JP2011168533A - Anti-influenza virus agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an effective anti-influenza virus agent by using a component originated from a highly safe natural product, and to provide a method for more utilizing a holdfast part of laminaria, especially the holdfast part of cultivated laminaria. <P>SOLUTION: The anti-influenza virus agent contains fucoidan originated from the holdfast part of laminaria, especially the holdfast part of the cultivated laminaria as an active ingredient. The fucoidan can be obtained by extracting the holdfast part of the laminaria. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to an anti-influenza virus agent having an infection-suppressing effect against influenza virus, and in particular, an active ingredient extracted from a kombu temporary root part that has been conventionally discarded without being used, particularly a cultured kombu temporary root part Is used as an anti-influenza virus agent.

  Influenza is a viral respiratory infection caused by influenza virus. The virus primarily infects respiratory epithelial cells, causing acute respiratory damage, with symptoms such as sudden fever, headache, and joint pain. Infection that spreads to the lower respiratory tract can cause severe pneumonia and can lead to death in high-risk patients such as the elderly, pregnant women, and patients with underlying diseases.

  Influenza viruses are enveloped RNA viruses belonging to the Orthomyxo family, and are classified into A, B, and C types due to their antigenic differences, but there are mainly new serotypes in A and B types, particularly A type. The epidemic is repeated every year by viruses that appear and have different antigenicity. Vaccination is an effective means to suppress the epidemic of influenza viruses, but it is difficult to prevent with vaccines alone because of the frequent changes in the antigenicity of the virus.

  Influenza occurs when the virus released by the droplets infects and proliferates in the mucosal epithelial cells of the human upper respiratory tract. To control infection, cell adsorption, membrane fusion, transcription and replication of viral genomic RNA, Antiviral drugs have been developed targeting growth processes such as budding of virus particles. Currently, antiviral drugs such as oseltamivir (Tamiflu) and zanamivir (Relenza), which inhibit the function of neuraminidase during virus emergence, are used for treatment of patients suffering from influenza. Viral drugs have problems with side effects and the emergence of resistant virus strains.

  In addition, various anti-influenza virus drugs using substances derived from natural products have been reported from the viewpoint of safety. For example, there are an influenza preventive / therapeutic agent containing a Sendan extract (Patent Document 1), an anti-influenza virus agent (Patent Document 2) containing various plant extracts as active ingredients, and the like.

  On the other hand, the inventors of the present invention have previously studied a method for using a temporary root portion that has been previously costly discarded in cultured kelp, and found that it can be used as a food material (Patent Document 3). That is, the temporary root part of the cultured kombu, unlike the kombu leaf that has been used as a food for a long time, has been found to contain a large amount of potassium and dietary fiber, food useful for reducing salt and dietary fiber supplementation The material is provided. Further, it has also been found that the temporary root portion of the cultured comb contains an effective antitumor component (Patent Document 4). However, the adiponectin production promoting action of fucoidan extracted from the kombu temporary root has not been known so far.

  The kombu is a dried product of the leafy bodies of the seaweed belonging to the genus Kombu in the family of the brown algae, and is usually commercialized except for the tip, lower end and temporary root of the leafy body. Moreover, what is sold as a root kelp is not the root of the kombu but the lower end of the frond close to the kombu temporary root. In natural kombu, the temporary root part is strongly attached to the bedrock, and it is difficult to separate it from rocks and earth and sand during collection. In cultured kelp, the rope with fertilized fertilized spores is tied to a thick rope and cultivated in the sea for easy collection. Prior to the invention by the present inventors, dumping of the cultivated kelp into the sea caused the problem of contamination, so it was landed and disposed of by landfill.

JP 2007-254319 A JP 2004-59463 A JP 2000-32963 A JP 2003-81862 A

  An object of the present invention is to provide an effective anti-influenza virus agent using a highly safe component derived from a natural product. Moreover, the further usage method of the temporary root part of a kombu, especially a cultured kombu temporary root part is provided.

  In the process of studying the use of cultured kombu temporary roots, the present inventors focused on fucoidan among the components derived from cultured kombu temporary roots, confirmed the anti-influenza virus effect in mice administered this, and Completed.

That is, the present invention is as follows.
1. An anti-influenza virus agent comprising fucoidan derived from a kombu temporary root part as an active ingredient.
2. 2. The anti-influenza virus agent according to 1 above, wherein fucoidan is obtained by extraction from a kombu temporary root.
3. 3. The anti-influenza virus agent according to 1 or 2 above, wherein the comb is a cultured comb.

