TWI724099B - Composition for improving or preventing herpes virus infection - Google Patents

Abstract

The purpose of the present invention is to provide a composition for improving or preventing herpes virus infection, so that the herpes virus infection model can ingest bifidobacteria. As a result, it can be seen that the amount of virus is reduced, and the development of infection symptoms is suppressed. Furthermore, it was found that even if the immune function of the herpes virus infection model is reduced, its inhibitory effect is not affected. Therefore, bifidobacteria are also effective in preventing the recurrence of herpes virus infection caused when the immune function of the host is reduced.

Description

Composition for improving or preventing herpes virus infection

The present invention relates to a composition for improving or preventing herpes virus infection. More specifically, it relates to a composition containing bifidobacteria as an effective ingredient for improving or preventing herpes virus infection.

Herpes virus infection is a disease caused by herpes virus infection, including herpes labialis caused by herpes simplex virus type 1 (HSV-1) infection, and genital herpes caused by herpes simplex virus type 2 (HSV-2) infection. As mentioned above, these diseases are caused by various herpes viruses, but they are the same in terms of latent infection and recurrence. That is, it is known that the herpes virus lurks in the ganglia after the initial infection of the body surface and recurs when the immune function of the host decreases due to stress or the like. In addition, nucleic acid analogues such as acyclovir and valacyclovir are used for the treatment of herpes virus infections (Non-Patent Documents 1 to 3), and furthermore, it has been approved to continue to administer the infection to the infected person in order to prevent recurrence . However, for these treatment methods, some side effects have been reported, and the high drug price has become a problem in terms of physical and economic burden on patients. Furthermore, when the treatment is continued for a long time by continuing the administration, the herpes virus is likely to acquire drug resistance. Therefore, it is required to replace the medical treatment of nucleic acid analogs. Therefore, it is required to explore and develop cheap and safe substances for improving or preventing herpes virus infections, but the current situation is that such substances have not yet been obtained. In addition, in recent years, intestinal bacteria such as bifidobacteria have verified the preventive effect of diseases or the effect of improving disease symptoms, etc., and tried to use them as safe drugs or foods. However, although there have been reports of symptom-improving effects for various diseases for bifidobacteria, etc., no examples of application in the treatment of herpes virus infections have been reported. [Prior Art Document] [Non-Patent Document] [Non-Patent Document 1] S. E Straus, H et al., N. Engl. J. Med., 1984, Volume 310, pages 1545-1550 [Non-Patent Document 2] JM Douglas et al., N. Engl. J. Med., 1984, volume 310, pages 1551 to 1556 [Non-Patent Document 3] LG Kaplowitz et al., JAMA, 1991, volume 265, pages 747 to 751

[Problems to be Solved by the Invention] The present invention was completed in view of the above-mentioned problems in the prior art, and the purpose is to find an inexpensive substance that is effective for improving or preventing herpes virus infection and has high safety. A further object is to provide a composition for improving or preventing herpes virus infection containing the substance as an active ingredient. [Technical Means to Solve the Problem] In order to solve the above-mentioned problems, the inventors studied the effectiveness of bifidobacteria in animal models of herpes virus infection. Specifically, the model mouse was orally ingested Bifidobacterium longum (BR-108 strain), which is an example of Bifidobacterium, to evaluate the amount of virus in the mouse and the degree of symptoms. As a result, it can be seen that by ingesting bifidobacteria, the amount of virus is reduced, and the development of infection symptoms is suppressed. In addition, it is also known that the antiviral activity of the bifidobacteria is persistent. Furthermore, it was found that even if the immune function of the model mice is reduced, the inhibitory effect is not much affected. Therefore, bifidobacteria are also effective in preventing the recurrence of herpes virus infection caused when the immune function of the host is reduced. Thus, the present invention has been completed. In more detail, the present invention provides the following inventions. (1) A composition for improving or preventing herpes virus infection, which contains bifidobacteria as an active ingredient. (2) The composition according to (1), wherein the above-mentioned bifidobacterium is Bifidobacterium longum. (3) The composition according to (1) or (2), wherein the aforementioned herpes virus infection is an infection caused by herpes simplex virus type 2. (4) The composition according to any one of (1) to (3), which is a composition for oral ingestion. Furthermore, like the strain BR-108 described later, Bifidobacterium is a dominant bacteria in the flora (feces, etc.) of normal infants and young children, so its safety can be described as certain. In addition, the cultivation method is also determined, so it can also be provided at low cost. [Effects of the invention] By ingesting the composition of the present invention, it is possible to improve or prevent herpes virus infection. In addition, the active ingredient of the composition of the present invention is bifidobacteria, which is inexpensive and has high safety. Furthermore, the composition of the present invention can be easily ingested on a daily basis, and furthermore, can continue to be easily ingested for a long period of time. In addition, the inhibitory effect of bifidobacteria on herpes virus infection continues, and further, even when the host's immune function is reduced, the inhibitory effect of bifidobacteria on herpes virus infection is maintained. Therefore, it is also useful in inhibiting the recurrence of herpes virus infection.

