KR102720037B1 - Nasal irrigation composition and preparation method thereof - Google Patents

Abstract

The present invention relates to a nasal cleansing composition comprising (a) 0.3 to 4.5 wt% of an ionic salt compound; (b) 0.1 to 10 wt% of a sulfated polysaccharide; (c) 0.0005 to 0.5 wt% of povidone-iodine; (d) 0.2 to 5.0 wt% of a sweetener; and (e) the remainder being water; and a method for preparing the same.
According to the present invention, a nasal cleansing composition and a method for producing the same can be provided, which exhibit a synergistic effect in killing and inhibiting respiratory infection pathogenic microorganisms, can be applied to the nasal cavity sensitive to stimulation, and can be effectively used for nasal cleansing.

Description

{Nasal irrigation composition and preparation method thereof}

The present invention relates to a nasal cleansing composition and a method for producing the same, and more specifically, to a nasal cleansing composition containing an ionic salt compound, a sulfated polysaccharide, and povidone-iodine as active ingredients, which can kill or inhibit bacteria or viruses that can infect the respiratory tract, and a method for producing the same.

Due to the recent COVID-19 outbreak, the number of patients with respiratory infections has been rapidly increasing worldwide, and the number of deaths due to severe symptoms has also been continuously increasing. COVID-19 is known to infect the upper respiratory tract, such as the pharynx, larynx, and trachea, and according to a recently published paper [Ji Hoon Ahn et al., Nasal ciliated cells are primary targets for SARS-CoV-2 replication in early stage of COVID-19, J. Clin. Invest., 2021;131(13)], it was confirmed that the COVID-19 virus replicates and proliferates in nasal ciliated cells. Patients infected with COVID-19 develop fever and upper respiratory tract infection symptoms after an average incubation period of about -6 days, and the maximum incubation period is known to be about 14 days. The shedding of the COVID-19 virus is confirmed 1-2 days before the onset of symptoms, and this viral shedding is known to continue for 7-12 days in moderately ill patients and up to 14 days in severely ill patients. Moreover, the COVID-19 virus continues to form various mutations, and recently, with delta mutations and even omicron mutations becoming prevalent, it has become difficult to respond with just a vaccine. Therefore, various treatment methods such as masks, hand washing, preventive vaccines, and treatments are required to prevent infection, and in particular, in terms of respiratory infection, treatment methods for cleaning or disinfecting the nasal and oral cavities can be very good alternatives.

In general, sodium chloride aqueous solution has been a traditional method for nasal irrigation in patients with rhinitis for a long time. According to a recent paper [Sandeep et al., A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold, Scientific reports (2019)9:1015], when nasal irrigation and oral gargling with 3% sodium chloride hypertonic solution were performed on patients with a cold known to be transmitted through the upper respiratory tract, the duration of illness was shortened by 1.9 days and the transmission to family members was reduced by 35%. These researchers subsequently reclassified the clinical results and analyzed them for patients infected with the coronavirus and summarized the results in a paper [Sandeep et al., Hypertonic saline nasal irrigation and gargling should be considered as a treatment option for COVID-19, J. Glob Health 2020; 10(1):010332], and reported that in the intervention group that used the solution for nasal irrigation and gargling, the duration of illness was reduced by 2.6 days, the duration of nasal congestion was reduced by 3.1 days, and the duration of coughing was reduced by 3.3 days compared to the control group. However, this appears to be due to the pulling and cleansing effect of the solution by osmotic pressure, and does not indicate a killing effect on the virus.

Another paper presented as an alternative method for treating the COVID-19 virus [Yejin Jang et al., Antiviral activity of lambdacarrageenan against influenza viruses and severe acute respiratory syndrome coronavirus 2, Scientific Reports (2021)11:821] applied lambda-carrageenan for antiviral purposes. In cell culture experiments, it was reported that lambda-carrageenan effectively inhibited influenza A and B with an EC50 (half maximal effective concentration) value of 0.3-1.4 ㎍/㎖, and effectively inhibited SARS-CoV-2 with an EC50 value of 0.9±1.1 ㎍/㎖. Lambda-carrageenan acts by binding to viral glycoprotein as an anionic polymer, thereby interfering with the initial virus-cell contact or preventing the virus from entering the cell. Therefore, it is known to not kill the virus itself.