  The anti-influenza virus agent of the present invention is excellent in anti-influenza virus action, and is excellent in safety because it uses ingredients derived from food materials whose safety has been confirmed. In addition, the present invention is also useful in that it has found another method of using a kombu temporary root, particularly a cultured kombu temporary root.

It is a figure which shows the name of each site | part of a comb, and its position. The result of the preliminary experiment of the influenza virus infection in a mouse | mouth is shown. It is a figure which shows the weight change of the mouse | mouth inoculated with the influenza virus. The survival curve of a mouse | mouth in a fucoidan administration group derived from a kombu temporary root part and a control group is shown. It is a figure which shows the virus titer in a lung. The change of the amount of cytokine production in a kobu temporary root part origin fucoidan administration group and an object group is shown.

  The fucoidan used in the present invention is a fucoidan derived from a kombu temporary root, particularly preferably a cultured kombu temporary root. Fucoidan is a general term for sulfated polysaccharides mainly composed of fucose contained in seaweed and the like, and there are differences in components and structures depending on the raw materials. Fucoidan obtained from the kombu temporary root portion is composed of L-fucoidan and Ga-fucoidan. L-fucoidan is a fucoidan also contained in the frond, and contains fucose and galactose as constituent sugars. Ga-fucoidan is a fucoidan peculiar to a temporary root part, and is mainly composed of fucose as a sugar, and is composed of mannose, galactose, xylose, and glucose. The kombu temporary root-derived fucoidan contains L-fucoidan and Ga-fucoidan in a ratio of 1: 1 to 2: 1.

  The fucoidan derived from the kombu temporary root used in the present invention is different from fucoidan derived from other seaweeds such as mekabu and Okinawa mozuku, and fucoidan derived from a frond in terms of constituent sugar. In particular, Ga fucoidan is not present in other seaweeds or foliar bodies, and is characterized by being present only in the kombu temporary root.

  As for fucoidan obtained from mekabu, two types of Fr-I and Fr-II are separated, and the constituent sugars excluding trace components are fucose, galactose, arabinose and xylose in Fr-I, and in Fr-II Fucose and galactose. Fucoidan obtained from Okinawa mozuku is composed of fucose and glucuronic acid. Fucoidan obtained from gagome kombu (foliate) includes F-fucoidan composed of fucose, U-fucoidan composed of fucose, mannose and glucuronic acid, and G fucoidan composed of galactose and fucose.

  The kombu temporary root used to obtain fucoidan in the present invention refers to a portion of the kombu portion shown in FIG. 1 that mainly includes temporary root (holdfast) and may contain a stipe (previously referred to as stipe). Is the part that was discarded without being used for food. Ordinary kombu products are manufactured from the part excluding the tip and bottom of the frond, and the bottom of the frond is called root kelp. In the present invention, the type of the comb that uses the temporary root includes macomb, honey comb, resilib, and the like, and is not particularly limited, but is preferably a cultured comb because it is easy to collect.

The fucoidan derived from the kombu temporary root part used in the present invention may be a crude fucoidan extracted from the kombu temporary root part or a purified fucoidan.
The method for obtaining fucoidan from the kombu temporary root is not particularly limited, and known fucoidan preparation methods can be used. Alternatively, an extraction operation using an aqueous solution containing a divalent cation such as calcium chloride, and a method combining these are applied. Further, in order to obtain crude fucoidan from the extract, inorganic salts such as sodium are removed by aggregation with a lower alcohol such as ethanol or by using an ultrafilter.

  Further, the crude fucoidan may be purified by a purification means such as chromatography. Further, the obtained fucoidan may be separated into Ga-fucoidan or L-fucoidan by a method such as ion exchange or gel filtration chromatography.