由表1及圖3所示之結果可知，ACV經口投予組(#2)中，投予後於2小時內抗HSV-2活性增強，其後活性緩慢減弱，6小時後活性消失。與此相對，雙歧桿菌投予組(#1)中，投予6小時後抗病毒活性變高，8小時後以後亦持續。 根據該結果，認為源自雙歧桿菌及其代謝產物等之生理活性物質藉由轉移至血中而發揮其抗HSV活性。又，亦可知該抗HSV活性為持續之活性。特別是於作為疱疹病毒感染症之現有藥的ACV之抗病毒活性減少時，雙歧桿菌之抗病毒活性增強，因此，可藉由與該現有藥併用而更有效率且有效果地改善及預防疱疹病毒感染症。 [產業上之可利用性] 如以上說明，根據本發明，藉由經口攝取雙歧桿菌，可使疱疹病毒之量減少，又，抑制疱疹病毒感染症之發展。進而，該效果可並不太受到宿主之免疫功能降低之影響地發揮，又，為持續性。因此，攝取雙歧桿菌於疱疹病毒感染症之復發預防方面亦有效。再者，雙歧桿菌為安全性較高、可廉價提供之物質。 因此，以雙歧桿菌為有效成分之本發明之組合物於疱疹病毒感染症之改善或預防方面有用。The present invention provides a composition containing bifidobacteria as an effective ingredient for improving or preventing herpes virus infection. In the present invention, "herpes virus infection" refers to a viral infection caused by a virus belonging to the herpesvirus family. Examples of such a virus include herpes virus belonging to the alpha herpesvirus subfamily (herpes simplex virus type 1 ( HSV-1), herpes simplex virus type 2 (HSV-2), human herpes virus 3 (HHV-3, varicella/zoster virus, VZV)), herpes virus belonging to the beta herpes virus subfamily (human herpes virus 5) (HHV-5, cytomegalovirus, CMV), human herpes virus 6 (HHV-6), human herpes virus 7 (HHV-7)), a herpes virus belonging to the gamma herpesvirus subfamily (human herpes virus 4 (HHV- 4. Epstein-Barr virus, EBV), human herpes virus 8 (HHV-8, Kaposi sarcoma-associated herpes virus)). In the present invention, "improvement" includes not only the complete treatment of herpes virus infection, but also the alleviation of symptoms and the inhibition of its development. "Prevention" includes inhibiting or delaying the onset of herpes virus infection and inhibiting its recurrence. Furthermore, improving or preventing also includes reducing the amount of herpes virus that is the cause of herpes virus infection. In addition, as shown in the examples described later, the effect of improving or preventing herpes virus infection can be evaluated by measuring the amount of virus using plaque analysis or quantifying the degree of symptoms using lesion scores. The "Bifidobacterium" as the effective ingredient of the composition of the present invention may be a bacterium belonging to the genus Bifidobacterium. Examples include Bifidobacterium longum, Bifidobacterium breve, and Bifidobacterium breve. Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Bifidobacterium pseudolongum, Bifidobacterium thermophilus (Bifidobacterium thermophilum), as long as it has the effect of improving or preventing herpes virus infection, there is no particular limitation. The bifidobacterium used in the composition of the present invention is preferably Bifidobacterium longum, and particularly preferably Bifidobacterium longum strain BR-108. Furthermore, BR-108 strain (BR-108) is a Bifidobacterium longum isolated from the stool of infants and young children, and it was deposited with the independent administrative legal person product evaluation technology base agency (NITE, 〒292-) on April 13, 2012. 0818 Room 122, Kamizukazuka 2-5-8, Kisarazu City, Chiba Prefecture (Deposit No.: NITE P-1317). In addition, the bifidobacterium is also a bacterium having the nucleotide sequence shown in SEQ ID NO:1 as the sequence of the 16SrRNA gene. In addition, only one kind of the above-mentioned bifidobacteria may be used in the composition of the present invention, or two or more species of bacteria may be used in the composition of the present invention. Furthermore, in the composition of the present invention, bifidobacteria can be used as live bacteria or as dead bacteria. Dead cells are preferable as the active ingredient of the composition of the present invention in terms of excellent heat resistance, stable quality, and tasteless and odorless. As dead bacteria in the composition of the present invention, heat sterilized bacteria can be used. Bacterial cells that have been heat-sterilized can be prepared by the following methods: cultures obtained by culturing bifidobacteria according to conventional methods, such as filtration, centrifugal separation, etc., to recover the cells, and then suspend them in water, etc., at a temperature below 120°C. (Preferably 80 to 120°C), heat treatment is performed within 30 minutes (3 seconds to 30 minutes), and then concentration, drying (freeze drying, etc.) and crushing treatment are performed as needed. Furthermore, the fine powder of the heat sterilized cells of Bifidobacterium longum BR-108 strain is commercially available under the product name "BR-108 (registered trademark)" (manufactured by Combi Functional Food Division). In addition, the bifidobacterium contained as an active ingredient in the composition of the present invention may be the bacteria as described above, or may be a substance contained in the bacteria, a secretion product of the bacteria, and a metabolite produced by the bacteria . The composition of the present invention can be in the form of a pharmaceutical composition for improving or preventing herpes virus infection, food and beverage (including animal feed), or a reagent for model animal experiments. The composition of the present invention can be formulated by a well-known pharmacological method. For example, it can be made into capsules, lozenges, pills, liquids, powders, granules, fine granules, film coatings, granules, throats, sublingual agents, chews, buccal preparations, pastes, syrups Oral or parenteral preparations, suspensions, elixirs, emulsions, coatings, ointments, plasters, pastes, transdermal absorption preparations, lotions, inhalants, aerosols, injections, suppositories, etc. To use. The present invention is a composition using Bifidobacterium as