Anti-influenza virus composition containing xanthan gum or fucoidan

Abstract

The present invention relates to an antiviral composition against influenza virus containing xanthan gum or fucoidan as an active ingredient, a pharmaceutical composition for preventing or treating influenza virus infection, and a method for preventing or treating influenza virus infection using the same.

Description

Technical Field

[0001] The present invention relates to an antiviral composition against Influenza virus containing xanthan gum or fucoidan as an active ingredient, a pharmaceutical composition for preventing or treating influenza virus infection, and a method for preventing or treating influenza virus infection using the same.

Background Art

[0002] Influenza virus is a type of orthomyxovirus and is a typical pathogenic virus that kills thousands to tens of thousands of people every season. Since the 20th century, influenza has mutated by crossing species barriers, causing influenza and becoming a virus with a high mutation rate that can render known drugs ineffective. This disease, generally called epidemic influenza, usually causes chills, fever, sore throat, muscle pain, cough, drowsiness, and fatigue. Such non-specific symptoms are more severe than those of the common cold but are not fatal enough to threaten life on their own. However, when accompanied by pneumonia or Reye's syndrome, it can cause fatal complications. Generally, respiratory infections occur mainly through the cough, sputum, or sneezing of infected individuals, and many variants occur when the infection spreads from other animals (especially birds) to humans. There are three types of influenza viruses: Influenza A virus, Influenza B virus, and Influenza C virus.

[0003] Among these, the influenza that caused a pandemic through interspecies transmission and spread in 2009, so-called novel influenza, is the Influenza A H1N1 type. It first occurred in Mexico and spread to many countries with the emergence of various variants, and the World Health Organization (WHO) defined this as a "global pandemic."

[0004] In the case of influenza, it is generally common practice to use prophylactic protective measures by administering purified inactivated strains before the influenza season. However, for patients who have already developed symptoms during the influenza season, prevention is impossible, and symptoms must be alleviated through therapeutic approaches. In the case of Tamiflu, which stopped the spread of a novel influenza virus that was spreading uncontrollably, it is highly effective, but there have been occasional reports in the media of adverse side effects such as hallucinations after taking it.

[0005] Traditionally used drugs for treating influenza include oseltamivir (brand name: Tamiflu), zanamivir (brand name: Relenza), peramivir, and amantadine.

[0006] Oseltamivir, known as Tamiflu, is currently used primarily to treat H1N1 A influenza. Tamiflu is the only avian influenza (AI) treatment manufactured exclusively worldwide.

[0007] This is an antiviral drug that exerts its therapeutic effect by inhibiting the function of enzymes that allow the virus to multiply, and it is most effective when administered within 48 hours of symptom onset.

[0008] Its main therapeutic effects include reducing the worsening of influenza symptoms, decreasing the incidence of secondary complications such as bronchitis or pneumonia, and shortening the incubation period of influenza. It is also used as a treatment for influenza A and B.

[0009] Zanamivir is sold under the brand name Relenza. It acts as a neuraminidase inhibitor and is used to treat influenza A and B.

[0010] However, oseltamivir has the side effect of potentially causing severe vomiting, and while zanamivir has high antiviral efficacy, it has the drawback of low bioavailability and is rapidly excreted by the kidneys.

[0011] Against this backdrop, there is a continuing need for the development of antiviral agents with excellent infection-inhibiting and therapeutic effects. [Overview of the project] [Problems that the invention aims to solve]

[0012] The technical problem that this invention aims to solve is to provide an antiviral composition against influenza virus that contains xanthan gum or fucoidan as an active ingredient.

[0013] Another technical problem that the present invention aims to solve is to provide a pharmaceutical composition for preventing or treating viral infections caused by the influenza virus, comprising xanthan gum or fucoidan as an active ingredient.

[0014] A further technical problem that the present invention aims to solve is to provide a method for preventing or treating influenza virus infection, the method comprising the step of administering a pharmaceutical composition to a subject.

