KR20100095854A - A new compound ponciol isolated from the mixed herbal extract and the use thereof - Google Patents

Abstract

PURPOSE: A novel compound, ponciol isolated from mixture herb extract is provided to prevent and treat inflammatory diseases by suppressing prostaglandin E2(PGE2). CONSTITUTION: A novel compound, ponciol is denoted by structural formula I. The ponciol is isolated from a mixture herb extract of Bupleuri Radix, scutellariae Radix, ponciri Fructus, rhei Rhizoma, and paeoniae Radix. A health food for preventing and treating inflammatory diseases contains the ponciol of structural formula I as an active ingredient.

Description

A new compound ponciol isolated from the mixed herbal extract and the use

The present invention relates to a new compound (Ponciol) which is a new compound isolated from the mixed herbal extracts of golden, fruit, rhubarb, peony and Shiho and compositions for the prevention and treatment of inflammatory diseases containing the same as an active ingredient.

Grun M et al., Acta Hepatogastroenterol (Stuttg), 24 , pp. 64-81, 1977.

De Silva LB et al., Phytochemistry, 20 , pp. 2776-2778, 1981

[Document 3] Korean Patent Application 10-2008-0133429

Macrophage is an effector cell that plays a major role in eliminating invading bacteria in vivo. Infected macrophages secrete pro-inflammatory cytokines such as IL-1, TNF-α, and IL-6 to activate other macrophages and stimulate cytoplasmic bacteria by stimulating other cells in the immune system. These cytokines, however, are responsible for eliminating tissue damage caused by inflammation. In other words, macrophages initiate inflammatory reactions by generating arachidonic acid in cells by external stimuli such as viruses and bacteria, and expressing arachidone by expressing COX-1 (cyclooxygenase-1) and COX-2 (cyclooxygenase-2). Prostaglandin E ₂ is secreted by participating in acid metabolism. Prostaglandins were first known as substances that help the uterine contractile function in the endometrium, but are now attracting attention as an inflammation-transmitting substance secreted by cell damage and increased pain when secreted by prostaglandins. In addition, nitric oxide and TNF-α are known to be involved in inflammatory reactions. In general, in the development of therapeutic agents and analgesics for inflammatory diseases, immune cells such as macrophages are stimulated with external stimulants such as lipopolysaccharides (LPS), and NO (nitric oxide), TNF-α, and prostaglandins in cells. after building the model such that E ₂ and so on are generated, by checking whether or not the administration of the inflammatory disease therapeutic agent or analgesic candidate suppressing generation of such NO (nitric oxide), TNF-α, prostaglandin E ₂ in these models A method of evaluating the anti-inflammatory or analgesic effect of the candidate is adopted. Until now, non-steroidal anti-inflammatory agents (NSAIDs), such as indomethacin and aspirin, which inhibit prostaglandin synthesis, are mainly used as anti-inflammatory agents, and steroids such as dexamethasone have been used as secondary prescriptions. However, these drugs have a variety of side effects, especially gastrointestinal disorders, serious side effects of liver and kidney dysfunction. In addition, lipopolysaccharide (Lipopolysaccharide, hereinafter referred to as LPS) rapidly increases the hepatic portal influx of endotoxins containing LPS, resulting in the activation of inflammatory cells in the liver (TNF-α, Tumor Necrosis Factor-α). ) Increases the secretion of hepatic inflammatory hepatitis, and the pathological expression of acute chronic inflammation in the liver reduces the expression of hepatocellular transporter protein, and the lowering of the transporter protein leads to disorders of bile excretion, blood of cholestatic liver disease Increased expression of alkaline markers such as Alkaline phosphatase (hereinafter referred to as ALP), γ-glutamyl transpeptidase (γ-GT), etc. (Grun M et al., Acta Hepatogastroenterol (Stuttg), 24 , pp. 64-81, 1977).

The novel compound Ponciol of the present invention is a compound of the Prenylated Coumarin family, and reported to be separated from Triphasia trifoliata, a plant similar to the previous plant, which is the most similar structurally, a tanza and a plant. (Triphasiol) is known (De Silva LB et al., Phytochemistry, 20 , pp. 2776-2778, 1981), but phonsiol has two hydroxyl groups instead of the ketone group of the isoprenyl group present in tripassiol. It is largely distinguished from the structure of faciol. The structurally relatively similar tripassiols were isolated from the herbal medicines similar to the medicinal herb extracts of Golden, fruit, rhubarb, peony and Siho among the components of the mixed herbal extracts of the present invention and the novel compounds of the present invention. In view of the fact that it contains a number of hydroxyl groups, the novel compound of the present invention was named phonsiool. To date, the physiological activity of prenylated coumarins structurally similar to the novel compound ponsiol of the present invention, including trifasiol, is unknown.

