기준으로 0.001g 내지 2g, 바람직하게는 0.01g 내지 0.1g의 비율로 포함할 수 있으나, 건강 및 위생을 목적으로 하거나 건강 조절을 목적으로 하는 장기간 섭취의 경우에는 상기 범위 이하일 수 있으며, 유효성분은 안전성 면에서 아무런 문제가 없기 때문에 상기 범위 이상의 양으로 사용될 수 있으므로 상기 범위에 한정되는 것은 아니다.In the food containing the composition of the present invention, the amount of the composition according to the present invention may comprise from 0.001% to 90% by weight of the total food weight, preferably from 0.1% to 40% by weight. In the case of a beverage, it may be included in a ratio of 0.001g to 2g, preferably 0.01g to 0.1g based on 100ml, in the case of long-term intake for health and hygiene purposes or health control purposes It may be less than the range, the active ingredient is not limited to the above range because it may be used in an amount above the range because there is no problem in terms of safety.
그러므로 본 발명은 본 발명에 따른 광천수 또는 광천수 농축물을 유효성분으로 함유하는 비염 또는 축농증의 예방 또는 개선을 위한 건강기능식품을 제공할 수 있으며, 상기 식품의 형태는 이에 제한되지는 않으나, 분말, 과립, 정제, 캡슐 또는 음료 형태일 수 있다.Therefore, the present invention can provide a health functional food for the prevention or improvement of rhinitis or sinusitis containing mineral water or mineral water concentrate according to the present invention as an active ingredient, the form of the food is not limited thereto, powder, It may be in the form of granules, tablets, capsules or beverages.
이하, 본 발명을 하기 실시예 및 실험예에 의해 상세히 설명한다. 단, 하기 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실험예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail by the following Examples and Experimental Examples. However, the following Examples and Experimental Examples are only illustrative of the present invention, and the content of the present invention is not limited by the following Experimental Examples.
<실시예 1><Example 1>
본 발명에 따른 광천수 채취 및 농축물 제조Mineral water extraction and concentrate preparation according to the present invention
본 발명자들은 비강 세척에 효과적으로 사용할 수 있는 광천수를 채취하기 위해 원수(原水)인 강원도 강릉시 옥계면 금진리 해변 해안단구 지역의 지하 110m 암반층에서 취수한 온천수를 채취하여 0.25 마이크로 미터의 라인필터를 이용하여 필터링하여 오염물질을 제거한 후, 전기투석기(전압: 5.5~7.5V, 전극액: 3% Na2SO4, CJTTS-2-10 ED, 창조테크노)를 이용하여 탈염하였다. 탈염 과정을 마친 후, 여과하고 진공동결 건조기(온도: -40~30℃, 진공도: 5mTorr)를 이용하여 건조 과정을 수행하였고, 이러한 과정으로 제조된 본 발명의 광천수 농축물을 하기와 같은 실험에 사용하였다.The present inventors collected the hot spring water taken from the 110m underground bedrock in the Geumjin-ri beach coastal area of Okgye-myeon, Gangneung-si, Gangneung-si, Gangwon-do, to collect mineral water that can be effectively used for nasal washing, and filtered by using a 0.25 micrometer line filter. After removing the contaminants, it was desalted using an electrodialysis machine (voltage: 5.5-7.5 V, electrode solution: 3% Na 2 SO 4, CJTTS-2-10 ED, Creative Techno). After the desalination process was filtered and dried using a vacuum freeze dryer (temperature: -40 ~ 30 ℃, vacuum degree: 5mTorr), the mineral water concentrate of the present invention prepared by this process in the following experiment Used.
<실시예 2><Example 2>
비부비동염이 유발된 쥐 모델 제작Modeling a Mouse Model Induced by Sinusitis
상기 실시예 1에 따른 본 발명의 광천수가 비강 세척용으로 사용하기 적합하며, 나아가 비부비동염과 같은 비염 질환을 치료할 수 있는 효과가 있는지 확인하기 위해, 비부비동염 질환이 유발된 쥐 모델을 제작하였는데, 즉, 250 gram의 건강하고 호흡기 질환이 없는 Sprague Dawley rat 을 대상으로 비부비동염을 유발하는 인자인 LPS를 Pseudomonas aeruginosa(L-4524, Sigma, St. Louis, Mo, USA)에서 추출한 것으로 생리식염수에 1mg/ml의 농도로 만들어 사용함) 0.1ml의 양으로 상기 쥐의 코에 주입하여 비부비동염이 유발된 쥐 모델을 제작하였다. 이때 상기 쥐는 병원균이 없는 환경에서 사육되었고, 멸균된 표준 쥐 사료(Ralston Purina, St. Louis, MO)와 물을 자유롭게 섭취하도록 하였다. 동물 실험은 가톨릭대학교 IACUC(Institutional Animal Care and Use Committee)의 승인하에서 이루어졌다. 이때 대조군으로는 LPS 대신 Saline(생리식염수) 용액을 쥐 코에 주입한 것을 사용하였다. In order to determine whether the mineral water of the present invention according to Example 1 is suitable for use for nasal washing, and furthermore, it is possible to treat rhinitis diseases such as rhinosinusitis, a rat model in which rhinosinusitis is induced was produced. That is, 250 mg of healthy, respiratory disease-free Sprague Dawley rats, LPS, a factor inducing rhinosinusitis, was extracted from Pseudomonas aeruginosa (L-4524, Sigma, St. Louis, Mo, USA). / ml) and injected into the nose of the mouse in an amount of 0.1ml to produce a rat model in which rhinosinusitis was induced. At this time, the mice were raised in an environment free of pathogens, and were allowed to freely ingest sterile standard rat food (Ralston Purina, St. Louis, MO) and water. Animal experiments were conducted with the approval of the Catholic University Institutional Animal Care and Use Committee. At this time, the control was used to inject Saline (physiological saline) solution in the rat nose instead of LPS.