[0015] A further technical problem that the present invention aims to solve is to provide the use of a composition containing xanthan gum or fucoidan as an active ingredient for preventing or treating influenza virus infection.

[0016] A further technical problem that the present invention aims to solve is to provide the use of a composition containing xanthan gum or fucoidan as an active ingredient for manufacturing a pharmaceutical for treating influenza virus infection. [Means for solving the problem]

[0017] According to one aspect of the present invention, an antiviral composition against influenza virus is provided, comprising xanthan gum or fucoidan as an active ingredient.

[0018] In this invention, the term "xanthan gum" refers to a naturally derived polysaccharide, which is low in toxicity and is an extracellular polysaccharide produced by the fermentation of the bacterium Xanthomonas campestris, a member of the Xanthomonas genus that causes leaf blight in beans. Aqueous solutions of xanthan gum have high viscosity at low concentrations, and this viscosity is maintained almost constant over a wide temperature range (10-70°C), a wide pH range (pH 6-9), and a wide electrolyte concentration range. Due to these rheological properties, xanthan gum is used as a stabilizer, thickener, and suspending agent in industries such as the food and pharmaceutical industries.

[0019] In this invention, "fucoidan" refers to a type of water-soluble dietary fiber, specifically a polysaccharide found in brown algae such as wakame and kelp. Depending on the harvest time and the species of brown algae, the average molecular weight of fucoidan varies from 100,000 to 2,000,000 Da, and the fucose content and sulfate group content, which have important effects on the physiological activity of fucoidan, also differ.

[0020] In this invention, the "influenza virus" has two surface antigens on its surface, namely the glycoprotein hemagglutinin (HA) and neuraminidase (NA), and contains eight segmented RNA molecules internally. HA binds to sialic acid residues on the surface of host cells, thereby enabling the virus to attach to and invade host cells. NA plays a role in inducing viruses that have completed replication in infected host cells to replicate in other host cells by cleaving the α-ketoside bond between the disaccharide portion of the cell surface and the neuraminidase residue. In vivo defense mechanisms against viruses either recognize HA and interfere with the binding of the virus to host cells, or bind to NA and inhibit the replication of viruses within infected host cells to adjacent cells. However, various combinations of 16 types of HA and 9 types of NA allow the virus to undergo numerous mutations, thereby acquiring resistance to defense mechanisms.

[0021] In one embodiment, the influenza virus may be an influenza A virus, and the influenza A virus may be of the H1N1 type, but is not limited thereto.

[0022] In the present invention, the term "antiviral" means any mechanism and activity that inhibits the entry of various subtypes of viruses and variant virus particles into host cells, or inhibits the replication or growth of virus particles in host cells after infection.

[0023] In one embodiment, the composition can be used for immunization measures against endemic, pre-pandemic, or pandemic caused by influenza virus.

[0024] The term "immunization" refers to the induction of immunity for preventing infectious diseases and encompasses all methods of enhancing or acquiring immunity in vivo.

[0025] According to another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating a viral infectious disease caused by an influenza virus, comprising xanthan gum or fucoidan as an active ingredient.

[0026] In the present invention, the term "influenza virus infection" means that the lungs and / or respiratory tract are infected with one of the influenza viruses. This may be accompanied by a respiratory disease and, if the inflammatory response deteriorates, may lead to tissue damage.

[0027] In one embodiment of the present invention, it has been confirmed that the administration of xanthan gum and / or fucoidan has a mitigating effect on the inflammation and tissue damage caused by influenza virus infection.

[0028] In one embodiment, when administered before and / or after viral infection, one of the symptoms of influenza virus infection, namely weight loss, was alleviated (Table 3, Table 8, Figure 1 and Figure 5), infiltration of inflammatory cells was reduced (Table 5, Table 9, Figure 2 and Figure 6), and it was also confirmed that the viral titers in the lungs and nasal cavities decreased (lungs: Table 10, Table 11, Figure 3 and Figure 7; nasal cavities: Table 12, Table 13, Figure 3 and Figure 8).