The inventors have invented a mixed herbal extract of golden, fruit, rhubarb, peony and shiho having excellent effects on liver protection and prevention and treatment of hepatitis (Korean Patent Application 10-2008-0133429). Based on these previous studies, new compounds were isolated from the mixed herbal extracts of golden, fruit, rhubarb, peony, peony and siho and continuously studied the pharmaceutical use of the compounds. The present invention was completed by confirming the effect of inhibiting the production of prostaglandin E ₂ (PGE ₂ ) induced by polysaccharide (LPS).

In order to achieve the above object, the present invention provides a novel compound Pontciol of the formula (I) or a pharmaceutically acceptable salt thereof:

The novel compounds of the present invention represented by the above formula (I) may be prepared as pharmaceutically acceptable salts according to methods conventional in the art.

As the pharmaceutically acceptable salt, acid addition salts formed by free acid are useful. Acid addition salts are prepared by conventional methods, for example by dissolving a compound in an excess of aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. Equimolar amounts of the compound and acid or alcohol (eg, glycol monomethylether) in water can be heated and the mixture can then be evaporated to dryness or the precipitated salts can be suction filtered.

In this case, organic acids and inorganic acids may be used as the free acid, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. may be used as the inorganic acid, and methanesulfonic acid, p -toluenesulfonic acid, acetic acid, trifluoroacetic acid, Citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid ( gluconic acid), galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanic acid, and hydroiodic acid.

In addition, bases can be used to make pharmaceutically acceptable metal salts. An alkali metal or alkaline earth metal salt is obtained by, for example, dissolving a compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and then evaporating and drying the filtrate. At this time, as the metal salt, it is particularly suitable to prepare sodium, potassium or calcium salt, and the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (for example, silver nitrate).

Pharmaceutically acceptable salts of the compounds of the invention include salts of acidic or basic groups which may be present in the compounds of the invention, unless otherwise indicated. For example, pharmaceutically acceptable salts include sodium, calcium and potassium salts of the hydroxy group, and other pharmaceutically acceptable salts of the amino group include hydrobromide, sulfate, hydrogen sulphate, phosphate, hydrogen phosphate, dihydrogen Phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p -toluenesulfonate (tosylate) salts, and methods or processes for preparing salts known in the art It can be prepared through.

The present invention provides a pharmaceutical composition for the prevention and treatment of inflammatory diseases containing the novel compound of the formula (I) ponsiol (Ponciol) as an active ingredient.

The novel compound ponsiol of the present invention is characterized in that it is separated from the mixed herbal extracts (G Korean Patent Application No. 10-2008-0133429) of golden, fruit, rhubarb, peony and shiho.

Hereinafter, the method for obtaining the novel compound of the present invention will be described in detail.

The mixed herbal extracts of golden, fruit, rhubarb, peony and shiho are mixed with 16 to 21 wt% of shredded golden, fruit and peony, 1 to 4 wt% rhubarb and 33 to 51 wt% shiho The first step to do; About 2 to 10 times (v / w), preferably about 3 to 6 times (v / w) volume of water, C ₁ to C ₄ lower alcohols or mixed solvents thereof, preferably Cold extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, heating extraction, preferably heating extraction at 80 to 100 ° C., preferably at 100 ° C. for 1 hour to 5 hours, preferably 3 hours. Repeating the second time to obtain an extract; Gold, fruit and rhubarb through the process described in Korean Patent Application No. 10-2008-0133429 in the third step, which is allowed to cool at 0 to 30 ° C, preferably at room temperature, and filtered to concentrate the filtrate under reduced pressure with a rotary pressure reducer or a lyophilizer. Mixed herbal extracts of, peony and shiho can be obtained.

Further, after suspending in water of 2 to 10 times, preferably 3 to 6 times (v / w) water of the extract obtained above, methylene chloride is added 1 to 4 times, preferably by adding an equal volume of water. Fractionating two to three times to separate the water-soluble layer (I) and the methylene chloride layer; A second step of drying the separated methylene chloride layer under reduced pressure with a rotary vacuum concentrator to obtain a methylene chloride fraction; A third step of adding butanol to the water-soluble layer (I) of the first step and fractionating 1 to 5 times, preferably 2 to 4 times, to separate the water-soluble layer (II) and the butanol layer; The butanol fraction and the water-soluble fraction may be obtained through the process described in Korean Patent Application No. 10-2008-0133429 of the fourth step of drying the separated butanol layer and the water-soluble layer under reduced pressure with a rotary pressure reducer.

