Toothpaste and oral hygiene product for oral cavity, mouth rinsing, nasal cavity, or throat

Abstract

To provide a toothpaste and an oral hygiene product for oral cavity, mouth rinsing, nasal cavity, or throat that achieve reduction of proliferation of influenza virus and exert an inactivation effect.SOLUTION: A toothpaste and an oral hygiene product for oral cavity, mouth rinsing, nasal cavity, or throat, which use kombu powder as an active ingredient, are used by remaining in oral cavity, nasal cavity, or throat for at least 15 seconds in order to reduce proliferation of influenza virus and exert an inactivation effect, and contain, in physiological saline or boiling water thereof, kombu powder having a particle diameter of 5 μm at a weight ratio of 2%.SELECTED DRAWING: Figure 7

Description

[Technical Field]

[0001] The present invention relates to a toothpaste and an oral hygiene product for use in the mouth, mouthwash, nasal cavity, or throat that reduces the proliferation of influenza viruses and has an inactivating effect. [Background technology]

[0002] The human oral cavity, throat including the trachea, and nasal cavities (collectively referred to as the "oral cavity" in this application) are the digestive organs through which food and drink are first introduced into the body, and also serve as the entrance to the respiratory organs through which air is taken in. Therefore, they are the first sites where bacteria, including various molds, and viruses are introduced into the body from the outside world.

[0003] Viruses such as influenza, which cannot replicate on their own (nm level in size), do not directly infect human cells, but instead infect and host bacteria that are orders of magnitude larger than the virus (μm level) with their own genes, and after the viral genes multiply within the host bacteria, the virus is transmitted to the human body via those bacteria.

[0004] The oral cavity is connected to the nostrils and throat, which are respiratory organs, and is the first organ through which air (oxygen) is breathed into the body (lungs), and is the first place that is easily invaded by foreign substances such as various bacteria, including mold, and viruses from the outside world.The oral cavity is also connected to the esophagus, and food and drink ingested into the oral cavity travels through the esophagus to the stomach, where nutrients from the food are digested and absorbed mainly in the small intestine, and water is absorbed in the large intestine.

[0005] Humans become infected with, for example, influenza viruses or suffer from respiratory diseases such as pneumonia and bronchitis when the causative viruses or bacteria attach to the mucous membranes of the throat, such as the nose, throat, or trachea, through breathing, causing infection and onset of the disease.

[0006] In addition, digestive diseases such as food poisoning in humans occur when viruses such as norovirus or mold that have become trapped in food or drink are taken in by the digestive organs in the body via the oral cavity and esophagus.

[0007] For this reason, in order to prevent diseases transmitted through the oral cavity or nasal cavity, it is also extremely important to inactivate various viruses that have entered the oral cavity, nasal cavity, and trachea in order to maintain human health.

[0008] Viral infections such as food poisoning caused by epidemic influenza, parainfluenza, norovirus, Middle East Respiratory Syndrome (MERS), acute viral bronchitis and pneumonia, measles, and more recently the novel coronavirus (SARS-CoV-2) that causes the novel coronavirus disease (COVID-19), which was recognized as a pandemic by the WHO in the spring of 2020, have been confirmed to spread through droplets of saliva and nasal mucus in the mouth of an infected person when they cough or sneeze.

[0009] In addition, viruses can survive for a relatively long time when attached to objects or the surface of the human body in a cold environment (low temperature and low humidity), and in particular, the low temperature of the human respiratory organs, including the throat, dries out the cilia in the lining of the upper respiratory tract and reduces ciliary activity (the upper respiratory tract barrier function), making person-to-person infection more likely to spread than in warm environments. Therefore, it is extremely important to constantly suppress the growth of bacteria in the oral cavity and to inactivate viruses in the oral cavity.

[0010] Furthermore, from the perspective of preventing bacterial and viral infections, it has been proven through use cases and various experiments around the world that wearing a mask is effective in minimizing the range of droplets released into the air by coughing and sneezing, and in reducing the amount of droplets released into the outside atmosphere.Frequent hand washing and gargling are also important.

[0011] As mentioned above, it has been reported that removing bacteria, including mold, and inactivating viruses in the oral cavity not only prevents periodontal disease and tooth decay, but also respiratory diseases including pneumonia, diabetes, heart disease, etc., and prevents the worsening of diseases caused by viral infections.

[0012] In recent years, various dentifrices (dental pastes, liquid toothpastes, or dental rinses) have been sold that claim to be effective in preventing periodontal disease and tooth decay by removing mold and bacteria from the oral cavity. Furthermore, functional food compositions and pharmaceutical compositions for oral antibacterial use that have antibacterial effects against normal oral bacteria that cause periodontal disease, caries such as tooth decay, and opportunistic infections have been proposed (see, for example, Patent Documents 1 and 2). [Prior art documents] [Patent documents]

[0013] [Patent Document 1] Japanese Patent Publication No. 2020-62006 [Patent Document 2] Japanese Patent Application Laid-Open No. 2008-182931 [Patent Document 3] Japanese Patent Application Publication No. 9-48715 Summary of the Invention [Problem to be solved by the invention]

[0014] However, many of the dentifrices (dental pastes, liquid toothpastes, dental rinses) currently sold widely in Japan and overseas contain, for example, 1,3,3-trimethyl (1,8-thioneol), which are originally disinfectants and suppress the growth of bacteria that cause periodontal disease, as bactericidal agents, such as thymol, methyl salicylate, and cetylpyridinium chloride, as well as dipotassium glycyrrhizinate, which has the effect of soothing inflammation in the gums and mouth.

[0015] As such, toothpastes (dental pastes, liquid toothpastes) containing antibiotics that have an inhibitory effect on some of the bacteria that cause periodontal disease and tooth decay are also on the market. However, these toothpaste chemicals with antibacterial properties are essentially disinfectants that are not desirable to ingest on a daily basis. If you brush your teeth after every meal using toothpaste containing such disinfectant ingredients, the ingredients will be absorbed into the body from the mouth via the esophagus and trachea, posing a risk of causing unforeseen consequences to the human body in the long term.

[0016] Furthermore, if antibiotics that have an inhibitory effect on some of the bacteria that cause periodontal disease and tooth decay are used for a long period of time, bacteria and viruses that are resistant to the antibiotics will inevitably emerge, making it extremely difficult to remove and kill them.

[0017] Furthermore, the oral antibacterial composition described in Reference 1, which has antibacterial effects against periodontal disease, caries-related bacteria, and normal oral bacteria that cause opportunistic infections, contains mastic components as its main functional component, and is a resin that is contained in chewing gum and the like, and is a substance that has an aromatic effect when dissolved in a polyhydric alcohol resin acid ester, and is not a composition that is suitable for daily ingestion into the body.

[0018] Furthermore, the substance disclosed in Patent Document 2, which is said to have the effect of inhibiting periodontal disease bacteria, is an antibiotic that can cause resistance to some oral bacteria that cause periodontal disease, including microorganisms belonging to the Bifidobacterium genus, and is difficult for many people to take on a daily, continuous basis, including the substance described in Patent Document 1. Furthermore, there are problems with the safety and durability of bactericidal activity when such antibiotics are taken on a daily basis.

[0019] Furthermore, Patent Document 3 lists many compositions extracted from red and brown algae extracts that exhibit antibacterial activity against Volphyromonas gingivalis. However, the test method described therein involves adding a bacterial strain that has been cultured for about a day and night to a liquid medium containing the composition, stirring the mixture, and then culturing it in an anaerobic environment at a temperature of 37°C for three days, after which the growth inhibitory effect on the test bacteria is confirmed by measuring the absorbance at a specific wavelength. Considering the daily time it takes to gargle for about several tens of seconds or to brush one's teeth for several minutes to 10 minutes, the short use of about 15 seconds or 30 to 60 seconds targeted by the present invention does not effectively inhibit or kill the growth of bacteria that cause oral disease, nor does it have the effect of inactivating viruses.

[0020] The present invention aims to provide a long-term oral hygiene additive and oral hygiene product that contains natural food ingredients and extracts thereof as active ingredients, whose safety has been confirmed by human consumption or ingestion over many years. The additive inhibits the growth of and kills multiple types of bacteria that are present in the oral cavity, respiratory tract, and upper digestive tract and cause oral diseases such as tooth decay and periodontal disease, and is also effective in inactivating various viruses such as epidemic influenza, parainfluenza, viral acute bronchitis and pneumonia, measles, and the novel coronavirus (SARS-CoV-2) that causes novel coronavirus disease (COVID-19). Furthermore, it has a remarkable effect when left in the oral cavity for a short period of time, such as 15 to 60 seconds.

[0021] Another object of the present invention is to provide an oral hygiene product that promotes good saliva secretion, activates ciliary activity to eliminate viruses and bacteria that have entered the larynx and upper respiratory tract, thereby enhancing the upper respiratory tract barrier function, and has the effect of sterilizing oral bacteria and inactivating viruses using natural foods or extracts thereof whose safety has been confirmed.