[0029] When the composition of the present invention is administered for the purpose of prevention or treatment, it exhibits an inhibitory effect against influenza virus, and at the same time, it can alleviate inflammation and reduce damage to lung tissue. In particular, in the case of highly pathogenic influenza virus, if the anti-inflammatory action does not function, a large number of inflammatory cells may infiltrate the lungs, and an excessive amount of inflammatory cytokines may be secreted, which may cause a cytokine storm. However, as described above, the pharmaceutical composition of the present invention can effectively respond thereto.

[0030] In addition, the pharmaceutical composition of the present invention can be applied to the use in the prevention or treatment of diseases that can be caused by influenza virus infection. For example, diseases that can be caused by influenza virus infection may be one or more selected from the group consisting of cold, influenza, cough, sneeze, runny nose, muscle pain, pharyngitis, sepsis, pneumonia, nasal congestion, laryngitis, sore throat, hoarseness, headache, pain in the sinuses, rhinitis, pharyngitis, bronchitis, asthma, fever, dyspnea, general malaise and chills, but are not limited thereto.

[0031] In the present invention, the term "prevention" means any function of the composition of the present invention that delays the occurrence of an infection caused by influenza virus.

[0032] In the present invention, the term "treatment" means any function of the composition of the present invention that improves the symptoms of an infectious disease caused by influenza virus or beneficially acts on the symptoms of the infectious disease.

[0033] [[ID=第十九]] In one embodiment, the pharmaceutical composition of the present invention may take parenteral dosage form, more specifically, it may be administered intranasally or into the nasal cavity. Intranasal or nasal administration may be carried out in the form of a spray, aerosol, or inhalation.

[0034] In addition, the pharmaceutical compositions of the present invention can be administered in pharmaceutically effective amounts, the term "pharmaceutically effective amount" meaning an amount sufficient to treat the disease with a reasonable benefit-to-risk ratio applicable to the medical treatment. The effective dose level may be determined depending on factors such as the patient's sex and age, the type and severity of the disease, the activity of the drug, the patient's sensitivity to the drug, the time of administration, the route of administration and the rate of excretion, the duration of treatment, concomitant medications, and other factors well known in the medical field.

[0035] Another aspect of the present invention relates to a kit for preventing or treating influenza viruses, comprising a pharmaceutical composition.

[0036] The kit of the present invention is not particularly limited in type, and kits of a form conventionally used in the relevant art may be used. The kit of the present invention may be packaged so that xanthan gum or fucoidan is contained in individual containers, or it may be packaged so that xanthan gum or fucoidan is contained in a single container divided into one or more compartments together with another drug or excipient, and each active ingredient may be packaged in a single-dose form for one administration, but is not limited thereto.

[0037] In the kit, xanthan gum or fucoidan may be administered at an appropriate time depending on the health condition of the recipient, and if necessary, may be administered simultaneously, sequentially, or in reverse order in combination with other additional drugs.

[0038] Another aspect of the present invention relates to a method for preventing or treating influenza virus infection, comprising the step of administering a pharmaceutical composition to a subject.

[0039] In the present invention, the term "subject" includes animals or humans having an influenza virus infection whose symptoms can be improved by administration of the pharmaceutical composition of the present invention. By administering the therapeutic composition of the present invention to a subject, influenza virus infection can be effectively prevented and treated.

[0040] In the present invention, the term "administration" means introducing a given substance into a human or animal by any suitable method, and the administration route of the therapeutic composition of the present invention may be orally or parenterally by any conventional route, as long as it can reach the target tissue. In addition, the therapeutic composition of the present invention may be administered by any device that allows the active ingredient to move to target cells.

[0041] The preferred dosage of the pharmaceutical composition of the present invention may vary depending on the patient's condition and weight, the severity of the disease, the dosage form, the route of administration, and the duration of administration, but a person skilled in the art can select it appropriately.

[0042] Another aspect of the present invention relates to the use of a pharmaceutical composition for treating influenza virus infection.