an intestinal bacterium as an active ingredient, which can be ingested non-invasively and simply by oral administration. That is, a preferred method of ingesting the composition of the present invention is by oral ingestion. In these formulations, it is possible to appropriately combine pharmacologically or as acceptable carriers for food and beverages, specifically physiological saline, sterilized water, vegetable oils, solvents, excipients, bases, emulsifiers, suspending agents, surfactants, Stabilizers, fragrances, fragrances, vehicles, preservatives, binders, diluents, isotonic agents, soothing agents, extenders, disintegrants, buffers, coating agents, lubricants, colorants, sweeteners Flavoring agents, thickeners, flavoring agents, dissolution aids or other additives, etc. When the composition of the present invention is used in the form of a pharmaceutical composition, it can be used in combination with known substances for the improvement or prevention of herpes virus infection. As the known substance, for example, acyclovir, valacyclovir, cidofovir, famciclovir, fomivir, foscarnet, ganciclovir, iodoside, penciclovir, and triflurure can be cited Nucleic acid analogs such as glycosides, valganciclovir, and arabinosine, DNA (deoxyribonucleic acid, deoxyribonucleic acid) synthesis inhibitors, etc. In addition, as shown in the following examples, when the antiviral activity of acyclovir decreases, the antiviral activity of bifidobacteria is enhanced. Therefore, it is combined with the known use for the improvement or prevention of herpes virus infections. The combined use of these substances can improve and prevent herpes virus infections more efficiently and effectively in the present invention. When the composition of the present invention is used in the form of a food or drink, the food or drink may be, for example, a health food, a functional food, a specific health food, a nutritional functional food, a functional labeled food, a nutritional supplement, and a patient's use. Food or animal feed. The food and drink of the present invention can be taken in the form of the composition as described above, and can also be taken in the form of various food and drink products. Specific examples of food and beverage products include fermented foods such as yogurt and lactic acid beverages, fermented beverages; edible oils, salad dressings, mayonnaise, margarine, and other oil-containing products; soups, milk drinks, soft drinks, teas Liquid foods such as beverages, alcoholic beverages, beverages, jelly-like beverages, and functional beverages; carbohydrate-containing foods such as rice, noodles, and bread; processed livestock foods such as ham and sausage; fish cakes, dried foods, salted fish, etc. Processed aquatic foods; processed vegetable foods such as pickles; semi-solid foods such as jelly; fermented foods such as miso; pastry, Japanese confectionery, candy, chewing gum, soft candy, ice cream, popsicles and other confectionery; curry, Soft canned products such as pouring juice and Chinese soup; instant soup, instant miso juice and other instant food or microwave oven food, etc. Furthermore, health food and drink prepared into powder, granule, lozenge, capsule, liquid, paste or jelly can also be mentioned. Furthermore, the manufacturing of the food and beverage in the present invention can be implemented by manufacturing techniques known in this technical field. One or two or more ingredients (for example, nutrients, etc.) that are effective for improving or preventing herpes virus infection may be added to the food and drink. Moreover, it can also be made into a multifunctional food and drink by combining it with other ingredients or other functional foods that exert functions other than the improvement. The composition of the present invention can be used for animals including humans, and there are no particular restrictions on animals other than humans, and can be used for various domestic animals, poultry, pets, experimental animals, and the like. Specifically, pigs, cows, horses, sheep, goats, chickens, wild ducks, ostriches, domestic ducks, dogs, cats, rabbits, hamsters, mice, rats, monkeys, etc. can be cited, but are not limited to these. In addition, as the object of the composition of the present invention, animals infected with herpes virus can be listed regardless of how it develops, and from the viewpoint of prevention, it can be administered or made to animals that are not infected with herpes virus or are suspected of being infected with herpes virus. Ingest the composition of the present invention. Furthermore, from the viewpoint of preventing recurrence, the composition of the present invention can be preferably used for animals carrying herpes viruses that have not shown symptoms. In the case of administering or ingesting the composition of the present invention, the dosage or intake is based on the subject’s age, weight, symptoms of herpes virus infection, health status, and type of composition (drugs, food and drink, etc.) Wait for the appropriate selection. For example, the dosage or intake of bifidobacteria per day is usually 0.5×10 ⁹ pieces/kg body weight～50×10 ⁹ /kg body weight, preferably 2×10 ⁹ pieces/kg body weight～50×10 ⁹ pieces /kg body weight. In addition, the present invention also provides a method for improving or preventing herpes virus infection in a subject, which is characterized by administering or ingesting a bifidobacterium or a composition containing bifidobacterium as an active ingredient to the subject as described above . Furthermore, the dosage or intake