PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING LIVER FIBROSIS COMPRISING 8-HYDROXYDEOXYGUANOSINE (OHDG)

The present invention is a method for effective treatment of victims of the [...] for developing, performing various studies automatically change, has been 8 provided OHdG varies. Said 8 provided OHdG is contained DNA or a DNA is separated to a DNS repair enzyme contained in [nyo 8 provided OHdG number by dividing the wetting ability to oxidative stress by measuring cell lines using the 8 provided OHdG characterized in that it has, through recent research, compete on the GTP binding activity of activated RAC1 RAC1-a GTP by through the NOX complex number billion billion number represents the resulting anti-corrosion but is potent antioxidant action and newly has been found, as an effective [...] reporting of the capacitor until now not been provided.

The present invention the outer planes and small animal model number the number victims of the bile duct through the agent, the administration of 8 a-OHdG according to serving as change, various [...] marker levels of agent animal model of centrifugal in but, by histamine 8 provided OHdG said receipt is accurate and reduced levels of various markers, the new number can be used as said 8 provided OHdG [...] treatment was examined. 8 A-OHdG of therapeutic effect not heretofore known for such [...], been solved for the first time by the present invention.

In order to achieve the above-described purposes, one aspect the present invention refers to a pharmaceutically acceptable salt thereof including agent or hepatic cirrhosis 8 provided OHdG or use of a pharmaceutical composition for preventing or treating number [...] substrate.

Terms of the present invention provide the means by which "8 a-OHdG(8 a-hydroxydeoxyguanosine)", "8 a-Oxo-a 2' - deoxyguanosine" or "8 a-oxo-a dG" is called referred [...] big derivative compound oxide. Said 8 provided OHdG is DNA of one of oxidation product, quantifying the level of oxidative stress applied concentration of intracellular 8 provided OHdG cells can be used.

Of the present invention the term "pharmaceutically acceptable salt" RM, electrostatic attraction by bonded to silica anion salt form which can be used therapeutically about number substances among salt 200b, typically metal salt, salt with organic base, a salt with inorganic acid, a salt with organic acid, a salt with basic or acidic amino acid can be like. For example, metal salt include an alkali metal salt (sodium salt, such as potassium salts), alkaline earth metal salt (calcium salt, magnesium salt, barium salts), can be aluminum salt and the like; salts with organic base include triethylamine, pyridine, blood choline, 2, 6 - base mote [tin, ethanolamine, diethanolamines, high pressure, cyclo [heyk thread amine, DC claw [heyk thread amine, N, N - d it cuts the qualitative ethylene diamine can be with such as salt; salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, salt with phosphoric acid or the like can be; bring a salt with an organic acid, acetic acid, styrene thermoplastic rubber, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methane sulfonic acid, benzene sulfonic acid, toluene sulfonic acid salt with p - such as can be; basic amino acid include a salt with arginine, lysine, ornithine or the like can be with salt; salts with acidic amino acids include aspartic, such as glutamic acid salt with can be.

Preferred salts include in particular, compound in when having an acid, alkali metal salt (e.g., sodium salt, such as potassium salts), alkaline earth metal salt (e.g., calcium salt, magnesium salt, barium salts) such as inorganic salts, organic salts such as ammonium salt which, compound in basic functional group if it has, hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, a salt with an inorganic acid such as phosphoric acid, acetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methane sulfonic acid, toluene sulfonic acid salt with an organic acid such as p - such as the pin is.

Terms "agent" of the present invention implies, normal hepatocytes damaged liver tissue such as collagen fibers modified state without contrary big diseases that show. 33:10 And mainly due to hepatocyte necrosis appear later, region 1 (zone 1) of contextual - cooperating with a digital TV context fibrous crosslinked (portal provided portal fibrous bridges) appear later cause hepatitis in known. In particular the pin is hepatic cirrhosis will disease such as arthritis.

