KR101494031B1 - Pharmaceutical composition for preventing or treating sepsis comprising genipin or derivative thereof - Google Patents

Abstract

The present invention is a pharmaceutical composition for preventing or treating septicemia comprising genipin or a derivative thereof. A pharmaceutical composition for treating or preventing septicemia and septic shock comprising the present invention as an active ingredient is a composition for treating sepsis or an effective treatment for sepsis, It is believed that it will be helpful in the treatment of those patients who are suffering from lack of drugs. It is also thought to reduce not only the wide range of therapeutic effects, but also the side effects frequently seen in chemicals since it is a natural substance-based treatment.

Description

[0001] The present invention relates to a pharmaceutical composition for preventing or treating septicemia comprising zenippin or a derivative thereof,

The present invention is a pharmaceutical composition for preventing or treating septicemia comprising genipin or a derivative thereof. Also disclosed is a food composition for improving septicemia comprising zenypine or a derivative thereof.

Sepsis is known to be the leading cause of ICU morbidity and mortality worldwide. In the United States, there are 750,000 patients with sepsis each year. The mortality rate is also very high at about 40%, but only one FDA-approved drug has yet to be effectively treated or treated. Therefore, the development of drugs for treating sepsis has a significant clinical significance and the marketability of therapeutic agents is very high. Based on this, researches are being actively carried out to develop a therapeutic agent for sepsis at home and abroad. One of the clinical characteristics in the progression of sepsis is activation of the inflammatory system in the body. Therefore, in order to treat sepsis, inflammation such as TNF-α, interleukin-1, interleukin-6 and HMGB1 Numerous attempts have been made to inhibit the mediator, but the survival rate of the patient has not improved.

On the other hand, genipin is a non - part of geniposide, a natural component of the iridido glycoside system, and is a component showing the main pharmacological effects of the gardenia fruit (gardenia). Jenny fosiod is metabolized to genipin by intestinal bacteria and Jenniforide is metabolized to α-naphthylisothiocyanate-induced mouse hepatotoxicity model in terms of serum bilirubin, alanine aminotransferase (ALT) and aspartate aminotransferase It has been shown to improve not only biochemical values but also pathological tissue lesions. Genipin has also been found to promote gastric acid secretion and antioxidant activity and inhibit nitric oxide (NO) production. However, no report has been made on the sepsis of genipin.

Under these circumstances, the present inventors have made intensive efforts to find a substance for treating sepsis caused by natural products. As a result, Genipin or a derivative thereof has been used as a septicemia model induced by CLP (cecal ligation and puncture) The present inventors completed the present invention by confirming that the effect of suppressing the hypersomnia reaction at the time of sepsis was attained by lowering the concentration of the early and late inflammatory cytokines in sepsis.

It is an object of the present invention to provide a pharmaceutical composition for preventing or treating septicemia comprising genipin or a derivative thereof.

It is a further object of the present invention to provide a method of preventing or treating sepsis comprising administering a composition comprising zenypine or a derivative thereof.

It is another object of the present invention to provide a food composition for improving septicemia comprising zenypin or a derivative thereof.

In one aspect, the present invention relates to a pharmaceutical composition for preventing or treating septicemia comprising genipin or a derivative thereof.

The term "genipin " in the present invention means a component exhibiting the main pharmacological effects of the gardenia fruit (gardenia) as a non-sugar portion of geniposide, which is a natural ingredient of the iridide glycoside system. . Jennifin has been reported to promote secretion of gastric acid and to improve antioxidative and nitric oxide (NO) production inhibition or pathological tissue lesions in a hepatotoxicity model. However, the treatment for sepsis disclosed in the present invention is the first Respectively.

[Chemical Formula]

According to one embodiment of the present invention, it was confirmed that the mortality was improved when treating with JENNIFINE after induction of sepsis with CLP (Fig. 1), and the inflammatory cytokines (TNF-a, interleukin- And MCP-1, HMGB-1) (Figs. 2 to 6). These results demonstrate that the present invention can treat sepsis.