of the bifidobacterium or the composition containing the bifidobacterium as an active ingredient is as described above, and can be administered or ingested once per day or divided into multiple times (for example, twice). In addition, the administration or ingestion period may be stopped depending on the degree of improvement of herpes virus infection. However, as described above, it is desirable to continue the administration or ingestion without stopping from the viewpoint of preventing recurrence. Furthermore, regarding "continuation", it can be continuation every day or continuation with an interval. In terms of effect, it is better to continue to administer or ingest bifidobacteria or contain bifidobacteria as active ingredients. combination. The product (medicine, food and drink, reagent) of the composition of the present invention or its instructions can be attached with a label for improving or preventing herpes virus infection. In addition, regarding food and beverages, in order to distinguish them from general foods in terms of form and targets, they can be used as supplements for products of the composition of the present invention as health functional foods (specified health foods, nutritional functional foods, and functionally labeled foods). On the label of health function. "Attaching a label to a product or manual" here means attaching a label to the product itself, container, packaging, etc., or attaching a label to manuals, additional documents, promotional materials, and other printed materials that reveal product information. [Examples] Hereinafter, the present invention will be described more specifically based on examples, but the present invention is not limited to the following examples. In order to understand the effectiveness of bifidobacteria against herpes viruses and the infections caused by them, the following experiments were carried out. (Bifidobacterium) In addition, the Bifidobacterium used is a strain of Bifidobacterium longum BR-108 (Bifidobacterium longum BR-108) isolated from human feces of infants and young children, and was deposited with an independent administrative legal person on April 13, 2012 Bacteria from the Product Evaluation Technology Foundation Agency (NITE, 〒292-0818 Room 122, Kamizokazu 2-5-8, Kisarazu City, Chiba Prefecture) (Deposit No.: NITE P-1317). In addition, the bacteria (manufactured by Combi Functional Food Division, product name: BR-108 (registered trademark)) obtained by heat-sterilizing, freeze-drying, and pulverizing the bacteria were ingested in mice as follows. (Herpes virus) In addition, the herpes virus used is HSV-2 UW268 strain (provided by Toyama Prefectural Institute of Health). The virus strain was infected with Vero cells at 0.01 PFU/cell, moved to -80°C after 20-24 hours, and then repeatedly frozen and thawed three times. Next, the culture was added to a 50 ml centrifuge tube, centrifuged at 1500 rpm for 10 minutes at 4°C, and 1 ml of the supernatant was dispensed into 1.5 ml microtubes at -80°C Save and maintain under. Then, one of them was taken out, and plaque analysis was performed with Vero cells to determine the amount of virus (PFU), which was used for the infection described later. Then, using these bifidobacteria and HSV-2, the following experiment was performed. That is, first, 7 days before HSV-2 inoculation described later, BALB/c mice (6 weeks old, female) were divided into the following groups, each with 10 mice, and the intake of Bifidobacterium (BR-108) was started. A: Negative control group (physiological saline) (also called "control group") B: BR-108 (0.42×10 ⁹ pcs/day) intake group (also called "BR 400 million pcs") C: BR-108 ( 2.1×10 ⁹ pieces/day) ingestion group (also called "BR 2 billion pieces") D: BR-108 (10.5×10 ⁹ pieces/day) ingestion group (also called “BR 10 billion pieces”). Furthermore, in such a way that the daily intake of each group was the above-mentioned amount, the mice were orally ingested twice a day (9 am and 6 pm) and BR-108 was suspended in physiological saline. By. In addition, for these mice, in order to synchronize the estrus cycle and increase the sensitivity of the genitals to HSV-2 infection, medroxyprogesterone acetate (medroxyprogesterone 17- acetate, 3 mg/individual). In addition, herpes virus infections are likely to cause onset, recurrence, severe, and prolonged periods due to decreased immune function. Therefore, in each of these mice ingestion groups, the immunosuppressant 5-FU (5-fluorouracil) was injected subcutaneously every other day from 7 days before HSV-2 vaccination to 13 days after the vaccination. Intake: 0.25 mg/0.1 ml/individual) and prepare immune-reduced groups (5 in each group). Then, HSV-2 (1×10 ⁴ PFU/20 μl/individual) was locally inoculated to the genitals of these mice. Then, 3 days after the inoculation, the genitals were washed locally with cold PBS (phosphate buffer saline) (100 μl), and the virus amount was determined by the following plaque analysis. The results obtained are shown in Figure 1. <Plaque analysis> The recovered local washing solution was first diluted appropriately with PBS. 100 μl of the obtained dilution was added to Vero cells cultured in a monolayer in a 35 mm petri dish, and incubated at room temperature for 1 hour to infect them. Then, the laminate was added with 0.8% methylcellulose and 2% fetal bovine serum MEM (minimum essential medium) medium (2 ml/culture dish), and cultured at 37°C for 2 days. After the cultivation, the medium was removed, and fixation and staining were performed with crystal violet. Then, the number of plaques is measured under a microscope, and the plaque-forming unit (PFU) is calculated from the measured number. <Evaluation based on lesion score> In addition, after HSV-2 inoculation, herpes symptoms and deaths were recorded, and evaluation was based on the following lesion score (lesion score). The results obtained are shown in Figure 2. 