[0043] A further aspect of the present invention relates to the use of an antiviral composition for manufacturing a pharmaceutical for treating influenza virus infection. The antiviral composition comprises xanthan gum or fucoidan as an active ingredient. [Effects of the Invention]

[0044] The present invention's antiviral composition against influenza virus, comprising xanthan gum or fucoidan as an active ingredient, exhibits preventive and therapeutic effects against influenza virus and reduces the development of tissue lesions and inflammatory cell infiltration caused by influenza virus infection. Therefore, it can be used in the development of antiviral agents for preventing or treating infections caused by influenza virus.

[0045] The effects of the present invention are not limited to those described above, but should be understood to encompass all effects that can be inferred from the detailed description of the present invention and the structure of the invention as described in the claims. [Brief explanation of the drawing]

[0046] [Figure 1] This figure shows the observed results of weight changes when the test substance was administered prior to influenza virus infection. [Figure 2] This figure shows the results of histopathological evaluations of patients who were administered the test substance prior to influenza virus infection, presented in a scored format. [Figure 3] This figure shows the results of measuring the viral titer in the lungs, measured by the copy number of the M2 gene and the polPA gene, after administering the test substance prior to influenza virus infection. [Figure 4] This figure shows the results of measuring the viral titer in the nasal cavity, measured by the copy number of the M2 gene and the polPA gene, after administering the test substance prior to influenza virus infection. [Figure 5] This figure shows the observed results of weight changes after administering the test substance following influenza virus infection. [Figure 6] This figure shows the results of histopathological evaluations of patients who were administered a test substance after influenza virus infection, presented in a scored format. [Figure 7] This figure shows the results of measuring the viral titer in the lungs after administering the test substance following influenza virus infection, using the copy number of the M2 gene and the polPA gene. [Figure 8] This figure shows the results of measuring the viral titer in the nasal cavity after administering the test substance following influenza virus infection, using the copy number of the M2 gene and the polPA gene. [Figure 9] This figure shows the observed results of weight changes according to xanthan gum content when the test substance was administered prior to influenza virus infection. [Figure 10]This figure shows, in a scored format, the results of histopathological evaluations based on xanthan gum content when the test substance was administered prior to influenza virus infection. [Figure 11] This figure shows the results of measuring viral titers in the lungs according to the xanthan gum content when the test substance was administered prior to influenza virus infection. [Figure 12] This figure shows the results of measuring viral titers in the nasal cavity according to the xanthan gum content when the test substance was administered prior to influenza virus infection. [Modes for carrying out the invention]

[0047] The present invention will be described in detail below with reference to examples. However, the following examples are for illustrative purposes only, and the present invention is not limited to these examples.

[0048] Preparation Example 1. Preparation of the test substance The test substance was prepared according to the composition shown in Table 1 below. Specifically, benzoic acid, citric acid, and sorbitol (D-sorbitol) were added to approximately 0.8 mL of purified water and stirred to dissolve. Then, according to the composition of each embodiment shown in Table 1 below, HPMC, xanthan gum, bentonite, and fucoidan were weighed and added as main components, and the mixture was stirred for more than 2 hours to dissolve. After that, purified water was added to make a total volume of 1 mL.

[0049] [Table 1]

[0050] Comparative Example 1. Combination of excipients A negative control substance was prepared by mixing benzoic acid, citric acid, sorbitol, and purified water, as a combination of excipients that did not contain the components HPMC, xanthan gum, bentonite, and fucoidan. The content of each excipient was the same as that shown in Table 1 above. The negative control substance prepared in this way was used as Comparative Example 1.

[0051] Comparative Example 2: Oseltamivir Oseltamivir was purchased from Sigma-Aldrich as one of the positive control substances and used as Comparative Example 2.

[0052] Oseltamivir, sold under the brand name Tamiflu, is an antiviral drug used to treat infections caused by the influenza virus, and is also used for preventative purposes. In particular, it is effective in inhibiting the H1N1 variant, which causes so-called novel influenza caused by mutations in the influenza A virus.

