JP5945317B2 - Influenza virus infection inhibitor - Google Patents

Influenza virus infection inhibitor Download PDF

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JP5945317B2
JP5945317B2 JP2014250875A JP2014250875A JP5945317B2 JP 5945317 B2 JP5945317 B2 JP 5945317B2 JP 2014250875 A JP2014250875 A JP 2014250875A JP 2014250875 A JP2014250875 A JP 2014250875A JP 5945317 B2 JP5945317 B2 JP 5945317B2
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influenza virus
extract
virus infection
influenza
daisies
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JP2015057432A (en
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智和 石塚
智和 石塚
宏 清野
宏 清野
純 國澤
純 國澤
圭司郎 吉田
圭司郎 吉田
志村 進
進 志村
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Lotte Co Ltd
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Description

インフルエンザウイルスの感染抑制効果を有する組成物の提供。   Provision of a composition having an effect of suppressing infection with influenza virus.

インフルエンザウイルスに感染すると高熱、頭痛、関節痛、全身倦怠等の臨床症状を示し、死亡する場合もある。インフルエンザウイルスは感染力が強く、一般的な風邪と異なり短期間で爆発的な流行を引き起こすのが特徴である。
インフルエンザの予防・治療法としては、ワクチン接種による予防やノイラミニダーゼ阻害剤等の薬剤による治療が一般的に知られている。しかし、ワクチンはインフルエンザウイルスのタイプによって効果が著しく異なるため万能ではなく、薬剤は副作用や耐性ウイルスの出現といった問題がある。
Infection with influenza virus may cause clinical symptoms such as high fever, headache, joint pain, general malaise, and may die. Influenza virus is highly infectious and is characterized by causing an explosive epidemic in a short period of time unlike a common cold.
As prevention / treatment methods for influenza, vaccination prevention and treatment with drugs such as neuraminidase inhibitors are generally known. However, vaccines are not all-purpose because their effects vary greatly depending on the type of influenza virus, and drugs have problems such as side effects and the emergence of resistant viruses.

このような背景から、インフルエンザウイルスの感染を予防または治療する組成物の開発が行われており、葛根湯(非特許文献1)、ラクトフェリンとラクトペルオキシダーゼ(非特許文献2)、有胞子性乳酸菌(特許文献1)、クロモグリク酸(特許文献2)、哺乳動物の初乳由来タンパク質画分(特許文献3)、シアロ糖鎖含有ポリマー(特許文献4)、蕎麦(特許文献5)、カシス(特許文献6)、各種植物抽出物(特許文献7、8)等がインフルエンザウイルス感染抑制効果を示す成分として開示されている。しかしながらこれらの成分は、いまだ十分なインフルエンザウイルス感染抑制効果を示すとは言えず、さらなる予防や治療法の開発が求められている。   From such a background, a composition for preventing or treating influenza virus infection has been developed. Kakkonto (Non-patent document 1), lactoferrin and lactoperoxidase (non-patent document 2), spore-forming lactic acid bacteria ( Patent document 1), cromoglycic acid (patent document 2), protein fraction derived from mammalian colostrum (patent document 3), sialo-glycan-containing polymer (patent document 4), buckwheat (patent document 5), cassis (patent document) 6) Various plant extracts (Patent Documents 7 and 8) are disclosed as components exhibiting an influenza virus infection-suppressing effect. However, these components still cannot be said to exhibit a sufficient inhibitory effect on influenza virus infection, and further development of prevention and treatment methods is required.