Meanwhile, povidone-iodine solution is one of the most widely used general-purpose disinfectants, and a 10% solution is used on areas at risk of infection such as the skin. Recently, a product has been released that can be used to disinfect pathogenic microorganisms by spraying a 0.45% povidone-iodine solution into the mouth as an oral spray. According to the paper by Didier et al. [Didier et al., Povidone iodine: Properties, mechanisms of action, and role in infection control and Staphylococcus aureus decolonization, Antimicrobial Agents and Chemotherapy, 2020; 64(9): E00682-20], povidone-iodine is a water-soluble iodophor that releases iodine as a complex of iodine and a water-soluble polymer carrier, polyvinylpyrrolidone, and it forms a dynamic equilibrium between free iodine, which has microorganism killing properties, and the povidone-iodine complex in aqueous solution. Its mechanism of action is that small molecules of iodine rapidly penetrate into microorganisms and oxidize major proteins, nucleotides, and fatty acids, ultimately leading to cell death. However, povidone-iodine solutions have a strong odor and are very irritating, so no products for use in the nasal cavity have been developed yet.

Accordingly, the inventors of the present invention have discovered that by mixing an ionic salt compound, a sulfated polysaccharide, and povidone-iodine, each having a different mechanism of action, in an appropriate composition, a synergistic effect is exhibited in killing and inhibiting pathogenic microorganisms, and that the mixture can be applied to the nasal cavity, which is sensitive to stimulation, and can be used to maximize the cleaning and disinfection of areas vulnerable to respiratory infections, such as nasal washing, and have completed the present invention.

Patent Document 1. Korean Patent Publication No. 10-1440533 Patent Document 2. Korean Patent Publication No. 10-2019-0002990

Accordingly, the present invention has been conceived in consideration of the above problems, and the purpose of the present invention is to provide a nasal cleansing composition which exhibits a synergistic effect in killing and inhibiting respiratory infection pathogenic microorganisms, can be applied to the nasal cavity sensitive to stimulation, and can be effectively used for nasal cleansing, and a method for producing the same.

To achieve the above-mentioned object, the present invention provides a nasal cleansing composition comprising: (a) 0.3 to 4.5 wt% of an ionic salt compound; (b) 0.1 to 10 wt% of a sulfated polysaccharide; (c) 0.0005 to 0.5 wt% of povidone-iodine; (d) 0.2 to 5.0 wt% of a sweetener; and (e) a balance of water.

The above ionic salt compound is characterized by at least one selected from the group consisting of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium carbonate, potassium carbonate and sodium bicarbonate.

The above ionic salt compound is characterized by having a particle diameter of 50 to 1,500 ㎛.

The above sulfated polysaccharide is characterized by at least one selected from the group consisting of fucan sulfate, agaran sulfate, carrageenan, galactan sulfate, rhamnan sulfate, spirulan, ulvan, xylomannan sulfate, chondroitin sulfate, heparin, sulfated cellulose, sulfated curdlan, sulfated dextran, sulfated xylan, sulfated glucan, sulfated mannose, and sulfated mannuronate.

The above sulfated polysaccharide is characterized by having a sulfate group content of 5.0 to 60.0 mol% and a molecular weight of 3,000 to 500,000.

The above povidone-iodine is characterized in that the iodine content is 9.0 to 12.0 wt%, and the molecular weight of povidone is 40,000 to 80,000.

The above sweetener is characterized by at least one selected from the group consisting of xylitol, sorbitol, sucrose, glucose, stevia, and sucralose.

The above sweetener is characterized by having a particle diameter of 50 to 1,500 ㎛.

