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WO2017183902A1 - Composition contenant des extraits de artemisia capillaris, sanguisorba officinalis et curcuma longa et un agent antiviral, en tant que principes actifs, destinée à prévenir ou traiter une maladie du foie - Google Patents

Composition contenant des extraits de artemisia capillaris, sanguisorba officinalis et curcuma longa et un agent antiviral, en tant que principes actifs, destinée à prévenir ou traiter une maladie du foie Download PDF

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WO2017183902A1
WO2017183902A1 PCT/KR2017/004184 KR2017004184W WO2017183902A1 WO 2017183902 A1 WO2017183902 A1 WO 2017183902A1 KR 2017004184 W KR2017004184 W KR 2017004184W WO 2017183902 A1 WO2017183902 A1 WO 2017183902A1
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Prior art keywords
hepatitis
liver disease
antiviral agent
turmeric
extract
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English (en)
Korean (ko)
Inventor
김범준
이장훈
인경수
장은경
이경태
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Kyung Hee University
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Kyung Hee University
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282—Artemisia, e.g. wormwood or sagebrush
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/739—Sanguisorba (burnet)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present invention relates to a composition for preventing or treating liver disease, which comprises phosphorus, fat and turmeric extract, and an antiviral agent as an active ingredient.
  • HBV Human hepatitis B virus
  • diseases such as self-controlling acute hepatitis, blunt hepatitis or chronic active hepatitis.
  • Chronic active hepatitis develops, causes cirrhosis and liver cancer, and can be acutely acute with liver failure (Brechot, C., J. Hepatol., 4, 269-279, 1987).
  • Rechot, C., J. Hepatol., 4, 269-279, 1987 When infected with chronic hepatitis, most patients show persistent or active hepatitis, while some do not. The pathogenesis or causative factors of the viral hepatitis are not clear yet.
  • liver damage caused by the hepatitis B virus is mediated by the host's immune cells (Milich, DR et al., J. Immunol., 143, 3141-3147, 1989).
  • Intensive studies have been conducted on the immune response of specific B and T cells and the direct or pathogenic mechanisms of viral proteins (R. Zschke, O. et al., Nature, 348, 252-254 (1990). ).
  • the causes of the clinical pathways that still vary from patient to patient are not clear.
  • Hepatitis B has been studied with great interest in its treatment because of its severity.
  • drugs and vaccines have been developed and have received good reviews in preclinical and clinical trials, but few drugs have been applied as actual therapeutics.
  • HBV hepatitis B virus
  • the only treatment for hepatitis B virus (HBV) hepatitis patients is human immunity. It depends on the system. Human immune action against HBV removes HBV particles, but on the other hand, destroys hepatocytes, so side effects of these immune actions can lead to fatal diseases.
  • HBV hepatitis B virus
  • infected hepatocytes are destroyed by cytotoxic T lymphocytes (CTLs), and virus particles released from the destroyed hepatocytes remove the neutralizing antibodies against the virus to prevent reinfection into the hepatocytes. Proliferation of should also be suppressed.
  • CTLs cytotoxic T lymphocytes
  • interferon, nucleic acid derivatives or immunomodulators only interferon- ⁇ has been shown to be the only therapeutic effect. have.
  • Interferon- ⁇ was first tested by Sculled et al in the mid-1970s as a treatment for chronic hepatitis B. It has been shown to be effective in inhibiting HBV replication. However, when interferon- ⁇ is administered three times a week for at least three months, on average, 20% of patients show a therapeutic effect that inhibits virus growth but do not show sustained inhibitory effects. Patients or children are resistant to interferon- ⁇ and therefore have a low therapeutic effect. In addition, it has recently been reported that only 50% or less of acute and chronic patients infected with hepatitis B virus are suitable for the treatment of interferon- ⁇ . Among the patients, various enzymes (AST, Only if the amount of SGOT, ALT, SGPT, etc. is increased, the interferon- ⁇ treatment can be expected to be effective. Therefore, it is urgent to develop a hepatitis B virus therapeutic agent that can treat patients who are resistant to interferon- ⁇ , but the research is still insufficient.