"Treating hepatic cirrhosis" terms of the present invention provide the means by which, due to the repetitive and hepatitis and in-between with damage and its duration of hepatocytes (liver fibrogenesis) and reproducing nodule (nodule) is less than fiber according to liver disease with symptoms means other. One end of which solidifies and simple mainly between materials, most simple leaf structure with reverse voltage of a three-dimensional positional relationship to central venous destroyed context of instant, about 20 to 40% in hepatocellular carcinoma is progressed into a known. The use when restored to normal liver cirrhosis progression between the traces of one to the other side of territory characterized, using a pharmaceutical composition of the present invention to the afflicted [...] target can be effected.

Terms "prevention" RM of the present invention, a pharmaceutical composition for preventing or treating liver cirrhosis or agent administered in vivo use of the present invention according to agent or use of delayed onset or billion number's big.

"Treatment" of the present invention provide the means by which terms, use of the present invention according to agent or pharmaceutical composition for preventing or treating hepatic cirrhosis or hepatic cirrhosis or improving agent administered in vivo use of normal cells such as cells converting angry [...] proceeds advantageously changing's big.

In the present invention number [...] 8 provided OHdG in liver tissues is the hydroxy proline, TGF-a β (transforming growth factor β), TIMP-a 1 (tissue inhibitor of metalloproteinases 1), collagen, α-a SMA (α smooth muscle actin), NOX1 (NADPH oxidase 1), NOX2 (NADPH oxidase 2), Rac1 (ras a-related C3 botulinum toxin substrate 1) expression of a variety of agent marker can number billion.

In the embodiment of the present invention the one, bile duct ligation (BDL) total number to a test object for detecting BAX and small animal model that agent performed number, said number 8 provided OHdG it became work agent in an animal model (8 a-hydroxydeoxyguanosine) comparing the expression level of the marker agent according to whether administration of his change. As a result, ketoprofen liver tissues level agent in an animal model but abruptly increases, followed by the administration of 8 a-OHdG decreases too soon (also 1), TGF-a β (transforming growth factor β), TIMP-a 1 (tissue inhibitor of metalloproteinases 1), collagen, α-a SMA (α smooth muscle actin), NOX1 and NOX2 (NADPH oxidase 1) (NADPH oxidase 2) abruptly increases in mRNA levels of liver tissues but also agent in an animal model, 8 a-OHdG(also 2a to 2f) has been followed by the administration of decreases, collagen, α-a SMA, NOX1 and NOX2 abruptly increases but also agent in an animal model of liver tissues at the protein level, followed by the administration of 8 a-OHdG is has been confirmed that the (also 3a to 3d) are used.

Said pharmaceutical compositions include pharmaceutical compositions commonly used number of the bath appropriate carrier, excipient can further include a number or dilution number, said carrier is a carrier which is cytolytic can be. Said carrier, excipient peak number and dilution number include lactoperoxidase, dextran lactose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate and mineral oil is cited.

On the other hand, pharmaceutical compositions of the present invention, acid number each according to conventional method, granules number, positive number, number capsule, suspension, emulsion, syrup, aerosol such as oral number type, external number, can be used in the form of a sterile injection solution and is supported by a left number number number. If filling normally used under anger number number number, a specific number, number coupled, wet number, number disintegrating, dilution number number number or excipients such as surfactants using tank number with each other. Positive number number number is solid for oral administration, ring number, acid number, number granules, such as included in a capsule number, said at least one excipient such solid number number number is stem cells extract for example, starch, calcium purification (calcium carbonate), sucrose (sucrose) or lactose (lactose), gelatin tank pressure is lowered number with each other. In addition number [...] magnesium in addition to simple excipients, are also used in lubricating number such as talc. For liquid oral suspension include number number number, number content, oil number, like a simple dilution number corresponding number syrup used commonly used in water, in addition to the paraffin droplet number various excipients, for example wet number, sweetener number, direction number, number and the like can be preserved. For parental administration number number is a sterile aqueous solution, non-aqueous for number, number suspension, oil number, freeze-dried number number, number left multiple myelomas are included. Non-aqueous for number, number suspension include propylene glycol (propylene glycol), polyethylene glycol, vegetable oil such as olive oil, such as the [ley which comes the [thu and ethyl ester is used as the injectable can be. As above [theyp brush left number for number (witepsol), mark with goal, twin (tween) 61, carcass five fingers, that it soaked, can be preparing gelatin is used as the alkali.