이후, LPS 주입에 의한 비부비동염의 유발 확인은 쥐 코의 점막을 대상으로 당업계에서 사용되고 있는 조직학적 분석과, PAS 염색을 통해 확인하였다. Thereafter, the induction of rhinosinusitis by LPS injection was confirmed through histological analysis and PAS staining that are used in the art for mucosal mucosa of rat nose.
표 1 쥐 코 점막에서의 조직학적 변화 분석
Table 1 Analysis of Histological Changes in Rat Nasal Mucosa
Absorbance | Mucosal thickness(mm) | PAS stained area(%) | ||||
group | 1st day | 4th day | 1st day | 4th day | 1st day | 4th day |
Saline | 0.085±0.038 | 0.097±0.024 | 1.01±0.26 | 1.21±0.67 | 16.54±1.93 | 16.39±1.34 |
LPS | 0.168±0.027 | 0.211±0.011 | 2.11±1.27 | 2.26±1.27 | 22.24±2.90 | 24.78±3.61 |
Absorbance | Mucosal thickness (mm) | PAS stained area (%) | ||||
group | 1st day | 4th day | 1st day | 4th day | 1st day | 4th day |
Saline | 0.085 ± 0.038 | 0.097 ± 0.024 | 1.01 ± 0.26 | 1.21 ± 0.67 | 16.54 ± 1.93 | 16.39 ± 1.34 |
LPS | 0.168 ± 0.027 | 0.211 ± 0.011 | 2.11 ± 1.27 | 2.26 ± 1.27 | 22.24 ± 2.90 | 24.78 ± 3.61 |
그 결과, 상기 표 1에 나타낸 바와 같이, LPS로 비부비동염이 유발된 쥐에서는 코 점막의 두께가 생리식염수를 처리한 대조군에 비해 증가한 것으로 나타났고, PAS 염색 면적도 증가한 것으로 나타났다.As a result, as shown in Table 1, in the LPS-induced rhinosinusitis mice, the thickness of the nasal mucosa was found to be increased compared to the control group treated with saline, and the PAS staining area was also increased.
또한, 도 1에 나타낸 바와 같이, LPS를 쥐 코에 투입한 후, 4일 경과한 후의 sinus mucosa를 현미경으로 관찰한 결과, LPS를 투입한 군이 대조군으로 생리식염수를 투입한 군에 비해 점막의 두께가 증가한 것으로 관찰됨에 따라 LPS 처리에 의해 비부비동염 쥐 모델이 잘 만들어졌음을 알 수 있었고, 이러한 결과는 도 2에 의한 PAS 염색 결과에서도 동일하게 확인되었다.In addition, as shown in FIG. 1, after the LPS was injected into the rat nose, sinus mucosa was observed under a microscope after 4 days, and the LPS-injected group of the mucosa was compared to the group in which saline was added to the control group. As observed to increase in thickness, it can be seen that the rhinosinusitis rat model was well made by LPS treatment, and these results were also confirmed in the PAS staining results of FIG. 2.
<실시예 3><Example 3>
본 발명에 따른 광천수 투여에 의한 비부비동염 증상 개선 및 치료 효과 분석Analysis of rhinosinusitis symptom improvement and treatment effect by mineral water administration according to the present invention
실시예 2에 의해 제조된 비부비동염 유발 쥐 모델을 대상으로 본 발명에 따른 광천수의 질환 치료 효능을 검사하기 위해, 실험 쥐 군을 다음과 같이 구분한 다음, 이후의 실험을 수행하였다. In order to examine the disease treatment efficacy of the mineral water according to the present invention in the rhinosinusitis-induced rat model prepared by Example 2, the experimental rat group was divided as follows, and the following experiment was performed.