  • Still another object of the present invention is to provide a health functional food for preventing and improving liver disease, which comprises phosphorus, fat milk and turmeric extract as active ingredients.
  • Still another object of the present invention is to provide a method for treating liver disease, comprising co-administration of an antiviral agent of hepatitis, hepatitis and turmeric extract and hepatitis B to a subject having a liver disease.
  • the present invention provides a pharmaceutical composition for treating liver disease, which comprises the extract of jinjin, fat milk and turmeric as an active ingredient.
  • the extract may be a mixture of phosphorus, fat milk and turmeric each weight ratio of 3: 1: 1.
  • the liver disease may be any one selected from fatty liver, hepatitis or cirrhosis.
  • the composition may be formulated or used in combination with an antiviral agent of hepatitis B.
  • the antiviral agent of hepatitis B may be at least one selected from entecavir, tenofovir, lamivudine, adefovir and clebudine. have.
  • the composition may inhibit or inhibit the expression of TNF- ⁇ , IL-1 ⁇ , TGF- ⁇ , collagenase I or collagenase IV.
  • the present invention provides a health functional food for preventing and improving liver disease, which comprises phosphorus, fat milk and turmeric extract as active ingredients.
  • the present invention provides a method for treating liver disease, comprising co-administration of the antiviral agent of hepatitis B and hepatitis B, turmeric extract and hepatitis B to a subject having a liver disease.
  • the antiviral agent of hepatitis B may be at least one selected from entecavir, tenofovir, lamivudine, adefovir and clebudine. have.
  • the liver disease may be any one selected from fatty liver, hepatitis or cirrhosis.
  • Combination administration of the antiviral agent of hepatitis, fat and turmeric extract with hepatitis B inhibits hepatitis B virus e antigen and effectively inhibits the expression of inflammatory cytokines TNF- ⁇ , IL-1 ⁇ or TGF- ⁇
  • TNF- ⁇ inflammatory cytokines
  • IL-1 ⁇ IL-1 ⁇
  • TGF- ⁇ inflammatory cytokines
  • Figure 2 confirmed the degree of HBV HBsAg (A) and HBV HBeAg inhibition (B) after administration of 30% ethanol extract of phosphorus, fat and turmeric, and by the combination administration of the antiviral agent (ETV) of the extract and hepatitis B The results of confirming the degree of HBV HBsAg (C) and HBV HBeAg inhibition (D) are shown.
  • Figure 3 shows the results of measuring the amount of pgRNA after administration of 30% ethanol extract of phosphorus, fat milk and turmeric.
  • Figure 4 is a result confirming the efficacy by the combined administration of antiviral agent of hepatitis, fat and turmeric extract and hepatitis B through the inhibition of HBV virion production in acute hepatitis B induced mice.
  • Figure 5 shows the results of measuring the cccDNA concentration after the co-administration of 30% ethanol extract of phosphorus, fat and turmeric and antiviral agent (ETV) of hepatitis B in acute hepatitis B induced mice.
  • Figure 7 shows the factors related to hepatic fibrosis by combination administration of antiviral agent of hepatitis, fat and turmeric extract and hepatitis B in acute hepatitis B induced mice, collagenage I, collagenase (collagenage) IV inhibitory effect was confirmed.
  • the present invention provides a composition for treating liver disease, which comprises an antiviral agent of phosphorus, fat and turmeric extract and hepatitis B as an active ingredient.
  • the currently used hepatitis B or liver disease treatments are inadequate in pharmacological effects due to no fundamental treatment, and in addition to weakening of virus elimination efficacy in long-term use, May cause side effects. Therefore, the inventors of the present invention, when combined with the antiviral agent of hepatitis B and hepatitis B and turmeric extract and the hepatitis B anti-viral proliferation effect compared to the conventional antiviral agent of hepatitis B alone, inflammatory cytokines and hepatic fibrosis Experiments confirmed that it can effectively suppress the expression of factors related to.