本発明者等は、インフルエンザウイルス感染抑制効果を示す物質を提供することを目的として、探索した結果、ヒナゲシ抽出物質が有効なインフルエンザウイルス感染抑制効果を示すことを見出した。本発明でインフルエンザウイルスの感染抑制効果が認められたヒナゲシ(ポピー)(学名:Papaver rhoeas L.)はケシ科の植物で別名を虞美人草といい、鎮静、催眠、止痛作用等があるといわれ、鎮咳薬や鎮静剤として用いられているが、ウイルスの感染抑制効果については全く知られていない。
ヒナゲシ(ポピー)の薬理作用に関し、ハーブを含む免疫賦活剤に関する特許(特許文献9)にハーブの一例としてポピーの記載があるものの、発明の具体性に欠ける文献であり、ポピーのウイルス感染抑制効果に関する記載も示唆もない。
As a result of searching for the purpose of providing a substance exhibiting an influenza virus infection inhibitory effect, the present inventors have found that a poppy extract material exhibits an effective influenza virus infection inhibitory effect. The poppy (Papaver rhoeas L.), which has been confirmed to be effective in suppressing influenza virus infection in the present invention, is a plant belonging to the family Poppyaceae, which is also known as a beautiful beauty grass and is said to have sedation, hypnosis, and analgesia. It is used as an antitussive and sedative, but it is not known at all about the virus infection-suppressing effect.
Regarding the pharmacological action of poppy (poppy), although there is a description of poppy as an example of herb in the patent on immunostimulant containing herb (Patent Document 9), it is a document lacking in the concreteness of the invention, and the virus infection suppression effect of poppy There is no description or suggestion about.

特開2008-13543号公報JP 2008-13543 Gazette 特開2004-352712号公報JP 2004-352712 A 特開2009-190994号公報JP 2009-190994 A 特開2008-31156号公報JP 2008-31156 A 特許第4185996号明細書Japanese Patent No. 4185996 特開2009-269861号公報JP 2009-269861 特開2005-343836号公報JP 2005-343836 A 特開2004-59463号公報JP 2004-59463 A 特開2002-370993号公報JP 2002-370993 A

Kurokawa M. et al.、Antiviral Research、2002年、56巻、183-188頁、Effect of interleukin-12 level augmented by Kakkon-to, a herbal medicine, on the early stage of influenza infection in mice.Kurokawa M. et al., Antiviral Research, 2002, 56, 183-188, Effect of interleukin-12 level augmented by Kakkon-to, a herbal medicine, on the early stage of influenza infection in mice. Shin K. et al.、Journal of Medical Microbiology、2005年、54巻、717-723頁、Effects of orally administered bovine lactoferrin and lactoperoxidase on influenza virus infection in mice.Shin K. et al., Journal of Medical Microbiology, 2005, 54, 717-723, Effects of orally administered bovine lactoferrin and lactoperoxidase on influenza virus infection in mice.

本発明は、インフルエンザウイルスの感染抑制効果を有する組成物を提供することである。   This invention is providing the composition which has the infection suppression effect of influenza virus.

本発明は、ヒナゲシの抽出物を有効成分とすることを特徴とする抗インフルエンザウイルス剤に関する。
さらに、本発明は、ヒナゲシを水を用いて、抽出し、その抽出液を凍結乾燥して精製することにより得た抽出物を有効成分とすることを特徴とする抗インフルエンザウイルス剤に関する。
さらにまた、本発明は、ヒナゲシ抽出物を含有する抗インフルエンザウイルス作用を有する飲食品に関する。
The present invention relates to an anti-influenza virus agent characterized by comprising an extract of daisies as an active ingredient.
Furthermore, the present invention relates to an anti-influenza virus agent characterized in that an extract obtained by extracting daisies with water and lyophilizing and purifying the extract is used as an active ingredient.
Furthermore, this invention relates to the food / beverage products which have an anti-influenza virus effect | action containing a dairy extract.

本発明のヒナゲシ抽出物は、IgA分泌促進効果やインフルエンザウイルス感染抑制効果を有し、インフルエンザに感染しにくい体質をつくると考えられ、のど飴の機能強化が可能に成る新素材である。   The corn poppy extract of the present invention is a new material that has an IgA secretion promoting effect and an influenza virus infection suppressing effect, and is considered to create a constitution that is difficult to be infected with influenza, and can enhance the function of throat candy.