In addition, the present invention provides a method for producing a nasal cleansing composition, comprising: (i) a step of grinding a sweetener component into particles of a predetermined size; (ii) a step of uniformly mixing the ground sweetener particles with sulfated polysaccharide and povidone-iodine; (iii) a step of grinding an ionic salt compound into particles of a predetermined size and then uniformly mixing the mixture with the mixture of step (ii); and (iv) a step of dissolving the mixture obtained in step (iii) in water.

In addition, the present invention provides a method for manufacturing a nasal cleansing composition, comprising: (I) a step of pulverizing an ionic salt compound and a sweetener component into particles of a predetermined size, respectively; (II) a step of uniformly mixing the pulverized ionic salt compound and sweetener particles; (III) a step of adding sulfated polysaccharide and povidone-iodine to the mixture obtained in step (II) while applying humidity, and mixing and drying the mixture; and (IV) a step of dissolving the dried mixture obtained in step (III) in water.

According to the present invention, a nasal cleansing composition and a method for producing the same can be provided, which exhibit a synergistic effect in killing and inhibiting respiratory infection pathogenic microorganisms, can be applied to the nasal cavity sensitive to stimulation, and can be effectively used for nasal cleansing.

Hereinafter, a nasal cleansing composition according to the present invention and a method for manufacturing the same will be described in detail with examples.

First, the present invention provides a nasal cleansing composition comprising: (a) 0.3 to 4.5 wt% of an ionic salt compound; (b) 0.1 to 10 wt% of a sulfated polysaccharide; (c) 0.0005 to 0.5 wt% of povidone-iodine; (d) 0.2 to 5.0 wt% of a sweetener; and (e) a balance of water.

The nasal cleansing composition of the present invention has a mechanism of action in which, when applied to the nasal cavity, an ionic salt compound draws body fluid, a sulfated polysaccharide binds to pathogenic microorganisms to prevent binding and penetration into body cells, and povidone-iodine oxidizes the pathogenic microorganisms, leading to their death.

At this time, the ionic salt compound may be at least one selected from the group consisting of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium carbonate, potassium carbonate and sodium bicarbonate, and the content thereof is preferably 0.3 to 4.5 wt% in the nasal cleansing composition in an aqueous solution state, and more preferably 0.5 to 3.5 wt%.

In addition, it is preferable that the aqueous solution in which the ionic salt compound is dissolved has an osmotic concentration of 270 mOsm/L or higher. The ionic salt compound can be used by dissolving it in distilled water or purified water, and it plays a role in washing out foreign substances in the nasal cavity. In addition, if a hypertonic solution is used rather than a body fluid, it can easily remove foreign substances attached to the surface of the nasal mucosa by drawing moisture in the body. However, if a hypertonic solution exceeding 4.5 wt% is used, it can cause unpleasant irritation in the nasal cavity.

In addition, the ionic salt compound preferably has a particle diameter of 50 to 1,500 ㎛, and more preferably 100 to 1,000 ㎛. The ionic salt compound can be used by dissolving it in distilled water or purified water. If the ionic salt compound particle diameter exceeds 1,500 ㎛, the time required for dissolution becomes long, which may be inconvenient to use, and if it is less than 50 ㎛, the surface area relative to the volume of the particle becomes relatively too large, and accordingly, the solubility increases, so that moisture in the air can be easily absorbed, which may cause the particles to clump together.

In addition, the sulfated polysaccharide may be at least one selected from the group consisting of fucan sulfate, agaran sulfate, carrageenan, galactan sulfate, rhamnan sulfate, spirulan, ulvan, xylomannan sulfate, chondroitin sulfate, heparin, sulfated cellulose, sulfated curdlan, sulfated dextran, sulfated xylan, sulfated glucan, sulfated mannose, and sulfated mannuronate, and the content thereof may be 0.1 to 10% in the aqueous nasal cleansing composition. It is preferably 10 wt%, and more preferably 0.3 to 5.0 wt%. If the content of the sulfated polysaccharide is less than 0.1 wt%, the antiviral effect may be minimal, and if the content exceeds 10 wt%, there is a disadvantage in that the viscosity is too high and it is difficult to distribute evenly throughout the nasal cavity.