  • the present invention provides a composition for treating liver disease, which comprises an antiviral agent of phosphorus, fat and turmeric extract and hepatitis B as an active ingredient.
  • the "antiviral agent of hepatitis B" may be at least one selected from entecavir, tenofovir, lamivudine, adefovir and clebudine, but is not limited thereto. But most preferably may be entercavir.
  • the extract of the phosphorus, fat or turmeric according to the present invention can be used to isolate and obtain the extract for phosphorus, fat and turmeric using a method known in the art extraction and separation, defined in the present invention
  • An 'extract' can be extracted from phosphorus, fat, and turmeric using an appropriate solvent.
  • any suitable solvent that may be used to obtain the extract may be used as long as it is a solvent acceptable in the art, and water or an organic solvent may be used.
  • Solvents such as benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane may be used alone or in combination. It is not limited.
  • any one of hot water extraction method, cold leaching extraction method, reflux cooling extraction method, solvent extraction method, steam distillation method, ultrasonic extraction method, elution method and compression method can be used.
  • the desired extract may further be subjected to a conventional fractionation process, it may be purified using conventional purification methods.
  • any known method can be used.
  • the pharmaceutical composition of the present invention may be prepared using a pharmaceutically acceptable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant may include an excipient, a disintegrant, a sweetener, a binder, a coating agent, and an expanding agent.
  • the adjuvant may include an excipient, a disintegrant, a sweetener, a binder, a coating agent, and an expanding agent.
  • Lubricants, lubricants or flavoring agents can be used.
  • the pharmaceutical composition may be preferably formulated into a pharmaceutical composition including one or more pharmaceutically acceptable carriers in addition to the above-described active ingredient for administration.
  • Formulation forms of the pharmaceutical compositions may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops or injectable solutions.
  • the active ingredient may be combined with an oral, nontoxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water and the like.
  • suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture.
  • Suitable binders include, but are not limited to, natural and synthetic gums such as starch, gelatin, glucose or beta-lactose, corn sweeteners, acacia, trackercance or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride and the like.
  • Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.
  • Acceptable pharmaceutical carriers in compositions formulated as liquid solutions are sterile and biocompatible, which include saline, sterile water, Ringer's solution, buffered saline, albumin injectable solutions, dextrose solutions, maltodextrin solutions, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers and bacteriostatic agents may be added as necessary. Diluents, dispersants, surfactants, binders and lubricants may also be added in addition to formulate into injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Furthermore, the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA can be formulated according to each disease or component, as appropriate in the art.
  • the antiviral agent of the jinjin, fat milk and turmeric extract and hepatitis B of the present invention may be included in 0.1 to 50% by weight relative to the total weight of the composition.
  • liver disease which can be treated, prevented, and improved the phosphorus, fat milk and turmeric extract of the present invention is not limited thereto, but may be fatty liver, hepatitis or cirrhosis, most preferably hepatitis B.
  • composition of the present invention can be used as a food composition in addition to the pharmaceutical composition for the treatment and prevention of liver disease
  • the food composition contains a variety of active ingredients, such as ordinary food composition, in addition to containing the active ingredients phosphorus, fat milk and turmeric extract Flavoring agents or natural carbohydrates and the like may be included as additional ingredients.
  • Examples of the natural carbohydrates described above include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • the aforementioned flavoring agents can advantageously be used natural flavoring agents (tautin), stevia extracts (for example rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.).
  • the food composition of the present invention may be formulated in the same manner as the pharmaceutical composition, used as a functional food, or added to various foods.
  • Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes, and health supplements. There is this.
  • the food composition is a variety of nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors in addition to the phosphorus, fat and turmeric extracts as active ingredients, colorants and neutralizers (such as cheese, chocolate), Pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages and the like.
  • the food composition of the present invention may contain a fruit flesh for producing natural fruit juice and fruit juice beverage and vegetable beverage.
  • fat milk and turmeric extract of the active ingredient of the present invention is a natural substance, so there is little toxicity and side effects, so it can be used with confidence even in long-term use.
  • the health functional food of the present invention may be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills and the like for the purpose of improving and preventing liver damage.