The term "derivative of genipin" in the present invention refers to a compound which exhibits the same activity as that of geninin and has an effect of preventing or treating sepsis, but examples thereof include geniposide, geniposide genipiodisic acid, penta-acetyl geniposide (Molecular Pharmacology, 70 (3), 997-1004, 2006), 6a-hydroxygeniposide, 6b-hydroxy jeniposide 6a-methoxygeniposide, or 6b-methoxygeniposide (Journal of Health Science, 52 (6), 743-747, 2006). Preferably Jenny < / RTI > It will be apparent to those skilled in the art that JENNIFOID is metabolized to JENNYPIN by intestinal bacteria in the body when consumed.

The term "sepsis" in the present invention refers to a state in which a serious inflammatory reaction occurs in a whole body by infection with a microorganism. The number of breaths increased more than 24 times per minute (ventilation), heart rate more than 90 times per minute (tachycardia), increase in leukocyte count in blood test, or significant decrease in respiratory rate If you have symptoms that are more than a branch, it is called systemic inflammatory response syndrome (SIRS). This systemic inflammatory response syndrome is called sepsis when it is caused by microbial infection. Pathogens from the body's infectious lesions persist or intermittently enter the bloodstream, settle in various organs, create lesions, and show severe systemic symptoms. Examples of causative bacteria include Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Mycobacterium tuberculosis pneumoniae fungi, and anaerobic bacteria. Until now, there is no definite treatment for this.

The present inventors confirmed that the survival rate of mice in which sepsis was induced was improved and the concentration of inflammation-induced cytokines in blood was inhibited, so that it was confirmed that zenypin or a derivative thereof is useful for prevention or treatment of sepsis.

The composition of the present invention can be used in the form of injections, pills, tablets or capsules conventionally used in pharmaceutical preparations.

In addition, the pharmaceutical composition according to the present invention can be administered through various routes. The route of administration of the pharmaceutical composition may be administered via any conventional route so long as the drug can reach the target tissue. Specifically, the composition may be administered intraperitoneally, intravenously, intramuscularly, subcutaneously, intradermally, orally, topically, intranasally, intrapulmonarily, rectally, but not exclusively. However, when orally administered, since the peptide is digested, it is preferable to formulate the oral composition so as to coat the active agent or protect it from decomposition at the top. Preferably in the form of an injection. In addition, the pharmaceutical composition may be administered by any device capable of transferring the active substance to the target cell.

Preferably, the pharmaceutical composition of the invention can prevent or treat sepsis by inhibiting organs damage due to sepsis. The organs are damaged organs due to sepsis and include organs that can inhibit organ damage by the composition of the present invention without limitation, but preferably may be any one or more of liver, kidney and heart. According to one embodiment of the present invention, the long-term damage index is analyzed by analyzing serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrigenase (LDH), blood urea nitrogen (BUN) and creatinine activity As a result, it was confirmed that the liver, kidney and heart were inhibited (Figs. 7 to 11).

The Jenny pin or derivative thereof of the present invention can prevent or treat liver damage by inhibiting the increase of serum concentration of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) in hepatocytes.

The term "aspartate aminotransferase" (AST) used in the present invention is also referred to as an aspartate aminotransferase, and is the primary enzyme for detecting liver damage. In normal conditions, AST is present in hepatocytes. However, when the liver is damaged, the enzyme enters the bloodstream and the AST level in the blood increases. The normal range of AST is 5 to 40 units per liter of serum.

The term " alanine aminotransferase "(ALT) as used herein refers to an alanine aminotransferase, an enzyme that exists in large amounts in hepatocytes and is an enzyme that is a marker specific to liver disease. The normal range of ALT is 7 to 56 units per liter of serum. Both of these enzymes catalyze a chemical reaction in the cell that transfers an amino group from a donor molecule to a donor molecule. In the case of AST, it is normally found in various tissues including liver, muscle, heart and brain. However, ALT is abundant in hepatocytes It is a specific index indicating liver status.

The present invention provides a method for preventing or treating renal damage by inhibiting the blood concentration of BUN (blood urea nitrogen) or creatinine (creatinine).

The Jenny pin or derivative thereof of the present invention can prevent or treat cardiac damage through inhibition of blood concentration increase of LDH (lactate dehydrigenase).

Preferably, the pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier, excipient or diluent.