インフルエンザウイルス接種後16日までの、ポピー抽出物投与群と対照群とのマウス生存率を示すグラフである。It is a graph which shows the mouse | mouth survival rate of a poppy extract administration group and a control group until 16th after influenza virus inoculation.

本発明者等は、インフルエンザウイルス感染抑制効果を示す物質を探索した結果、ヒナゲシ(ポピー)抽出物に注目し、このヒナゲシ抽出物を投与して飼育したマウスと非投与マウスとに同じ量のインフルエンザウイルスを感染させて、その後の経過を観察すると、ヒナゲシ抽出物を投与したマウスの方がインフルエンザウイルス感染による体重減少が緩やかになり、生存率も改善傾向にあることを見出した。
以下、具体例を実施例で説明する。なお、本発明は以下の具体例に限定されるものではない。
As a result of searching for a substance exhibiting an influenza virus infection inhibitory effect, the present inventors focused on a poppy extract, and the same amount of influenza was administered to mice fed and administered with this poppy extract. When the virus was infected and the subsequent course was observed, it was found that the mice administered with the extract of dairy poppy had a moderate weight loss due to influenza virus infection and the survival rate is also improving.
Hereinafter, specific examples will be described in Examples. In addition, this invention is not limited to the following specific examples.

(実施例1)
ヒナゲシ熱水抽出物の調製
ヒナゲシ(ポピー)(花)100gを粉砕した後、試料の重量に対して10倍量の水を加え、70℃で2時間抽出した。不溶物を濾過した後、得られた抽出液を凍結乾燥してヒナゲシ熱水抽出物37.5gを得た。
Example 1
Preparation of corn poppy hot water extract After pulverizing 100 g of corn poppy (flower), 10 times the amount of water was added to the weight of the sample and extracted at 70 ° C. for 2 hours. After filtering the insoluble matter, the extract obtained was freeze-dried to obtain 37.5 g of dairy hot water extract.

(実施例2)
マウスへの反復舌下投与によるインフルエンザウイルス感染抑制効果
7週齢のマウス(BALB/c系)30匹を対照群(14匹)と投与群(16匹)に分け、普通飼料(MF, オリエンタル酵母)で飼育した。投与群には飼育開始時からヒナゲシ(花)熱水抽出物を4mg/dayの用量で水溶液として毎日舌下投与し、対照群は同量の水のみを舌下投与した。4週目にインフルエンザウイルスを麻酔下で経鼻接種(100pfu/50μl PBS/匹)し、接種後16日までの体重を測定した。インフルエンザウイルスはA/PR/8/34(H1N1)株を用い、ヒナゲシ(花)熱水抽出物の舌下投与はウイルス感染後も行った。ウイルス接種時の各動物の体重は以下の表1の通りであり、両群間に有意差を認めなかった。
(Example 2)
Inhibition of influenza virus infection by repeated sublingual administration to mice
Thirty 7-week-old mice (BALB / c strain) were divided into a control group (14 mice) and a treatment group (16 mice), and were bred with normal feed (MF, oriental yeast). From the start of the breeding, dairy (flower) hot water extract was sublingually administered daily as an aqueous solution at a dose of 4 mg / day, and the control group received only the same amount of water sublingually. At 4 weeks, influenza virus was intranasally inoculated (100 pfu / 50 μl PBS / animal) under anesthesia, and body weight was measured up to 16 days after inoculation. A / PR / 8/34 (H1N1) strain was used as the influenza virus, and sublingual administration of daisy (flower) hot water extract was performed after virus infection. The weight of each animal at the time of virus inoculation is as shown in Table 1 below, and no significant difference was observed between the two groups.