  • health functional food refers to a food manufactured and processed using raw materials or ingredients having functional properties useful for the human body according to the Health Functional Food Act No. 6767, and nutrients for the structure and function of the human body. It is meant to be consumed for the purpose of regulating or obtaining a useful effect for health use such as physiological action.
  • the health functional food of the present invention may include a conventional food additive, and the suitability as a food additive, unless otherwise specified, in accordance with the General Regulations of the Food Additives and General Test Methods approved by the Food and Drug Administration, etc. Judging by the standards and standards.
  • Food Additive Reduction examples include chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Natural additives such as dark blue pigment, licorice extract, crystalline cellulose, high color pigment and guar gum; And mixed preparations such as sodium L-glutamate, algae additives, preservatives and tar dyes.
  • the health functional food in the form of tablets is a mixture of the jinjin, fat milk and turmeric extract of the active ingredient of the present invention with excipients, binders, disintegrants and other additives, and then granulated in a conventional manner, and then a lubricant and the like. Compression molding, or the mixture may be directly compression molded.
  • the health functional food in the form of tablets may contain a mating agent, if necessary.
  • Hard capsules among the health functional foods in the form of capsules can be prepared by filling a mixture of additives, such as excipients, phosphorus, fat and turmeric extracts, which are the active ingredients of the present invention, into conventional hard capsules.
  • a mixture of turmeric extract and additives such as excipients may be prepared by filling a capsule base such as gelatin.
  • the soft capsule agent may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, as necessary.
  • the health functional food in the form of a cyclic form can be prepared by molding a mixture of the jinjin, fat milk and turmeric extract and excipients, binders, disintegrating agents and the like as the active ingredients of the present invention, and, if necessary, sucrose or Other coatings may be applied, or the surface may be coated with materials such as starch, talc.
  • the health functional food in the form of granules can be prepared by granulation of a mixture of jinjin, fat milk and turmeric extract and excipients, binders, disintegrants and the like, which are the active ingredients of the present invention, and a flavoring agent, if necessary. And a copper may be contained.
  • the health functional food may be prepared in the form of tablets, capsules, pills or liquids, for example, beverages, meat, chocolate, foods, confectionary, pizza, ramen, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes And health supplements.
  • the present invention provides a method for treating liver disease, comprising co-administration of the antiviral agent of hepatitis B and hepatitis B, turmeric extract and hepatitis B to a subject having a liver disease.
  • the method of treating liver disease of the present invention comprises administering to the individual a therapeutically effective amount of an antiviral agent of hejin, fat and turmeric extract and hepatitis B.
  • the specific therapeutically effective amount for a particular individual can be determined by the specific composition, including the type and severity of the reaction to be achieved, whether or not other agents are used in some cases, the age, weight, general health, sex and diet, time of administration, It is desirable to apply differently depending on the route of administration and the rate of release of the composition, the duration of treatment, and the various factors and similar factors well known in the medical arts, including drugs used with or concurrent with the specific composition. Therefore, the effective amount of the composition suitable for the purpose of the present invention is preferably determined in consideration of the above matters.
  • the subject is applicable to any mammal, and the mammal includes humans and primates, as well as domestic animals such as cattle, pigs, sheep, horses, dogs, and cats.
  • the present inventors washed phosphorus, fat milk, turmeric with water, dried in the shade, and then finely powdered.
  • 45 g of powdered phosphorus, 15 g of fat milk, 15 g of turmeric was added to 70% ethanol and extracted by cold extraction at room temperature for 3 days, filtered under reduced pressure with a filter paper (Watman, USA), and the filtrate was concentrated on a vacuum rotary concentrator. After removing the ethanol solvent at room temperature to give 29.45 g of crude extract of phosphorus, fat milk, turmeric as an extracted residue.
  • KCT-O1 group in the present invention is a complex extract of the phosphorus, fat milk and turmeric of the present invention prepared by the method of Preparation Example 1, KCT-O2 group is 45: 15: 15 : 12: Extracted by mixing in a mixture of 12: KCT-03 group means the extract extracted the Injincheonggantang.