표 2 실험 쥐 군 분류
TABLE 2 Experimental rat group classification
투여 용액 | 쥐 | |
A | 아무것도 처리하지 않음 | 정상 쥐 |
B | 생리식염수만 처리함 | 정상 쥐 |
C | LPS 만을 처리함 | 비부비동염 유발 쥐 |
D | LPS+생리식염수 처리함 | 비부비동염 유발 쥐 |
E | LPS+25% 광천수 | 비부비동염 유발 쥐 |
F | LPS+50% 광천수 | 비부비동염 유발 쥐 |
G | LPS+100% 광천수 | 비부비동염 유발 쥐 |
Dosing solution | rat | |
A | Does nothing | Normal rat |
B | Treats only saline | Normal rat |
C | Handles only LPS | Rhinosinusitis-induced rats |
D | LPS + saline solution | Rhinosinusitis-induced rats |
E | LPS + 25% Mineral Water | Rhinosinusitis-induced rats |
F | LPS + 50% Mineral Water | Rhinosinusitis-induced rats |
G | LPS + 100% Mineral Water | Rhinosinusitis-induced rats |
이때, 상기 25%, 50% 및 100%의 광천수는 상기 실시예 1에서 제조한 광천수 농축물이 25%(v/v), 50%(v/v)가 되도록 생리식염수로 희석한 것을 말하며, 100%는 광천수 농축물 100%를 사용한 것으로 말하며, 이때 LPS는 상기 실시예 2에 기술된 바와 같이 제조한 것을 사용하였고, 상기 A~G의 처리군은 투여용액을 0.1ml의 양으로 쥐의 코에 주입하였다.At this time, the 25%, 50% and 100% mineral water means that the mineral water prepared in Example 1 diluted with physiological saline such that 25% (v / v), 50% (v / v), 100% refers to 100% mineral water concentrate, wherein LPS was prepared as described in Example 2, and the treatment group of A ~ G used the dose of 0.1ml in the amount of the nose of the rat. Injected into.
상기와 같이 각각의 용액이 처리된 쥐 군을 대상으로 Evans blue 시약을 사용하여 혈장 내 유출 정도를 조사하였는데, 이는 비강 내 염증현상이 증가하는 경우 혈장 내 유출이 증가하기 때문에 염색 정도의 측정을 통해 비강 내 염증 정도를 분석하는 방법으로 사용되고 있다. Evans blue 유출 정도의 분석은 먼저 Evans blue 용액(Sigma, 40 mg/ml in Salinee) 1 ml를 상기 쥐들의 외경정맥에 주입하였고, 주입한 후 1분이 지난 다음, 각 쥐로부터 코 조직 샘플을 수득한 다음, 상기 샘플을 60에서 1ml의 포름아마이드(Sigma, USA)에 24시간 동안 담가두었다. 이후, 샘플을 9,000 rpm 및 20℃의 조건에서 30초 동안 원심분리한 후에, microplate reader(model 680, Biorad, USA)를 이용하여 상기 원심분리하여 얻은 상등액의 흡광도를 630nm에서 측정하였다.As described above, the degree of plasma outflow was investigated in the rat group treated with each solution by using Evans blue reagent, which is measured by measuring the degree of staining because the plasma outflow increases when inflammation of the nasal cavity increases. It is used to analyze the degree of inflammation in the nasal cavity. The analysis of the degree of Evans blue effusion was first performed by injecting 1 ml of Evans blue solution (Sigma, 40 mg / ml in Salinee) into the external jugular vein of the mice, one minute after the injection, and a nasal tissue sample from each rat The samples were then immersed in 60 to 1 ml of formamide (Sigma, USA) for 24 hours. Thereafter, the sample was centrifuged for 30 seconds at 9,000 rpm and 20 ° C., and then the absorbance of the supernatant obtained by centrifugation using a microplate reader (model 680, Biorad, USA) was measured at 630 nm.
그 결과, 도 3에 나타낸 바와 같이, 염증으로 인한 Evans blue의 유출정도는 LPS 투여에 의해 비부비동염 유발 쥐 군(C)이 가장 많이 유출된 것으로 나타난 반면, 종래 치료용도로 사용되는 생리식염수를 처리한 군(D)은 C군에 비해 유출 정도가 감소한 것으로 나타났으나, 본 발명의 광천수를 처리한 군이 생리식염수 처리 군보다 Evans blue 유출정도가 더 감소된 것으로 나타났고, 특히 25% 광천수를 처리한 군(E)에 비해 50% 광천수 및 100% 광천수를 처리한 군(F 및 G)이 더 현저하게 유출 정도가 감소한 것으로 나타났다. 이러한 결과는 Evans blue의 유출정도를 흡광도로 측정한 도 4의 결과를 통해서도 알 수 있었다. As a result, as shown in Figure 3, the outflow of Evans blue due to inflammation appeared to be the most outflow of the rhinosinusitis-induced rat group (C) by LPS administration, while treating the normal saline used for conventional treatment In one group (D), the outflow degree was reduced compared to the C group, but the treated group of the mineral water of the present invention showed that the Evans blue outflow was reduced more than the physiological saline treatment group, especially 25% mineral water. Compared to the treated group (E), the effluent decreased more significantly in the groups treated with 50% mineral water and 100% mineral water (F and G). These results were also found through the results of FIG. 4 measured by the absorbance of Evans blue.