Figure 0005945317
Figure 0005945317

本実施例において得られた結果を表2、表3および図1に示す。
表2及び表3は、インフルエンザウイルス接種後16日までのマウスの体重変化をグラムで示したものであり、ポピー抽出物投与群と対照群の個別データと平均データを示す。
図1は、インフルエンザウイルス接種後16日までの、ヒナゲシ抽出物投与群と対照群とのマウス生存率をプロットしたものである。
表2及び表3において、日数はインフルエンザウイルス接種後の経過日数、体重変化はウイルス接種時の体重からの変化量を示した。表2及び表3中の×はマウスが死亡したことを示す。
The results obtained in this example are shown in Table 2, Table 3, and FIG.
Tables 2 and 3 show the weight change of mice up to 16 days after influenza virus inoculation in grams, and show individual data and average data of the poppy extract administration group and the control group.
FIG. 1 is a plot of the survival rate of mice in the corn poppy extract administration group and the control group up to 16 days after influenza virus inoculation.
In Tables 2 and 3, the number of days indicates the number of days elapsed after inoculation with influenza virus, and the change in body weight indicates the amount of change from the body weight at the time of virus inoculation. X in Table 2 and Table 3 indicates that the mouse died.

図1から明らかなように、インフルエンザウイルス接種後16日経過時において、対照群は14匹中5匹の生存(生存率36%)に対し、ポピー抽出物投与群では16匹中10匹の生存(生存率63%)であった。ログランクテストの結果、12日目までの生存率では投与群が対照群に比べて有意に高く、16日目までの生存率では投与群が対照群に比べて高い傾向であった。
また、体重変化については、t−検定の結果、3日目から7日目までの期間は対照群に比べて投与群の体重減少が有意に抑えられており、投与群のほうがウイルス感染による体重減少が緩やかと考えられた。
As can be seen from FIG. 1, at 16 days after influenza virus inoculation, the control group survived 5 out of 14 animals (survival rate 36%), whereas the poppy extract-administered group survived 10 out of 16 animals. (Survival rate 63%). As a result of the log rank test, the administration group was significantly higher than the control group in the survival rate up to the 12th day, and the administration group tended to be higher than the control group in the survival rate up to the 16th day.
As for the change in body weight, as a result of the t-test, the weight loss of the administration group was significantly suppressed during the period from the 3rd day to the 7th day compared to the control group, and the weight of the administration group was decreased due to virus infection. The decline was considered moderate.

以上の結果から、ヒナゲシ抽出物の投与によってウイルス感染によるマウスの死亡や体重減少が抑えられると考えられた。   From the above results, it was considered that administration of corn poppy extract can suppress the death and weight loss of mice due to virus infection.

Figure 0005945317
Figure 0005945317

Figure 0005945317
Figure 0005945317

次に、インフルエンザウイルス感染抑制効果を示した本発明のヒナゲシ抽出物を用いて、錠剤、チューインガム、キャンディ、チョコレート、ビスケット、グミゼリー、錠菓、アイスクリーム、シャーベット、飲料を常法にて調製した。以下にその処方を示した。   Next, tablets, chewing gum, candy, chocolate, biscuits, gummy jelly, tablet confectionery, ice cream, sherbet, and beverages were prepared by a conventional method using the corn poppy extract of the present invention that showed an influenza virus infection inhibitory effect. The prescription is shown below.

(実施例3)
下記処方にしたがって錠剤を調製した。
D−マンニトール 33.6%
乳糖 33.6
結晶セルロース 8.5
ヒドロキシプロピルセルロース 4.3
ヒナゲシ抽出物 20.0
100.0%
(Example 3)
Tablets were prepared according to the following formulation.
D-mannitol 33.6%
Lactose 33.6
Crystalline cellulose 8.5
Hydroxypropylcellulose 4.3
Daisies extract 20.0
100.0%

(実施例4)
下記処方にしたがってチューインガムを調製した。
ガムベース 20.0%
砂糖 54.7
グルコース 15.0
水飴 9.5
香料 0.5
ヒナゲシ抽出物 0.3
100.0%
Example 4
Chewing gum was prepared according to the following formulation.
Gum base 20.0%
Sugar 54.7
Glucose 15.0
Minamata 9.5
Fragrance 0.5
Daisies extract 0.3
100.0%