  • the present inventors treated Entecavir or Tenofovir at a concentration of 200 ⁇ g / ml in a HepG2.2.15 HBV-containing cell line, and treated KCT-O1, KCT-O2, KCT-O3 with 10, 25, 50, After further treatment at a concentration of 100 and 250 ⁇ g / ml, the cells were incubated for 24 hours, and the culture solution was recovered and subjected to HBeAg ELISA to measure the concentration of HBeAg.
  • HBeAg was not inhibited as compared to the control group treated with nothing, but the phosphorus, fat, turmeric complex herbal extract of the present invention and hepatitis B antiviral agent In the KCTO1 treatment group administered in combination, it was confirmed that the HBeAg inhibitory effect in a concentration-dependent (see Fig. 1).
  • the KCT-01 prepared by the method of Preparation Example 2 was also treated with HepG2.2.15 HBV-containing cell lines at concentrations of 31.5, 62.5, 125, and 250 ⁇ g / ml, and the culture solution was recovered to carry out HBsAg ELISA and HBeAg ELISA to obtain HBsAg and As a result of measuring the concentration of HBeAg it was confirmed that there is an inhibitory effect depending on the concentration.
  • hepatitis B antiviral alone was not administered, hepatitis B eantigen was not inhibited.
  • the herbal extract of the present invention was administered in combination with the hepatitis B antiviral agent, hepatitis B eantigen was effectively inhibited.
  • the method has the effect that can be used in the treatment of various liver diseases, including hepatitis B.
  • the present inventors further treated KCT-01 prepared by the method of Preparation Example 2 to a HepG2.2.15 HBV-containing cell line at concentrations of 0, 25, and 250 ⁇ g / ml, and then cultured for 48 hours, and recovered the culture solution.
  • RNA was extracted from and the concentration of pgRNA was measured using Real-time RT-qPCR method.
  • the inventors of the present invention have shown that when Entecavir was administered alone and Entecavir and Enjin, using C57BL6 mice in which HBV DNA was injected by hydrodynamic injection to show signs similar to acute hepatitis B. Blood HBsAg concentration was measured when co-administration of fat milk and turmeric complex herbal extracts.
  • mice used were 8-week-old males of about 20 g from Charles Liver Laboratory (MA, USA), and all mice were pAAV / HBV with HBV DNA sequence inserted into adeno-associated virus.
  • Acute hepatitis B was injected by injecting the vector at a rate of 0.3 ml / min through the mouse tail vein at a volume of 8% of the body weight of the experimental animal. After 24 hours, PBS, entecavir, entecavir and jinjin, fat, and turmeric complex herbal extracts were injected. Injection through the tail vein of mice.
  • Serum was isolated by blood collection on the 1st, 4th, 7th and 10th day after injection of test substance (0 hour), and diluted 10-fold with goat serum (Genesis HBsAg ELISA 3.0, Green Cross MS, Korea). Blood HBsAg concentration was measured using the same method, and liver tissue tissues were ground at 14 days after injection, DNA was extracted using phenol and chloroform, and the amount of cccDNA was measured by real-time PCR. .
  • Example 4 Injin, Oil , Turmeric Inhibition of Inflammation Inhibition by Treatment of Complex Herbal Extract and Hepatitis B Antiviral Agent
  • liver tissue from lethal acute hepatitis B-induced mice, pulverized the tissue by adding 1 mL of trizol solution, and centrifuged at 12,000 x g for 10 minutes. The supernatant was transferred to a new tube, 200 ⁇ l of chloroform was added, and vortexed. After transferring the supernatant to a new tube, isopropanol and supernatant were added in a 1: 1 ratio.
  • Primer sequences used in the present invention are shown in Table 1 below.
  • inflammatory cytokines TNF- ⁇ , IL-1 ⁇ and hepatic fibrosis-related factors TGF- ⁇ and collagenase I and IV were treated when hepatitis B antiviral agent entecavir was compared with the control group.