0: Asymptomatic 1: Mild redness 2: Moderate redness and swelling 3: Redness and swelling with exudate 4: Hind limb paralysis 5: Death. As shown in Fig. 1, the amount of the virus in the genitals was measured 3 days after inoculation with HSV-2. As a result, it was found that the amount of virus was reduced by ingesting Bifidobacterium (BR-108). Furthermore, it was also confirmed that the decrease tends to show a dose-dependence. In addition, it was also shown that the reduction was alleviated due to immunosuppressant treatment. Furthermore, as shown in Fig. 2, it can also be seen that by ingesting bifidobacteria, the rapid development of genital herpes symptoms one week after HSV-2 inoculation is suppressed (delayed). Especially at the time point six days after HSV-2 inoculation, although the lesion score reached 2.5 or more in the control group that did not ingest bifidobacteria, the lesions in the group that ingested 10 billion bifidobacteria every day The score is suppressed to "zero" (asymptomatic state). In addition, regarding its dosage dependence, it was confirmed that medium and high dosages (BR 2 billion and BR 10 billion) have a stronger tendency to inhibit the development of symptoms than low dosages (BR 400 million). Furthermore, with regard to the suppression of genital herpes symptoms, no significant effects caused by immunosuppressant treatment were found. Furthermore, at the end (in the control group, up to 9 days after HSV-2 inoculation, in the bifidobacteria ingestion group, up to 12 days after HSV-2 inoculation), the mortality rate was 100% in either administration group. Furthermore, it is known that during the recurrence process of herpes virus, that is, from the latent infection state to the relapse of the disease, the amount of the proliferated virus is a major determinant of whether the disease is onset. It is also predicted that by administering bifidobacteria at this time, the amount of virus production in the body is reduced as shown in Fig. 1, and the disease can be prevented. Therefore, prevention of recurrence can also be expected. In addition, in the model animal experiment shown in Fig. 2, because the conditions for the death of all mice in the control group were set, it is thought that a much larger load was applied than the amount of virus at the time of relapse in humans. <Detection of anti-HSV activity> As described above, it is clear that oral intake of bifidobacteria can reduce the amount of herpes virus and inhibit the development of herpes virus infection. Then, in order to clarify the mechanism by which the virus growth inhibition effect by bifidobacteria is achieved, the following experiment was performed. That is, the inventors hypothesized that the antiviral active ingredients derived from bifidobacteria are absorbed and transferred to the blood to contribute to the possibility of the path of viral proliferation inhibition participating in the mechanism. Based on this hypothesis, they were administered orally After the bifidobacteria, the serum was collected at a time point of 0.5 to 8 hours to evaluate its anti-HSV activity. More specifically, the following procedures were used to detect anti-HSV activity. 1) First, BALB/c mice (female, 6 weeks old) were orally administered BR-108 (1.0×10 ¹⁰ Pcs/0.4 ml/day) or acyclovir (ACV) (1 mg/0.4 ml/day). Furthermore, for each administration group, n=3×7 sampling is performed. In addition, 3 untreated mice were also prepared as controls. ^{2) HSV-2 (2×10 4} PFU/20 μl/mouse) was locally inoculated to the genitals of the above-mentioned mice. 3) BR-108 or Acyclovir was also administered in the morning 3 days after infection. Then, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, and 8 hours after the administration, blood was collected from each mouse, and serum was separated from the blood. 4) Next, each obtained serum was diluted 10-fold with the culture medium to make 100 μl/ml. 5) In addition, Vero cells were cultured in a 48-well culture dish, HSV-2 (0.1 PFU/ml) was added the next day, and incubated at room temperature for 1 hour to infect them. 6) After washing with PBS, add the serum diluent of 1) above at 200 μl/well, and incubate at 37°C. 7) After 24 hours of incubation, the culture (cells and culture medium) was recovered and stored frozen at -80°C. 8) Perform freezing and thawing three times, and appropriately dilute with PBS to 10 ¹ to 10 ⁵ times. Next, the diluted solution was used for plaque analysis using Vero cells (35-mm petri dishes). The 0 hour zone uses serum collected from untreated mice at 30 minutes on the day of sampling in 3) above. Serum was replaced by PBS in the control area. 9) Then, calculate the number of plaques in each serum when the number of plaques in the control area in the above analysis is 100%, and evaluate the anti-sera of the serum isolated from mice that were orally administered BR-108 or ACV over time. HSV-2 activity. The obtained results are shown in Table 1 and FIG. 3 below. Furthermore, the values in Table 1 represent the mean ± SD (standard deviation) of the number of plaques (%) in the serum of 3 animals in each group. In addition, Fig. 3 is a graph obtained by drawing the values described in Table 1 into a graph. [Table 1]