As used herein, the term "pharmaceutically acceptable carrier" refers to a carrier or diluent that does not irritate the organism and does not interfere with the biological activity and properties of the administered compound. Examples of the pharmaceutical carrier which is acceptable for the composition to be formulated into a liquid solution include sterilized and sterile water suitable for the living body such as saline, sterilized water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, One or more of these components may be mixed and used. If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.

Preferably, the pharmaceutical composition of the present invention can be formulated or used in combination with an anti-inflammatory agent, an antithrombotic agent, a blood coagulation inhibitor, an antibiotic, an antibacterial agent and an anti-allergic agent.

In another aspect, the present invention relates to a method for preventing or treating septicemia comprising the step of administering the zenith pin or a pharmaceutical composition thereof.

The term "administering" in the present invention means introducing the pharmaceutical composition of the present invention to a patient by any suitable method, and the route of administration of the composition of the present invention is not limited to a variety of oral or parenteral routes ≪ / RTI >

The method of treatment using the Xeniprin of the present invention is the same as described above, and the treatment method of the present invention includes administering the Xeniphine in a pharmaceutically effective amount. It will be apparent to those skilled in the art that the appropriate total daily dose may be determined by the practitioner within the scope of sound medical judgment. In addition, it can be administered once or several times in divided doses. For purposes of the present invention, however, the specific therapeutically effective amount for a particular patient will depend upon the nature and extent of the reaction to be achieved, the particular composition, including whether or not other agents are used, the age, weight, Sex and diet of the patient, the time of administration, the route of administration and the rate of administration of the composition, the duration of the treatment, the drugs used or concurrently used with the specific composition, and similar factors well known in the medical arts. The subject to which the composition of the present invention is administered includes, but is not limited to, mammals including humans, such as cows, pigs, horses, rabbits, mice, and humans.

In another aspect, the present invention relates to a food composition for improving septicemia comprising genipin or a derivative thereof.

The food composition for improving sepsis of the present invention may be in the form of pills, powders, granules, infusions, tablets, capsules or liquids. Examples of the food to which the composition of the present invention can be added include various foods, beverages , Gum, tea, vitamin complex, and health supplement foods. The Jenny pin or derivative thereof of the present invention is derived from a natural product and can be used as a food additive because of a small side effect.

The composition for preventing and treating septicemia comprising genipin or a derivative thereof, or an effective ingredient thereof, or a pharmaceutically acceptable salt thereof, as an essential ingredient that can be contained in the food composition for improving sepsis of the present invention, The other ingredients are not particularly limited, and they may contain various herbal medicine extracts, food-aid additives, natural carbohydrates and the like as additional ingredients such as ordinary foods. Further, as mentioned above, the food-aid additive may be further added, and the food-aid additive includes food-aid additives customary in the art, for example, flavorings, flavors, colorants, fillers, stabilizers and the like .

Examples of such natural carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above .

In addition to the above, the food composition for improving septicemia of the present invention may further contain flavoring agents such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and thickening agents (cheese, chocolate etc.), pectic acid and its salts , Alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks and the like. In addition, it may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination.

The term "health functional food " in the present invention refers to a food prepared by processing a specific ingredient as a raw material for the purpose of health assisting or by extracting, concentrating, refining, mixing, or the like a specific ingredient contained in a food raw material, Refers to a food which is designed and processed so that the body control function such as bio-defense, regulation of biorhythm, prevention and recovery of disease and the like can be sufficiently exhibited to the living body by the above components. Recovery, and so on.

As described above, the pharmaceutical composition for treating or preventing septicemia and septic shock comprising the Jenny pin or its derivative as an active ingredient of the present invention is useful as an effective treatment for sepsis or for treating patients suffering from the shortage of therapeutic drug Will be. It is also a natural remedy, which will reduce not only the wide range of treatment effects but also the frequent side effects of chemicals. Therefore, it can be utilized as a sepsis treatment agent or a food composition for improving sepsis.