<실시예 4><Example 4>
본 발명에 따른 광천수 투여에 의한 코 점막 두께 변화 측정Measurement of change in nasal mucosa thickness by mineral water administration according to the present invention
상기 실시예 3에서 실험한 각 쥐 군(A~G)을 대상으로 각 쥐로부터 코 점막을 채취하여 점막의 두께를 헤마토크실렌-에오신 염색을 통해 분석하였는데, 이를 위해 각 쥐로부터 채취한 코 점막을 2% 포르말린에서 고정시킨 다음, 10% 포르말린액으로 고정시키고, 파라핀으로 포매한 후, 5 두께의 마이크로톰(microtome)으로 세절하였다. 이후 헤마토실린-에오신(hematoxyline-eosin)으로 염색하여 광학현미경으로 관찰하였다. Nasal mucosa was collected from each rat in each rat group (A-G) tested in Example 3, and the thickness of the mucosa was analyzed by hematoxylin-eosin staining. Was fixed in 2% formalin, then fixed with 10% formalin liquid, embedded in paraffin, and then sliced into 5 micrometers of microtome. After staining with hematoxylin-eosin (hematoxyline-eosin) was observed by light microscopy.
그 결과, 도 5 및 도 6에 나타낸 바와 같이, LPS로 비부비동염이 유발된 쥐군의 경우, 비부비동염이 유발되지 않은 쥐 군에 비해 점막 두께가 현저히 증가한 것으로 관찰되었고, LPS 및 생리식염수를 처리한 군의 경우, LPS만을 처리한 군에 비해 점막의 두께는 감소한 것으로 나타났고, 이러한 점막 두께 감소는 본 발명의 광천수를 50%로 처리한 군과 유사하게 나타났으며, 본 발명의 광천수를 100% 처리한 군은 생리식염수 처리 군에 비해 점막 두께가 더 감소된 것으로 나타났다. As a result, as shown in Figs. 5 and 6, in the rat group in which rhinosinusitis was induced by LPS, mucosal thickness was significantly increased compared to the rat group in which no rhinosinus was induced, and treated with LPS and saline. In the case of the group, the thickness of the mucosa was found to be reduced compared to the group treated with LPS alone, and the decrease in the thickness of the mucosa was similar to the group treated with 50% of the mineral water of the present invention, and the mineral water of the present invention was 100%. The treated group was found to have a lower mucosal thickness than the normal saline treated group.
<실시예 5>Example 5
본 발명의 광천수에 의한 MUC5AC 유전자의 발현 감소 효과 측정Determination of the expression reduction effect of MUC5AC gene by mineral water of the present invention
기도의 점액 과분비 질환의 경우, MUC5AC 유전자가 과다발현되고 있다는 내용이 알려진 바 있으며, 따라서 MUC5AC 유전자의 발현을 억제할 경우, 과다한 점액분비를 감소시켜 점액 과분비로 인한 질환의 치료효과를 얻을 수 있다. In the case of mucus hypersecretion of the airway, it is known that the MUC5AC gene is overexpressed. Therefore, when the expression of the MUC5AC gene is suppressed, excessive mucus secretion can be reduced to obtain a therapeutic effect of the disease caused by mucus hypersecretion.
이에 본 발명자들은 본 발명의 광천수가 MUC5AC 유전자의 발현을 억제하는 활성이 있는지를 확인하기 위해, 상기 실시예 3에서 사용한 각 쥐 군으로부터 비강 조직을 분리한 다음, 상기 조직으로부터 RNA를 추출한 다음, MUC5AC 유전자를 증폭할 수 있는 프라이머를 사용하여 RT-PCR을 수행함으로써, MUC5AC 유전자의 발현 정도를 분석하였다. RNA는 추출키트((iNtRON Biotechnology, Inc., Gyeonggi-do, Korea)를 사용하여 사용자 제안 방법에 따라 RNA를 추출하였고, MUC5AC 에 대한 PCR 반응은 95℃ 에 15분 반응시킨 후, 94℃에서 1분, 55℃ 에서 1분, 72℃에서 1분의 반응을 32회 반복 수행하였다. glyceraldehyde 3-phosphate dehydrogenase (GAPDH) 의 PCR 반응은 94℃에서 4분 반응시키고, 94℃에서 1분, 60℃에서 1분, 72℃에서 1분의 반응을 35회 반복 수행하였다. 또한, 이때 사용한 프라이머들을 Gene Runner software (Hastings Software Inc., Las Vegas, Nev, USA)에서 디자인한 것으로 GenBenk에서 구입한 것을 사용하였으며, 각 프라이머의 서열은 다음과 같다.In order to confirm whether the mineral water of the present invention has an activity of inhibiting the expression of the MUC5AC gene, the present inventors separated the nasal tissue from each rat group used in Example 3, extracted RNA from the tissue, and then extracted MUC5AC. The expression level of the MUC5AC gene was analyzed by performing RT-PCR using a primer capable of amplifying the gene. RNA was extracted using the extraction kit ((iNtRON Biotechnology, Inc., Gyeonggi-do, Korea) according to the user's proposed method, PCR reaction for MUC5AC was reacted for 15 minutes at 95 ℃, 1 at 94 ℃ The reaction was repeated 32 times for 1 minute at 55 ° C. and 1 minute at 72 ° C. The PCR reaction of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was performed at 94 ° C. for 4 minutes, at 94 ° C. for 1 minute, and at 60 ° C. The reaction was repeated 35 times for 1 minute at 72 ° C. The primers used were designed by Gene Runner software (Hastings Software Inc., Las Vegas, Nev, USA) and purchased from GenBenk. The sequence of each primer is as follows.