Preferably, after drying the kombu temporary root, it is pulverized using ordinary powdering means such as pulverizing with a pulverizer, and fucoidan is extracted from the resulting kombu temporary root powder with an inorganic acid such as hydrochloric acid. A preferred embodiment of the fucoidan extraction and purification method is as follows.
(Extraction of water-soluble components)
Add 10 to 13 times the amount of water adjusted to pH 2.0 to 2.5 with acid such as hydrochloric acid to the powder obtained by drying and crushing cultured kombu temporary roots, and extract at 70 to 80 ° C for about 2 to 3 hours. Do. The extraction operation is repeated 2-3 times, and the supernatant is collected and centrifuged. The obtained supernatant is filtered with a filter paper or the like to obtain a clarified liquid. In order to facilitate the subsequent operation, the clarified liquid is concentrated under reduced pressure using an evaporator. When concentrating, since precipitation will contain crude fucoidan, it is desirable to prevent precipitation as much as possible. The concentrated solution is centrifuged to remove the precipitate.
(Extraction of crude fucoidan)
2 to 3 times the amount of lower alcohol such as ethanol is added to the clarified liquid obtained above to cause precipitation, and the precipitate obtained by centrifugation is recovered and dried. This is about 7 to 10 times the amount of hydrochloric acid or the like. Dissolve in water adjusted to pH 2.0-2.5 with acid and let stand for about 6-12 hours. The solution obtained by suction filtration is concentrated, and 2 to 3 times the amount of lower alcohol such as ethanol is added to cause precipitation, and the precipitate obtained by centrifugation is collected and dried. This operation is repeated about 1 to 2 times to obtain a crude fucoidan.

Another method is to obtain crude fucoidan by removing sodium and the like present in the clarified liquid from the clarified liquid obtained above using an ultrafilter having a molecular weight of 10,000.
(Purification of fucoidan)
The dried precipitate (crude fucoidan) is purified by a method such as chromatography. Preferably, purified fucoidan derived from a kombu temporary root can be obtained by liquid chromatography using an anion resin.

  The fucoidan obtained as described above was able to improve the survival rate for mice inoculated with influenza virus, as demonstrated in the following test examples. Specifically, fucoidan derived from the kombu temporary root was orally administered before virus inoculation, and the survival rate of the mice was examined. As a result, a significant difference was found compared to the subject group. Therefore, by administering the kombu temporary root part-derived fucoidan of the present invention, it can be expected to have a preventive effect or prevent aggravation against influenza virus infection.

  The anti-influenza virus agent of the present invention contains fucoidan derived from kombu temporary root as an active ingredient, and if necessary, a substance commonly used in formulation, such as excipients, binders, disintegrants, diluents, suspensions. Adjuvants such as turbidizers, emulsifiers, stabilizers, flavoring agents, and flavoring agents may be added and formulated into appropriate forms such as tablets, granules, powders, and troches. As an administration method, oral administration is preferable, and the dose is preferably about 10 to 100 mg / day of body weight per kg of an adult as fucoidan.

  In addition, since the active ingredient of the anti-influenza agent of the present invention is derived from natural products and has high safety, it can be used by adding to foods or as oral compositions such as nutritional supplements and health foods. it can.

  When it is set as an oral composition, it can manufacture by mix | blending additives, such as an excipient | filler conventionally used in the foodstuff field, a sweetener, a fragrance | flavor, and a coloring agent, with the fucoidan obtained as mentioned above. This composition can be formulated into various forms such as powders, granules, tablets, capsules, drinks, jelly and the like by conventional methods, and can be taken orally, for example, as a dietary supplement or health food. Moreover, this invention oral composition may mix | blend fucoidan with normal food-drinks.

  In order to describe the present invention in more detail below, examples are shown, but the present invention is not limited thereto. Below, the case where a cultured kombu temporary root part is used as a kombu temporary root part is demonstrated concretely.