[0022] There are various problems to be solved by the oral hygiene product of the present invention, but they can be summarized as achieving the following objectives (1) to (3): (1) When eaten or drunk on a daily basis, the texture and taste are not strange, and rather, they contain umami components and are themselves nutritious. Furthermore, even when ingested after coming into contact with sensitive mucous membranes in the human body, such as the throat, nostrils, mouth, or respiratory organs, including the bronchi, they do not cause any pain, discomfort, or problems with taste or smell. (2) It is not a drug that kills specific bacteria, but an oral hygiene product that is safe even if used continuously. It enters the digestive organs, such as the esophagus and stomach, through the oral cavity, inactivating various viruses and sterilizing various bacteria that cause periodontal disease and dental caries by remaining in the oral cavity for a short period of time, such as 30 to 60 seconds. (3) It is not a drug or medicine for treating a specific disease, and there is no risk of health safety issues even if it is taken / used for a long period of time. Also, there is no risk of resistant viruses or bacteria developing. [Means for solving the problem]

[0023] Therefore, the present invention provides a toothpaste and oral hygiene products for use in the oral cavity, mouthwash, nasal cavity, or throat, which contain kelp powder as an active ingredient and are intended to remain in the oral cavity, nasal cavity, or throat for at least 15 seconds, and more effectively, for 30 seconds, in order to reduce the proliferation of influenza viruses and inactivate them. The hygiene product according to the present invention contains 2% by weight of kelp powder with a particle size of 5 μm in physiological saline, or may contain 2% by weight of kelp powder with a particle size of 5 μm in physiological saline dissolved in boiling water. The toothpaste includes paste, liquid, and powder types, and the oral hygiene products and mouthwashes include dental rinses, mouthwashes, and oral inflammation medications.

[0024] The nasal hygiene products include nasal drops and nasal sprays, and the throat hygiene products include lozenges and throat sprays that are dissolved in the mouth.

[0025] The oral hygiene products include throat lozenges, chewing gum, and pacifier foods that remain in the mouth for a certain period of time to stimulate saliva secretion.

[0026] The oral hygiene product described above stimulates saliva secretion and interacts with saliva, enhancing its antiviral inactivation effect by simply remaining in the mouth, nostrils, and throat for approximately 15 to 60 seconds. Furthermore, the oral hygiene product not only kills bacteria that cause periodontal disease and dental caries, but also bacteria such as Escherichia coli and Staphylococcus aureus, effectively preventing viruses that cannot replicate in their own cells from infecting the human body via bacteria.

[0027] As shown in the present specification, [Table] and [Figure], such viruses include not only influenza viruses but also SARS-CoV-2 and norovirus.

[0028] Furthermore, saliva itself has bactericidal and antiviral effects, and it is thought that these bactericidal and antiviral effects of saliva are achieved by the binding of sialic acid in saliva to bacteria and viruses, preventing infection before they reach receptors on the surface of cells in the throat and upper respiratory tract. [Effects of the Invention]

[0029] The oral hygiene product of the present invention is present in the oral cavity, throat, respiratory tract, and upper digestive tract, and is particularly effective in inactivating epidemic influenza viruses when used for approximately 30 to 60 seconds.It has made it possible to provide oral hygiene products whose active ingredients are natural food ingredients and extracts thereof that have been eaten or ingested by humans for many years and whose safety has been confirmed. [Brief explanation of the drawings]

[0030] [Figure 1] The following shows the test results (1) of the effectiveness of the oral hygiene product (oral cavity, throat including respiratory tract, and nostrils) according to the present invention against PED virus, a coronavirus whose morphology is similar to that of SARS-CoV-2. [Figure 2] The results of a test (2) on the effectiveness of kelp, a type of seaweed that is the main ingredient of this oral hygiene product, as well as the main components of seaweed, alginic acid, fucoidan, and iodine, and the combined components of alginic acid, fucoidan, and iodine, against the novel coronavirus SARS-CoV-2 are presented. [Figure 3] The results of a test (3) on the effectiveness of this oral hygiene product, which contains alcohol as its main ingredient, against the PED virus are shown below. [Figure 4] The results of tests on the effectiveness of the seaweeds kelp and wakame, which are the main ingredients of this oral hygiene product, as well as the components of seaweed, iodine, arginine, and fucoidan, and the combined component of iodine, arginine, and fucoidan, against the PED virus are shown below (4). [Figure 5A] The test results (5) show the bactericidal effect of the main ingredient of this oral hygiene product on E. coli. [Figure 5B] The test results (5) show the bactericidal effect of the main ingredient of this oral hygiene product on Staphylococcus aureus. [Figure 6] The main ingredients of this oral hygiene product, L-glutamic acid, beta-carotene, sea lettuce, red wine (containing 14% alcohol and polyphenols), laminaran, and fucoidan, are shown in the test results (6) for their effectiveness against the PED virus. [Figure 7] The test results (7) of the effectiveness of the main ingredient of the oral hygiene product according to the present invention against influenza viruses are shown. [Figure 8] The results of a test (8) on the effectiveness of the main ingredient of this oral hygiene product against the novel coronavirus SARS-CoV-2 are shown below. [Figure 9] The results of a test (9) on the effectiveness of the seaweed kelp powder, its main component fucoidan powder, gyokuro tea leaf powder, and a mixture of these that make up this oral hygiene product against Porphimonas gingivalis, a bacteria that causes periodontal disease, are shown below. [Figure 10]The results of a test (10) on the effectiveness of the seaweed kelp powder, its main component fucoidan powder, gyokuro tea leaf powder (gyokuro powder), and a mixture of these that make up this oral hygiene product against Porphimonas gingivalis, a bacteria that causes periodontal disease, are shown. DETAILED DESCRIPTION OF THE INVENTION

[0031] The main component of the oral hygiene product according to the present invention is derived from a product extracted from kelp or seaweed belonging to brown algae and seaweed extract.

[0032] Therefore, before describing the detailed description of the invention in detail, a brief description of kelp and its components will be provided.

[0033] Kelp belongs to the seaweed family, which is a general term for algae that grow in the sea. Unlike seaweed, algae do not flower but reproduce through spores. Most seaweed is edible.

[0034] Seaweed is classified by color into species such as cyanobacteria, diatoms, green algae, brown algae, and red algae, with kelp belonging to the brown algae family. However, the color of kelp depends on the depth of the water where it grows, i.e., the amount of sunlight that reaches it; it is green in shallow waters, brown in deeper areas, and red in areas with the least amount of light. Many of the brown algae that kelp belongs to are used as food, including wakame, hijiki, mozuku, and mekabu. Green laver belongs to the green algae family, while funori and amanoiri belong to the red algae family.

[0035] There are 14 genera and 45 species of kelp, a type of brown seaweed, identified in Japan. Of these, kelp, a cold-water brown seaweed, is found along the Pacific coast north of Miyagi Prefecture and in the seas throughout Hokkaido, with Hokkaido being the main production area. Most of the domestic kelp production is harvested in Hokkaido.

[0036] Kelp contains arginine, alginic acid, and fucoidan, a unique mucilaginous polysaccharide found only in seaweed. Arginine is known to have a blood pressure lowering effect, while fucoidan is known to have anti-thrombus and cancer-preventing effects.

[0037] Fucoidan is a type of sulfated polysaccharide. It is a dietary fiber found in large amounts in the mucilage of brown algae such as kelp, wakame (including Mekabu, a part of it), and mozuku. Similar substances have also been found in animals such as sea cucumbers, which have antiviral properties as described in Patent Document 1 above.

[0038] The arginine, alginic acid, and fucoidan contained in kelp are compounds consisting of tens to hundreds of thousands of L-fucose (polysaccharide) molecules linked together via A1-2 and A1-4 bonds, with an average molecular weight of approximately 200,000. Fucoidan is classified into U-fucoidan, which contains glucuronic acid; F-fucoidan, which consists only of sulfated fucose; and G-fucoidan, which contains galactose.

[0039] Unlike mushrooms (such as agaricus) and other polysaccharide (sugar chain) components, L-fucose has a sulfate group bound to it. L-fucose is found in large amounts in brown algae (such as mozuku, mekabu, kelp, akamoku, and Sargassum species such as seaweed), and is often described as the sticky component of seaweed.

[0040] In contrast, arginine is an acidic polysaccharide composed of two types of uronic acid, called mannuronic acid (M) and guluronic acid (G). The hardness and elasticity of arginine change significantly depending on the ratio of (M) and (G) bonds, so it is used in a variety of applications, such as as an ingredient in puddings, jellies, ice cream, and jams, as an emulsifier for yogurt and cheese, and in artificial salmon roe. In kelp, it exists in a jelly state, bound with calcium and magnesium.

[0041] Arginine is known to have the following physiological actions (1) to (3). (1) Blood pressure lowering effect Excessive salt intake disrupts the balance of sodium and potassium ions in the blood, causing blood vessels to constrict and raising blood pressure. In particular, when arginine bound to potassium is ingested with food, stomach acid separates the potassium from the arginine. The arginine then travels to the intestines, where it binds with the sodium ions contained in the food and is carried out of the body. Meanwhile, potassium separated from arginine becomes potassium ions, is absorbed by the intestines, and expels sodium from the blood. In this way, arginine has a dual function of lowering blood pressure. (2) Activating digestive enzymes When arginine is taken with food, it promotes digestion by increasing the activity of digestive enzymes such as amylase and protease in the intestine. (3) Removal of harmful substances When harmful substances and pollutants accumulate in the body, they can cause various abnormalities and diseases. In an experiment in which arginine was given to laboratory animals contaminated with radioactive strontium, it was reported that it helped excrete the radioactive element from the body.

[0042] By the way, kelp is rich in dietary fiber, the main components of which are arginine and fucoidan, which have a different chemical structure from the dietary fiber found in vegetables and grains.

[0043] As mentioned above, these two polysaccharides are contained in the slimy components of kelp. In addition to dietary fiber, dried kelp also contains amino acids that create umami and mannitol, which has a sweet taste. It also contains minerals such as magnesium and calcium, as well as iodine, making it an excellent food for nutritional supplementation.