<프라이머 서열>Primer Sequence
MUC5AC 정방향 프라이머; 5'-CATAGCCTCCTCTTGTTC-3' MUC5AC forward primer; 5'-CATAGCCTCCTCTTGTTC-3 '
MUC5AC 역방향 프라이머; 3'-ATTCCTGTAGCAGTAGTGAG-5' MUC5AC reverse primer; 3'-ATTCCTGTAGCAGTAGTGAG-5 '
GAPDH 정방향 프라이머; 5'-GCTGGTGCTGAGTATGTCGT-3' GAPDH forward primer; 5'-GCTGGTGCTGAGTATGTCGT-3 '
GAPDH 역방향 프라이머; 3'-GAATGGGAGTTGCTGTTGAA-5'GAPDH reverse primer; 3'-GAATGGGAGTTGCTGTTGAA-5 '
그 결과, 도 7에 나타낸 바와 같이, 아무것도 처리하지 않은 군과 PBS만을 처리한 군에 비해 LPS로 비부비동염을 유발한 군에서는 점액 과다 분비작용을 하는 MUC5AC 유전자의 발현이 약 3배 이상으로 현저하게 증가한 것으로 나타났으며, LPS와 함께 생리식염수를 처리한 군과 본 발명의 광천수를 처리한 군에서는 LPS만을 처리한 군에 비해 MUC5AC 유전자의 발현이 감소된 것으로 나타났으며, 본 발명의 광천수 처리군은 광천수 농도에 비례하여 MUC5AC 유전자의 발현이 감소되는 것으로 나타났다.As a result, as shown in FIG. 7, the expression of the MUC5AC gene, which functions as a mucus hypersecretion, is significantly more than three times higher in the LPS-induced rhinosinusitis than in the non-treated group and the PBS-only group. In the group treated with saline with LPS and treated with mineral water of the present invention, the expression of MUC5AC gene was decreased compared to the group treated with LPS alone, and the mineral water treated group of the present invention. Was shown to decrease the expression of MUC5AC gene in proportion to mineral water concentration.
따라서 이러한 실험 결과를 통해 본 발명자들은 본 발명에 따른 광천수의 경우, 염증 등으로 유발되는 코 점막의 부종 및 두께를 감소시키는 효과가 있고, 염증 정도도 개선시키는 효과가 있으며, 점액 과분비를 유도하는 MUC5AC 유전자의 발현을 감소시키는 효과도 우수하여, 축농증 및 비염 등과 같은 코 질환 치료제 및 비강 세척수로 사용할 수 있다는 사실을 알 수 있었다. Therefore, through these experimental results, the present inventors have an effect of reducing the swelling and thickness of the nasal mucosa caused by inflammation, etc., in the case of mineral water according to the present invention, and also improves the degree of inflammation, MUC5AC inducing mucus hypersecretion It is also excellent in reducing the expression of the gene, it can be seen that it can be used as a nasal disease treatment and nasal wash water, such as sinusitis and rhinitis.