The sulfated functional group of sulfated polysaccharides has an anion in the form of -OSO ₃ ^- , which can interact with the positively charged glycoprotein region of the virus to interfere with the initial virus-cell contact, and can also interact with the virus by covering the positive charge of the viral receptor, thereby preventing virus penetration. On the other hand, it can interact with the viral membrane protein to interfere with virus internalization. Through these various interactions of sulfated polysaccharides, infection can be inhibited by interfering with the contact, penetration, and internalization of viruses with cells.

The above sulfated polysaccharide preferably has a sulfation functional group content of 5.0 to 60.0 mol%, and more preferably 15.0 to 40.0 mol%. In the sulfated polysaccharide, the sulfation functional group is an anion that can interact with cations of viruses and cells to prevent attachment, penetration, internalization, etc. of viruses. If the sulfation functional group is less than 5.0 mol%, this effect is bound to be limited, and if the sulfation functional group exceeds 60.0 mol%, the molecular weight may become too small due to autolysis, and the polysaccharide may easily detach from the nasal mucosa.

In addition, the molecular weight of the sulfated polysaccharide is preferably 3,000 to 500,000, and more preferably 10,000 to 300,000. When applied to the nasal mucosa, the sulfated polysaccharide must remain for a relatively long time to have a long duration. However, if the molecular weight is less than 3,000, it can easily flow down and be removed, and if the molecular weight exceeds 500,000, the viscosity is high, making it difficult to evenly spray or spray into the nasal cavity.

In addition, the povidone-iodine content in the aqueous solution state of the nasal cleansing composition is preferably 0.0005 to 0.5 wt%, and more preferably 0.001 to 0.3 wt%. If the povidone-iodine content is less than 0.0005 wt%, the virus removal ability may be weak, and if the povidone-iodine content exceeds 0.5 wt%, it may be difficult to apply due to severe irritation in the nasal cavity.

Meanwhile, the iodine content in the povidone-iodine may be 9.0 to 12.0 wt%, and the molecular weight of povidone may be 40,000 to 80,000. If the iodine content is less than 9.0 wt%, the disinfecting effect cannot be properly exerted, and if the content exceeds 12.0 wt%, there is a possibility of severe irritation or side effects. In addition, if the molecular weight of povidone is less than 40,000, it cannot stably capture iodine, and if the molecular weight exceeds 80,000, there is a disadvantage in that the viscosity is high and it is difficult to evenly distribute over the entire desired area when spraying or sprinkling.

In addition, the sweetener may be at least one selected from the group consisting of xylitol, sorbitol, sucrose, glucose, stevia, and sucralose, and the content thereof is preferably 0.2 to 5.0 wt% in the nasal cleansing composition in an aqueous solution state. If the content of the sweetener component is less than 0.2 wt%, it is difficult to uniformly mix with povidone-iodine, and if the content exceeds 5.0 wt%, there is a concern that it may taste too sweet, causing discomfort in use.

The sweetener may have a particle diameter of 50 to 1,500 ㎛. If the particle diameter is less than 50 ㎛, it is easy to scatter during mixing and is not evenly mixed. If the particle diameter exceeds 1,500 ㎛, it may take too long to dissolve in water, which may be inconvenient.

In addition, the present invention provides a method for producing a nasal cleansing composition, comprising: (i) a step of grinding a sweetener component into particles of a predetermined size; (ii) a step of uniformly mixing the ground sweetener particles with sulfated polysaccharide and povidone-iodine; (iii) a step of grinding an ionic salt compound into particles of a predetermined size and then uniformly mixing the mixture with the mixture of step (ii); and (iv) a step of dissolving the mixture obtained in step (iii) in water.