From the results shown in Table 1 and Figure 3, it can be seen that in the ACV oral administration group (#2), the anti-HSV-2 activity increased within 2 hours after the administration, then the activity gradually weakened, and the activity disappeared after 6 hours. In contrast, in the bifidobacteria administration group (#1), the antiviral activity increased 6 hours after the administration, and continued after 8 hours. Based on this result, it is considered that physiologically active substances derived from bifidobacteria and their metabolites are transferred into the blood to exert their anti-HSV activity. In addition, it is also known that the anti-HSV activity is a continuous activity. Especially when the antiviral activity of ACV, which is an existing drug for herpes virus infection, is reduced, the antiviral activity of bifidobacteria is enhanced. Therefore, it can be more efficiently and effectively improved and prevented by combining with the existing drug Herpes virus infection. [Industrial Applicability] As explained above, according to the present invention, by orally ingesting bifidobacteria, the amount of herpes virus can be reduced and the development of herpes virus infection can be suppressed. Furthermore, the effect can be exerted without being affected by the decrease in the immune function of the host, and again, it is continuous. Therefore, ingestion of bifidobacteria is also effective in preventing the recurrence of herpes virus infection. Furthermore, Bifidobacterium is a substance with high safety and low cost. Therefore, the composition of the present invention using bifidobacteria as an active ingredient is useful for improving or preventing herpes virus infection.