FIG. 1 shows the results of observing the survival rate changes by intravenous administration of zenypin (1, 2.5 and 5 mg / kg) in a CLP (Cecal ligation and puncture) induced mouse sepsis model. And the survival rate of the mice was observed for 10 days after the administration of the JENNIFIN immediately after the CLP. Immediately after CLP, the administration of zeniprin resulted in an improvement in mortality due to CLP-induced sepsis.
FIG. 2 shows the results of confirming the effect of Jeniprin on the concentration of serum TNF-a at 6 hours after CLP in a CLP-induced multi-bacterial sepsis model. Jenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg. Values represent the mean ± SEM of mice 9-11 per experimental group. ^** represents a significant difference (P <0.01) from the sham group; ⁺ Is CLP Group (P <0.05).
FIG. 3 shows the results of confirming the effect of the genistein on the concentration of serum interleukin-1 beta at 6 hours after CLP in a CLP-induced multi-bacterial sepsis model. Jenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg. Values represent the mean ± SEM of mice 9-11 per experimental group. ^** represents a significant difference (P <0.01) from the sham group; ⁺⁺ is CLP Group (P <0.01).
FIG. 4 shows the results of confirming the effect of the genistein on the concentration of serum interleukin-6 at 6 hours after CLP in the CLP-induced multi-bacterial sepsis model. Jenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg. Values represent the mean ± SEM of mice 9-11 per experimental group. ^** represents a significant difference (P <0.01) from the sham group; ⁺⁺ is CLP Group (P <0.01).
FIG. 5 shows the results of confirming the effect of the genistein on serum MCP-1 concentration at 6 hours after CLP in the CLP-induced multi-bacterial sepsis model. Jenipine was administered intravenously immediately after CLP at a dose of 2.5 mg / kg. Values represent the mean ± SEM of mice 9-11 per experimental group. ^** represents a significant difference (P <0.01) from the sham group; ⁺ Is CLP Group (P <0.05).
FIG. 6 shows the results of confirming the effect of Jeniprin on the concentration of serum HMGB1 at 24 hours after CLP in a CLP-induced multi-bacterial sepsis model. Jenipine 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 sham group; ⁺ Is CLP Group (P <0.05). The above represent representative western blot bands of each group.
Figure 7 shows the effect of Jeniprin on the concentration of serum ALT at 1, 3, 6, 12, 24 and 48 hours after CLP in a CLP-induced multi-bacterial sepsis model. Jenipine 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 **} indicate significant differences (p <0.05, P <0.01) from the sham group; ⁺ , ⁺⁺ is CLP (P <0.05, P <0.01), respectively.
Figure 8 shows the effect of Jeniprin on the concentration of serum AST at 1, 3, 6, 12, 24 and 48 hours after CLP in a CLP-induced multi-bacterial sepsis model. Jenipine 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 sham group; ⁺ , ⁺⁺ is CLP (P <0.05, P <0.01), respectively.
Figure 9 shows the effect of Jeniprin on the concentration of serum BUN at 1, 3, 6, 12, 24 and 48 hours after CLP in a CLP-induced multi-bacterial sepsis model. Jenipine 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 **} indicate significant differences (p <0.05, P <0.01) from the sham group; ⁺ Is CLP Group (P <0.05).
Figure 10 shows the effect of Jeniprin on the concentration of serum creatinine at 1, 3, 6, 12, 24 and 48 hours after CLP in a CLP-induced multi-bacterial sepsis model. Jenipine 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 **} indicate significant differences (p <0.05, P <0.01) from the sham group; ⁺⁺ is CLP Group (P <0.01).
Figure 11 shows the effect of Jeniprin on the concentration of serum LDH at 1, 3, 6, 12, 24 and 48 hours after CLP in a CLP-induced multi-bacterial sepsis model. Jenipine 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 sham group; ⁺⁺ is CLP Group (P <0.01).

Hereinafter, the present invention will be described in detail with reference to Examples and Production Examples. However, the embodiments and manufacturing examples according to the present invention can be modified in various other forms, and the scope of the present invention should not be construed as being limited to the above-described embodiments and manufacturing examples. Embodiments and manufacturing examples of the present invention are provided to enable those skilled in the art to more fully understand the present invention.

Production Example 1. Preparation of genipin

Production Example 1-1. Injection preparation

Genipin ............................................. ........ 500 mg

Distilled water for injection ............................................... ... qty

Distilled water for injection was added to the total volume of 25 ml. The above components were mixed according to the usual injection preparation method, then filled in a brown bottle and sterilized to prepare an injection.

