KR101702460B1 - Composotion comprising novel p-terphenyl derivatives from the fruiting bodies of Pseudomerulius curtisii for preventing or treating of influenza virus infection diseases - Google Patents

Abstract

The present invention relates to a composition for preventing or treating influenza virus infectious diseases comprising novel p-terphenyl compounds isolated from fruiting bodies of Pseudomerulius curtisii. The p-terphenyl compounds have excellent effects of inhibiting neuraminidase activity of H5N1 influenza virus, thereby being used for preventing or treating influenza virus infectious diseases and related diseases.

Description

TECHNICAL FIELD [0001] The present invention relates to novel p-terphenyl derivatives for preventing or treating influenza virus infectious diseases comprising, as an active ingredient, novel paraphenyl compounds separated from fruiting body of mushroom mushroom fruiting bodies. virus infection diseases}

The present invention relates to a composition for the prevention or treatment of influenza virus infectious diseases comprising, as an active ingredient, a novel paraphenyl compound isolated from a bear mushroom fruiting body.

H5N1, H7N7, and H9N2 viruses are known to cause human infections caused by highly pathogenic avian influenza viruses, which can cause massive human casualties, panic, and economic disruption, resulting in the death of more than two million people worldwide in the case of panemal influenza The World Health Organization (WHO) is calling for international measures (2005, Global Influenza Preparedness Plan).

Recently, in Korea, three outbreaks of avian influenza in 2003, 2006 and 2008 led to massive economic losses in the poultry industry and socioeconomic as well as confirmation of the possibility of infection in mammals. In Korea, the incidence of asymptomatic influenza pandemic influenza There is a serious social problem with the occurrence.

Currently, the only treatment for avian influenza and swine flu is oseltamivir phosphate, an oral therapeutic agent developed as a selective inhibitor of viral originated neuraminidase, and inhaled zanamivir. However, Tamiflu, which is used as an oral therapeutic agent, has side effects such as nausea, vomiting, nervous system or mental disorder and should be prepared for the case of Tamiflu resistant virus used for oral treatment. Recently, the emergence of resistant viruses against Tamiflu, which is already lethal to the spread of the H1N1 virus, has been reported, and even human-to-human transmission of the Tamiflu-resistant virus has been found. Thus, antiviral agents developed to date exhibit severe side effects and require a great deal of attention to their application. In addition, the development of a vaccine has a problem of low efficacy when the virus type of the prevalent virus is not matched with the virus of the vaccine. Therefore, there is an increasing need to develop a new influenza virus agent having excellent infection control effect and excellent stability.

On the other hand, Pseudomerulius curtisii is a wild mushroom that grows on the pine wood as a single life or nesting, and after the flower mushroom has been changed into a new one, it has been changed into brown worms belonging to the wrinkle mushroom and Pseudomerulius of Tapinellaceae to be. The bear mushroom has no stem, the god is semicircular, fan-shaped, yellow, and the wrinkle is dark yellow, and has a remarkably obscure shape. Many studies on medicinal products and health foods using mushrooms and their extracts have been reported to be performed externally (Lee, IK et al., Bioorg Med Chem., 17, 4674-4680, 2009) However, no studies have been conducted on the isolation of effective compounds from the extracts of mushroom mushroom and its inhibitory effect on influenza activity.

The inventors of the present invention have been studying natural products and compounds separated therefrom in order to develop a drug having an excellent effect of preventing or treating influenza infection. It has been found that a novel paraphenyl compound isolated from a bean mushroom extract is a novel compound of the H5N1 influenza virus It was confirmed that the effect of inhibiting the enzyme activity of laminidase was excellent, and the present invention was completed.

It is an object of the present invention to provide a composition for the prevention or treatment of influenza virus infectious diseases comprising as an active ingredient a novel paraphenyl compound isolated from a bear mushroom fruiting body.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating an influenza virus infection disease comprising, as an active ingredient, a p-terphenyl compound represented by the following formula (1).

[Chemical Formula 1]

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The present invention also provides a food composition for preventing or ameliorating an influenza virus infectious disease comprising the paraphenyl compound represented by the above formula (1) as an active ingredient.

The novel paraphenyl compound of the present invention is excellent in the effect of inhibiting the activity of the neuraminidase enzyme of H5N1 avian influenza virus, and thus can be effectively used for the prevention or treatment of influenza virus infection and related diseases.

The present invention provides a composition for preventing or treating influenza virus infectious diseases comprising a novel paraphenyl compound as an active ingredient.

