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WO2012033261A1 - Composition pharmaceutique pour prévention ou traitement de la septicémie, contenant de la génipine ou un dérivé de celle-ci - Google Patents

Composition pharmaceutique pour prévention ou traitement de la septicémie, contenant de la génipine ou un dérivé de celle-ci Download PDF

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Publication number
WO2012033261A1
WO2012033261A1 PCT/KR2010/008866 KR2010008866W WO2012033261A1 WO 2012033261 A1 WO2012033261 A1 WO 2012033261A1 KR 2010008866 W KR2010008866 W KR 2010008866W WO 2012033261 A1 WO2012033261 A1 WO 2012033261A1
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sepsis
preventing
pharmaceutical composition
clp
derivative
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PCT/KR2010/008866
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English (en)
Korean (ko)
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이선미
김태훈
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성균관대학교 산학협력단
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Publication of WO2012033261A1 publication Critical patent/WO2012033261A1/fr

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    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Definitions

  • the present invention relates to a pharmaceutical composition for preventing or treating sepsis, including genipin or a derivative thereof.
  • the present invention relates to a food composition for improving sepsis comprising jennypin or a derivative thereof.
  • genipin is a non-sugar portion of the geniposide (geniposide), a natural component of the iridoid glycoside lineage is a component that represents the main pharmacological effect of the gardenia fruit (garia).
  • Geniposide is metabolized to intestinal bacteria by intestinal bacteria in the body, and geniposide is bilirubin, alanine aminotransferase (ALT) and blood in a hepatotoxicity model of mice induced with ⁇ -naphthylisothiocyanate. It has been shown to improve pathological tissue lesions as well as biochemical levels of aspartate aminotransferase (AST). It has also been found that jennypin promotes the secretion of gastric acid and inhibits antioxidant activity and nitric oxide (NO) production. However, no report has been disclosed regarding the prevention or treatment of sepsis with jennypin.
  • sepini from the sepsis model induced by CLP cecal ligation and puncture
  • CLP cecal ligation and puncture
  • One object of the present invention is to provide a pharmaceutical composition for preventing or treating sepsis, which comprises genipine or a derivative thereof as an active ingredient.
  • Still another object of the present invention is to provide a method for preventing or treating sepsis, which comprises administering a composition comprising jennypin or a derivative thereof.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of sepsis, comprising as an active ingredient nippin or a derivative thereof.
  • the term "genipin” in the present invention refers to a component that represents the main pharmacological efficacy of the gardenia fruit (garia) as a non-sugar portion of the geniposide, a natural component of the iridoid glycoside family, It can be represented as.
  • xenicin stimulates the secretion of gastric acid, inhibits antioxidant activity and nitric oxide (NO) production, or improves pathological tissue lesions in hepatotoxicity models
  • NO nitric oxide
  • the mortality is improved when treatment with nippin (see FIG. 1), and also inflammatory cytokines in the blood (TNF- ⁇ , interleukin-1 ⁇ , interleukin- 6, MCP-1 and HMGB-1) was confirmed to decrease the concentration (see Figures 2 to 6), these results demonstrate that the phenine of the present invention can treat sepsis.
  • the term "derived from jennypin” refers to the same activity as jennypin, and include compounds that have a preventive or therapeutic effect of sepsis, including, but not limited to, geniposide (geniposide), genipiodisic acid (genipiodisic acid) Penta-acetyl geniposide; Molecular Pharmacology, 70 (3), 997-1004, 2006, 6a-hydroxygeniposide, 6b-hydroxygeniposide, 6b-dhydroxygeniposide , 6a-methoxygeniposide, 6b-methoxygeniposide, and the like (Journal of Health Science, 52 (6), 743-747, 2006). Preferably it may be geniposide. It is apparent to those skilled in the art that zenithposide is metabolized to jennypin by the intestinal bacteria in the body at the time of ingestion.