The butanol fraction obtained through the process described in Korean Patent Application No. 10-2008-0133429 described above was prepared using high-performance liquid chromatography using 20%, 30% and 40% of acetonitrile and water mixtures using water and acetonitrile as mobile phases. Dividing into three fractions and drying under reduced pressure; A second step of obtaining a small fraction by performing high-performance liquid chromatography using 30% acetonitrile fraction of the acetonitrile fraction of the first step using water and acetonitrile as a mobile phase and increasing acetonitrile content; The small fraction may be separated and purified through the third step of manufacturing the high-performance liquid chromatography under isocratic conditions of 50% methanol.

The present invention provides a pharmaceutical composition for the prophylaxis and treatment of inflammatory diseases containing the novel compound ponsiol (Ponciol) separated and purified by the manufacturing process as an active ingredient.

The inflammatory disease as defined herein includes liver damage, hepatitis, inflammation of various organs in vivo, arthritis, dermatitis, oral inflammation, rhinitis or hemorrhoids, preferably liver damage or hepatitis It is characterized by.

A pharmaceutical composition containing the compound of the present invention as an active ingredient contains 0.1 to 50% by weight of the compound, based on the total weight of the composition.

However, the composition as described above is not necessarily limited thereto, and may vary according to the condition of the patient and the type and extent of the disease.

The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.

The compositions of the present invention can be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral formulations, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. Carriers, excipients and diluents that may be included in the composition comprising the compound include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations may contain at least one excipient such as starch, calcium carbonate, sucrose, or the like. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Oral liquid preparations include suspending agents, liquid solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The preferred dosage of the composition of the present invention varies depending on the condition and the weight of the patient, 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. However, for the desired effect, the compound of the present invention is preferably administered at 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg per day. The administration may be carried out once a day or divided into several doses. Therefore, the above dosage does not limit the scope of the present invention in any aspect.

The composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

In another aspect, the present invention provides a health functional food for the prevention and improvement of inflammatory diseases containing the novel compound ponsiol (Ponciol) separated and purified by the manufacturing process as an active ingredient.

The composition comprising the compound of the present invention can be used in various ways, such as drugs, food and beverages for the prevention and improvement of inflammatory diseases. Examples of the food to which the compound of the present invention may be added include various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, and may be used in the form of powders, granules, tablets, capsules, or beverages. have.

The compounds of the present invention may be added to foods or beverages for the purpose of preventing and ameliorating inflammatory diseases. In this case, the amount of the compound in the food or beverage is generally added to the health food composition of the present invention to 0.01 to 15% by weight of the total food weight, the health beverage composition is 0.02 to 10 g, preferably based on 100 ml Can be added in a ratio of 0.3 to 1 g.

The health beverage composition of the present invention, in addition to containing the compound as an essential ingredient in the indicated proportions, has no particular limitation on the liquid component and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like Sugar, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 mL of the composition of the present invention.

In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

The new compound ponciol isolated from the mixed herbal extracts of golden, fruit, rhubarb, peony and shiho having the hepatoprotective and hepatitis preventive and therapeutic effects of the present invention is induced to lipopolysaccharide (LPS) in macrophages. By confirming the effect of inhibiting the production of prostaglandin E ₂ (PGE ₂ ), it can be used in pharmaceutical compositions and health functional foods useful for the prevention and treatment of inflammatory diseases.

Hereinafter, the present invention will be described in detail by reference examples, examples and experimental examples.

However, the following Reference Examples, Examples, and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Reference Examples, Examples, and Experimental Examples.

Example 1 Isolation of New Compound Ponsiol

1-1. Preparation of Mixed Herbal Extract (Korean Patent Application 10-2008-0133429)

120 g of shredded gold, fruit and peony purchased from Gyeongdong market (Seoul, Korea) were mixed with 240 g of Siho and 15 g of rhubarb, and 3 L of water was added thereto at 100 ° C. for 2 hours. Heated extraction was repeated twice. 20 g of mixed herbal extracts of golden, fruit, rhubarb, peony and shiho through the process described in Korean Patent Application No. 10-2008-0133429, which is cooled to room temperature, filtered, and the filtrate is frozen at -70 ° C, and then concentrated by a lyophilizer. (Yield: 3.25%) was obtained and used as a sample for the following experimental example (hereinafter referred to as "SHP-1").