  • the inflammatory cytokine TNF- ⁇ , IL-1 ⁇ and hepatic fibrosis were more effectively treated in the group treated with entecavir, injin, fat, and turmeric complex herbal extracts compared to the group treated with entercavir alone. It was confirmed that the factors related to TGF- ⁇ , collagenase (collagenage) I and IV are inhibited (see FIGS. 6 and 7).

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Abstract

La présente invention concerne une composition contenant des extraits de Artemisia capillaris, Sanguisorba officinalis et Curcuma longa et un agent antiviral, en tant que principes actifs, destinée à prévenir ou traiter une maladie du foie. La co-administration d'extraits de Artemisia capillaris, Sanguisorba officinalis et Curcuma longa et d'un agent antiviral pour l'hépatite B selon la présente invention supprime l'antigène e du virus de l'hépatite B et inhibe efficacement l'expression de la cytokine inflammatoire TNF-α, IL-1β ou TGF-β, de telle sorte que l'inhibition de la cirrhose ou du cancer du foie ainsi que le traitement de l'hépatite B peuvent être attendus.
PCT/KR2017/004184 2016-04-21 2017-04-19 Composition contenant des extraits de artemisia capillaris, sanguisorba officinalis et curcuma longa et un agent antiviral, en tant que principes actifs, destinée à prévenir ou traiter une maladie du foie Ceased WO2017183902A1 (fr)

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Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108478765A (zh) * 2018-05-22 2018-09-04 杨国惠 一种治疗肝硬化腹水的中药丸剂及其制备方法
KR102069125B1 (ko) * 2018-06-18 2020-01-22 대한민국 강황 추출물을 포함하는 간손상 예방 및 치료용 약학 조성물
KR102092729B1 (ko) * 2018-06-18 2020-03-24 대한민국(농촌진흥청장) 강황 추출물을 포함하는 간손상 예방 및 치료용 약학 조성물
US20240226214A1 (en) * 2020-03-30 2024-07-11 Yale University Methods for treating inflammatory and fibrotic diseases and disorders
KR20240058030A (ko) 2022-10-24 2024-05-03 농업회사법인 주식회사 넥스트온 결명 새싹 및 메밀 새싹을 포함하는 지방 축적 억제용 조성물

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1249180A (zh) * 1998-09-28 2000-04-05 傅家树 防治肝炎病的单方中草药—地榆
KR20110117540A (ko) * 2010-04-21 2011-10-27 원광대학교산학협력단 지유 추출물을 유효성분으로 함유하는 헬리코박터 감염 질환의 예방 또는 치료용 약학적 조성물 및 건강식품
KR20150046916A (ko) * 2013-10-23 2015-05-04 권수영 간 섬유화 또는 간경화 치료 또는 예방용 조성물

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20040043707A (ko) * 2002-11-16 2004-05-27 김상태 인진쑥, 애엽, 유근피, 적양, 오가피, 대두 lph펩타이드, 백석목, 메밀을 주성분으로 함유하는 숙취제거, 간염, 간암 치료의 의약 조성물

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1249180A (zh) * 1998-09-28 2000-04-05 傅家树 防治肝炎病的单方中草药—地榆
KR20110117540A (ko) * 2010-04-21 2011-10-27 원광대학교산학협력단 지유 추출물을 유효성분으로 함유하는 헬리코박터 감염 질환의 예방 또는 치료용 약학적 조성물 및 건강식품
KR20150046916A (ko) * 2013-10-23 2015-05-04 권수영 간 섬유화 또는 간경화 치료 또는 예방용 조성물

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
RECHTMAN, M. M.: "Curcumin inhibits hepatitis B virus via down- regulation of the metabolic coactivator PGC-1a", FEBS LETTERS, vol. 584, 2010, pages 2485 - 2490, XP027093735 *
ZHAO, Y.: "Isolation, synthesis and anti-hepatitis B virus evaluation of p-hydroxyacetophenone derivatives from Artemisia capillaris", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 25, 2015, pages 1509 - 1514, XP029148580, DOI: doi:10.1016/j.bmcl.2015.02.024 *

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