The composition comprises a pharmaceutical composition and a food composition.

Hereinafter, the present invention will be described in detail.

The paraphenylphenyl compound as an active ingredient of the present invention can be represented by the following general formula (1).

[Chemical Formula 1]

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The compound can be used in the form of a pharmaceutically acceptable salt, and includes all salts, hydrates and solvates produced by conventional methods.

As salts, acid addition salts formed by pharmaceutically acceptable free acids are useful. The acid addition salt is prepared in a conventional manner, for example, by dissolving the compound in an excess amount of an aqueous acid solution and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. The same molar amount of the compound and the acid or alcohol (e.g., glycol monomethyl ether) in water may be heated and then the mixture may be evaporated to dryness, or the precipitated salt may be subjected to suction filtration. As the free acid, organic acids and inorganic acids can be used. As the inorganic acids, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid and the like can be used. Examples of the organic acids include methanesulfonic acid, p- toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, citric acid, lactic acid, glycollic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid and hydroiodic acid may be used. It is not limited.

In addition, bases can be used to make pharmaceutically acceptable metal salts. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess amount of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the non-soluble compound salt, and evaporating and drying the filtrate. At this time, as the metal salt, it is preferable to produce sodium, potassium or calcium salt particularly, but not limited thereto. The corresponding silver salt can also be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).

Pharmaceutically acceptable salts of such compounds include, unless otherwise indicated, salts of acidic or basic groups that may be present in the compounds. For example, pharmaceutically acceptable salts may include sodium, calcium and potassium salts of hydroxy groups, and other pharmaceutically acceptable salts of amino groups include hydrobromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, (Mesylate) and p -toluenesulfonate (tosylate) salt, and the like, and a method for producing a salt known in the art ≪ / RTI >

The paraphenyl compounds of the present invention are useful for the treatment of pseudomerulius from the fractions fractionated from the curtisii fruity body extract, preferably from the fractions.

The mugwort mushroom can be used without limitation, such as cultivated or marketed, and the fruit body extract can be obtained by conventional extraction and fractionation methods, and commercially available ones can be purchased and used.

In the present invention, water extract, C ₁ -C ₄ alcohol or a mixed solvent thereof may be used as an extractant of the mugwort fruiting body of the present invention, preferably methanol or ethanol.

In one embodiment of the present invention, dried mushroom mushrooms were shredded in shade, put in an extraction container, added with an appropriate amount of alcohol, allowed to stand at room temperature for 7 days, and then filtered with filter paper or the like. This extraction process may be repeated several times, and then a method such as concentration or lyophilization may be additionally performed.

The fractions of Fusarium oxysporum fruiting bodies of the present invention are obtained by successively fractionating the Fusarium oxysporum fucanus extract with hexane, chloroform, ethyl acetate and n-butanol, Of the solvent fraction, preferably the ethyl acetate fraction.

The paraphenylphenyl compound of the present invention can be easily obtained by a known method used for separation and fractionation of water from the fractions, column chromatography and the like, alone or in suitable combination.

Since the paraphenyl compound of the present invention has an excellent effect of inhibiting H5N1 neuraminidase activity, it can be effectively used for the prevention or treatment of influenza virus infection.

Since the influenza virus infection may cause diseases including flu, cold, sore throat, bronchitis or pneumonia, the composition of the present invention may also be used for the prevention or treatment of the above diseases.

The flu may be avian influenza, swine flu or swine flu, preferably avian influenza.

The composition of the present invention may contain at least one known active ingredient having the effect of preventing or treating influenza virus infection together with the novel paraphenyl compound of the present invention.

The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions. In addition, it can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral formulations such as syrups and aerosols, external preparations, suppositories and sterilized injection solutions according to a conventional method. Suitable formulations known in the art are preferably those as disclosed in Remington ' s Pharmaceutical Science, recently, Mack Publishing Company, Easton PA. Examples of carriers, excipients and diluents which may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. When the composition is formulated, it is prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, Gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The term "administering" as used herein is intended to provide any individual of the invention with a composition of the invention in any suitable manner.

The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and the weight of the individual, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. For the desired effect, the paraphenyl compound of the present invention may be administered in an amount of 1 mg / kg to 1000 mg / kg per day, or may be administered once a day or divided into several times.

The pharmaceutical composition of the present invention may be administered to a subject in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection.

The composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers for the prevention and treatment of influenza virus infection.