Pharmaceutical compositions unexpectedly give rise said positive number, number ring, acid number, number granules, capsule number, suspension number, number content, oil number, number syrup, sterile aqueous solution, non-aqueous for number, number suspension, oil number, left number number number selected from the group consisting of freeze-dried and may have either number type.

Pharmaceutical compositions of the present invention said number but not included in the content of 8 a-OHdG pass it on one, of the total weight of the final composition to 0. 0001 To comprise 50% by weight and, preferably 0. 001 To 10% by weight can be of content.

Said of the present invention can be administered in an amount effective pharmaceutical pharmaceutical compositions, of the present invention terms "pharmaceutically effective amount" RM, rational possibility [hyey/ risk ratio applicable to medical treatment in an amount sufficient to treat conditions which means, individual effective capacity level types and severity, age, sex, drug, drug sensitivity, administration time, routes and discharge ratio, a treatment period, simultaneous use the sealed elements and other medical fields can be determined according to well-known element. Pharmaceutical compositions of the present invention individual treatment or administration of other therapeutic number number on with administration of treatment can be administered simultaneously can be sequential or the ratio of number of the existing method. And can be single or multiple administration. Said element in an amount of at least considers both the maximum effect can be obtained without adverse administering an amount as important disclosed.

Pharmaceutical compositions dosage is intended use of the present invention, addiction diseases also, patient's age, weight, sex, past power, or as the active ingredient can be determined by considering one skilled the material used for the case. For example, pharmaceutical compositions of the present invention 1 adult per is about 0. 1 Ng to about 100 mg/kg, preferably 1 ng to about 10 mg/kg can be administered, particularly the frequency number but not one administration of the present invention, administering a single administration or capacity can be many times by dividing 1 1.

In other embodiments, the present invention refers to said developing agent or the pharmaceutical composition for treating liver fibrosis or cirrhosis that might potentially be, including administering to a subject a human agent or a method for preventing or treating hepatic cirrhosis [...] number the number [...] substrate.

Pharmaceutical compositions of the present invention is effected by administering the present invention according to terms "individual" can be agent or hepatic cirrhosis or fibrosis symptoms loop developing treating as long as modified, amount, porcine, chlorine, camel, nutritional, comprises two such as animals or humans. The present invention according to an animal by administering to an individual a pharmaceutical composition, agent or use of hepatic cirrhosis can be effective in preventing and treating. The present invention according to said treatment method is method for treating human [...] animal handler number, the number is not one. I.e., in the case of the present invention according to human composition for treatment of symptoms may be better effected by administering when considered, even can be fully using human treatment.

Terms of the present invention, an object of the present invention pharmaceutical compositions "administration" includes any suitable method to introducing it is, target tissue which can reach an oral or parental routes of administration can be by a variety of routes.

Said destination or conventional method used in the art pharmaceutical compositions unexpectedly give rise needed, routes, dose can be appropriately depending on a subject in need thereof. Examples of routes of oral, parenteral, subcutaneous, intraperitoneally, lung, and can be administered to the nasal, parenteral injection is intramuscular, intravenous, in artery, [thwu leisure under blood either intraperitoneally or multiple myelomas are included. In addition nitrile according to the publicly known method can be an appropriate dose and administration is selected, the number of the present invention administered as a pharmaceutical composition in the treatment chamber the amount and kind of conditions administration, routes, sex, health condition, dietary, age and weight of an individual, various diseases and severe degree factor can be properly.

In the present invention the terms "pharmaceutically effective amount" to medicinal uses of rational possibility [hyey/ risk ratio applicable to a sufficient amount which means increased vascular permeability or a billion number, type and individual effective capacity level severity, age, sex, drug, drug sensitivity, administration time, routes and discharge ratio, a treatment period, simultaneous use the sealed elements and other medical fields can be determined according to well-known element. Composition of the present invention individual treatment or administration of other therapeutic number number on with administration of treatment can be administered simultaneously can be sequential or the ratio of number of the existing method. And can be single or multiple administration. Said element in an amount of at least maximum effect can be obtained without adverse considers both the amount administered important, can be determined by one skilled for hereinafter.