In addition, the present invention provides a method for manufacturing a nasal cleansing composition, comprising: (I) a step of pulverizing an ionic salt compound and a sweetener component into particles of a predetermined size, respectively; (II) a step of uniformly mixing the pulverized ionic salt compound and sweetener particles; (III) a step of adding sulfated polysaccharide and povidone-iodine to the mixture obtained in step (II) while applying humidity, and mixing and drying the mixture; and (IV) a step of dissolving the dried mixture obtained in step (III) in water.

Hereinafter, specific examples and comparative examples of the present invention, along with test examples testing the bacterial and viral killing or inhibition effects of nasal cleansing compositions prepared therefrom, are described.

(Example 1)

As a sweetener, sucrose is ground into particles having an average size of about 500 ㎛, and 2 g of the ground sucrose is uniformly mixed with 0.7 g of galactan sulfate as a sulfated polysaccharide and 0.25 g of povidone-iodine. Next, 2.7 g of sodium chloride as an ionic salt compound is ground into particles having an average size of about 300 ㎛, and then added to the obtained mixture and uniformly mixed. The obtained homogeneous mixture is placed in an aluminum pouch, heat is applied, and the mixture is sealed. The pouch is opened and dissolved in 250 ㎖ of purified water to prepare a nasal wash.

(Example 2)

As a sweetener, sorbitol is ground into particles having an average size of about 500 μm, and 2.5 g of the ground sorbitol is uniformly mixed with 1.0 g of chondroitin sulfate as a sulfated polysaccharide and 0.5 g of povidone-iodine. Next, 3.0 g of potassium chloride as an ionic salt compound is ground into particles having an average size of about 500 μm, and then added to the obtained mixture and uniformly mixed. The obtained homogeneous mixture is placed in an aluminum pouch, heated, sealed, and then the pouch is opened and dissolved in 250 ml of distilled water or purified water to prepare a nasal wash.

(Example 3)

As a sweetener, xylitol is ground into particles having an average size of about 1,000 ㎛, and 3.0 g of the ground xylitol is uniformly mixed with 1.0 g of sulfated polysaccharide, dextran sulfate, and 0.75 g of povidone-iodine. Next, 3.0 g of potassium chloride and 0.5 g of sodium carbonate as ionic salt compounds are mixed, ground into an average size of about 700 ㎛, and added to the obtained mixture, followed by uniform mixing. The obtained homogeneous mixture is placed in an aluminum pouch, heated, and sealed, and then the pouch is opened and dissolved in 250 ㎖ of distilled or purified water to prepare a nasal wash.

(Example 4)

As ionic salt compounds, 2 g of potassium chloride and 1 g of potassium carbonate, and as a sweetener, 3 g of glucose were each ground to an average size of about 500 ㎛, and the two ground particles were uniformly mixed. Moisture was sprayed onto the mixture as a fine mist to increase the humidity to 90% or higher, and then 1.0 g of sulfated xylan and 1.0 g of povidone-iodine as sulfated polysaccharides were added and mixed. After sufficiently and evenly mixing for 30 minutes or more, the mixture was dried by blowing dry air at 60°C. The dried homogeneous mixture was put into an aluminum pouch, heat was applied, and the mixture was sealed. The pouch was opened and the mixture was dissolved in 250 ml of distilled water or purified water to prepare a nasal wash.

(Example 5)

As an ionic salt compound, 4 g of sodium chloride, and as a sweetener, 3 g of glucose were each ground to an average size of about 300 ㎛, and the two types of ground particles were uniformly mixed. Moisture was sprayed onto the mixture as a fine mist to increase the humidity to 90% or higher, and then 1.5 g of fucan sulfate and 1.0 g of povidone-iodine as sulfated polysaccharides were added and mixed. After sufficiently and evenly mixing for 30 minutes or more, the mixture was dried by blowing dry air at 60°C. The dried homogeneous mixture was put into an aluminum pouch, heat was applied, and the mixture was sealed. The pouch was opened and the mixture was dissolved in 250 ml of distilled water or purified water to prepare a nasal wash.