[0044] Fucoidan, a slippery substance found in kelp and other seaweeds, is said to have numerous biological activities, including anticoagulant action, cell adhesion inhibitory action, anti-inflammatory action, cell protection from viral infections, and antitumor action.

[0045] Iodine is an essential mineral found mainly in kelp and other foods, and has long been used as the main ingredient in mouthwash to reduce inflammation in the back of the mouth and trachea. However, the amount of iodine required by the human body is said to be 0.095-0.13 mg per day (equivalent to 40-60 mg in kelp), so if you are taking it on a daily basis, you must be careful not to exceed this limit.

[0046] Fucoidan, a water-soluble dietary fiber that is a slimy component found in kelp, is said to slow the movement of ingested food from the stomach to the small intestine. When digestion slows down in the stomach, fucoidan stimulates the stomach lining using sulfate groups.

[0047] The antiviral or virus inactivating agent containing the product extracted from kelp or seaweed and seaweed extract according to the present invention may be part of this function of fucoidan.

[0048] In other words, fucoidan and its components contained in kelp may contribute to enhancing the defensive capabilities of immune cells throughout the body by stimulating mucosal immune function in the intestines. For example, when fucoidan is held by M cells present in the human body, lymphocytes (NK cells, T cells, B cells) attack it, NK cells, a type of lymphocyte involved in immunity, are activated, and when activated lymphocytes enter the bloodstream, they promote the secretion of antibodies, thereby boosting immunity.

[0049] Furthermore, in the present invention, it is preferable to produce the product by adding citric acid to seaweed and seaweed extracts. Here, citric acid is an organic compound contained in citrus fruits and is a hydroxy acid. It has a refreshing sour taste and is widely used as a food additive, so there are no safety issues.

[0050] Citric acid also inhibits the activity of phosphofructokinase in the glycolytic pathway and is one of the factors that regulate the influx from glycolysis to the citric acid cycle, and because it indirectly breaks down lactic acid in the muscles in the citric acid cycle, it was once said to have a post-exercise fatigue-reducing effect. This is because citric acid also forms a chelate complex with calcium, which is considered to be one of the fatigue-causing substances, and this calcium binding is generally important in the trade-off with the reduction in acidosis in lactic acid breakdown, which is why it can be seen as having an effect on fatigue reduction.

[0051] Depending on age, approximately 1000 to 1500 mL of saliva is secreted per day. It has also been confirmed that the amount of saliva secreted decreases with age. This makes the elderly more susceptible to viral and bacterial infections, and if infected, the condition is more likely to become severe.

[0052] For this reason, what is extremely important in relation to the present invention is that the sour taste of citric acid stimulates saliva secretion when eaten.

[0053] Most of the water in saliva is secreted by the parotid and submandibular glands, with additional saliva from minor salivary glands (palatine, lingual, buccal, labial, molar, and Ébner's glands). At rest, 60-70% of saliva comes from the submandibular gland. The site of excretion of saliva from the submandibular and sublingual glands is the area under the tongue (floor of the mouth).

[0054] On the other hand, when citric acid is consumed, its taste stimulating effect promotes saliva secretion. Saliva has been confirmed to have functions such as digestion, oral self-cleaning, oral mucosal protection, pH regulation, and even antibacterial and antiviral effects. In this way, the large amount of saliva excreted by citric acid and the antiviral effects of saliva suppress the amount of virus and the prolonged infectivity.

[0055] Furthermore, in the present invention, it is preferable to produce the product by adding baking soda to seaweeds and seaweed extracts. As mentioned above, baking soda is a highly safe food additive that has traditionally been consumed as baking powder, a weakly alkaline food ingredient used to make cookies, pancakes, etc. rise.

[0056] Baking soda, made in accordance with the provisions of the Food Sanitation Act, is sometimes used as a medicine to treat excess stomach acid as an antacid. Because gastric juice contains hydrochloric acid, the sodium bicarbonate that makes up baking soda breaks down, producing carbon dioxide bubbles. These bubbles stimulate the taste buds and stomach, promoting the secretion of more saliva and gastric juices.

[0057] I. [Confirmation Test (1)] In light of the above, the applicant of the present application first conducted a test (1) using an external testing institution to test the inactivation effect of the seaweed that constitutes the oral hygiene product for the mouth, nasal passages or throat according to the present invention on the PED virus, which is the coronavirus whose morphology is closest to that of SARS-CoV-2.

[0058] It should be noted that I. [Confirmation Test (1)] to VIII. [Confirmation Test (8)], which will be described in order below in this application, were conducted by the applicant at the request of an external, authoritative testing institution, and this application presents the reports of the first through eighth test results from said testing institution without any manipulation or evaluation of the test results. However, because the virus reduction numbers of the test materials showing the confirmation test results are expressed in logarithmic notation of 10, a table has been added in which the logarithmic values ​​are converted to decimal notation to make the values ​​easier to understand.

[0059] (A) Test materials: seaweed and seaweed extracts Test material I: Seaweeds and seaweed extracts were dissolved in saline to make a 2% solution.

[0060] Test material II: Seaweeds and seaweed extracts were dissolved in boiling water (100°C) in physiological saline to a concentration of 2% and then cooled before use. Sterile phosphate buffer was used as a control material.

[0061] (B) Test microorganism The microorganism (virus) used in the test was the P-5V strain of PED virus (Porcine epidemic diarrhea virus).

[0062] The PED virus (Porcine epidemic diarrhea virus), commonly known as the swine infectious disease virus, is a member of the Alphacoronavirus genus of the Coronaviridae family. It has spikes that protrude radially (like a crown or corona) from the envelope surface, and its genome is a positive-stranded single-stranded RNA. It is the type of coronavirus most similar to the novel coronavirus (COVID-19) that caused the 2020 pandemic.

[0063] It has been scientifically proven that viruses belonging to the Alphacoronavirus genus of the Coronaviridae family have corona-shaped spikes that protrude radially from the surface of the envelope, and the tips of these spikes attach to the surface of the cell membranes that make up the human body, allowing the virus to penetrate into the human body and ultimately lead to infection.

[0064] Therefore, since the inactivation effect against the PED virus belonging to the genus Alphacoronavirus of the Coronaviridae family was confirmed in the above-mentioned confirmatory test of the present application, it is expected that there is an extremely high possibility that the inactivation effect will also be exerted against the novel coronavirus (COVID-19).

[0065] Vero cells were used to culture PED virus (porcine epidemic diarrhea virus). Vero cells are derived from kidney epithelial cells of African green monkeys and are a cell line used for cell culture. Along with Hela cells, they are one of the most commonly used cell lines.

[0066] (C) Establishment of wards In the test group, 0.1 mL of the virus solution was added to 1 mL of the above-mentioned test material (a 2% solution of seaweed and seaweed extract dissolved in physiological saline), and the sensitization time was set to 1 minute after the start of the test.

[0067] As a control, 0.1 mL of the virus solution was simply added to 1 mL of phosphate buffer without adding any of the above test materials, and the sensitization times were 0 and 1 minute after the start of the test.

[0068] (D) Test Method The test was carried out with reference to "Virus Experimental Science, General Theory, Revised Second Edition, Maruzen Co., Ltd., Virus Neutralization Test Method."

[0069] (E) Test Procedures (E-1) Preliminary Exam: Prior to the test, the effects of the test materials on cultured cells (cytotoxicity) were investigated.

[0070] The test material was diluted 10-fold with phosphate buffer solution and then inoculated into cultured cells. The highest concentration that showed normal cell condition after culture was confirmed, and the virus concentration to be used in the test was determined. As a result, poor cell growth was confirmed in the 100-fold solution of the test material for cytotoxicity. For this reason, it was found that the test required diluting the mixture of the test material and virus solution 100 times or more before inoculating the cells. For this reason, the virus addition concentration was set at 10 6 TCID 50 / mL or more.

[0071] (E-2) Main test: Mixing test liquids According to the test category, 1 mL of each test material and phosphate buffer solution was taken, and the virus solution was added to the concentration determined in the preliminary test.

[0072] After adding the virus solution, the mixture was allowed to stand at room temperature (25°C) for a predetermined period of time.

[0073] (E-3) Main test: Cell inoculation and bacterial count After the sensitization for each test section, the mixture was serially diluted 10-fold, and 100 μL of each was inoculated onto cells cultured in a 96-well plate.

[0074] The determination was made by culturing the cells at 37°C in carbon dioxide gas (5%) for 5 days, then observing the cultured cells under a microscope and confirming the presence or absence of viral growth by detecting CPE (cytopathic encephalopathy) in the cultured cells, and calculating the concentration.

[0075] (F)Result Figure 1 shows the test results (1) of the effectiveness of the main ingredients of the oral hygiene product of the present invention against PED virus, a coronavirus with a morphology similar to SARS-CoV-2. Table 1 summarizes the test results.

[0076] The vertical axis of FIG. 1, as well as the subsequent FIGS. 2 to 7, is expressed as an exponent of 10, meaning that each step down is one-tenth.

[0077] In the control group (a comparative test group without test materials), no change in the amount of virus was observed from the start of the test until 1 minute after the start of the test (10 6.1 TCID 50 / mL).

[0078] [Table 1]

[0079] On the other hand, in the test group, <10 3.5 TCID 50 / mL (below the detection limit: reduction of 99.7% or more). This result of "below the detection limit: reduction of 99.7% or more" indicates an astonishingly high virus inactivation effect.

[0080] (G) Consideration This time, we tested the inactivation effect of the test material on the PED virus (Porcine Epidemic Diarrhea Virus), commonly known as the swine coronavirus.The results showed that the material had an astonishing viral inactivation effect of over 99.7% within one minute of contact.