[0053] Comparative Example 3. Cold Mask Nasal Spray Cold Mask nasal spray (Hanmi Pharmaceutical Co., Ltd.) was purchased as one of the positive control substances and used as Comparative Example 3.

[0054] Experimental Example 1: Confirmation of preventive effect against viruses SPF (Specific Pathogen Free) female C57BL / 6 mice (7 weeks old, Samtako, South Korea) were used. The animals were housed in a 12-hour light / dark cycle under conditions of 23±3°C and 55±15% relative humidity, and each test group was configured to ensure a uniform distribution of average body weight.

[0055] In addition, the H1N1 influenza A virus was inoculated into developing fertilized eggs, and the culture medium was collected after 48 hours. The collected virus was then quantified, and the LD (Low-Dose) was determined. 50 The following was calculated: 1 LD of the prepared virus solution. 50 The solution was diluted to the desired consistency, and 30 μl of the diluted solution was used.

[0056] Using the animal models described above, the composition of each test group and the dosage of each test substance were set as shown in Table 2 below. G1 was the normal control group, and G2 was the infected control group. Comparative Examples 1-3 corresponded to groups G3-G5, respectively, and the substances in Examples 1-4 corresponded to groups G6-G9. Administration of each substance began 2 hours before viral infection and was administered twice a day (bis in die: BID) at 8-hour intervals for 7 days.

[0057] Comparative Example 2 was administered orally (per oral: PO), while Comparative Examples 1 and 3, as well as Examples 1-4, were administered intranasally (intranasal administration: IN). The test animals were restrained using the dorsal skin fixation method. In the case of Comparative Example 2, the test substance was directly administered into the stomach using an oral gastric tube. In the cases of Examples 1, 2, and 4, the test substance was administered into the nasal cavity by spraying, and in the case of Example 3, the test substance was shaken well before administration to form a suspension, and then administered into the nasal cavity by dropwise injection using a micropipette.

[0058] [Table 2]

[0059] 1-1. Measuring weight The body weight of each animal was measured once a day using an electronic balance. As shown in Table 3 and Figure 1 below, the results showed that groups G4 and G5, which were administered with the positive control substance, and groups G6 to G9, which were administered with the test substances from Examples 1 to 4, showed significantly higher levels after 3 DPI (3 days post-infection) compared to the control group G3.

[0060] Infection with the influenza virus leads to excessive cell infiltration in the respiratory tract, production of inflammatory mediators such as IFN, and consequently, weight loss. Administration of the test substances in Examples 1-4 of the present invention was confirmed to alleviate weight loss, one of the symptoms of influenza infection.

[0061] [Table 3]

[0062] 1-2. Histopathological examination The effect of administering the test substance of the present invention on influenza-induced inflammation and tissue damage is measured against influenza A virus (H1N1) at 1 LD50. 50 The study evaluated C57BL / 6 mice infected with the specified titer. The viral infection study design and test groups were as shown in Table 2 above. Except for G1, animals in the remaining test groups were euthanized at a rate of 5 animals per group per day on days 3, 5, and 7 from the date of viral inoculation, and necropsy was performed. In the case of G1, all animals were euthanized and necropsy was performed on day 5 from the date of viral inoculation. Animals other than those scheduled for necropsy on the specified dates were observed until day 7 from the date of viral inoculation.

[0063] During the autopsy, the nasal cavity was swabbed using a cotton swab moistened with PBS, and the swab was frozen and stored at -70°C until analysis for viral titer measurement.

[0064] The excised lung was divided into two sections, including the lesion site. The portion for histopathological examination was fixed with 10% neutral buffered formalin (NBF), while the portion for viral titer measurement was kept frozen at -70°C until analysis.