(Reference Example 1)
(Extraction of fucoidan from cultured kombu temporary root)
The dried cultured kombu temporary root was coarsely pulverized with a crusher (cutter mill), and then finely powdered with a fine crusher (sample mill) to obtain a cultured kombu temporary root powder. To 500 g of the cultured kombu temporary root powder, 5000 mL of water was added, adjusted to pH 3 with hydrochloric acid, and extracted at 75 ° C. for 3 hours. After repeating this operation three times, the solid content was removed, and centrifugation (3000 rpm, 20 minutes) was performed. The obtained supernatant was filtered to obtain a clarified liquid. In order to facilitate the subsequent operation, the clarified liquid was concentrated under reduced pressure until the liquid volume became about one-tenth so as to prevent precipitation. The concentrated solution was centrifuged to remove the precipitate.
(Extraction of crude fucoidan)
Two times the amount of ethanol was added to the clear liquid obtained above to cause precipitation. After centrifugation, the precipitate was dried, dissolved in about seven times the amount of water, and adjusted to pH 2 with hydrochloric acid. And left to stand for about 1 hour. The solution obtained by suction filtration was concentrated, and twice the amount of ethanol was added again to cause precipitation. After centrifugation, the precipitate was dried. This operation was repeated about twice to obtain 16.3 g of crude fucoidan.
(Reference Example 2)
Analysis of fucoidan derived from cultured kombu temporary roots
(1) Separation of Ga-fucoidan and L-fucoidan 4.5 g of the crude fucoidan obtained as described above was dissolved in 500 mL of water and mounted on a column packed with 500 mL of DEAE-TOYOPEARL 650M. After washing with 500 mL of water, fucoidan was eluted with 500 mL of 0.5 M NaCl (Ga-fucoidan was extracted) and further with 500 mL of 1.0 M NaCl (L-fucoidan was extracted). When flowing the eluent, 20 mL of the liquid eluted from the column outlet was collected by a fraction collector, and a part of each fraction was sampled and analyzed by HPLC. The HPLC analysis conditions are as follows. Column: Asahipak GS-520H, detector: differential refraction, eluent: 0.3 M NaNO ₃ , flow rate: 1.0 mL / min, column temperature: 60 ° C. Fractions having peaks of each fucoidan were collected, concentrated with an evaporator, dialyzed with a dialysis membrane having a molecular weight cut off of 1000 for 25 hours, and further concentrated. The resulting concentrated solution was lyophilized.
(2) Constituent sugars in fucoidan Each fucoidan (30 mg) was dissolved by adding 10 mL of 1 mol / L sulfuric acid and hydrolyzed (110 ° C., 2.5 hours) in an autoclave. After neutralization with barium carbonate (neutralization was confirmed with pH test paper), centrifugation (3000 rpm, 20 minutes) was performed. The supernatant was filtered, the solvent was distilled off with an evaporator, and further dried with an electric dryer at 55 ° C. for 3 hours. Thereafter, water was added to make a constant volume of 4 mL, and this was used as a sample solution.

Separately, 10 mg each of glucose, xylose, galactose, fucose and mannose was weighed, and water was added to make up a constant volume of 8 mL to obtain a standard solution.
For 20 μL of the standard solution and the sample solution, the peak height of each sugar was measured by high performance liquid chromatography under the following conditions, and the concentration of each sugar was calculated from the peak ratio of the standard solution and the sample solution.

Column: Polysphere CHPB
Detector: Differential refraction Column temperature: 80 ° C
Flow rate: 0.4 mL / min Eluent: H ₂ O
Table 1 shows the analysis results of the constituent sugars of each fucoidan.
(3) Uronic acid in fucoidan
Dissolve 10 mg each of Ga-fucoidan and L-fucoidan in water, and then adjust the volume of Ga-fucoidan solution to 50 mL and L-fucoidan solution to 10 mL.

  Add 1 mL of the sample solution to a 9 mL screw tube, add 5 mL of Reagent 1 (0.57 g of sodium tetraboride dissolved in 60 mL of concentrated sulfuric acid) while cooling, and heat in a boiling water bath for 10 minutes. After cooling to room temperature, 0.2 mL of Reagent 2 (0.025 g of carbazole dissolved in 20 mL of 99.5% ethanol) is added and heated again in a boiling water bath for 15 minutes. After cooling to room temperature, the absorbance is measured at 530 nm and quantified from a calibration curve prepared with sodium glucuronate.

Table 1 shows the measurement results of uronic acid of each fucoidan.
(4) Sulfate groups in Ga-fucoidan and L-fucoidan 10 ml of 1 mol / L hydrochloric acid was added to 10 mg of each fucoidan and dissolved, and then hydrolyzed (105 ° C., 5 hours) in an autoclave. After cooling, water was added to make a constant volume of 100 mL to obtain a sample solution. Separately, 147.9 mg of sodium sulfate was weighed and water was added to make exactly 100 mL (1000 ppm SO ₄ standard solution). 1 mL, 3 mL, and 5 mL of the prepared standard solutions were taken, and water was added to make exactly 100 mL, which were 10 ppm, 30 ppm, and 50 ppm SO ₄ standard solutions, respectively.

For 10 μL of the sample solution and standard solution, the peak height of sulfate groups was measured by high performance liquid chromatography under the following conditions.
A calibration curve was created from the peak height of the standard solution, and the concentration of sulfate groups in the sample solution was determined from the peak height of the sample solution and the calibration curve, and the sulfate group content was calculated.

Column: Shodex IC I-525A
Column temperature: 40 ° C
Eluent: 2.3 mM phthalic acid + 2.5 mM Tris mixed solution Flow rate: 1.5 mL / min Detector: Electric conductivity Table 1 shows the analysis results of sulfate groups of each fucoidan.