1-2. Preparation of Fractions (Korean Patent Application 10-2008-0133429)

1-2-1. Preparation of Methylene Chloride Fraction

10 g of "SHP-1" obtained in Example 1-1 was suspended in 1 L of water, and then 1 L of methylene chloride was added to separate the water layer and the methylene chloride layer on the separatory funnel, and this process was repeated twice. It was. 950 mg of methylene chloride fraction (hereinafter referred to as “SHP-1 (M)”) and an aqueous solution were prepared by the process described in Korean Patent Application No. 10-2008-0133429, which was dried under reduced pressure at 30 ° C. using a rotary vacuum condenser. It was obtained and used as a sample of the following experimental example.

1-2-2. Preparation of Butanol Fraction

 1 L of saturated butanol was added to the aqueous solution of Example 1-2-1 and separated into a water layer and a butanol layer on a separatory funnel, and the process was repeated twice. 4.2 g of butanol fraction (hereinafter referred to as “SHP-1 (Bu)”) and water through the process described in Korean Patent Application No. 10-2008-0133429, wherein the butanol layer and the water layer were dried under reduced pressure at 50 ° C. using a rotary vacuum condenser. 4.5 g of soluble fraction (hereinafter referred to as “SHP-1 (W)”) were obtained and used as samples in the following experimental example.

1-3. Isolation of Novel Compound Ponsiol

1.2 g of butanol fraction “SHP-1 (Bu)” obtained in Example 1-2-2 was subjected to high performance liquid chromatography [Gilson 321 system; Elution rate: 12 ml / min, total elution time: 120 min, column: Waters C18, 300 × 30 mm, 15 μm] using 20%, 30% and 40% acetonitrile and water mixture with water and acetonitrile as mobile phases. Divided into three fractions. Each fraction was dried under reduced pressure at 40 ° C. with a rotary vacuum concentrator.

High-performance liquid chromatography method using 600mg of 30% acetonitrile fraction in the acetonitrile fraction by increasing the content of acetonitrile from 10% to 100% using water and acetonitrile as a mobile phase [Gilson 321 system; Elution rate: 12 ml / min, total elution time: 120 min, column: Waters C18, 300 × 30 mm, 15 μm], containing the new compound ponsiol of the present invention and previously reported rapontisin at 18 min. A small fraction 70 mg was obtained.

70 mg of the small fraction was subjected to high performance liquid chromatography (Gilson 306 system; Elution rate: 2 ml / min, column: Econosil ^® RP-18, 10 μ, 250 × 22 mm] was used to separate and purify the ponsiol (1 mg) of the novel structure having the following structural formula and physical properties at 20 minutes retention time.

Ponciol

^{1 H NMR (500 MHz, DMSO-} d 6); δ 7.94 (1H, d, J = 9.5 Hz, H-4), 7.52 (1H, d, J = 8.5 Hz, H-5), 7.04 (1H, d, J = 8.5 Hz, H-6), 6.25 (1H, d, J = 9.5 Hz, H-3), 5.05 (1H, d, J = 5.5 Hz, 2'-OH), 4.47 (1H, s, 3'-OH), 4.44 (1H, s, 3 "-OH), 4.35 (1H, dd, J = 10.0, 2.0 Hz, H ₂ -1'a), 4.29 (1H, d, J = 6.0 Hz, 2" -OH), 3.89 (1H, dd, J = 10.0, 8.0 Hz, H ₂ -1'b), 3.58 (1H, ddd, J = 8.0, 5.5, 2.0 Hz, H-2 '), 3.50 (1H, ddd, J = 9.0, 6.0, 2.5 Hz , H-2 "), 2.92 (1H, dd, J = 13.0, 2.5 Hz, H ₂ -1" a), 2.87 (1H, dd, J = 13.0, 9.0 Hz, H ₂ -1 "b), 1.16 and 1.10 (each 3H, s, H ₃ -4 'and H _3-5 '), 1.15 and 1.14 (each 3H, s, H ₃ -4 "and H _3-5 ").

^{13 C NMR (125 MHz, DMSO-} d 6); δ 161.0 (C-2), 160.4 (C-7), 153.5 (C-8a), 145.2 (C-4), 127.4 (C-5), 117.0 (C-8), 113.6 (C-3), 113.0 (C-4a), 110.1 (C-6), 77.1 (C-2 "), 76.0 (C-2 '), 71.2 (C-3'), 70.9 (C-1 '), 28.2 and 25.0 ( C-4 'and C-5'), 27.3 and 25.1 (C-4 "and C-5"), 25.6 (C-1 ").