[0065] Tissue fixed with 10% NBF was subjected to common tissue processing procedures such as trimming, dehydration, paraffin embedding, and sectioning to prepare specimens for histopathological examination. Hematoxylin and eosin (H&E) staining was then performed, and histopathological changes were observed using a light microscope (Olympus BX53, Japan). Lung lesions were observed and evaluated by scoring according to the degree of inflammatory cell infiltration. The evaluation criteria are shown in Table 4 below.

[0066] [Table 4]

[0067] As a result, as shown in Table 5 and Figure 2 below, the scores for G4 and G7 were significantly lower than those for G2 and G3 on day 3 post-infection (3DPI). Furthermore, it was confirmed that the scores of the G4 and G5 groups, which were administered the positive control substance, and the G6-G9 groups, which were administered the respective test substances from Examples 1-4, were lower than those of G2 and G3 up to day 7 post-infection.

[0068] [Table 5]

[0069] These results indicate that administering the test substances of Examples 1-4 of the present invention for preventive purposes can reduce lung tissue damage and lesion formation caused by the influenza virus.

[0070] 1-3. Measurement of viral titer The amount of virus present in lung tissue collected 5 days after viral infection was quantified by real-time qRT-PCR. A specific amount of Wizol® (WizbioSolution, Seongnam, Korea) reagent was added to the collected lung tissue, the tissue was homogenized using tissue grinding beads, and total RNA was extracted from the supernatant. The extracted total RNA was quantified using Nanodrop (NanoDrop2000, Thermo Scientific). Using 1 μg of total RNA, cDNA was synthesized with the WizScript® cDNA synthesis kit (WizbioSolution), and then an appropriate amount of the cDNA reaction product was subjected to real-time qPCR using WizPure® qPCR Master-UDG (WizbioSolution) reagent according to the manufacturer's instructions. The viral genes present in the lung tissue were quantified using primers and probes for M2 (matrix protein 2) and polPA (polymerase PA) specific to influenza virus (A / Puerto Rico / 8 / 1934 (H1N1)). The amount of viral RNA present in lung tissue was expressed as the number of viral genes per 1 ng of total RNA. The sequences of each primer and probe are shown in Table 6 below.

[0071] [Table 6]

[0072] Subsequently, a standard curve was created, and the amount of virus remaining in the sample was quantitatively analyzed by applying each of the above genes to this curve.

[0073] As a result, as shown in Figure 3, the reduction of M2 and polPA genes in the lungs when the test substances of Examples 1 to 4 of the present invention were administered was not significant. In contrast, in the nasal cavity, administration of the test substances of Examples 1 to 4 of the present invention resulted in a decrease in M2 and polPA genes, as shown in Figure 4, indicating a preventive effect against influenza virus infection via the nasal cavity. In particular, a more significant reduction in viral titer was observed in groups G6, G7, and G9, which were administered Examples 1, 2, and 4.

[0074] Experimental Example 2. Confirmation of therapeutic effect against viruses An animal model was constructed in the same manner as in Experimental Example 1, and infected with the influenza A H1N1 virus. However, to confirm the therapeutic effect, the test substance was administered after viral infection.

[0075] Specifically, the composition of each test group and the dosage of each test substance were as shown in Table 7 below. G1 was the normal control group, and G2 was the infected control group. Comparative Examples 1-3 corresponded to groups G3-G5, respectively, and the substances in Examples 1-4 corresponded to groups G6-G9. Administration of each substance began 24 hours after viral infection and was administered twice a day (bis in die: BID) at 8-hour intervals for 6 days. The administration method for each route of administration was the same as in Experimental Example 1.

[0076] [Table 7]

[0077] 2-1. Measuring Weight The body weight of each animal was measured once a day using an electronic balance. As shown in Table 8 and Figure 5 below, the G6-G9 groups, which were administered each test substance from Examples 1-4, showed significantly higher levels on day 5 after infection (5 DPI) compared with the control group G3.

[0078] These results confirm that even when the test substances of Examples 1 to 4 of the present invention are administered after infection, weight loss, one of the symptoms of influenza infection, can be alleviated.