Fig. 1 is a graph showing the results of measuring the amount of the virus in the genitals of mice inoculated with herpes simplex virus type 2 (HSV-2) 3 days after the inoculation. "BR 400 million", "BR 2 billion" and "BR 10 billion" indicate that the HSV-2 vaccinated mice ingested 400 million, 2 billion and 10 billion Bifidobacterium (BR-108 strain) every day. The result. In addition, the "control group" refers to the result of the aforementioned HSV-2 inoculated mice that did not ingest the bifidobacterium. Furthermore, "+" indicates the result of the above-mentioned HSV-2 inoculated mice treated with immunosuppressive agents, and "-" indicates the result of the above-mentioned HSV-2 inoculated mice that have not been treated with immunosuppressive agents. In addition, the histogram and the bars attached to it indicate the mean ± SD (mean ± standard deviation). Furthermore, "*" means that a statistically significant difference is confirmed compared with the control group without immunosuppressant treatment (P<0.05), and "#" means that it is statistically confirmed compared with the control group treated with immunosuppressant The significant difference (P<0.05). Furthermore, statistically significant differences are evaluated by Dunnet test and Mann-Whitney U test. Figure 2 is a graph showing changes over time in lesion scores (average values) in mice vaccinated with HSV-2. Furthermore, the labels in the diagram are the same as those in Figure 1. Fig. 3 is a graph showing the time-dependent changes in the amount of virus (antiviral activity) in the blood of mice inoculated with HSV-2 after ingesting bifidobacteria or acyclovir (ACV). The vertical axis represents the ratio (%) of the amount of virus in the blood of each mouse when the amount of virus in the blood in the control area is 100%. The time on the horizontal axis represents the time after the mice ingested Bifidobacterium or ACV. In addition, the histogram and the bars attached to it represent the mean ± SD.

[Deposit Country] JP Japan [Deposit Organization] National Institute of Technology and Evaluation Patent Microorganisms Depositary (NPMD) Independent Administrative Legal Person Product Evaluation Technology Foundation Agency Licensed Microorganism Depositary [Deposit Date] 2012/04/13 [Deposit Number] NITE BP- 01317

<110> Combi Corporation Chubu University (CHUBUUNIVERSITY EDUCATIONAL FOUNDATION)

<120> Composition for improving or preventing herpes virus infection

<150> JP2016-014817

<151> 2016-01-28

<160> 1

<170> PatentIn version 3.5

<210> 1

<211> 1508

<212> DNA

<213> Bifidobacterium longum

<400> 1

Claims (3)

A composition for improving or preventing herpes virus infection, which contains Bifidobacterium as an effective ingredient. The above-mentioned Bifidobacterium is the Bifidobacterium longum strain BR-108 deposited under the deposit number: NITE BP-1317. The composition of claim 1, wherein the aforementioned herpes virus infection is an infection caused by herpes simplex virus type 2. The composition of claim 1 or 2, which is a composition for oral ingestion.

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