Experimental Example 1 Prostaglandin E Induced by Lipopolysaccharide ₂ Inhibitory effect

Parameter ^TM PGE ₂ assay kit (R & D Systems) was used to measure the inhibitory effect of the production of prostaglandins (PGE ₂ ).

Inflammatory responses were induced by treating lipopolysaccharide (LPS; lipopolysaccharide) at a concentration of 1 μg / μl in Raw264.7 cells (ATCC, 1 × 10 ⁵ cells). After treating the separated and purified ponsiol in Example 1-3 with 10 ㎍ / ml and reacted for 24 hours, 80 ㎕ of the supernatant was diluted with 160 ul of diluent buffer, goat anti-mouse The wells coated with polyclonal antibodies were subjected to a competitive reaction as PGE ₂ conjugates. Antibody-antibody reaction was performed for 24 hours by adding an antibody to PGE ₂ contained in the Parameter ^TM PGE ₂ assay kit, followed by comparative quantitation by measuring the color development at 450 nm. As a control group, a negative control group, LPS alone treatment group, indomethacin (7 μg / ml concentration) treatment group, and dexamethasone (20 μg / ml concentration) treatment group were used.

Experimental results showed that the prostaglandin E ₂ (PGE ₂ ) was purified by lipopolysaccharide (LPS) in Raw264.7 cells. In the experimental model induced production, 10 μg / ml administration group (Ponciol), LPS monotherapy group (LPS +), negative control group (LPS-), dexamethasone treatment group of the novel compound ponsiol separated and purified in Example 1-3 (Dex) and indomethacin treated group (Ind) show the effect of inhibiting the production of prostaglandin E ₂ (PGE ₂ ) in FIG. 1.

As shown in FIG. 1, the 10 μg / ml administration group of ponsiol was able to confirm the effect of inhibiting prostaglandin E ₂ (PGE ₂ ) production at a level similar to the 20 μg / ml treatment group of dexamethasone (Dex).

Hereinafter, the formulation examples of the composition comprising the compound ponsiol isolated from the mixed herbal extracts of golden, fruit, rhubarb, peony and peony of the present invention will be described, but the present invention is not intended to limit the present invention but only to be described in detail. to be.

Formulation Example 1 Preparation of Powder

Ponsiol 20 mg

Lactose 100 mg

Talc 10 mg

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Formulation Example 2 Preparation of Tablet

Ponsiol 10 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

Formulation Example 3 Preparation of Capsule

Ponsiol 10 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

Formulation Example 4 Preparation of Injection

Ponsiol 10 mg

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na2HPO4,12H2O 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Formulation Example 5 Preparation of Liquid

 Ponsiol 20 mg

10 g of isomerized sugar

5 g of mannitol

Purified water

After dissolving each component in purified water according to the usual method of preparing a liquid solution, adding lemon flavor appropriately, mixing the above components, adding purified water, adjusting the whole to 100 ml by adding purified water, and then filling into a brown bottle. The solution is prepared by sterilization.

Formulation Example 6 Preparation of Healthy Food

Ponsiol 1000 mg

Vitamin mixture quantity

70 [mu] g of vitamin A acetate

Vitamin E 1.0 mg

0.13 mg vitamin B1

0.15 mg of vitamin B2

0.5 mg vitamin B6

0.2 [mu] g vitamin B12

10 mg vitamin C

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 ㎍ of folic acid

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

15 mg of potassium phosphate monobasic

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

100 mg of calcium carbonate

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.

Formulation Example 7 Preparation of Healthy Drink

Ponsiol 1000 mg

Citric acid 1000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water was added to a total of 900 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >

Although the composition ratio is a composition that is relatively suitable for the preferred beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

1 is a diagram showing the effect of the novel compound ponsiol inhibits the production of lipopolysaccharide (LPS) -induced prostaglandin E ₂ (PGE ₂ ) in Raw264.7 cells.

Claims (5)

Novel compounds Pontciol of the formula (I) or a pharmaceutically acceptable salt thereof:

A pharmaceutical composition for the prevention and treatment of inflammatory diseases, comprising the novel compound ponsiol of claim 1 as an active ingredient. The pharmaceutical composition according to claim 2, wherein the inflammatory disease is liver damage, hepatitis, inflammation of various organs in vivo, arthritis, dermatitis, oralitis, rhinitis or hemorrhoids. Health functional foods for the prevention and improvement of inflammatory diseases containing the novel compound ponsiol of claim 1. The dietary supplement of claim 4 which is a powder, granule, tablet, capsule or beverage.

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