[0079] [Table 8]

[0080] 2-2. Histopathological examination Similar to Experimental Example 1, Parts 1-2, five animals per group were euthanized and necropped on days 3, 5, and 7 from the date of virus inoculation. In the case of G1, all animals were euthanized and necropped on day 5 from the date of virus inoculation for histopathological examination. Subsequently, they were evaluated using the same scoring criteria as in Table 4 above.

[0081] As a result, as shown in Table 9 and Figure 6 below, at all autopsy time points, the degree of inflammatory cell infiltration in the G6-G9 groups administered with each test substance from Examples 1-4 tended to be lower overall than that of G3. At 5 days (5DPI) and 7 days (7DPI) post-infection, the scores for G4, G7, and G9 were significantly lower than those for G2 and G3. In particular, the degree of inflammatory cell infiltration in G7 and G9 was found to be remarkably low.

[0082] [Table 9]

[0083] These results demonstrate that even when the test substances of Examples 1 to 4 of the present invention are administered after influenza virus infection, they exhibit therapeutic effects against the influenza virus, thereby reducing lung tissue damage and lesion formation caused by the influenza virus.

[0084] 2-3. Measurement of viral titer Similar to Experimental Example 1, parts 1-3, RNA was extracted from lung and nasal swab samples, and the amount of residual virus was quantitatively analyzed by detecting the M2 gene and polPA gene using qRT-PCR.

[0085] As a result, as shown in Tables 10, 11, and Figure 7 below, in the lung tissue of animals necropped at 7 DPI, both the M2 gene and the polPA gene were found to be reduced in the G5 positive control group and in the test substance administration groups G7 and G9 compared to the G3 control group. In addition, in the G6 group, both the M2 gene and the polPA gene were found to be reduced in the lung tissue of animals necropped at 5 DPI compared to the G3 control group.

[0086] [Table 10]

[0087] [Table 11]

[0088] In addition, as shown in Tables 12, 13, and Figure 8 below, in nasal cavity samples taken from animals autopsied in 7DPI, it was confirmed that both the M2 gene and the polPA gene were reduced in the G5 positive control group and the test substance administration groups G6, G7, and G9 compared to the G3 control group.

[0089] [Table 12]

[0090] [Table 13]

[0091] From the results above, it was confirmed that administering the test substances of Examples 1, 2, and 4 of the present invention reduced the viral titer, thus demonstrating their effectiveness in treating influenza virus infection.

[0092] Experiment Example 3. Confirmation of antiviral effect according to xanthan gum content. To confirm the antiviral effect depending on the xanthan gum content, an animal model was constructed in the same manner as in Experimental Example 1, and influenza A H1N1 virus was administered. The specific composition of each test group and the setting of the dosage of each test substance are shown in Table 14 below.

[0093] [Table 14]

[0094] 3-1. Measuring Weight The weight of each animal was measured once a day using an electronic balance. As shown in Table 15 and Figure 9 below, the test groups G5-G7, which were administered xanthan gum, all showed higher levels than the G3 group. In other words, it was confirmed that weight loss, one of the symptoms of influenza infection, can be alleviated even when xanthan gum is administered at low, medium, or high concentrations.

[0095] [Table 15]

[0096] 3-2. Histopathological examination Similar to Experimental Examples 1-2, six animals per group were euthanized and necropped on days 3, 5, and 7 from the date of virus inoculation, and in the case of G1, all animals were euthanized and necropped on day 5 from the date of virus inoculation for histopathological examination. Subsequently, they were evaluated using the same scoring criteria as in Table 4 above.

[0097] As a result, as shown in Table 16 and Figure 10 below, the degree of inflammatory cell infiltration in groups G5-G7, administered with each of the test substances from Examples 5-7, was lower than that in group G3 at all autopsy time points. In particular, the degree of inflammatory cell infiltration in group G5, administered with a low concentration of xanthan gum, was found to be remarkably low.

[0098] [Table 16]

[0099] These results indicate that xanthan gum can reduce lung tissue damage and lesion formation caused by the influenza virus across its entire concentration range.