(Example 6)

As an ionic salt compound, 3 g of calcium chloride, and as a sweetener, 3 g of xylitol were each ground to an average size of about 700 ㎛, and the two ground particles were uniformly mixed. Moisture was sprayed onto the mixture as a fine mist to increase the humidity to 90% or higher, and then 1.2 g of xylomannan sulfate as a sulfated polysaccharide and 1.5 g of povidone-iodine were added and mixed. The mixture was sufficiently and evenly mixed for 30 minutes or more, and then dried by blowing dry air at 60°C. The dried homogeneous mixture was put into an aluminum pouch, heat was applied, and the pouch was opened and dissolved in 250 ml of distilled water or purified water to prepare a nasal wash.

(Comparative Example 1)

A nasal rinse was prepared by mixing 3 g of potassium chloride, 3 g of xylitol, and 1.0 g of dextran sulfate. At this time, the average size of the potassium chloride particles was 2,000 ㎛ or more. The obtained mixture was put into an aluminum pouch, heated, and sealed, and then the pouch was opened and dissolved in 250 ㎖ of distilled water or purified water to prepare a nasal rinse.

(Comparative Example 2)

A mixture of 3 g of potassium chloride, 3 g of xylitol, and 0.75 g of povidone-iodine was prepared. At this time, the average size of the potassium chloride particles was 2,000 ㎛ or more. The obtained mixture was placed in an aluminum pouch, heated, and sealed. The pouch was then opened and dissolved in 250 ㎖ of distilled water or purified water to prepare a nasal wash.

(Comparative Example 3)

4 g of sodium chloride and 3 g of glucose were mixed, and water was sprayed with a fine mist to increase the humidity to 90% or higher, and 1.5 g of fucan sulfate was added and mixed. At this time, the average size of the sodium chloride particles was 2,000 ㎛ or higher. After drying the mixture, it was placed in an aluminum pouch, heat was applied, and it was sealed. Then, the pouch was opened and dissolved in 250 ㎖ of distilled water or purified water to prepare a nasal wash.

(Comparative Example 4)

4 g of sodium chloride and 3 g of glucose were mixed, and water was sprayed with a fine mist to increase the humidity to 90% or higher, then 1.0 g of povidone-iodine was added and mixed. At this time, the average size of the sodium chloride particles was 2,000 ㎛ or higher. After drying the mixture, it was placed in an aluminum pouch, heat was applied, and the pouch was sealed, then the mixture was opened and dissolved in 250 ㎖ of distilled or purified water to prepare a nasal wash.

(Test examples 1 to 6)

Prepare standard strains of Gram-positive ( Streptococcus pneumoniae ) and Gram-negative ( Klebsiella pneumoniae ), and perform the inactivation test once at 20.0±1.0℃ according to EN13727:2012+A2:2015. Add the suspension of the test microorganism under dirty condition [3.0 g/L BSA + 3.0 mL/L erythrocytes] as an interference substance to the sample test solution. After a specific contact time (e.g., 15 seconds, 30 seconds), take 1 mL, and immediately neutralize the bactericidal activity in this part of the solution with 3% Tween 80 + 0.1% histidine + 0.3% lecithin + 0.5% sodium thiosulphate. For each test suspension, spread two 1 mL samples on at least two plates, respectively. The number of surviving test microorganisms in the mixture is calculated for each sample and the reduction factor is determined for the corresponding test suspension. A reduction of ≥5log ₁₀ (≥99.999%) bacteria compared to the control is considered to indicate effective antibacterial efficacy according to European standards.

The results of Test Examples 1 to 6, which measured the dissolution rate, mixing uniformity, and antibacterial efficiency of nasal washes prepared from Examples 3 and 5 of the present invention and Comparative Examples 1 to 4, are shown in Table 1 below. It can be confirmed that the nasal washes prepared from Examples 3 and 5 of the present invention were mixed more uniformly and stably, had greatly improved dissolution rates, and had very excellent antibacterial efficiency compared to the nasal washes prepared from Comparative Examples 1 to 4.