  • the term "septicemia” refers to a condition in which a serious inflammatory response occurs in the whole body by infection with a microorganism. Fever symptoms that rise above 38 degrees or hypothermia below 36 degrees, respiratory rate increases above 24 times per minute (empty breathing), heart rate above 90 beats per minute (tachycardia), and increases or significant decreases in white blood cell counts on blood tests If you have more than two symptoms, this is called systemic inflammatory response syndrome (SIRS). This systemic inflammatory response syndrome is called sepsis when it is caused by infection of microorganisms.
  • SIRS systemic inflammatory response syndrome
  • Pathogens in the body's infectious paths are continuously or intermittently entered into the bloodstream and settled in various organ tissues to create lesions and show severe systemic symptoms, and are susceptible to weak, elderly, and weak people.
  • the causative organisms include Staphylococcus, Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Pneumococcal bacteria, Fungi, and Anaerobic bacteria. To date, there is no clear treatment for this.
  • the present inventors confirmed that the survival rate of sepsis-induced mice was improved, and the concentration of inflammation-induced cytokines in the blood was suppressed, thereby confirming that nippine or a derivative thereof was useful for the prevention or treatment of sepsis.
  • compositions of the present invention can be used in the form of injections, pills, tablets or capsules commonly used in pharmaceutical preparation.
  • the pharmaceutical compositions according to the invention can be administered via several routes.
  • the route of administration of the pharmaceutical composition may be administered via any general route as long as the drug can reach the target tissue. Specifically, intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, nasal administration, pulmonary administration, rectal administration, but is not limited thereto.
  • intraperitoneal administration intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, nasal administration, pulmonary administration, rectal administration, but is not limited thereto.
  • the oral composition since the peptide is digested, it is desirable to formulate the oral composition to coat the active agent or to protect it from degradation in the stomach. It may preferably be administered in the form of an injection.
  • the pharmaceutical composition may be administered by any device in which the active agent may migrate to the target cell.
  • the pharmaceutical composition of the invention can prevent or treat sepsis by inhibiting damage to organs caused by sepsis.
  • the organ is an organ damaged by septicemia, and any organ which can be prevented from being damaged by the composition of the present invention includes, but is not limited to, any one or more organs of the liver, kidney and heart.
  • the long-term damage indicators were analyzed by serum altine (ALT), aspartate aminotransferase (AST), AST (aspartate aminotransferase), LDH (lactate dehydrigenase), BUN (blood urea nitrogen) and creatinine (Creatinine) activity analysis. As a result, it was confirmed that the damage to the liver, kidney and heart was inhibited (see FIGS. 7 to 11).
  • Jenny pin or derivatives thereof of the present invention can perform the prevention or treatment of liver damage through the inhibition of blood concentration increase of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) in hepatocytes.
  • AST aspartate aminotransferase
  • ALT alanine aminotransferase
  • AST aspartate aminotransferase
  • aspartate aminotransferase used in the present invention is also called aspartate aminotransferase, and is a primary enzyme for detecting liver damage. However, when the liver is damaged, the enzyme enters the blood and increases the AST level in the blood.
  • the normal range of AST is 5-40 units per liter of serum.
  • ALT alanine aminotransferase
  • alanine aminotransferase an enzyme that is present in large amounts in liver cells and is an enzyme that is specific for liver disease.
  • the normal range of ALT is 7-56 units per liter of serum. Both enzymes catalyze the chemical reaction in the cell that transfers amino groups from donor molecules to donor molecules, and AST is normally found in a variety of tissues including liver, muscle, heart and brain, but ALT is present in large amounts in hepatocytes. It is a specific indicator of liver status.
  • Jenny pin or derivatives thereof of the present invention can perform the prevention or treatment of kidney damage through the inhibition of the blood concentration increase of BUN or creatinine.
  • Jenny pin or derivatives thereof of the present invention can perform the prevention or treatment of heart damage through the inhibition of the increase in the blood concentration of LDH.
  • composition of the present invention may further comprise a pharmaceutically acceptable carrier, excipient or diluent.
  • the term "pharmaceutically acceptable carrier” refers to a carrier or diluent that does not irritate an organism and does not inhibit the biological activity and properties of the administered compound.
  • 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 solution, maltodextrin solution, 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.
  • the pharmaceutical composition of the present invention may be formulated or used in combination with anti-inflammatory agents, antipyretic analgesics, anticoagulants, antibiotics, antibacterial agents and anti-allergic agents.