<실시예 6><Example 6>
본 발명의 광천수에 비염 및 축농증 증상 개선 효과 Effect of improving rhinitis and sinusitis symptoms on mineral water of the present invention
본 발명자들은 본 발명에 따른 광천수가 실제적으로 비염 및 축농증 환자들의 증상을 개선할 수 있는지 확인하기 위해, 가톨릭대학교 성모병원에서 비염 및 축농증으로 판정받은 환자들을 각 실험군 별 5명씩 선별하여 1일 3회씩(아침 기상시, 오후 2시, 저녁 취침전) 10ml 주사기를 이용하여 머리를 숙이고 상기 본 발명의 광천수를 비강 내에 주입하고 1분정도씩 기다린 뒤 흘려보내도록 하였다. 이러한 과정을 10일 동안 반복하게 하고 5일째와 10일째에 개선된 상태를 5점 척도법으로 평가하였다. 이때 상기 광천수는 광천수 농축물을 물에 50%(v/v)로 함유한 용액을 사용하였고. 결과는 하기 표 3에 나타내었다. 이때 대조군으로는 생리식염수만을 사용한 것과 종래 비염 증상 개선을 위한 비강 세척용으로 사용하는 생리식염수를 사용하였다. The inventors of the present invention, to determine whether the mineral water according to the present invention can actually improve the symptoms of rhinitis and sinusitis patients, screening five patients for each experimental group three times a day determined by rhinitis and sinusitis at Catholic University St. Mary's Hospital (In morning weather, 2 pm, before bedtime) 10ml syringe was used to bow the head and the mineral water of the present invention was injected into the nasal cavity and waited for about 1 minute to let flow. This procedure was repeated for 10 days and the improved condition was evaluated on a 5 point scale on Day 5 and Day 10. In this case, the mineral water used was a solution containing 50% (v / v) of mineral water concentrate in water. The results are shown in Table 3 below. At this time, only the saline was used as a control group and saline used for nasal washing for improving the symptoms of conventional rhinitis.
표 3 평가 기준
TABLE 3 Evaluation standard
점수 | 척도 | 증상 |
0 | 전혀 개선없음 | 콧물과 재채기가 아주 심함 |
1 | 약간 개선됨 | 코막힘과 재채기가 자주 발생함 |
2 | 중등도 개선됨 | 코막힘과 재채기가 가끔 발생함 |
3 | 많이 개선됨 | 코막힘과 재채기가 거의 없음 |
4 | 완전히 개선됨 | 코막힘과 재채기가 전혀 없음 |
| Measure | Symptom | |
0 | No improvement at all | Runny nose and very sneezing | |
One | Slightly improved | Frequent stuffy nose and sneezing | |
2 | Improved moderate | Sometimes nasal congestion and sneezing | |
3 | Much improved | Almost no stuffy nose and sneezing | |
4 | Fully improved | No stuffy nose or sneezing at all |
표 4 비염 및 축농증 증상 개선효과
Table 4 Improvement of rhinitis and sinusitis symptoms
생리식염수 | 생리식염수 | 본 발명의 광천수 | |
0일 | 0.1 | 0.1 | 0.1 |
5일 | 0.1 | 1.3 | 2.2 |
10일 | 0.2 | 2.2 | 3.6 |
Saline solution | Saline solution | Mineral water of the | |
0 days | 0.1 | 0.1 | 0.1 |
5 days | 0.1 | 1.3 | 2.2 |
10 days | 0.2 | 2.2 | 3.6 |
비염 및 축농증 환자를 대상으로 본 발명의 광천수에 의한 질환의 증상 개선 효과는 상기 표 3에 나타낸 바와 같이, 본 발명의 광천수를 사용한 경우, 종래 사용되고 있는 생리식염수를 사용한 경우에 비해 질환의 증상 개선 정도가 월등히 우수하다는 것을 알 수 있었다.Symptom improvement effect of the disease caused by mineral water of the present invention in rhinitis and sinusitis patients, as shown in Table 3, the degree of symptom improvement of disease compared to the case of using the conventional saline solution, the mineral water of the present invention Was found to be superior.
이제까지 본 발명에 대하여 그 바람직한 실시예들을 중심으로 살펴보았다. 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본So far I looked at the center of the preferred embodiment for the present invention. Those of ordinary skill in the art to which the present invention pertains may include the present invention
질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할 수 있을 것이다. 그러므로 개시된 실시 예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특허청구범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다. It will be appreciated that the present invention may be embodied in a modified form without departing from the quality thereof. Therefore, the disclosed embodiments should be considered in descriptive sense only and not for purposes of limitation. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the scope will be construed as being included in the present invention.
Claims (8)
- 대한민국 강원도 강릉시 옥계면 금진3리 92-1번지 해안단구 지역 온천지의 지하 1100m 지점에서 취수한 해양성 광천수를 유효성분으로 포함하는 비강 세척용 조성물.Nasal washing composition comprising marine mineral water taken from the 1100m underground of the hot spring area, 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, Korea.