(5) Composition of Kombu temporary root-derived fucoidan From the results shown in Table 1, it can be seen that Ga fucoidan specific to fucoidan derived from Kombu temporary root includes galactose, xylose, mannose and glucose as constituent sugars in addition to fucose.
(Reference Example 3)
(Fucoidan extraction from farmed kombu temporary roots)
The dried cultured kombu temporary root was coarsely pulverized with a crusher (cutter mill), and then finely powdered with a fine crusher (sample mill) to obtain a cultured kombu temporary root powder. A sample of 360 g was added to 4680 mL of a 0.25 w / v% citric acid-hydrate solution and stirred. It was immersed in a 75 ° C. water bath and heated for 3 hours after the suspension reached 70 ° C. After cooling, the mixture was centrifuged at 4500 rpm for 20 minutes, and the supernatant was suction filtered.
(Extraction of crude fucoidan)
The clear liquid obtained above was concentrated 10 times with an ultrafilter equipped with a filter having a molecular weight cut off of 10,000. Next, the same amount of water as the concentrated solution was added to concentrate twice, and this operation was performed twice, and then the concentrated solution was heated at 90 ° C. for 20 minutes. After cooling, lyophilization was performed and the weight was measured to obtain 11.7 g of crude fucoidan.

(tablet)
Ingredients Content 1 tablet Fucoidan derived from kombu temporary root 250mg
Sorbitol 200mg
Stearic acid Mg 8mg
Saccharin Na 2mg
460mg total

(Granule)
Ingredients Content per pack Fucoidan derived from kombu temporary root 1000mg
D-mannitol 800mg
Macrogol 200mg
Polyvinylpyrrolidone 50mg
Saccharin Na 5mg
Perfume
Total 2055mg

(Liquid)
Ingredients per serving Fucoidan derived from kombu temporary root 1000mg
10 mg ethyl paraoxybenzoate
Methyl paraoxybenzoate 5mg
Saccharin Na 10mg
Perfume
Appropriate amount of water
50mL total
(Test Example 1)
(1) Preliminary test Before this test, as a preliminary test, the mouse death status was confirmed for 14 days after influenza virus inoculation, and the virus titer used in this test was confirmed.

  Thirty 6-week-old BALB / c (SPF) female mice were inoculated nasally with etheric anesthesia at 10 PFU, 100 PFU, and 1000 PFU / 25 μL of influenza virus A / PR / 8/34 (HINI). Observed daily for life and death.

Since the result shown in FIG. 2 was obtained, 1000 PFU (LD ₅₀ value) is used in this test.
(2) Anti-influenza virus effect test of fucoidan derived from kombu temporary root part The animals used were 75 4-week-old BALB / c (SPF) female mice, and the virus used was influenza virus A / PR / 8/34 ( HINI).

  As the test substance, the fucoidan produced in Reference Example 3 was used, and each test substance was dissolved to the optimum concentration with distilled water for injection. The administration liquid volume was 10 mL / kg, and oral gavage was performed using a syringe and a stomach tube. The dose was 25, 50, 100 mg / kg / day, 3 doses. The test substance was administered once a day from 2 weeks before virus inoculation to 3 days after inoculation, a total of 18 times.

The virus was inoculated by nasal inoculation with the LD ₅₀ value (1000 PFU) obtained in the preliminary test. The group composition was as follows.
Group 1: no infection and no treatment (negative control); n = 15
Group 2: Infected and untreated (positive control); n = 15
Group 3: Infected and administered test substance 25 mg / kg / day; n = 16
Group 4: Infected and administered test substance 50 mg / kg / day; n = 16
Group 5: Infected and administered test substance 100 mg / kg / day; n = 16
Test substance is administered once a day for 2 weeks before the virus administration, then the virus is inoculated once, then the test substance is administered once a day for 3 days, and the survival situation for 10 days after virus infection. It was confirmed. In addition, the administration was stopped because the mice were weakened 4 days after the virus infection, but since this was performed simultaneously for all the groups, it was judged that the survival rate was not affected.