  • the present invention provides a method for preventing or treating sepsis, which comprises administering nippin or a pharmaceutical composition comprising the same.
  • the present invention provides the use of jennypin or derivatives thereof for the prevention or treatment of sepsis.
  • prevention refers to any action that inhibits or delays the development of cystosis by administration of the pharmaceutical composition of the present invention.
  • treatment refers to any action in which the symptoms of sepsis are improved or beneficially changed by administration of the pharmaceutical composition of the present invention.
  • administration refers to introducing a pharmaceutical composition of the present invention to a patient in any suitable manner, and the route of administration of the composition of the present invention may be various oral or parenteral routes as long as the target tissue can be reached. It can be administered through.
  • subject means an animal including, but not limited to, humans, monkeys, cows, horses, sheep, pigs, chickens, turkeys, quails, cats, dogs, mice, rats, axes or guinea pigs, In one embodiment it refers to a mammal and in another embodiment a human.
  • terapéuticaally effective amount used in combination with an active ingredient in the present invention means an amount of genipidine or a derivative thereof effective for treating or preventing a subject disease.
  • the method of treatment with jennypin of the present invention is the same as described above, the method of treatment of the present invention comprises administering to a subject in need thereof a therapeutically effective amount of nippine or a pharmaceutical composition thereof. . It will be apparent to those skilled in the art that a suitable total daily dose may be determined by the practitioner within the correct medical judgment. It may also be administered once or in divided doses.
  • the specific therapeutically effective amount for a particular patient is determined by the specific composition, including the type and extent of the reaction to be achieved, whether or not other agents are used in some cases, the age, weight, general health of the patient, It is desirable to apply differently depending on various factors and similar factors well known in the medical field, including sex and diet, time of administration, route of administration and rate of composition, duration of treatment, drugs used with or co-specific with the specific composition.
  • Individuals to which the composition of the present invention is administered include, but are not limited to, mammals including humans, for example, cows, pigs, horses, rabbits, mice, and humans.
  • the present invention provides a food composition for improving sepsis, including jennypin or derivatives thereof.
  • Food composition for improving sepsis of the present invention includes the form of pills, powders, granules, acupuncture, tablets, capsules or liquids, and the like to which the composition of the present invention can be added, for example, various foods, beverages , Gums, teas, vitamin complexes, and dietary supplements.
  • Jenny pin of the present invention or a derivative thereof is derived from a natural product, there is little side effect can be used as a food additive.
  • the composition having an anti-septic and therapeutic activity including the nippin or a derivative thereof, or an active ingredient thereof, or a pharmaceutically acceptable salt thereof is included.
  • the food supplement additive may further include food supplement additives, including food supplement additives conventional in the art, such as flavoring agents, flavoring agents, coloring agents, fillers, stabilizers, and the like.
  • natural carbohydrates examples 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.
  • natural flavoring agents tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. .
  • the food composition for improving sepsis of the present invention includes various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors such as flavoring agents, colorants and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof.
  • Alginic acid and salts thereof organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like.
  • Others may contain pulp for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components can be used independently or in combination.
  • Sepsis improved food composition comprising the nippin of the present invention or derivatives thereof may be provided in the form of dietary supplements.
  • the term "health functional food” in the present invention refers to a food prepared and processed by a method of extracting, concentrating, refining, and mixing a specific ingredient as a raw material or contained in a food ingredient for the purpose of health supplement, It refers to foods that are designed and processed to sufficiently exert bioregulatory functions on the living body, such as biological defense, control of biological rhythms, prevention and recovery of diseases by the components, and the health functional foods are for the prevention of diseases and recovery of diseases. It can perform a function related to such.
  • the pharmaceutical composition for the treatment or prevention of sepsis and septic shock which comprises the Jenny pin or a derivative thereof of the present invention as an active ingredient, is effective for treating sepsis and the treatment of patients suffering from a situation where there is a shortage of therapeutic drugs. Will help.