[0081] As mentioned above, the genome of the PED virus (Porcine epidemic diarrhea virus) is a positive single-stranded RNA, and since it is the type of coronavirus that is most similar to the new coronavirus (COVID-19), it was predicted that it would also have a significant inactivation effect on the new coronavirus "SARS-CoV-2."

[0082] II. [Confirmation Test (2)] Therefore, having confirmed the remarkable antiviral and virus inactivation effects of the seaweed in the oral hygiene product of the present invention against the PED virus described above, the applicant of the present application next conducted a test to confirm its effectiveness against the new coronavirus "SARS-CoV-2." The details of this test are described below.

[0083] (A) Test materials: seaweed and seaweed extracts Test material 1: 2% kelp powder particle size 5 μm saline solution Test material 2: 2% kelp powder particle size 5 μm saline solution (prepared by dissolving in boiling water) Test material 3: 2% arginine powder in saline Test material 4: 2% fucoidan powder in saline solution (prepared by dissolving in boiling water) Test material 5: 2% iodine powder in saline solution (prepared by dissolving in boiling water) Test material 6: 2% (arginine + fucoidan + iodine) powder in saline solution As a control material, sterilized phosphate buffer solution was used.

[0084] (B) Test microorganism The microorganism (virus) used was SARS-CoV-02 (novel coronavirus). This SARS-CoV-02 is a human isolate that was isolated and cultured from saliva using Vero cells, and amplification of the SARS-CoV-2 gene was confirmed using real-time PCR (Ministry of Health, Labour and Welfare notification method).

[0085] The cultured cells, Vero cells, are an established cell line derived from the kidney epithelium of African green monkeys.

[0086] (C) Establishment of wards As a control, 0.1 mL of the virus solution was added to 1 mL of phosphate buffer solution, and the sensitization time was set to 0 seconds and 60 seconds after the start of the test.

[0087] In the test group, 0.1 mL of the virus solution was added to 1 mL of the above test material, and the sensitization time was set to 15 seconds, 30 seconds, and 60 seconds after the start of the test.

[0088] (D) Test Method The test was carried out with reference to "Virus Experimental Science, General Theory, Revised Second Edition, Maruzen Co., Ltd., Virus Neutralization Test Method."

[0089] (E) Test Procedures (E-1) Preliminary Exam: Prior to the test, the effects of the test materials on cultured cells (cytotoxicity) were investigated.

[0090] The test material was serially diluted 10-fold with phosphate buffer and then inoculated into cultured cells. The highest concentration that showed normal cell condition after culture was confirmed, and the virus concentration to be used in the test was determined.

[0091] As a result, the cytotoxicity was as shown in the table below, and poor cell growth was confirmed at a maximum of 10 times the test material. Therefore, it was found that when testing, it was necessary to dilute the mixture of test material and virus solution by 10 times or more before inoculating it into the cells. In addition, the virus addition concentration was 10 6 TCID 50 / mL or more.

[0092] [Table 2A]

[0093] (E-2) Main test: Mixing test liquids According to the test category, 1 mL of each test material and phosphate buffer solution was taken, and the virus solution was added to the concentration determined in the preliminary test.

[0094] After adding the virus solution, the mixture was allowed to stand at room temperature (25°C) for a predetermined period of time.

[0095] (E-3) Main test: Cell inoculation and bacterial count After sensitization for each test section, the mixture was serially diluted 10-fold, and 100 μL of each was inoculated onto cells cultured in a 96-well plate.

[0096] The determination was made by culturing the cells at 37°C in carbon dioxide gas (5%) for 5 days, then observing the cultured cells under a microscope to confirm the presence or absence of virus growth based on the appearance of CPE (cytopathic encephalopathy) in the cultured cells, and calculating the concentration.

[0097] (F)Result Figure 2 shows the results of tests on the effectiveness of kelp, a type of seaweed that is the main ingredient of the oral hygiene product of the present invention, as well as the main components of seaweed: alginic acid, fucoidan, and iodine, and a mixture of alginic acid, fucoidan, and iodine, against the novel coronavirus SARS-CoV-2. Tables 2A, 2B, and 2C summarize the details of the test results shown in Figure 2. Table 2C makes Table 2B easier to understand.

[0098] In the control group, no change in viral load was observed between the start of the test and 60 seconds after the start of the test (10 6.5 TCID 50 / mL).

[0099] On the other hand, in test area 1, the virus infectivity was reduced by 99.7% at 15 seconds and 99.9% at 60 seconds after the start; in test area 2, the virus infectivity was reduced by 99.7% at 15 seconds and 99.9% at 60 seconds; in test area 3, the virus infectivity was reduced by 59.3% at 15 seconds and 93.7% at 60 seconds; in test area 4, the virus infectivity was reduced by 97.5% at 15 seconds and 99.7% at 60 seconds; in test area 5, the virus infectivity was reduced by 90.0% at 15 seconds and 99.0% at 60 seconds; and in test area 6, the virus infectivity was reduced by 98.4% at 15 seconds and 99.8% at 60 seconds.

[0100] The viral infectivity titers for SARS-CoV-02 mentioned above were generally close to the detection limit, and this test confirmed an astonishingly high viral inactivation effect.

[0101] Furthermore, since both the seaweed and seaweed extract are 2% solutions and the particle size of the kelp powder is 5 μm, it has been found that the present invention can be used without discomfort when applied to oral hygiene products including mouthwashes, oral, nasal or throat cleansers.

[0102] [Table 2B]

[0103] [Table 2C]

[0104] (G) Consideration This time, a test was conducted to test the inactivation effect of the test materials on SARS-CoV-2, and the results showed that a maximum of 60 seconds of contact had an inactivation effect of 93.7-99.9%.

[0105] III. [Confirmation Test (3)] Furthermore, the applicant of the present application conducted a test to confirm the effect of adding alcohol to the main ingredient of the oral hygiene product of the present invention on the PED virus. The details are described below.

[0106] (A) Test materials: seaweed and seaweed extracts Test material 1: 2% kelp powder particle size 5 μm saline solution Test material 2: 2% kelp powder particle size 5 μm saline solution (prepared by dissolving in boiling water) Test material 3: 1% kelp powder particle size 5μm saline solution (prepared by dissolving in boiling water) Test material 4: 0.5% kelp powder particle size 5 μm saline solution (prepared by dissolving in boiling water) Test material 5: 25% alcohol content barley shochu diluted 3 times with purified water (prepared by dissolving in boiling water) Test material 6: 25% 5% alcohol kelp shochu diluted 3 times with purified water (prepared by dissolving in boiling water) Sterile phosphate buffer was used as a control material.

[0107] (B) Test microorganism The microorganism (virus) used in the test was the P-5V strain of PED virus (Porcine epidemic diarrhea virus).

[0108] The cultured cells were Vero cells (a cell line derived from the kidney epithelium of African green monkeys).

[0109] (C) Establishment of wards In the test group, 0.1 mL of the virus solution was added to 1 mL of the above test material, and the sensitization time was set to 15 seconds, 30 seconds, and 60 seconds after the start of the test.

[0110] As a control, 0.1 mL of the virus solution was added to 1 mL of phosphate buffer solution, and the sensitization time was set to 0 seconds and 60 seconds after the start of the test.

[0111] (D) Test Method The test was carried out with reference to "Virus Experimental Science, General Theory, Revised Second Edition, Maruzen Co., Ltd., Virus Neutralization Test Method."

[0112] (E) Test Procedures (E-1) Preliminary Exam: Prior to the test, the effects of the test materials on cultured cells (cytotoxicity) were investigated.

[0113] The test material was serially diluted 10-fold with phosphate buffer and then inoculated into cultured cells. The highest concentration that showed normal cell condition after culture was confirmed, and the virus concentration to be used in the test was determined.

[0114] As a result, the cytotoxicity was as shown in the table below, and poor cell growth was confirmed at a maximum of 10 times the test material. Therefore, it was found that when testing, it was necessary to dilute the mixture of test material and virus solution by 10 times or more before inoculating it into the cells. In addition, the virus addition concentration was 10 6 TCID 50 / mL or more.

[0115] [Table 3A]

[0116] (E-2) Main test: Mixing test liquids According to the test category, 1 mL of each test material and phosphate buffer solution was taken, and the virus solution was added to the concentration determined in the preliminary test.

[0117] After adding the virus solution, the mixture was allowed to stand at room temperature (25°C) for a predetermined period of time.

[0118] (E-3) Main test: Cell inoculation and bacterial count After sensitization for each test section, the mixture was serially diluted 10-fold, and 100 μL of each was inoculated onto cells cultured in a 96-well plate.

[0119] The determination was made by culturing the cells at 37°C in carbon dioxide gas (5%) for 5 days, then observing the cultured cells under a microscope to confirm the presence or absence of virus growth based on the appearance of CPE (cytopathic encephalopathy) in the cultured cells, and calculating the concentration.

[0120] (F)Result The test results for PED virus are shown in Figure 3 and Tables 3A, 3B, and 3C. Table 3C is an easier-to-understand version of Table 3B.

[0121] In the control group, no change in viral load was observed between the start of the test and 60 seconds after the test started (10 6.7 TCID 50 / mL).

[0122] On the other hand, in test area 1, the virus infectivity was reduced by 99.7% at 15 seconds and 99.9% at 60 seconds after the start, in test area 2 by 99.7% at 15 seconds and 99.9% at 60 seconds, in test area 3 by 99.8% at 60 seconds, in test area 4 by 97.4% at 60 seconds, in test area 5 by 93.6% at 60 seconds, and in test area 6 by 97.4% at 60 seconds after the start.