General conditions were observed once daily for all cases. Body weight was measured at the time of arrival, the start of administration of the test substance, and twice a week for all surviving cases.
Results and body weight changes The body weight changes of each group are shown in FIG. As shown in FIG. 3, there was no significant difference between the groups from the start of administration to the day of virus inoculation. In the virus inoculated group (groups 2 to 5), the body weight was drastically decreased as compared with the negative control (group 1), but no significant difference was observed between the groups in the virus inoculated group. In addition, the data after virus inoculation are data only for survival cases.
-Survival rate The survival curve of each group was shown in FIG. As shown in FIG. 4, the mice died from the 5th day to the 8th day after the virus inoculation. Survival rate 10 days after virus inoculation was 26.7% in the control group, 37.5% in the 25 mg / kg administration group, 56.3% in the 50 mg / kg administration group, 62.5% in the 100 mg / kg administration group, and 100 mg / kg administration. The group was significantly different from the control group (χ ² test, P value 0.0451).
(Test Example 2)
In Test Example 1, the anti-influenza virus effect of the kombu temporary root-derived fucoidan was confirmed using the survival rate of mice as an index, and the effect of increasing the survival rate in a dose-dependent manner was observed. In this test example, virus titer and cytokine production were examined as part of the elucidation of the mechanism of this effect.

  The same test substance and mice as those in Test Example 1 (94 mice) were used. The test substance was administered once a day from 2 weeks before virus inoculation to 2 days after inoculation. Each test substance was dissolved to the optimum concentration with distilled water for injection. The administration liquid volume was 10 mL / kg, and oral gavage was performed using a syringe and a stomach tube. The dose was 50 and 100 mg / kg / day.

The test substance was orally administered from 2 weeks before the virus inoculation, the virus (A / PR / 8/34 (HINI)) was inoculated, and the test substance was continuously administered until the second day of the inoculation. A solvent was administered to the negative control group and the positive control group. On the third day of inoculation, blood was collected and the lungs were removed.
Blood fractionated serum and measured INF-γ, IL-4, IL-12 and IL-6 concentrations. For lungs, virus titers and cytokines were measured. In addition, histopathological observation of the lung was performed. The test progress and group composition were as follows.

Results-Intrapulmonary virus titer To measure the virus titer in lung homogenate, a plaque assay was performed using MDCK cells. In Experiment 1, the virus titer was significantly decreased in the high dose group (Table 3).

In Experiment 2, the virus titer 2 days after infection was reduced by 70% in the high dose group (FIG. 5).
-Pathological observation Lungs were removed 1, 2 and 3 days after infection to prepare sections, and changes in lung tissue images due to influenza infection were observed. In the control group, thickening of the alveolar wall 1 day after infection and infiltration of leukocytes into the alveolar space were observed. Two days after the infection, thickening of the alveolar wall and infiltration of leukocytes into the alveolar space became more prominent, and there were portions where severe inflammation was observed 3 days after the infection. In the fucoidan administration group, inflammation was reduced.
Cytokines TNF-α, INF-β, INF-γ, IL-6, IL-4, IL-12, and IL-18 contained in serum and lung homogenate were quantified by ELISA. There was no difference in the amounts of serum INF-γ, IL-6, IL-4, IL-12 (data not shown), but in lung homogenates, TNF-α 1 day after infection and 3 days after infection IL-12 and INF-γ were significantly decreased by the administration of fucoidan, and IL-6 and IL-18 also decreased. INF-β was detected only 2 days after infection in the control group (FIG. 6).

  Influenza viruses primarily infect respiratory epithelial cells and cause acute respiratory damage. When infection spreads to the lower respiratory tract, it becomes severe pneumonia. The protective response at the early stage of viral infection includes damage of infected cells by neutrophils, production of type I IFN from infected cells, and late damage of cells by CTLs and IgG2a by plasma cells.

  From the result of the measurement of the virus titer performed to confirm the anti-influenza virus effect of fucoidan, it was found that fucoidan has an anti-influenza effect. As a result of quantification of pulmonary cytokines, there was a significant decrease in TNF-α, INF-γ, and IL-12 in the fucoidan administration group. In the fucoidan-administered group, the virus titer one day after the infection was reduced as compared to the control group, and it is considered that the amount of cytokine production also decreased.

  Thus, it is considered that the immunity of mice was activated by the administration of the kombu temporary root-derived fucoidan, and the immunity against influenza virus was improved.

Claims (3)

An anti-influenza virus agent containing fucoidan derived from a kombu temporary root as an active ingredient. The anti-influenza virus agent according to claim 1, wherein fucoidan is obtained by extraction from a kombu temporary root. The anti-influenza virus agent according to claim 1 or 2, wherein the comb is a cultured comb.

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