  • the pharmaceutical composition of the present invention is a therapeutic agent based on natural products, it will not only exhibit a wide range of therapeutic actions but also significantly reduce side effects frequently occurring in chemicals. Therefore, the pharmaceutical composition of the present invention can be usefully used as a sepsis treatment or a supplement for improving sepsis.
  • Figure 1 shows the results of observation of the survival rate change according to the administration of nippin (1, 2.5 and 5 mg / kg) in the mouse sepsis model induced by CLP (Cecal ligation and puncture).
  • the survival rate of the mice was observed for 10 days after the administration of jennypin immediately after CLP.
  • nippin has been shown to improve mortality due to CLP-induced sepsis.
  • Figure 2 shows the results of confirming the effect of jennypin on the concentration of serum TNF- ⁇ at 6 hours after CLP in the CLP-induced multibacterial sepsis model.
  • Zenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg. Values represent mean ⁇ SEM of 9-11 mice per experimental group. ** Represents a significant difference (P ⁇ 0.01) from the sham group; + CLP Significant difference (P ⁇ 0.05) from the group.
  • FIG. 3 shows the results of confirming the effect of jennypin on the concentration of serum interleukin-1 ⁇ at 6 hours after CLP in the CLP-induced multibacterial sepsis model.
  • Zenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg. Values represent mean ⁇ SEM of 9-11 mice per experimental group. ** Represents a significant difference (P ⁇ 0.01) from the Siamese group; ++ CLP Significant difference (P ⁇ 0.01) from the group.
  • FIG. 4 shows the results of confirming the effect of jennypin on the concentration of serum interleukin-6 at 6 hours after CLP in the CLP-induced multibacterial sepsis model.
  • Zenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg. Values represent mean ⁇ SEM of 9-11 mice per experimental group. ** Represents a significant difference (P ⁇ 0.01) from the Siamese group; ++ CLP Significant difference (P ⁇ 0.01) from the group.
  • Figure 5 shows the results confirming the effect of jennypin on the concentration of serum MCP-1 at 6 hours after CLP in the CLP-induced multibacterial sepsis model.
  • Zenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg. Values represent mean ⁇ SEM of 9-11 mice per experimental group. ** Represents a significant difference (P ⁇ 0.01) from the Siamese group; + CLP Significant difference (P ⁇ 0.05) from the group.
  • Figure 6 shows the results of confirming the effect of jennypin on the concentration of serum HMGB1 24 hours after CLP in the CLP-induced multibacterial sepsis model.
  • Zenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg.
  • Values represent mean ⁇ SEM of 6 mice per experimental group. ** Represents a significant difference (P ⁇ 0.01) from the Siamese group; + CLP Significant difference (P ⁇ 0.05) from the group.
  • the above shows representative Western blot bands for each group.
  • Figure 7 confirms the effect of jennypin on the concentration of serum ALT at 1, 3, 6, 12, 24 and 48 hours after CLP in the CLP-induced multibacterial sepsis model.
  • Zenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg. Values represent mean ⁇ SEM of 6 mice per experimental group. * And ** Represents a significant difference (P ⁇ 0.05, P ⁇ 0.01) from the Siamese group; + And ++ CLP Significant differences (P ⁇ 0.05, P ⁇ 0.01) from the group are shown.
  • Figure 8 confirms the effect of jennypin on the concentration of serum AST at 1, 3, 6, 12, 24 and 48 hours after CLP in the CLP-induced multibacterial sepsis model.
  • Zenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg. Values represent mean ⁇ SEM of 6 mice per experimental group. ** Represents a significant difference (P ⁇ 0.01) from the Siamese group; + And ++ CLP Significant differences (P ⁇ 0.05, P ⁇ 0.01) from the group are shown.
  • Figure 9 confirms the effect of jennypin on the concentration of serum BUN at 1, 3, 6, 12, 24 and 48 hours after CLP in the CLP-induced multibacterial sepsis model.
  • Zenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg. Values represent mean ⁇ SEM of 6 mice per experimental group. * And ** Represents a significant difference (P ⁇ 0.05, P ⁇ 0.01) from the Siamese group; + CLP Significant difference (P ⁇ 0.05) from the group.