In the present invention, the term "health functional food" refers to a food having a biological control function such as prevention and improvement of disease, bio-defense, immunity, recovery after disease and aging inhibition.

The composition of the present invention may be added to a health functional food for the purpose of preventing or improving influenza virus infection. When the novel para-phenylphenyl compound of the present invention is used as a food additive, the novel para-phenyl compound can be used as it is or can be used together with other food or food ingredients, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). In general, the novel paraphenyl compound of the present invention is added in an amount of 15% by weight or less, preferably 10% by weight or less, based on the raw material in the production of food or beverage. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of controlling health, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.

There is no particular limitation on the kind of the food. Examples of foods to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen and other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health foods in a conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. The natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharine and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may comprise flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. Although the ratio of such additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, preferred examples, experimental examples, and formulation examples are provided to facilitate understanding of the present invention. However, the following examples, experimental examples and preparation examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited thereto.

Example  One. Mushroom mushroom  The extract and Fraction  Produce

In order to prepare the mushroom extract of Bombyx mori, the mushroom fruiting body of Bombyx mori was extracted with methanol as an extraction solvent at room temperature for 7 days. The mixture was allowed to stand at room temperature for 7 days and then filtered and concentrated with a filter paper to obtain an extract. The extract was diluted with water and extracted with an equal amount of hexane, chloroform, ethyl acetate and butanol, and concentrated under reduced pressure to obtain respective solvent fractions.

Example  2. compound  Separation of 1 to 6 tablets and structure identification

The ethyl acetate fraction of Bombyx mushroom obtained in Example 1 was subjected to silica gel column chromatography using chloroform: methanol (50: 1-1: 1, v / v) and chloroform: methanol (1: v / v) to obtain fractions. ODS sep-pak cartridges were then run on 25-100% methanol. Subsequently, preparative HPLC was carried out using 40-60% methanol, and the above compounds 1 to 6 were separated. ¹ H NMR, ¹³ C NMR and mass spectrum of the separated compounds were measured to confirm the chemical formula.

2-1. Compound 1

¹ H NMR ( CD ₃ OD ) : ¹ H NMR spectra indicated that two 1,4-disubstituted benzenes constituting the para-phenyl phenyl compound were observed at 6.79, 6.80, 7.14 and 7.18 ppm, and 5.13 ppm Olefinic methine, oxygenated methine at 3.97 ppm, methine and methylene at 2.20-3.06 ppm, and two methyl cations at 1.63 ppm and 1.03 ppm, respectively. This indicates that the present compound is a paraphenyl-based compound composed of one 3-hydroxybutyl group and one 3-methylcyclopent-3-enecarboxyl group. Based on these results, we searched the database and found that this compound was a novel paraphenyl compound.

Mass spectrum : The high-resolution FAB mass spectrum was finally measured to confirm the molecular weight and molecular formula. As a result, the chemical structure was determined by a new paraphenyl compound having a molecular formula C ₂₉ H ₂₈ O ₉ and a molecular weight of 520 in agreement with the measured value m / z 521.1812 [M + H] ⁺ .

2-2. Compound 2

No. C H 1,1 " 124.9, 124.8 2,6,2 ", 6 " 132.5, 132.6 7.18, 7.14 (d, J = 8.4) 3,5,3 ", 5 " 115.9, 116.0 6.84, 6.83 (d, J = 8.4) 4.4 " 158.0, 158.1 1 ', 4' 123.8, 123.9 2 ', 5' 134.7, 134.8 3 ', 6' 142.3, 142.5 1a 175.8 2a 43.0 3.06 (m) 3a 37.0 2.39, 2.20 (m) 4a 139.5 5a 123.2 5.13 (m) 6a 40.9 2.42, 2.33 (m) 7a 16.1 1.63 (s) 1b 170.5 2b 20.2 1.89 (s)

¹ H NMR ( CD ₃ OD ) : ¹ H NMR spectra indicated that two 1,4-disubstituted benzenes constituting the p -terphenyl compound were observed between 6.84 and 7.18 ppm, and at 5.13 ppm olefin methine, Two methyl cations were observed at 2.20-3.06 ppm at methylene and at 1.63 ppm and 1.89 ppm. This indicates that the present compound is a paraphenyl-based compound composed of one acetyl group and one 3-methylcyclopent-3-enecarboxyl group. Based on the above results, the database was searched and it was estimated that this compound was a novel paraphenyl-based compound.