In other embodiments, the present invention refers to 8 provided OHdG or a pharmaceutically acceptable salt thereof including agent or treating hepatic cirrhosis for improving food composition number [...] substrate.

In the present invention number 8 provided OHdG [...] DNA oxidation product is formed which are of one of the food, food composition to form said 8 provided OHdG is for improving the functional use of the bath agent or hepatic cirrhosis number number bath can be used.

Said food composition contained in the pharmaceutically acceptable salt content are specially the 8 provided OHdG or not but one number, relative to the weight of the total weight of food 0. 001 To 10% by weight, more preferably 0. 1 To 1 weight % can be included. With reference to the cases where the food these 10g 1 to 100 ml, preferably at a rate of 2 to 7g can be included. In addition, said composition normally used number morning fair food odor, taste, which can additionally be fixed to the time comprise an active ingredient. For example, vitamin A, C, D, E, B1, B2, B6, B12, niacin (niacin), biotin (biotin), supplemental (folate), Pantothenic acid (panthotenic acid) can be like. In addition, zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu) can be of glutinous rice. In addition, lysine, tryptophan, cysteine, valine amino acids such as can. In addition, antiseptic number (sorbitol empty mountain potassium, benzoic acid sodium, salicylic acid, such as draw nitric acid natrium), sterilization number (and highly [...][...], such as sodium hypochlorite), anti-oxidation number (butyl the [tu rock city it knows it will doze (BHA), butyl [tu rock city [thol type n (BHT) or the like), coloring number (such as tar dye), color number (sodium nitrite, such as sodium oh nitric acid), bleaching number (sodium sulfite), seasoning (MSG glutamic acid sodium and the like), sweetener (it puts new, cycle [...], saccharin, sodium and the like), perfume (vanillin, lactone or the like), expansion number (alum, hydrogen potassium D - tartaric acid), reinforced number, emulsion number, number more (good [lyo), coating number, number [...], foam billion number number, number for, improved number of food additive (food additives) can be added. Said additive is selected depending on the type of food is suitable is 1.

On the other hand, or a pharmaceutically acceptable salt thereof including said 8 provided OHdG food composition for improving or treating non-allergic inflammatory disease treating agent or hepatic cirrhosis cirrhosis number functional foods can be high pressure liquid coolant agent.

In specific embodiments, use of said food composition agent or hepatic cirrhosis can be processed foods can improve the number high pressure liquid coolant, for example, confectionery, beverage, liquor, fermented food, canned, milk food, meat processing in the form of a health food or food noodle 1308. number ethanol bath. , the cake a wheen biscuits, pie, cake, bread, candy, jelly, gum, etc. Serial (grain meal substitute such as [phwu rake the condenser microphone). A functional beverage, carbonated beverage, functional ion beverage, juice (for example, apple, times, grapes, aloe, citrus, peach, carrot, tomato juice or the like), etc. organoleptic properties as well. The liquor products, whisky, Soju, beer, coupled in, cork etc.. Fermented food soy sauce, soybean paste, etc. of the product. Thus canned canned (for example, tuna, fishy smell, pike, turban shell such as canned), canned products (beef, pork, chicken, turkey such as canned), agricultural products (corn, peach, file applicator such as canned) canned comprises. Food milk cheese, butter, yogurt etc.. Meat processing food product may be a pork cutlet, browser cutlet, chicken cutlet, sausage. Switch, certain depth from current, etc. slice of roast. Noodles such as seal comprise a new aspect. In addition said composition retort food, soup or the like can be used.

Of the present invention terms "health functional food (functional food)" RM, food for specified health use (food for special health use, FoSHU) terms identical to, processed to medical biological output control efficiency in addition feeder cells generally, medical efficacy which means high food, said food product may be a agent or hepatic cirrhosis improvement for obtaining useful effect in use of positive number, capsule, powder, granules, liquid, a variety of ring form number bath 1308.