  • Figure 10 confirms the effect of jennypin on serum creatinine concentrations at 1, 3, 6, 12, 24 and 48 hours after CLP in the CLP-induced multibacterial sepsis model.
  • Zenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg. Values represent mean ⁇ SEM of 6 mice per experimental group. * And ** Represents a significant difference (P ⁇ 0.05, P ⁇ 0.01) from the Siamese group; ++ CLP Significant difference (P ⁇ 0.01) from the group.
  • Figure 11 confirms the effect of jennypin on the concentration of serum LDH at 1, 3, 6, 12, 24 and 48 hours after CLP in the CLP-induced multibacterial sepsis model.
  • Zenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg. Values represent mean ⁇ SEM of 6 mice per experimental group. ** Represents a significant difference (P ⁇ 0.01) from the Siamese group; ++ CLP Significant difference (P ⁇ 0.01) from the group.
  • the pharmaceutical composition of the present invention significantly improved mortality due to sepsis in sepsis model mice induced by cecal ligation and puncture (CLP), a clinical sepsis-like model. It has been shown to improve multiple organdysfunction syndrome (hereinafter referred to as 'MODS') by inhibiting damage to major organs that significantly affect mortality such as the heart. This will be described with reference to specific embodiments and drawings.
  • CLP group is a group of CLP-induced sepsis model mice administered with an injection containing physiological saline instead of jennypin, and sham is a mouse that does not induce sepsis as a control.
  • mice were inhaled anesthesia with ether and then sepsis was induced via CLP according to the method reported in Chaudry et al., Surgery, 85 (2): 205-211, 1979.
  • the end of the cecal valve was ligated with 3.0 silk sutures to prevent intestinal obstruction, and the 20-gauge needle was Two holes in the cecum were used to drain a certain amount of fecal material. 4 ml / 100 g b.
  • wt. saline was injected via subcutaneous injection.
  • Drug administration was performed by dissolving jennypin (1, 2.5 and 5 mg / kg) in physiological saline and then intravenously 0 hours after CLP.
  • a vehicle is a physiological saline injection instead of jennypin.
  • jennypin has an effect of improving mortality due to sepsis induced by CLP (FIG. 1).
  • the anti-inflammatory response of sepsis induction was observed, and the anti-inflammatory effects of nippin administration were confirmed by measuring the concentrations of inflammatory cytokines (TNF- ⁇ , interleukin-1 ⁇ , interleukin-6, and MCP-1).
  • TNF- ⁇ , interleukin-1 ⁇ , interleukin-6, and MCP-1 inflammatory cytokines
  • jennypin inhibits the production of inflammatory cytokines in CLP-induced sepsis, thereby inhibiting the over-inflammatory response in sepsis.
  • Serum was isolated by collecting blood 24 hours after CLP.
  • the concentration of HMGB1 in the isolated serum was measured by Western blot immunoassay. More specifically, the protein quantified in the separated serum was separated by SDS-PAGE, followed by electrophoresis on a polyvinyllidene fluoride (PVDF) membrane (Millipore, USA) using a semi-dry transblot device (Bio-Rad Laboratories, USA).
  • the membrane was washed with TBS / T (Tris-Buffered Saline / Tween 20) and then blocked with TBS / T containing 5% (w / v) skim milk for 1 hour at room temperature.
  • TBS / T Tris-Buffered Saline / Tween 20
  • HMGB-1 primary antibody (1: 1000 dilution, Abcam, USA) at 4 ° C for one day, and then reacted with HRP-horseradish peroxidase-conjugated secondary antibody (ERP) to detect ECL ( iNtRON Biotechnology, Korea) induced color development.
  • ERP HRP-horseradish peroxidase-conjugated secondary antibody
  • Each band was evaluated by ImageQuant TM TL (Amersham Biosciences / GEHealthcare, USA) density measurement.
  • ALT alanine aminotransferase
  • BUN blood urea nitrogen
  • 'LDH' lactate dehydrigenase
  • Injectables were prepared by mixing the above components according to the conventional method for preparing injectables, filling them into brown bottles and sterilizing them.
  • the above ingredients were mixed and refilled to a size of five or five rings using a conventional pill manufacturing method to prepare a pill.