[0123] [Table 3B]

[0124] [Table 3C]

[0125] (G) Consideration This time, a test was conducted to test the inactivation effect of the test material on PED virus (porcine infectious coronavirus).The results showed that a maximum of 60 seconds of contact had an inactivation effect of 93.6-99.9%.

[0126] IV. [Confirmation Test (4)] Furthermore, the applicant of the present application has conducted tests to confirm the effects on PED virus of the seaweeds kelp and wakame, which are the main ingredients of the oral hygiene product of the present invention, as well as the main components of seaweeds, iodine, arginine, and fucoidan, and also the combined component of iodine, arginine, and fucoidan. The details of these tests are described below.

[0127] (A) Test materials: seaweed and seaweed extracts Test material 1: 2% kelp powder in saline solution Test material 2: 2% kelp powder saline solution (prepared by dissolving in boiling water) Test material 3: 2% kelp powder aqueous solution Test material 4: 2% wakame powder in saline solution Test Material 5: 2% iodine powder in saline solution Test material 6: 2% arginine powder in saline Test material 7: 2% fucoidan powder in saline solution Test material 8: 2% (iodine + fucoidan + arginine powder) saline solution Sterile phosphate buffer solution was used as a control material.

[0128] (B) Test microorganism The microorganism (virus) used in the test was the P-5V strain of PED virus (Porcine epidemic diarrhea virus), a coronavirus infectious to pigs.

[0129] The cultured cells were Vero cells (a cell line derived from the kidney epithelium of African green monkeys).

[0130] (C) Establishment of wards In the test group, 0.1 mL of the virus solution was added to 1 mL of the above test material, and the sensitization time was set to 15 seconds, 30 seconds, and 60 seconds after the start of the test.

[0131] As a control, 0.1 mL of the virus solution was added to 1 mL of phosphate buffer, and the sensitization time was set to 0, 15, 30, and 60 seconds after the start of the test.

[0132] (D) Test Method The test was carried out with reference to "Virus Experimental Science, General Theory, Revised Second Edition, Maruzen Co., Ltd., Virus Neutralization Test Method."

[0133] (E) Test Procedures (E-1) Preliminary Exam: Prior to the test, the effects of the test materials on cultured cells (cytotoxicity) were investigated.

[0134] The test material was serially diluted 10-fold with phosphate buffer and then inoculated into cultured cells. The highest concentration that showed normal cell condition after culture was confirmed, and the virus concentration to be used in the test was determined.

[0135] The results of the cytotoxicity tests are as shown in the table below. Poor cell growth was confirmed even at a maximum of 100 times the test material. For this reason, it was found that the test required diluting the mixture of test material and virus solution by 100 times or more before inoculating the cells. 6 TCID 50 / mL or more.

[0136] [Table 4A]

[0137] (E-2) Main test: Mixing test liquids According to the test category, 1 mL of each test material and phosphate buffer solution was taken, and the virus solution was added to the concentration determined in the preliminary test.

[0138] After adding the virus solution, the mixture was allowed to stand at room temperature (25°C) for a predetermined period of time.

[0139] (E-3) Main test: Cell inoculation and bacterial count After sensitization for each test section, the mixture was serially diluted 10-fold, and 100 μL of each was inoculated onto cells cultured in a 96-well plate.

[0140] The determination was made by culturing the cells at 37°C in carbon dioxide gas (5%) for 5 days, then observing the cultured cells under a microscope to confirm the presence or absence of virus growth based on the appearance of CPE (cytopathic encephalopathy) in the cultured cells, and calculating the concentration.

[0141] (F)Result The test results for PED virus are shown in Figure 4, Table 4A, Table 4B, and Table 4C. Table 4C is a table that makes Table 4B easier to understand.

[0142] In the control group, no change in viral load was observed between the start of the test and 60 seconds after the test started (10 6.5 TCID 50 / mL).

[0143] On the other hand, the virus infectivity reduction was 99.8% at 30 seconds after the start in test area 1, over 99.9% at 30 seconds after the start in test area 2, 99.7% at 60 seconds after the start in test area 3, 98.4% at 60 seconds after the start in test area 4, 98.4% at 60 seconds after the start in test area 5, 59.3% at 60 seconds after the start in test area 6, 99.0% at 60 seconds after the start in test area 7, and 99.5% at 60 seconds after the start in test area 8.

[0144] [Table 4B]

[0145] [Table 4C]

[0146] (G) Consideration This time, a test was conducted to test the inactivation effect of the test material on PED virus (porcine infectious coronavirus).The results showed that a maximum of 60 seconds of contact had an inactivation effect of 59.3 to 99.9%.

[0147] V. [Confirmation Test (5)] Furthermore, the applicant of the present application conducted a test to confirm the bactericidal effect of the main component of the oral hygiene product of the present invention against Escherichia coli and Staphylococcus aureus, the details of which are described below.

[0148] (A) Test materials: seaweed and seaweed extracts Test material 1: 2% kelp powder in saline solution Test material 2: 2% kelp powder saline solution (prepared by dissolving in boiling water) Sterile saline was used as a control material.

[0149] (B) Test microorganism The microorganisms used in the test were Escherichia coli (ATCC117775) and Staphylococcus aureus (ATCC6538).

[0150] The above microorganisms were pre-cultured in a nutrient medium and then added to sterilized purified water for approximately 10 minutes. 8 The test bacterial solution was prepared to a concentration of CFU / mL.

[0151] (C) Establishment of wards In the test group, 0.1 mL of test bacteria solution was added to 10 mL of the control material, and the sensitization time was set to 30 seconds and 60 seconds after the start of the test.

[0152] As a control group, 0.1 mL of test bacteria solution was added to 10 mL of the test material, and the sensitization time was set to 0, 30, and 60 seconds after the start of the test.

[0153] (D) Test Method The test was carried out with reference to "JIS Z 2801 (antibacterial processed products - antibacterial testing method, disinfection effect)" and the carbolic acid coefficient method.

[0154] (E) Test Procedures (E-1) Microbiological testing method (measurement of bacterial count in test solution) The test solution was diluted appropriately with sterile saline and cultured on nutrient agar medium and each selective medium (Escherichia coli: desoxycholate agar medium, Staphylococcus aureus: egg yolk-added mannitol salt medium). Culture was carried out under aerobic conditions at 35°C for 24 to 48 hours, and the number of colonies that grew after culture was counted to obtain the bacterial count.

[0155] (E-2) Test Method The test material and the control material were placed in a sterilized test tube, and 0.1 mL of the test bacteria solution was added to 10 mL of the material and mixed well.

[0156] According to the test settings, the number of remaining viable bacteria was measured immediately after mixing and after reacting at room temperature for a certain period of time according to the microbiological testing method.

[0157] (F)Result [E. coli] The test results are shown in Table 5A.

[0158] In the control group, the number remained the same from the start to the end of the test, at 640,000 CFU / mL. Sixty seconds after the start of the test, the number in test group 1 was 360,000 CFU / mL (a 43.7% decrease), and in test group 2 it was 320,000 CFU / mL (a 50.0% decrease).

[0159] [Table 5A]

[0160] [Staphylococcus aureus] The test results are shown in Table 5B.

[0161] In the control group, the number remained almost the same from the start to the end of the test, at 2,300,000 CFU / mL. 60 seconds after the start of the test, the number in test group 1 was 1,100,000 CFU / mL (a 52.1% decrease), and in test group 2 it was 1,600,000 CFU / mL (a 30.4% decrease).

[0162] [Table 5B]

[0163] (G) Consideration As a result of the test, a 43.7% reduction in Escherichia coli was confirmed in Test Material 1 after 60 seconds of contact, and a 50.0% reduction in Test Material 2. Additionally, a 52.1% reduction in Staphylococcus aureus bacteria was confirmed in Test Material 1 after 60 seconds of contact, and a 30.4% reduction in Test Material 2.

[0164] VI. [Confirmation Test (6)] Furthermore, the applicant conducted tests to confirm the effects of L-glutamic acid, beta-carotene, red wine (containing 14% alcohol and polyphenols), laminaran, and fucoidan, which are additives added to the main components of the oral hygiene product of the present invention, on the PED virus. The details are described below.

[0165] (A) Test materials: seaweed, seaweed extracts, and additives Test material 1: 2% L-glutamic acid powder in physiological saline solution (prepared by boiling water solution) Test material 2: 2% beta-carotene powder in saline solution (prepared by dissolving in boiling water) Test material 3: 2% Ulva microparticle powder in physiological saline solution (prepared by dissolving in boiling water) Test material 4: 14% alcohol red wine liquid Test material 5: 1% kelp 5μm powder, 14% alcohol, red wine solution (prepared by dissolving in boiling water) Test material 6: 1% laminaran powder in saline solution (prepared by dissolving in boiling water) Test material 7: Fucoidan aqueous solution Sterile phosphate buffer solution was used as a control material.

[0166] (B) Test microorganism The microorganism (virus) used in the test was the P-5V strain of PED virus (Porcine epidemic diarrhea virus), a coronavirus infectious to pigs.

[0167] The cultured cells were Vero cells (a cell line derived from the kidney epithelium of African green monkeys).

[0168] (C) Establishment of wards In the test group, 0.1 mL of the virus solution was added to 1 mL of the above test material, and the sensitization time was set to 15 seconds, 30 seconds, and 60 seconds after the start of the test.

[0169] As a control, 0.1 mL of the virus solution was added to 1 mL of phosphate buffer solution, and the sensitization time was set to 0 seconds and 60 seconds after the start of the test.