- 제1항에 있어서,The method of claim 1,상기 광천수는 미네랄 성분으로서, 칼륨 200~230mg/L, 나트륨 7000~9500mg/L, 칼슘 1400~1700mg/L, 마그네슘 900~1100mg/L, 아연 3~9mg/L, 스트론튬 25~35mg/L, 셀레늄 200~500ug/L, 바나듐 65~75ug/L, 게르마늄 0.5~1.5ug/L, 망간 10~40ug/L, 코발트 1~3ug/L, 티탄 600~950ug/L, 구리 3~9ug/L, 리튬 0.02~0.09mg/L, 염소이온 16000~19500mg/L, 불소이온 1.5~3.0mg/L, 브롬이온 40~56mg/L, 황산이온 3000~4500mg/L, 보론 0.8~1.2mg/L 및 이산화규소 0.5~15mg/L를 함유하는 것을 특징으로 하는 비강 세척용 조성물.The mineral water is a mineral component, potassium 200 ~ 230mg / L, sodium 7000 ~ 9500mg / L, calcium 1400 ~ 1700mg / L, magnesium 900 ~ 1100mg / L, zinc 3 ~ 9mg / L, strontium 25 ~ 35mg / L, selenium 200 ~ 500ug / L, Vanadium 65 ~ 75ug / L, Germanium 0.5 ~ 1.5ug / L, Manganese 10 ~ 40ug / L, Cobalt 1 ~ 3ug / L, Titanium 600 ~ 950ug / L, Copper 3 ~ 9ug / L, Lithium 0.02 ~ 0.09mg / L, chlorine ion 16000 ~ 19500mg / L, fluorine ion 1.5 ~ 3.0mg / L, bromine ion 40 ~ 56mg / L, sulfate ion 3000 ~ 4500mg / L, boron 0.8 ~ 1.2mg / L and silicon dioxide A nasal washing composition comprising 0.5-15 mg / L.
- 제1항에 있어서,The method of claim 1,상기 광천수는 탈염처리 및 증발 농축한 농축물이고, 상기 농축물은 조성물 총 중량을 기준으로 0.5~50%(v/v)로 함유하는 것을 특징으로 하는 비강 세척용 조성물.The mineral water is a desalted and evaporated concentrate, the concentrate is contained in the nasal washing composition containing 0.5 to 50% (v / v) based on the total weight of the composition.
- 제1항에 있어서,The method of claim 1,상기 조성물은 액상, 페이스트상, 연고, 또는 스프레이용 제제인 것을 특징으로 하는 비강 세척용 조성물.The composition is a nasal cleaning composition, characterized in that the liquid, paste, ointment, or a spray formulation.
- 대한민국 강원도 강릉시 옥계면 금진3리 92-1번지 해안단구 지역 온천지의 지하 1100m 지점에서 취수한 해양성 광천수를 유효성분으로 포함하는 비염 또는 축농증의 예방 또는 치료용 조성물.A composition for the prevention or treatment of rhinitis or sinusitis comprising marine mineral water taken from 1100m underground in the hot spring area of 92-1, Geumjin 3-ri, Okgye-myeon, Gangneung-si, Gangwon-do, Korea.
- 제5항에 있어서,The method of claim 5,상기 광천수는 미네랄 성분으로서, 칼륨 200~230mg/L, 나트륨 7000~9500mg/L, 칼슘 1400~1700mg/L, 마그네슘 900~1100mg/L, 아연 3~9mg/L, 스트론튬 25~35mg/L, 셀레늄 200~500ug/L, 바나듐 65~75ug/L, 게르마늄 0.5~1.5ug/L, 망간 10~40ug/L, 코발트 1~3ug/L, 티탄 600~950ug/L, 구리 3~9ug/L, 리튬 0.02~0.09mg/L, 염소이온 16000~19500mg/L, 불소이온 1.5~3.0mg/L, 브롬이온 40~56mg/L, 황산이온 3000~4500mg/L, 보론 0.8~1.2mg/L 및 이산화규소 0.5~15mg/L를 함유하는 것을 특징으로 하는 비염 또는 축농증의 예방 또는 치료용 조성물.The mineral water is a mineral component, potassium 200 ~ 230mg / L, sodium 7000 ~ 9500mg / L, calcium 1400 ~ 1700mg / L, magnesium 900 ~ 1100mg / L, zinc 3 ~ 9mg / L, strontium 25 ~ 35mg / L, selenium 200 ~ 500ug / L, Vanadium 65 ~ 75ug / L, Germanium 0.5 ~ 1.5ug / L, Manganese 10 ~ 40ug / L, Cobalt 1 ~ 3ug / L, Titanium 600 ~ 950ug / L, Copper 3 ~ 9ug / L, Lithium 0.02 ~ 0.09mg / L, chlorine ion 16000 ~ 19500mg / L, fluorine ion 1.5 ~ 3.0mg / L, bromine ion 40 ~ 56mg / L, sulfate ion 3000 ~ 4500mg / L, boron 0.8 ~ 1.2mg / L and silicon dioxide A composition for preventing or treating rhinitis or sinusitis, which contains 0.5 to 15 mg / L.