¹³ C NMR ( CD ₃ OD ) : As a result of ¹³ C NMR spectroscopy, it was shown to be a paraphenyl group consisting of one acetyl group analogous to ¹ H NMR spectrum and one 3-methylcyclopent-3-enecarboxyl group. Based on the above results, the database was searched and it was estimated that this compound was a novel paraphenyl-based compound.

Mass spectrum : The high-resolution FAB mass spectrum was finally measured to confirm the molecular weight and molecular formula. As a result, the chemical structure was determined with a new paraphenyl-based compound of molecular formula C ₂₇ H ₂₄ O ₈ , molecular weight of 476, in agreement with the theoretical value m / z 499.1367 [M + Na] +.

2-3. Compound 3

No. C H 1,1 " 125.0, 125.1 2,6,2 ", 6 " 132.7 7.12, 7.15 (d, J = 8.4) 3,5,3 ", 5 " 116.0 6.82 (d, J = 8.4) 4.4 " 158.2 1 ', 4' 124.0 2 ', 5' 134.8 3 ', 6' 142.5, 142.6 1a 175.8 2a 43.1 3.03 (m) 3a 37.1 2.43, 2.31 (m) 4a 139.6 5a 123.2 5.07 (m) 6a 41.0 2.38, 2.26 (m) 7a 16.1 1.63 (s) 1b 173.0 2b 36.4 2.15 (t) 3b 19.2 1.43 (m) 4b 13.8 0.74 (t)

¹ H NMR ( CD ₃ OD ) : ¹ H NMR spectrum was measured. As a result, it was found that two 1,4-disubstituted benzenes constituting the paraphenyl group compound between 6.82 and 7.15 ppm, olefin methine at about 5.07 ppm, Two methyl cations were observed at methane and methylene, at 1.63 ppm and 0.74 ppm at between -3.03 ppm and 1.43 ppm. Analysis of ¹ H NMR spectra indicated that this compound is a novel paraphenyl-based compound consisting of one butyryl group and one 3-methylcyclopent-3-enecarboxyl group.

¹³ C NMR ( CD ₃ OD ) : As a result of ¹³ C NMR spectroscopy, it was shown to be a paraterphenyl system consisting of one butyryl group analogous to ¹ H NMR spectrum and one 3-methylcyclopent-3-enecarboxyl group. Based on the above results, the database was searched and it was estimated that this compound was a novel paraphenyl-based compound.

Mass Spectrum: it was finally measuring the high-resolution FAB mass spectrum to confirm the molecular weight and molecular formula, and the results of measurements m / z 505.1860 [M + H ] + and the theoretical value is in good agreement with the molecular formula C ₂₉ H ₂₈ O _8, molecular weight 504 The chemical structure of the new paraphenyl compounds was determined.

2-4. Compound 4

The following chemical structures were determined through ¹ H NMR, ¹³ C NMR and mass spectrum as described above.

2-5. Compound 5

The following chemical structures were determined through ¹ H NMR, ¹³ C NMR and mass spectrum as described above.

2-6. Compound 6

The following chemical structures were determined through ¹ H NMR, ¹³ C NMR and mass spectrum as described above.

Experimental Example  One: From Bear Mushroom  The separation of the isolated compounds 1-6 H5N1  Neuraminidase ( neuraminidase ) Inhibition activity measurement

The inhibitory activity against other types of neuraminidase was measured using the H5N1 influenza A virus neuraminidase (R & D system, 7597) and the substrate 4-Methylumbelliferyl-DN-acetylneuraminic acid (SIGMA M8639). First, mud mushroom and its fractions were dissolved in methanol, and 10 μL each of them was added. 50 μL of the final concentration of 200 μM was added to the substrate, and 90 μL of 50 mM MES buffer (pH 6.5) containing 5 mM CaCl ₂ and 500 mM NaCl . The enzymatic activity of neuraminidase was activated with 50 mM MES buffer (pH 6.5) containing 30 mM CaCl ₂ and 500 mM NaCl at 37 ° C for 24 hours before use. After that, 50 μL of the enzymatic enzyme neuraminidase (enzyme final concentration 50 ng / mL) was added and reacted. The inhibition activity of neuraminidase was measured by measuring the light absorbance at 365 nm and the luminescence at 445 nm using a fluorescence spectrometer Respectively. The inhibitory activity (%) was calculated by the following formula, and the concentration showing the inhibition rate of 50% was described by IC ₅₀ , and the results are shown in Table 3 below. At this time, the control group means the experimental group without sample.