[0170] (D) Test Method The test was carried out with reference to "Virus Experimental Science, General Theory, Revised Second Edition, Maruzen Co., Ltd., Virus Neutralization Test Method."

[0171] (E) Test Procedures (E-1) Preliminary Exam: Prior to the test, the effects of the test materials on cultured cells (cytotoxicity) were investigated.

[0172] The test material was serially diluted 10-fold with phosphate buffer and then inoculated into cultured cells. The highest concentration that showed normal cell condition after culture was confirmed, and the virus concentration to be used in the test was determined.

[0173] As a result, the cytotoxicity was as shown in Table 6A, and poor cell growth was confirmed at a maximum of 10 times the test material. Therefore, it was found that when testing, it was necessary to dilute the mixture of test material and virus solution by 10 times or more before inoculating it into the cells. In addition, the virus addition concentration was 10 6 TCID 50 / mL or more.

[0174] [Table 6A]

[0175] (E-2) Main test: Mixing test liquids According to the test category, 1 mL of each test material and phosphate buffer solution was taken, and the virus solution was added to the concentration determined in the preliminary test. After adding the virus solution, the mixture was left to stand at room temperature (25°C) for the specified time.

[0176] (E-3) Main test: Cell inoculation After sensitization for each test section, the mixture was serially diluted 10-fold, and 100 μL of each was inoculated onto cells cultured in a 96-well plate.

[0177] The determination was made by culturing the cells at 37°C in carbon dioxide gas (5%) for 5 days, then observing the cultured cells under a microscope to confirm the presence or absence of virus growth based on the appearance of CPE (cytopathic encephalopathy) in the cultured cells, and calculating the concentration.

[0178] (F)Result The test results are shown in Figure 6 and Tables 6A, 6B, and 6C. Table 6C is a table that makes Table 6B easier to understand.

[0179] In the control group, no change in viral load was observed between the start of the test and 60 seconds after the test started (10 6.5 TCID 50 / mL).

[0180] In test area 1, the virus infectivity was reduced by 37.5% at 15 seconds and 90.0% at 60 seconds; in test area 2, the virus infectivity was reduced by 75.3% at 15 seconds and 90.0% at 60 seconds; in test area 3, the virus infectivity was reduced by 59.3% at 15 seconds and 93.7% at 60 seconds; in test area 4, the virus infectivity was reduced by 37.5% at 15 seconds and 99.7% at 60 seconds; in test area 5, the virus infectivity was reduced by 99.7% at 15 seconds and 99.9% at 60 seconds; in test area 6, the virus infectivity was reduced by 95.9% at 15 seconds and 99.3% at 60 seconds; and in test area 7, the virus infectivity was reduced by 98.4% at 15 seconds and 99.8% at 60 seconds.

[0181] [Table 6B]

[0182] [Table 6C]

[0183] (G) Consideration This time, we conducted a test to determine the inactivation effect of the test material on PED virus (porcine infectious coronavirus).The results showed that a maximum of 60 seconds of contact had an inactivation effect of 90.0-99.9%.

[0184] VII. [Confirmation Test (7)] The applicant of the present application conducted a test to confirm the effectiveness of the main ingredient of the oral hygiene product of the present invention against influenza viruses as follows. The details are described below.

[0185] (A) Test materials: seaweed and seaweed extracts Test material 1: 2% kelp powder particle size 5 μm saline solution Test material 2: 2% kelp powder particle size 5 μm saline solution (prepared by dissolving in boiling water) Sterile phosphate buffer was used as a control material.

[0186] (B) Test microorganism The test microorganism (virus) used was influenza virus (swine influenza virus H1N1 IOWA strain).

[0187] The cultured cells are MDCK cells (a cell line derived from canine kidney).

[0188] (C) Establishment of wards In the test group, 0.1 mL of the virus solution was added to 1 mL of the above test material, and the sensitization time was set to 15 seconds, 30 seconds, and 60 seconds after the start of the test.

[0189] As a control, 0.1 mL of the virus solution was added to 1 mL of phosphate buffer solution, and the sensitization time was set to 0 seconds and 60 seconds after the start of the test.

[0190] (D) Test Method The test was carried out with reference to "Virus Experimental Science, General Theory, Revised Second Edition, Maruzen Co., Ltd., Virus Neutralization Test Method."

[0191] (E) Test Procedures (E-1) Preliminary Exam: Prior to the test, the effects of the test materials on cultured cells (cytotoxicity) were investigated.

[0192] The test material was serially diluted 10-fold with phosphate buffer and then inoculated into cultured cells. The highest concentration that showed normal cell condition after culture was confirmed, and the virus concentration to be used in the test was determined.

[0193] As a result, poor cell growth was confirmed in all test materials diluted 10 times. Therefore, it was found that the test material and virus solution mixture must be diluted 10 times or more before inoculating the cells. 6 TCID 50 / mL or more.

[0194] (E-2) Main test: Mixing test liquids According to the test category, 1 mL of each test material and phosphate buffer solution was taken, and the virus solution was added to the concentration determined in the preliminary test. After adding the virus solution, the mixture was left to stand at room temperature (25°C) for the specified time.

[0195] (E-3) Main test: Cell inoculation After sensitization for each test category, the mixture was diluted 10-fold and 100 μL of each was inoculated onto cells cultured in a 96-well plate.

[0196] After culturing at 37°C in carbon dioxide gas (5%) for 5 days, the culture supernatant in each well was collected, and the presence or absence of virus growth was confirmed by hemagglutination reaction, and the virus concentration was calculated.

[0197] (F)Result The test results are shown in Figure 7 and Tables 7A and 7B.

[0198] In the control group, no change in viral load was observed between the start of the test and 60 seconds after the test started (10 6.9 TCID 50 / mL).

[0199] In test area 1, the virus infectivity was reduced by 99.3% at 15 seconds and 99.9% at 60 seconds after the start of the test, and in test area 2, the virus infectivity was reduced by 99.3% at 15 seconds and 99.9% at 60 seconds.

[0200] [Table 7A]

[0201] [Table 7B]

[0202] (G) Consideration This time, we conducted a test to see if the test material could inactivate influenza viruses. The results showed that contact for 15 to 60 seconds had an inactivation effect of 99.3 to 99.9%.

[0203] VIII. [Confirmation Test (8)] Based on the results of the above [Confirmation Test (1)] to [Confirmation Test (7)], the applicant further conducted Confirmation Test (8) to confirm in more detail the inactivation effect of kelp and its extracts against viruses, including SARS-CoV-2.

[0204] Figure 8 shows the results of a test (8) on the effectiveness of the main ingredients of the oral hygiene product of the present invention against SARS-CoV-2, a novel coronavirus.

[0205] (A) Test materials: seaweed and seaweed extracts Test material 1: 2% kelp powder particle size 5 μm saline solution Test material 2: 2% kelp powder particle size 5 μm saline solution Test material 3: 2% kelp powder particle size 5 μm saline solution (prepared by boiling water solution) Test material 4: 2% kelp powder particle size 5 μm saline solution (prepared by boiling water solution) Test material 5: 2% kelp powder particle size 5 μm saline solution (prepared by boiling water solution) Test material 6: 2% kelp powder particle size 5 μm saline solution (prepared by boiling water solution) Test material 7: 2% kelp powder particle size 5 μm saline solution (prepared by boiling water solution) Test material 8: 2% laminaran powder in saline solution Test material 9: 2% phloroglucinol powder in saline solution (prepared by boiling water solution) Test material 10: 2% Arame powder in saline solution (prepared by dissolving in boiling water) As a control material, sterilized phosphate buffer solution was used.

[0206] Incidentally, the above-mentioned "Test Materials 1," "Test Materials 2," and "Test Materials 3" to "Test Materials 7" are the same, but this is done to confirm the variation in effects under the same test conditions and to understand the reliability of the test results.

[0207] (B) Test microorganism The microorganism (virus) used in this study was SARS-CoV-02 (novel coronavirus). This SARS-CoV-02 was a human isolate, isolated and cultured from saliva using Vero cells. Real-time PCR was then used to confirm amplification of the SARS-CoV-2 gene (as required by the Ministry of Health, Labor and Welfare). The cultured cells used in this study were Vero cells (a cell line derived from the kidney epithelium of African green monkeys).

[0208] (C) Establishment of wards As a control, 0.1 mL of the virus solution was added to 1 mL of phosphate buffer solution, and the sensitization time was set to 0 seconds and 60 seconds after the start of the test.

[0209] In the test group, 0.1 mL of the virus solution was added to 1 mL of the above test material, and the sensitization time was set to 15 seconds, 30 seconds, and 60 seconds after the start of the test.

[0210] (D) Test Method The test was carried out with reference to "Virus Experimental Science, General Theory, Revised Second Edition, Maruzen Co., Ltd., Virus Neutralization Test Method."

[0211] (E) Test Procedures (E-1) Preliminary Exam: Prior to the test, the effects of the test materials on cultured cells (cytotoxicity) were investigated.

[0212] The test material was serially diluted 10-fold with phosphate buffer and then inoculated into cultured cells. The highest concentration that showed normal cell condition after culture was confirmed, and the virus concentration to be used in the test was determined.

[0213] As a result, the cytotoxicity was as shown in the table below, and poor cell growth was confirmed at a maximum of 10 times the test material. Therefore, it was found that when testing, it was necessary to dilute the mixture of test material and virus solution by 10 times or more before inoculating it into the cells. In addition, the virus addition concentration was 10 6 TCID 50 / mL or more.