(実施例5)
下記処方にしたがってキャンディを調製した。
砂糖 50.0%
水飴 33.0
クエン酸 1.0
香料 0.2
L−メントール 1.0
ヒナゲシ抽出物 0.5
水 14.3
100.0%
(Example 5)
Candy was prepared according to the following formulation.
Sugar 50.0%
Minamata 33.0
Citric acid 1.0
Fragrance 0.2
L-Menthol 1.0
Daisies extract 0.5
Water 14.3
100.0%

(実施例6)
下記処方にしたがってチョコレートを調製した。
カカオビター 20.0%
全脂粉乳 20.0
カカオバター 17.0
粉糖 41.85
レシチン 0.45
香料 0.1
ヒナゲシ抽出物 0.6
100.0%
(Example 6)
Chocolate was prepared according to the following formulation.
Cocoa bitter 20.0%
Whole milk powder 20.0
Cocoa butter 17.0
Powdered sugar 41.85
Lecithin 0.45
Fragrance 0.1
Daisies extract 0.6
100.0%

(実施例7)
下記処方にしたがってビスケットを調製した。
砂糖 31.7%
小麦粉 26.8
片栗粉 26.8
バター 3.2
卵 10.2
重曹 0.3
ヒナゲシ抽出物 1.0
100.0%
(Example 7)
Biscuits were prepared according to the following recipe.
31.7% sugar
Flour 26.8
Starch flour 26.8
Butter 3.2
Egg 10.2.
Baking soda 0.3
Daisies extract 1.0
100.0%

(実施例8)
下記処方にしたがってグミゼリーを調製した。
ポリデキストロース水溶液 40.0%
ソルビトール水溶液 8.0
パラチノース水溶液 9.0
マルトース水溶液 20.0
トレハロース水溶液 11.0
ゼラチン 10.0
酒石酸 1.0
ヒナゲシ抽出物 1.0
100.0%
(Example 8)
Gummy jelly was prepared according to the following formulation.
Polydextrose aqueous solution 40.0%
Sorbitol aqueous solution 8.0
Palatinose aqueous solution 9.0
Maltose aqueous solution 20.0
Trehalose aqueous solution 11.0
Gelatin 10.0
Tartaric acid 1.0
Daisies extract 1.0
100.0%

(実施例9)
下記処方にしたがって錠菓を調製した。
砂糖 76.1%
グルコース 19.0
ショ糖脂肪酸エステル 0.2
香料 0.2
ヒナゲシ抽出物 0.5
水 4.0
100.0%
Example 9
Tablet confectionery was prepared according to the following formulation.
76.1% sugar
Glucose 19.0
Sucrose fatty acid ester 0.2
Fragrance 0.2
Daisies extract 0.5
Water 4.0
100.0%

(実施例10)
下記処方にしたがってタブレットを調製した。
砂糖 35.85%
ショ糖脂肪酸エステル 0.15
ヒナゲシ抽出物 60.0
水 4.0
100.0%
(Example 10)
Tablets were prepared according to the following formulation.
35.85% sugar
Sucrose fatty acid ester 0.15
Daisies extract 60.0
Water 4.0
100.0%

(実施例11)
下記処方にしたがってアイスクリームを調製した。
卵黄 11.0%
砂糖 14.0
牛乳 37.0
生クリーム 37.0
バニラビーンズ 0.5
ヒナゲシ抽出物 0.5
100.0%
(Example 11)
Ice cream was prepared according to the following formulation.
Yolk 11.0%
Sugar 14.0
Milk 37.0
Fresh cream 37.0
Vanilla beans 0.5
Daisies extract 0.5
100.0%