Inhibition activity (%) = ((RFU of control RFU sample) / control RFU) x 100

Samples (M) IC ₅₀ K _i Inhibition type Zanamivir (Relenza ^® ) 2.6 (nM) - - Compound 1 27.2 - - Compound 2 15.4 31.1 Noncompetitive Compound 3 9.3 15.6 Noncompetitive Compound 4 7.0 23.9 Noncompetitive Compound 5 20.0 56.8 Noncompetitive Compound 6 25.0 - -

As shown in Table 3, the compounds 1 to 6 isolated from the fragrant ethyl acetate fraction of the present invention inhibited H5N1 neuraminidase enzyme activity in a concentration-dependent manner, and IC ₅₀ values were 27.2 nM (1), 15.4 nM (2), 9.3 nM (3), 7.0 nM (4), 20.0 nM (5) and 25.0 nM (6)

This means that the paraphenyl derivatives of the present invention can be used for the prevention or treatment of influenza virus infection and related diseases by inhibiting the activity of H5N1 influenza virus.

Hereinafter, a pharmaceutical composition for preventing or treating influenza virus infectious disease comprising the novel paraphenyl compound of the present invention as an active ingredient, and a preparation example of a food composition for prevention or improvement are described, but the present invention is not limited thereto It is just a specific description.

Formulation Example 1. Preparation of pharmaceutical preparations

One. Sanje  Produce

20 mg of the paraphenyl compound of the present invention

Lactose 100 mg

Talc 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

2. Preparation of tablets

10 mg of the paraphenyl compound of the present invention

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

3. Preparation of capsules

10 mg of the paraphenyl compound of the present invention

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

4. Preparation of injections

10 mg of the paraphenyl compound of the present invention

180 mg mannitol

Sterile sterilized water for injection 2974 mg

_{Na 2 HPO 4 · 2H 2 O} 26 mg

(2 ml) per 1 ampoule in accordance with the usual injection preparation method.

5. Manufacture of liquids

20 mg of the paraphenyl compound of the present invention

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.

Formulation Example 2. Preparation of food preparation

1. Manufacture of health food

100 mg of the paraphenyl compound of the present invention

Vitamin mixture quantity

70 g of vitamin A acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

0.2 g of vitamin B12

Vitamin C 10 mg

Biotin 10 g

Nicotinic acid amide 1.7 mg

Folate 50 g

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

2. Manufacture of health drinks

100 mg of the paraphenyl compound of the present invention

Vitamin C 15 g

Vitamin E (powder) 100 g

19.75 g of ferrous lactate

3.5 g of zinc oxide

Nicotinic acid amide 3.5 g

Vitamin A 0.2 g

Vitamin B1 0.25 g

Vitamin B2 0.3g

Water quantification

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The resulting solution was filtered and sterilized in a sterilized 2 L container, ≪ / RTI >

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Claims (15)

A pharmaceutical composition for preventing or treating an influenza virus infection disease comprising, as an active ingredient, a p-terphenyl compound represented by the following formula (1).
[Chemical Formula 1]

In Formula 1, R ₁ and R ₂ are each

And

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; ≪ / RTI > delete delete delete delete delete delete The compound of claim 1, wherein the compound is selected from the group consisting of Pseudomerulius The present invention relates to a pharmaceutical composition for preventing or treating an influenza virus infection disease, 9. The pharmaceutical composition according to claim 8, wherein the fraction is fractionated from an extract of Fusarium oxysporum fuciformis. Claim 9 wherein the extract is water, C ₁ -C ₄ alcohols, or of preventing or treating a pharmaceutical composition, characterized in that the extraction with a mixed solvent thereof, the influenza virus infection on. 10. The pharmaceutical composition according to claim 9, wherein the fraction is fractionated with ethyl acetate. The pharmaceutical composition according to claim 1, wherein the composition inhibits H5N1 neuraminidase activity. The pharmaceutical composition according to claim 1, wherein the influenza virus infection disease is at least one selected from the group consisting of influenza, cold, sore throat, bronchitis and pneumonia. 14. The pharmaceutical composition according to claim 13, wherein the influenza is avian influenza, swine flu or swine flu. 1. A food composition for preventing or ameliorating an influenza virus infection disease comprising, as an active ingredient, a p-terphenyl compound represented by the following formula (1).
[Chemical Formula 1]

In Formula 1, R ₁ and R ₂ are each

And

;

And

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And

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