[0214] [Table 8A]

[0215] (E-2) Main test: Mixing test liquids According to the test category, 1 mL of each test material and phosphate buffer solution was taken, and the virus solution was added to the concentration determined in the preliminary test.

[0216] After adding the virus solution, the mixture was allowed to stand at room temperature (25°C) for a predetermined period of time.

[0217] (E-3) Main test: Cell inoculation and bacterial count After sensitization for each test section, the mixture was serially diluted 10-fold, and 100 μL of each was inoculated onto cells cultured in a 96-well plate.

[0218] The determination was made by culturing the cells at 37°C in carbon dioxide gas (5%) for 5 days, then observing the cultured cells under a microscope to confirm the presence or absence of virus growth based on the appearance of CPE (cytopathic encephalopathy) in the cultured cells, and calculating the concentration.

[0219] (F)Result The test results for SARS-CoV-02 are shown in Figure 8, Table 8A, Table 8B, Table 8C, and Table 8D. Tables 8C and 8D are simplified versions of Table 8B for easier understanding.

[0220] In the control group, no change in viral load was observed between the start of the test and 60 seconds after the test started (10 6.3 TCID 50 / mL).

[0221] On the other hand, in test area 1, it was 99.3% at 15 seconds and 99.9% at 60 seconds after the start, in test area 2 it was 99.6% at 15 seconds and 99.9% at 60 seconds, in test area 3 it was 99.7% at 15 seconds and 99.7% at 60 seconds, in test area 4 it was 99.3% at 15 seconds and 99.9% at 60 seconds, in test area 5 it was 99.6% at 15 seconds and 99.9% at 60 seconds, in test area 6 it was 99.6% at 15 seconds and 99.9% at 60 seconds, In test area 1, the virus infectivity was reduced by 99.3% in 15 seconds and 99.9% in 60 seconds; in test area 7, the virus infectivity was reduced by 99.6% in 15 seconds and 99.9% in 60 seconds; in test area 8, the virus infectivity was reduced by 90.0% in 15 seconds and 96.0% in 60 seconds; in test area 9, the virus infectivity was reduced by 96.0% in 15 seconds and 98.4% in 60 seconds; and in test area 10, the virus infectivity was reduced by 99.0% in 15 seconds and 99.6% in 60 seconds.

[0222] [Table 8B]

[0223] [Table 8C]

[0224] [Table 8D]

[0225] The detailed results of the above-mentioned I. [Confirmation Test (1)] to VIII. [Confirmation Test (8)] are summarized in Tables 9 to 12D.

[0226] Table 9 summarizes the virus inactivation effect of each seaweed component.

[0227] As shown in Table 9, the main components of the seaweed, which is the main ingredient of the oral hygiene product of the present invention, have been confirmed to have a significant inactivation effect (reduction in virus count) on the novel coronavirus "SARS-CoV-2" that causes COVID-21 and the "PED virus," which is similar to "SARS-CoV-2." This suggests that they will also have a similar significant inactivation effect on mutated strains of the novel coronavirus "SARS-CoV-2."

[0228] [Table 9]

[0229] Table 10 summarizes the virus inactivation effect (virus reduction rate) for SARS-CoV-2, PEDV (PED virus), and influenza virus. In addition, the number of tests was increased for saline solution containing 2% kelp powder with a particle size of 5 μm and saline solution containing a boiled solution of the same 2% kelp powder with a particle size of 5 μm, and the variation in the inactivation effect was confirmed.

[0230] As shown in Table 10, similar to Table 10 above, it has been confirmed that the main components of the seaweed, which is the main ingredient of the oral hygiene product of the present invention, have a significant inactivation effect (drastically reduced virus count) against the novel coronavirus "SARS-CoV-2" that causes COVID-21, "influenza virus," and "PED virus" similar to SARS-CoV-2. From this, it is easy to predict that they will also have a similar significant inactivation effect against various types of "influenza virus" such as the Hong Kong type and the Soviet type, and various mutant species of "SARS-CoV-2."

[0231] [Table 10]

[0232] Table 11 summarizes the inactivation effect of saline containing 2% powdered microparticles of several types of seaweed (kelp, wakame, ulva, and tsuruarame) on the PED virus.

[0233] As shown in Table 11, it was confirmed that it has a significant inactivation effect (dramatic reduction in the number of viruses) on the PED virus, which is similar to the novel coronavirus SARS-CoV-2 that causes COVID-21.

[0234] [Table 11]

[0235] Table 12A summarizes the inactivation effect of seaweed powder, the main ingredient of the oral hygiene product of the present invention, on PED viruses, which are similar to SARS-CoV-2.

[0236] As shown in Table 12A, similar to Table 10 above, it has been confirmed that seaweed powder, which is the main ingredient of the oral hygiene product of the present invention, has a significant inactivation effect (dramatic reduction in the number of viruses) on the PED virus, which is similar to SARS-CoV-2.

[0237] [Table 12A]

[0238] Table 12B summarizes the inactivation effects of the main ingredients and various additives that make up the seaweed, which is the main ingredient of the oral hygiene product of the present invention, on the novel coronavirus "SARS-CoV-2" that causes COVID-21 and the "PED virus," which is similar to "SARS-CoV-2."

[0239] As shown in Table 12B, it has been confirmed that the main components and various additives that make up the seaweed, which is the main ingredient of the oral hygiene product of the present invention, have a significant inactivation effect (dramatic reduction in the number of viruses) on the novel coronavirus "SARS-CoV-2" that causes COVID-21 and the "PED virus" that is similar to "SARS-CoV-2."

[0240] [Table 12B]

[0241] Table 12C summarizes the inactivation effect of alcohol and kelp-containing alcoholic beverages on the novel coronavirus SARS-CoV-2 that causes COVID-21 and the PED virus, which is similar to the SARS-CoV-2 virus.

[0242] As shown in Table 12C, as has been previously known, it has been confirmed that wine containing alcohol and kelp components has a significant inactivation effect (dramatic reduction in virus counts) on the PED virus, which is similar to the novel coronavirus SARS-CoV-2 that causes COVID-21.

[0243] [Table 12C]

[0244] Table 12D is a table summarizing the results of the bactericidal effect of seaweed powder, which is the main ingredient of the oral hygiene product of the present invention, against Escherichia coli and Staphylococcus aureus.

[0245] As shown in Table 12D, it was confirmed that the seaweed powder, which is the main ingredient of the oral hygiene product of the present invention, has a significant bactericidal effect against Escherichia coli and Staphylococcus aureus. This shows that the seaweed powder, which is the main ingredient of the oral hygiene product of the present invention, also has a bactericidal effect against other bacteria that cause food poisoning.

[0246] [Table 12D]

[0247] Table 13 summarizes the inactivation effect (dramatic reduction in virus count) of the main ingredients and additives that make up the seaweed, which is the main ingredient of the oral hygiene product of the present invention, on the novel coronavirus "SARS-CoV-2" that causes COVID-21 and the "PED virus," which is similar to "SARS-CoV-2."

[0248] As shown in Table 13, it has been confirmed that the main components and additives that make up the seaweed, which is the main ingredient of the oral hygiene product of the present invention, have a significant inactivation effect (dramatic reduction in the number of viruses) on the new coronavirus "SARS-CoV-2" that causes COVID-21 and the "PED virus," which is similar to "SARS-CoV-2."

[0249] Table 13 summarizes the inactivation effect of seaweed powder, which is the main ingredient of the oral hygiene product of the present invention, and its ingredients against viruses such as the novel coronavirus SARS-CoV-2 that causes COVID-21, the PED virus similar to SARS-CoV-2, and the norovirus, as well as the bactericidal effect against Escherichia coli and Staphylococcus aureus.

[0250] As shown in Table 13, it has been confirmed that seaweed powder and its ingredients, which are the main ingredients of the oral hygiene product of the present invention, not only have a significant inactivating effect on viruses such as the new coronavirus "SARS-CoV-2" that causes COVID-21, "PED virus" which is similar to SARS-CoV-2, and "norovirus," but also have a bactericidal effect on "E. coli" and "Staphylococcus aureus."

[0251] [Table 13]

[0252] (G) Consideration This time, a test was conducted to determine the inactivation effect of the test materials on SARS-CoV-2. The results showed that a maximum of 60 seconds of contact had an inactivation effect of 96.0-99.9%.

[0253] IX. [Confirmation Test (9)] Based on the detailed test results of the above [Confirmation Test (1)] to [Confirmation Test (8)], the applicant conducted a "Confirmation Test (9) on the inhibition and sterilization of the growth of the causative bacteria that cause periodontal disease or dental caries," which is the problem that the present invention aims to solve.

[0254] Figure 9 shows the results of a test (9) on the effects of kelp powder, a type of seaweed that constitutes the oral hygiene product of the present invention, its main component fucoidan powder, gyokuro tea leaf powder (gyokuro powder), and a mixture of these on Porphimonas gingivalis, a bacterium that causes periodontal disease.

[0255] (A) Test materials: seaweed and seaweed extracts Test material 1: 2% kelp powder particle size 5μm saline solution (prepared by boiling water solution) Test material 2: Fucoidan water (prepared by dissolving in boiling water) Test material 3: 2% fucoidan powder in physiological saline solution (prepared by boiling water solution) Test material 4: 2% gyokuro powder in physiological saline solution (prepared by boiling water solution) Test material 5: 2% gyokuro powder + kelp powder particle size 5μm physiological saline solution (prepared by boiling water solution) Test material 6: 2% gyokuro powder + 2% fucoidan powder particle size 5μm physiological saline solution (prepared by boiling water solution) 2% kelp powder particle size 5μm saline solution (prepared by boiling water solution) Sterile saline was used as a control material.