(実施例12)
下記処方にしたがってシャーベットを調製した。
オレンジ果汁 16.0%
砂糖 31.0
ヒナゲシ抽出物 3.0
水 50.0
100.0%
(Example 12)
A sherbet was prepared according to the following formulation.
Orange juice 16.0%
Sugar 31.0
Daisies extract 3.0
Water 50.0
100.0%

(実施例13)
下記処方にしたがって飲料を調製した。
オレンジ果汁 30.0%
異性化糖 15.33
クエン酸 0.1
ビタミンC 0.04
香料 0.1
ヒナゲシ抽出物 0.01
水 54.42
100.0%
(Example 13)
A beverage was prepared according to the following formulation.
Orange juice 30.0%
Isomerized sugar 15.33
Citric acid 0.1
Vitamin C 0.04
Fragrance 0.1
Daisies extract 0.01
Water 54.42
100.0%

本発明のヒナゲシ抽出物は、インフルエンザウイルス感染抑制効果を示すことから、インフルエンザウイルスを抑制するための種々の医薬品並びに飲食品に適用できる。   The corn poppy extract of the present invention exhibits an influenza virus infection suppressing effect, and thus can be applied to various pharmaceuticals and foods and drinks for suppressing influenza virus.

Claims (8)

ヒナゲシの花由来の抽出物を有効成分とし、抽出溶媒として、70℃の熱水を使用することを特徴とする抗インフルエンザウイルス剤の製造方法A method for producing an anti-influenza virus agent , comprising using an extract derived from flowers of daisies as an active ingredient and hot water at 70 ° C. as an extraction solvent . さらに、抽出時間が2時間であることを特徴とする、請求項1記載の抗インフルエンザウイルス剤の製造方法 Further, the extraction time is characterized 2 hours der Rukoto method of anti-influenza virus agent according to claim 1, wherein. さらに、得られた抽出液を凍結乾燥することを特徴とする、請求項1または2に記載の抗インフルエンザウイルス剤の製造方法。Furthermore, the obtained extract is freeze-dried, The manufacturing method of the anti-influenza virus agent of Claim 1 or 2 characterized by the above-mentioned. 舌下投与によるインフルエンザウイルス感染抑制作用を有する前記抗インフルエンザウイルス剤を提供するための、請求項1乃至3のいずれか1項に記載の抗インフルエンザウイルス剤の製造方法。The method for producing an anti-influenza virus agent according to any one of claims 1 to 3, for providing the anti-influenza virus agent having an inhibitory action against influenza virus infection by sublingual administration. ヒナゲシの花由来の抽出物を有効成分とし、抽出溶媒として、70℃の熱水を使用することを特徴とする、抗インフルエンザウイルス用医薬製剤の製造方法A method for producing a pharmaceutical preparation for anti-influenza virus , comprising using an extract derived from flowers of daisies as an active ingredient and hot water at 70 ° C. as an extraction solvent . さらに、抽出時間が2時間であることを特徴とする、請求項5に記載の抗インフルエンザウイルス用医薬製剤の製造方法。Furthermore, extraction time is 2 hours, The manufacturing method of the pharmaceutical formulation for anti-influenza viruses of Claim 5 characterized by the above-mentioned. さらに、得られた抽出液を凍結乾燥することを特徴とする、請求項5または6に記載の抗インフルエンザウイルス用医薬製剤の製造方法。Furthermore, the obtained extract is freeze-dried, The manufacturing method of the pharmaceutical formulation for anti-influenza viruses of Claim 5 or 6 characterized by the above-mentioned. 舌下投与によるインフルエンザウイルス感染抑制作用を有する前記抗インフルエンザウイルス用医薬製剤を提供するための、請求項5乃至7のいずれか1項に記載の抗インフルエンザウイルス用医薬製剤の製造方法。The method for producing a pharmaceutical preparation for anti-influenza virus according to any one of claims 5 to 7, for providing the pharmaceutical preparation for anti-influenza virus having an inhibitory action on influenza virus infection by sublingual administration.
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