Sample Log ₁₀ reduction factor dissolution
speed mix
Uniformity Klebsiella
pneumoniae Streptococus
pneumoniae 15 seconds 30 seconds 15 seconds 30 seconds Test Example 1 Example 3 >5.67 >5.67 >5.30 >5.30 <50 seconds ○ Test Example 2 Comparative Example 1 <2.60 <2.60 <2.32 <2.32 >120 seconds △ Test Example 3 Comparative Example 2 3.76 4.87 3.24 4.56 >120 seconds × Test Example 4 Example 5 >5.80 >5.80 >5.35 >5.35 <30 seconds ◎ Test Example 5 Comparative Example 3 <2.52 <2.52 <2.31 <2.31 >120 seconds △ Test Example 6 Comparative Example 4 4.58 >5.14 4.24 4.86 >120 seconds ×

※Mixing uniformity: × Uneven/unstable mixing, △ Uneven mixing, ○ Uniform mixing, ◎ Uniform/stable mixing

(Examples 7 to 12)

Virus culture is performed by propagating SARS-CoV-2 in Vero-E6 (ATCC) cells and maintaining Vero-E6 cells in DMEM-5% FBS. To prepare virus stocks, confluent cell monolayers are infected with SARS-Cov-2 and cultured at 37°C, 5% _CO2 for 7 days. When cytopathic effect appears under a microscope, the supernatant is collected, centrifuged, and stored at -80°C. For the PVP-I Cytotoxicity Assay, uninfected Vero-E6 cells are prepared and cultured in DMEM-5% FBS dilutions containing PVP-I serially diluted up to 10-fold. After culturing at 37°C for 4 days, the presence of cytopathic effect is checked to determine the lowest PVP-I concentration without cytotoxicity. The PVP-I virus killing time test is performed by mixing 100 ㎕ of virus with 700 ㎕ of PVP-I test product in the presence of 200 ㎕ of PBS containing 0.3 g/L BSA as an interference substance. The virus control is prepared with 700 ㎕ PBS and PVP-I product. The virus is exposed to the PVP-I product at 21℃ for 30 seconds, and the reaction is stopped by adding 100 ㎕ to 900 ㎕ DMEM-5%. Immediately, ten-fold serial dilutions are made, and 100 ㎕ of each dilution is inoculated onto Vero-E6 cells in a 96-well microplate. The plates are cultured at 37℃ for 4 days and the cytopathic effect is evaluated. The virus titer is calculated as the median tissue culture infecious dose (TCID ₆₀ /mL) using the Spearman-Karber method.

The results of Test Examples 7 to 12 measuring the antiviral effects of nasal washes prepared from Examples 3 and 5 of the present invention and Comparative Examples 1 to 4 are shown in Table 2 below. It can be confirmed that the nasal washes prepared from Examples 3 and 5 of the present invention have much better antiviral effects than the nasal washes prepared from Comparative Examples 1 to 4.

Sample Log ₁₀ reduction factor SARS-CoV MERS-Cov Influenza virus A
subtype H1N1 Clean Dirty Clean Dirty Clean Dirty Test Example 7 Example 3 5.47±0.52 5.02±0.33 5.50±0.42 5.17±0.49 5.81±0.38 5.94±0.41 Test Example 8 Comparative Example 1 0.84±0.22 0.49±0.47 0.72±0.43 0.55±0.63 1.01±0.44 0.57±0.68 Test Example 9 Comparative Example 2 4.61±0.74 4.58±0.66 4.86±0.36 4.52±0.38 4.97±0.42 4.62±0.58 Test Example 10 Example 5 5.57±0.34 5.08±0.71 5.45±0.21 5.19±0.50 5.94±0.72 6.00±0.21 Test Example 11 Comparative Example 3 0.91±0.46 0.77±0.24 0.92±0.48 0.79±0.63 1.45±0.32 1.21±0.83 Test Example 12 Comparative Example 4 4.99±0.57 4.75±0.87 5.01±0.37 4.88±0.49 5.06±0.50 4.87±0.71