[0100] 3-3. Measurement of viral titer Similar to Experimental Example 1, parts 1-3, RNA was extracted from lung and nasal swab samples, and the amount of residual virus was quantitatively analyzed by detecting the M2 gene and polPA gene using qRT-PCR.

[0101] As a result, as shown in Tables 17, 18, and Figure 11 below, in the lung tissue of animals autopsied at 3DPI and 5DPI, it was confirmed that both the M2 gene and the polPA gene were reduced in the test substance administration groups G5-G7 compared to the G3 control group.

[0102] [Table 17]

[0103] [Table 18]

[0104] In addition, as shown in Tables 19, 20, and Figure 12 below, in nasal cavity samples taken from animals that underwent autopsy at 7DPI, it was confirmed that both the M2 gene and the polPA gene were reduced in the test substance administration groups G5-G7 compared to the G3 control group.

[0105] [Table 19]

[0106] [Table 20]

[0107] The results above confirm that xanthan gum reduces the titer of the influenza virus across the entire concentration range, and therefore it is effective in preventing and / or treating influenza virus infection.

[0108] Experimental Example 4. Statistical Analysis The results of each of the above experimental examples were analyzed using either a parametric or nonparametric multiple comparison procedure, assuming normality of the data.

[0109] In the case of parametric multiple comparisons, the normality of the data was assumed, and the data was tested using parametric one-way analysis of variance (one-way ANOVA). If the result was significant, Dunnett's multiple comparison test was used for post-hoc analysis to analyze significant differences between test groups. In the case of nonparametric multiple comparisons, the data was tested using the Kruskal-Wallis H test. If the result was significant, the Mann-Whitney U test was used for post-hoc analysis to analyze significant differences between test groups. Statistical analysis was performed using Prism 9.4.1 (GraphPad Software Inc., San Diego, California, USA), and a p-value of less than 0.05 was considered statistically significant.

[0110] The above description of the present invention is provided for illustrative purposes only, and it will be understood by those skilled in the art to the extent of the invention that it can be easily modified into other specific forms without altering the technical idea or indispensable features of the invention. Therefore, it should be understood that the above embodiments are illustrative and not limiting in all respects. For example, each component described in the singular form may be implemented in a distributed form, and similarly, each component described as distributed may be implemented in an integrated form.

[0111] The scope of this invention is expressed by the claims set forth below, and the meaning and scope of all variations or modifications derived from the claims and equivalent concepts thereto should be interpreted as being encompassed within the scope of this invention.

Claims

1. An antiviral composition against influenza virus, comprising xanthan gum or fucoidan as an active ingredient.

2. The antiviral composition according to claim 1, wherein the influenza virus is influenza A virus.

3. The antiviral composition according to claim 2, wherein the influenza A virus is of the H1N1 type.

4. The antiviral composition according to claim 1 for immunization against influenza virus infection.

5. A pharmaceutical composition comprising xanthan gum or fucoidan as an active ingredient for preventing or treating viral infections caused by the influenza virus.

6. The pharmaceutical composition according to claim 5, wherein the viral infection caused by the influenza virus is selected from the group consisting of common cold, influenza, sore throat, laryngitis, pharyngitis, rhinitis, bronchitis, asthma, sepsis, and pneumonia.

7. The pharmaceutical composition according to claim 5, for parenteral administration.

8. The pharmaceutical composition according to claim 7, wherein the parenteral administration is intranasal administration or administration into the nasal cavity.

9. The pharmaceutical composition according to claim 8, wherein intranasal or nasal administration is performed in the form of a spray, aerosol, or inhalation.

10. A method for treating influenza virus infection, comprising administering the pharmaceutical composition described in claim 5 to a target.

11. Use of the pharmaceutical composition according to claim 5 for treating influenza virus infection.

12. Use of the antiviral composition according to claim 1 for manufacturing a pharmaceutical product for treating influenza virus infection.

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