[0256] (B) Test microorganism (bacteria) Porphyromonas gingivalis (ATCC33277) was used as the donor microorganism (bacteria). This test microorganism (bacteria) was pre-cultured in a blood medium and then diluted with sterile purified water for approximately 10 minutes. 8 The test bacterial solution was adjusted to a concentration of cfu / mL.

[0257] (C) Establishment of wards As a control group, 0.1 mL of test bacteria solution was added to 10 mL of the control material, and the sensitization time was set to 0, 30, and 60 seconds after the start of the test.

[0258] In test areas 1-6, 0.1 mL of test bacteria solution was added to 10 mL of test material, and the sensitization time was set at 30 and 60 seconds after the start of the test.

[0259] The sensitization time was set to 30 seconds and 60 seconds based on the assumption that this is the time that the oral hygiene product according to the present invention, such as a toothpaste, remains in the oral cavity.

[0260] (D) Test Method The test was carried out with reference to "JIS Z 2801 (antibacterial processed products, antibacterial testing methods, bactericidal effect)" and the carbolic acid coefficient method.

[0261] (E) Test Procedures (E-1) Microbiological testing method (measurement of bacterial count in test solution) The test solution was diluted appropriately with sterile saline and cultured on blood agar medium. The culture was carried out under anaerobic conditions at 35°C for 10 days, and the number of colonies that grew after the culture was counted to determine the bacterial count. (E-2) Test Method The test material and the control material were placed in a sterilized test tube, and 0.1 mL of the test bacteria solution was added to 10 mL of the material and mixed thoroughly.

[0262] According to the test settings, the number of remaining viable bacteria was measured immediately after mixing and after reacting at room temperature for a certain period of time according to the microbiological testing method. (F)Result The test results of the above-mentioned confirmation test (9) are shown in Figure 9, Table 14, Table 15A and Table 15B. Tables 15A and 15B are tables that make the test results shown in Table 14 easier to understand.

[0263] Test results As shown in Table 14, in the control group, the number of 1.2 × 10 6 CFU / mL.

[0264] On the other hand, in test areas 1-6, the results were as follows 60 seconds after the start of the test.

[0265] Test area 1: 5.3 x 10 5 CFU / mL (55.8% decrease) Test area 2: 6.8 x 10 5 CFU / mL (43.3% decrease) Test area 3: 7.8 x 10 5 CFU / mL (35.0% decrease) Test area 4: 1.0 x 10 6 CFU / mL (16.6% decrease) Test area 5: 8.8 x 10 5 CFU / mL (26.6% decrease) Test area 6: 1.1 x 10 6 CFU / mL (8.3% decrease) The above values ​​are the average values ​​of three trials.

[0266] [Table 14]

[0267] (G) Consideration As a result of the above test, the test materials were confirmed to be effective in reducing the number of Porphyromonas gingivalis bacteria, and it was determined that a reduction of 8.3 to 55.8% was achieved within 60 seconds of contact with each test material.

[0268] [Table 15A]

[0269] [Table 15B]

[0270] X. [Confirmation Test (10)] Based on the results of the above-mentioned [Confirmation Test (9)], the applicant further conducted a "Confirmation Test (10) on the inhibition and sterilization of the growth of the causative bacteria that cause periodontal disease or dental caries," which is the problem that the present invention aims to solve.

[0271] Figure 10 shows the results of a test (10) on the effects of kelp powder, a type of seaweed that constitutes the oral hygiene product of the present invention, its main component fucoidan powder, gyokuro tea leaf powder (gyokuro powder), and a mixture of these on Porphimonas gingivalis, a bacterium that causes periodontal disease.

[0272] (A) Test materials: seaweed, seaweed extracts, and additives Test material 1: 5% kelp powder particle size 5 μm saline solution (prepared by dissolving in boiling water) Test material 2: 0.5% isopropyl methylphenol saline solution Test material 3: 2% iodine powder in saline solution (prepared by dissolving in boiling water) Test material 4: 2% iodine powder in saline solution (prepared by dissolving in boiling water) Test material 5: 4% fucoidan powder in saline solution (prepared by dissolving in boiling water) Test material 6: 2% laminaran powder in saline solution Test material 7: 2% phloroglucinol (polyphenol) powder in saline solution (prepared in 217488N3 solution for boiling water) Test material 8: 2% sodium alginate powder in saline solution (prepared by boiling water solution) Test material 9: 2% erythritol powder in saline solution (prepared as a boiling solution) Test material 10: 2% mannitol powder in physiological saline solution (prepared as a boiling solution) Sterile saline was used as a control material.

[0273] (B) Test microorganism (bacteria) Porphyromonas gingivalis (ATCC33277) was used as the donor microorganism (bacteria). This test microorganism (bacteria) was pre-cultured in a blood medium and then diluted with sterile purified water for approximately 10 minutes. 8 The test bacterial solution was adjusted to a concentration of cfu / mL.

[0274] (C) Establishment of wards As a control group, 0.1 mL of test bacteria solution was added to 10 mL of the control material, and the sensitization time was set to 0, 30, and 60 seconds after the start of the test.

[0275] In test plots 1-10, 0.1 mL of test bacteria solution was added to 10 mL of test material, and the sensitization time was set at 30 and 60 seconds after the start of the test.

[0276] The sensitization time was set to 30 seconds and 60 seconds because it was assumed that the oral hygiene product according to the present invention, such as a toothpaste, would remain in the oral cavity.

[0277] (D) Test Method The test was carried out with reference to "JIS Z 2801 (antibacterial processed products, antibacterial testing methods, bactericidal effect)" and the carbolic acid coefficient method.

[0278] (E) Test Procedures (E-1) Microbiological testing method (measurement of bacterial count in test solution) The test solution was diluted appropriately with sterile saline and cultured on blood agar medium. The culture was carried out under anaerobic conditions at 35°C for 10 days, and the number of colonies that grew after the culture was counted to determine the bacterial count. (E-2) Test Method The test material and the control material were placed in a sterilized test tube, and 0.1 mL of the test bacteria solution was added to 10 mL of the material and mixed thoroughly.

[0279] According to the test settings, the number of remaining viable bacteria was measured immediately after mixing and after reacting at room temperature for a certain period of time according to the microbiological testing method. (F)Result The test results of the above confirmation test (9) are shown in FIG. 10 and Table 16.

[0280] Test results As shown in Table 16, in the control group, the number of 1.2 × 10 6 CFU / mL.

[0281] On the other hand, in test areas 1-6, the results were as follows 60 seconds after the start of the test.

[0282] Test area 1: 5.2 x 10 5 CFU / mL (56.6% decrease) Test area 2: 5.2 x 10 5 CFU / mL (56.6% decrease) Test area 3: 1.6 x 10 5 CFU / mL (86.6% reduction) Test area 4: 1.8 x 10 5 CFU / mL (85.0% decrease) Test area 5: 6.2 x 10 5 CFU / mL (48.3% decrease) Test area 6: 2.5 x 10 5 CFU / mL (79.1% decrease) Test area 7: 1.8 x 10 5 CFU / mL (85.0% decrease) Test area 8: 1.1 x 10 6 CFU / mL (8.3% decrease) Test area 9: 1.1 x 10 6 CFU / mL (8.3% decrease) Test area 10: 1.0 x 10 6 CFU / mL (16.6% decrease) The above values ​​are the average values ​​of three trials.

[0283] [Table 16]

[0284] Table 17 is shown below. It should be noted that Table 17 is a table that combines Tables 15A, 15B, and 16 for easier understanding.

[0285] [Table 17]

[0286] (G) Consideration As a result of the above test, the test materials were confirmed to be effective in reducing the number of Porphyromonas gingivalis bacteria, and it was determined that a reduction of 8.3 to 55.8% was achieved within 60 seconds of contact with each test material.

[0287] As described above, the present invention provides a toothpaste and oral hygiene product for use in the mouth, nose, or throat, which contains kelp powder as an active ingredient and is left in the mouth, nose, or throat for at least 15 seconds to reduce the proliferation of influenza viruses and inactivate them, and which contains 2% by weight of kelp powder with a particle size of 5 μm in saline or boiling saline.

Claims

1. A toothpaste and oral hygiene product for use in the mouth, nose, or throat, which contains kelp powder as an active ingredient and is to be left in the mouth, nose, or throat for at least 15 seconds in order to reduce the proliferation of influenza viruses and to inactivate them.

2. 2. The sanitary product according to claim 1, wherein the saline solution contains 2% by weight of kelp powder having a particle size of 5 μm.

3. 2. The sanitary product according to claim 1, wherein the sanitary product contains 2% by weight of kelp powder having a particle size of 5 μm in physiological saline dissolved in boiling water.

4. The sanitary product according to any one of claims 1 to 3, wherein the influenza virus is Swine Influenza Virus H1N1 TOWA strain.

5. The oral hygiene product according to any one of claims 1 to 3, wherein the toothpaste is in a paste, liquid, or powder form, and the oral hygiene product and the oral hygiene product for rinsing include a dental rinse, a mouthwash, and an anti-stomatitis agent.

6. The oral hygiene product according to any one of claims 1 to 3, wherein the nasal hygiene product includes nasal drops and nasal spray liquid, and the throat hygiene product includes a lozenge or throat spray that is dissolved in the mouth for use.

7. The oral hygiene product according to claim 1 , wherein the oral hygiene product includes a throat lozenge, chewing gum, or pacifier food that remains in the mouth and stimulates saliva secretion.

8. The oral hygiene product according to claim 1 , wherein the mouthwash comprises drinking water.

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