* Reaction time: 15s

Claims (10)

(a) 0.3 to 4.5 wt% of one or more ionic salt compounds selected from the group consisting of potassium chloride, calcium chloride, magnesium chloride, sodium carbonate, potassium carbonate and sodium bicarbonate;
(b) 0.1 to 10 wt% of at least one sulfated polysaccharide selected from the group consisting of fucan sulfate, agaran sulfate, galactan sulfate, rhamnan sulfate, spirulan, ulvan, xylomannan sulfate, chondroitin sulfate, heparin, sulfated cellulose, sulfated curdlan, sulfated dextran, sulfated xylan, sulfated glucan, sulfated mannose and sulfated mannuronate;
(c) povidone-iodine 0.0005 to 0.5 wt%;
(d) 0.2 to 5.0 wt% of at least one sweetener selected from the group consisting of sucrose, glucose, stevia and sucralose; and
(e) a nasal cleansing composition comprising a residual amount of water; delete A nasal cleansing composition according to claim 1, characterized in that the particle diameter of the ionic salt compound is 50 to 1,500 ㎛. delete A nasal cleansing composition in claim 1, characterized in that the sulfated polysaccharide has a sulfate group content of 5.0 to 60.0 mol% and a molecular weight of 3,000 to 500,000. A nasal cleansing composition, characterized in that in claim 1, the content of iodine in the povidone-iodine is 9.0 to 12.0 wt%, and the molecular weight of povidone is 40,000 to 80,000. delete A nasal cleansing composition according to claim 1, wherein the sweetener has a particle diameter of 50 to 1,500 ㎛. (i) a step of grinding at least one sweetener selected from the group consisting of sucrose, glucose, stevia, and sucralose into particles of a certain size;
(ii) a step of uniformly mixing the pulverized sweetener particles with at least one sulfated polysaccharide selected from the group consisting of fucan sulfate, agaran sulfate, galactan sulfate, rhamnan sulfate, spirulan, ulvan, xylomannan sulfate, chondroitin sulfate, heparin, sulfated cellulose, sulfated curdlan, sulfated dextran, sulfated xylan, sulfated glucan, sulfated mannose, and sulfated mannuronate, and povidone-iodine;
(iii) a step of grinding at least one ionic salt compound selected from the group consisting of potassium chloride, calcium chloride, magnesium chloride, sodium carbonate, potassium carbonate and sodium bicarbonate into particles of a certain size and then uniformly mixing it with the mixture of step (ii); and
(iv) A method for producing a nasal cleansing composition, comprising the step of dissolving the mixture obtained in step (iii) in water. (I) a step of grinding at least one ionic salt compound selected from the group consisting of potassium chloride, calcium chloride, magnesium chloride, sodium carbonate, potassium carbonate and sodium bicarbonate and at least one sweetener component selected from the group consisting of sucrose, glucose, stevia and sucralose into particles of a predetermined size;
(II) a step of uniformly mixing the above-mentioned pulverized ionic salt compound and sweetener particles;
(III) a step of adding at least one sulfated polysaccharide selected from the group consisting of fucan sulfate, agaran sulfate, galactan sulfate, rhamnan sulfate, spirulan, ulvan, xylomannan sulfate, chondroitin sulfate, heparin, sulfated cellulose, sulfated curdlan, sulfated dextran, sulfated xylan, sulfated glucan, sulfated mannose, and sulfated mannuronate, and povidone-iodine to the mixture obtained in the step (II) while adding humidity, and mixing and drying; and
(IV) A method for producing a nasal cleansing composition, comprising: a step of dissolving the dried mixture obtained in step (III) in water.