- 제5항에 있어서,The method of claim 5,상기 광천수는 상기 광천수는 탈염처리 및 증발 농축한 농축물이고, 상기 농축물은 조성물 총 중량을 기준으로 0.5~50%(v/v)로 함유하는 것을 특징으로 하는 비염 또는 축농증의 예방 또는 치료용 조성물.The mineral water is a concentrate of the demineralized and evaporated concentrated mineral water, the concentrate is contained for 0.5 to 50% (v / v) based on the total weight of the composition for the prevention or treatment of rhinitis or sinusitis. Composition.
- 제5항에 있어서,The method of claim 5,상기 광천수는 염증으로 인한 비강 내 점막의 부종을 감소시키고, 점액 과분비 유발 인자인 MUC5AC 유전자의 발현을 감소시키는 효과를 갖는 것을 특징으로 하는 비염 또는 축농증의 예방 또는 치료용 조성물.The mineral water reduces the swelling of the intranasal mucosa due to inflammation, and has the effect of reducing the expression of the mucin hypersecretion-inducing factor MUC5AC gene, characterized in that the composition for the prevention or treatment of rhinitis or sinusitis.
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KR10-2011-0125138 | 2011-11-28 | ||
KR1020110125138A KR101326472B1 (en) | 2011-11-28 | 2011-11-28 | Composition for cleaning nasal cavity comprising mineral water |
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Cited By (3)
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WO2016028504A1 (en) * | 2014-08-16 | 2016-02-25 | SOFIBEL S.A.S. - a company ultimately owned by CHURCH & DWIGHT CO. INC. | Nasal composition having anti-viral properties |
WO2022254042A1 (en) * | 2021-06-04 | 2022-12-08 | Olys Pharma Srl | Pluri-ionic complex for the prevention or treatment of neurogenic inflammation |
WO2023232997A1 (en) * | 2022-06-03 | 2023-12-07 | Ynios Pharma | Multi-ionic complex for the prevention or treatment of inflammation |
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RU2637438C1 (en) * | 2016-12-28 | 2017-12-04 | Ирина Евгеньевна Куранчева | Means for nasal cavity, nasopharynx and oral cavity rinsing |
KR102227420B1 (en) | 2017-06-30 | 2021-03-15 | 대봉엘에스 주식회사 | Composition for cleaning nasal cavity |
RU2665959C1 (en) * | 2017-11-21 | 2018-09-05 | Андрей Никифорович Васильев | Spray for emergency prevention of acute respiratory viral infections |
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JP2001247446A (en) * | 2000-03-06 | 2001-09-11 | Toa Yakuhin Kk | Cleaning agent with deep sea water |
JP2002212081A (en) * | 2001-01-23 | 2002-07-31 | Goshu Yakuhin Kk | Nasal irrigation agent formulated with ocean deep water |
KR20040031799A (en) * | 2002-10-01 | 2004-04-14 | 임 그리워 | Pharmaceutical composition containing the concentrate of Bando Deep Ocean Water having antiallergical activity |
KR20050021201A (en) * | 2003-08-26 | 2005-03-07 | 진해개발주식회사 | Compositions for antialergy with the concentrated underground water |
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KR101171068B1 (en) * | 2010-04-01 | 2012-08-03 | 주식회사 동양생명과학 | Pharmaceutical Compositions for Diabetes Improvement and Prevention Containing Mineral Compositions as Effective Component |
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2011
- 2011-11-28 KR KR1020110125138A patent/KR101326472B1/en not_active Expired - Fee Related
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JP2001247446A (en) * | 2000-03-06 | 2001-09-11 | Toa Yakuhin Kk | Cleaning agent with deep sea water |
JP2002212081A (en) * | 2001-01-23 | 2002-07-31 | Goshu Yakuhin Kk | Nasal irrigation agent formulated with ocean deep water |
KR20040031799A (en) * | 2002-10-01 | 2004-04-14 | 임 그리워 | Pharmaceutical composition containing the concentrate of Bando Deep Ocean Water having antiallergical activity |
KR20050021201A (en) * | 2003-08-26 | 2005-03-07 | 진해개발주식회사 | Compositions for antialergy with the concentrated underground water |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2016028504A1 (en) * | 2014-08-16 | 2016-02-25 | SOFIBEL S.A.S. - a company ultimately owned by CHURCH & DWIGHT CO. INC. | Nasal composition having anti-viral properties |
WO2022254042A1 (en) * | 2021-06-04 | 2022-12-08 | Olys Pharma Srl | Pluri-ionic complex for the prevention or treatment of neurogenic inflammation |
BE1029458B1 (en) * | 2021-06-04 | 2023-01-09 | Olys Pharma | Multiionic complex for the prevention or treatment of neurogenic inflammation |
WO2023232997A1 (en) * | 2022-06-03 | 2023-12-07 | Ynios Pharma | Multi-ionic complex for the prevention or treatment of inflammation |
BE1030588B1 (en) * | 2022-06-03 | 2024-01-08 | Ynios Pharma | Multi-ion complex for the prevention or treatment of inflammation |
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KR20130059048A (en) | 2013-06-05 |
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