  • the tablets were prepared by mixing the above components and tableting according to a conventional method for preparing tablets.
  • the capsules were prepared by mixing the above components and filling the gelatin capsules according to a conventional method for preparing capsules.
  • Vitamin B2 ... .0.15 mg
  • Vitamin B6 ... ..0.5 mg
  • Vitamin B12 ... .0.2 ⁇ g
  • Nicotinic Acid Amide ... 1.7 mg
  • composition ratio of the above-mentioned vitamin and mineral mixtures is a composition which is a composition suitable for a relatively healthy food in a preferred embodiment, and may be changed arbitrarily.
  • Vitamin E (powder) ......................................... .100 g
  • Vitamin A ... .... 0.2 g
  • Vitamin B1 ... ..0.25 g
  • Vitamin B2 ... ... 0.3 g
  • the prepared solution was filtered and placed in a sterile 2 L container.
  • the container was sealed and sterilized and stored in a refrigerated state before being used for preparing a healthy beverage composition.
  • the pharmaceutical composition comprising the active ingredient of Jenny pin or derivatives of the present invention is a therapeutic agent based on natural products, it not only has a wide range of therapeutic actions but also significantly reduces side effects frequently seen in chemicals, thereby treating sepsis and septic shock or It can be usefully used for prevention.

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Abstract

La présente invention concerne une composition pharmaceutique pour la prévention ou le traitement de la septicémie, laquelle composition contient de la génipine ou un dérivé de celle-ci. Tout en étant proche d'un procédé ou d'un médicament efficace pour le traitement de la septicémie, la composition pharmaceutique, selon la présente invention, peut être utile pour la prévention ou le traitement de la septicémie ou d'un choc septique. En outre, la composition pharmaceutique, selon la présente invention, est un agent thérapeutique à base de produits naturels et, ainsi, il est possible de réduire les effets secondaires qui apparaissent fréquemment lors de l'utilisation de matériaux chimiques, en plus d'avoir une grande plage d'effets thérapeutiques.
PCT/KR2010/008866 2010-09-08 2010-12-10 Composition pharmaceutique pour prévention ou traitement de la septicémie, contenant de la génipine ou un dérivé de celle-ci WO2012033261A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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Families Citing this family (3)

* Cited by examiner, † Cited by third party
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KR101712450B1 (ko) 2015-03-31 2017-03-06 서울대학교산학협력단 게니핀을 포함하는 비만 개선용 식품 조성물, 비만 치료용 약학 조성물, 비만 치료용 동물용 의약품 및 사료 조성물
KR102282082B1 (ko) 2019-12-06 2021-07-27 경상국립대학교산학협력단 3,4-다이하이드로아이소퀴놀린 유도체, 이의 제조방법 및 이를 포함하는 패혈증 예방 또는 치료용 조성물
CN113004356B (zh) * 2021-03-05 2023-10-27 上海交通大学 新型京尼平衍生物，及其制备方法和应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1045841B1 (fr) * 1997-11-05 2002-12-04 Choongwae Pharma Corporation Nouveau derive de genepine faisant montre d'une activite protectrice du foie
US20080319042A1 (en) * 2007-02-13 2008-12-25 Harry Fong Compositions and methods for treatment of liver disease
US20090214654A1 (en) * 2008-02-21 2009-08-27 Isenburg Jason C Treatment of aneurysm with application of connective tissue stabilization agent in combination with a delivery vehicle

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1045841B1 (fr) * 1997-11-05 2002-12-04 Choongwae Pharma Corporation Nouveau derive de genepine faisant montre d'une activite protectrice du foie
US20080319042A1 (en) * 2007-02-13 2008-12-25 Harry Fong Compositions and methods for treatment of liver disease
US20090214654A1 (en) * 2008-02-21 2009-08-27 Isenburg Jason C Treatment of aneurysm with application of connective tissue stabilization agent in combination with a delivery vehicle

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118593471A (zh) * 2024-05-30 2024-09-06 昆明医科大学 京尼平β-甲基衍生物Gen-17在制备预防或治疗急性重症肺炎药物中的应用

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