Production Example 1-2. Manufacture of pills

Genipin ............................................. ........ 25 mg

Corn starch ................................................ .... 100 mg

Binder ................................................. ............

The above components were mixed, and a pellet was produced by a conventional pelletizing method in accordance with the size of the ozagra or the large pellet.

Production Example 1-3. Manufacture of tablets

Genipin ............................................. ........ 25 mg

Lactose ................................................. ............... 100 mg

Starch ................................................. ............... 100 mg

Magnesium stearate ...................................... Amount

The above components were mixed and tablets were prepared by tableting according to a conventional method for producing tablets.

Production Example 1-4. Preparation of capsules

Genipin ............................................. ......... 25 mg

Lactose ................................................. ............... 50 mg

Starch ................................................. ............... 50 mg

Talc ................................................. ............... 2 mg

Magnesium stearate ...................................... Amount

The above components were mixed and filled in gelatin capsules according to the conventional preparation method of capsules to prepare capsules.

Specimens used in each example were tested using genipin of the form as prepared in the above Preparation Example.

The pharmaceutical composition of the present invention significantly improved the mortality due to sepsis in sepsis-model mice induced by cecal ligation and puncture (CLP), which is a clinical sepsis-like model, and the mortality rate of liver, kidney and heart (MODS) by inhibiting the damage of major organs that have a great effect on the organs. This will be described with reference to specific embodiments and drawings. In the following description and Figs. 1 to 11, the CLP group is a CLP-induced sepsis model mouse group administered with an injection containing physiological saline instead of Jenny pin, and sham is a control group and did not induce sepsis.

Example 1. Evaluation of survival rate for sepsis in Genipin

1-1. Induced sepsis with cecal ligation and puncture

After the mice were anesthetized with ether, sepsis was induced via CLP according to the method of Chaudry et al. (1979) (Surgery, 85 (2), 205-211, 1979). After the cecum was exposed to the outside, the distal end of the cecal valve was ligated with a 3.0-silk suture line, and a 20-gauge needle was inserted into the end of the cecal valve to prevent intestinal obstruction. Two holes were made in the cecum to release a certain amount of fecal material. The cecum, including the feces, is placed back into the abdominal cavity and sutured to prevent dehydration 4 ml / 100 g b. wt of physiological saline was injected via subcutaneous injection.

1-2. Drug administration method

Drug administration was performed by dissolving zenith (1, 2.5, and 5 mg / kg) in physiological saline and intravenously at 0 hours after CLP.

1-3. Survival rate observation

After the administration of the drug at 0 hour after CLP, death was checked once every 24 hours (days 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 days) Were observed. The vehicle is an injection preparation containing physiological saline instead of jenny pin in Production Example 1. [

As a result, it was confirmed that genipin acts to improve mortality due to CLP-induced sepsis (Fig. 1).

Example  2. Genipin's  Evaluation of anti-inflammatory efficacy in sepsis

2-1. Analysis of blood inflammatory cytokine levels

(TNF-α, interleukin-1β, interleukin-6, and MCP-1) were measured by measuring the concentrations of inflammatory cytokines (TNF-α, interleukin-6 and MCP-1). That is, blood was collected at 6 hours after CLP, and the serum was separated and separated, and the concentrations of TNF-α, interleukin-1β, interleukin-6 and MCP-1 were measured using an ELISA assay kit (BD Biosciences, USA) Respectively.

As a result, TNF-α, interleukin-1β, interleukin-6 and MCP-1 concentrations were decreased after administration of zeniprin in sera from mice with CLP-induced sepsis (FIGS. 2 to 5). Therefore, it can be seen that the genitin inhibits the production of inflammation - induced cytokines in CLP - induced sepsis and inhibits the hyper - inflammatory reaction during sepsis.

2-2. Blood HMGB -1 concentration analysis

Blood was collected 24 hours after CLP and serum was isolated. The concentration of HMGB1 in the separated serum was measured by Western blot immunoassay. More specifically, proteins quantified from the separated serum were separated by SDS-PAGE, and then electrophoresed on PVDF (polyvinylidene fluoride) membrane lipore (USA) using a semi-dry trans blotting apparatus (Bio-Rad Laboratories, USA) Membranes were washed with TBS / T (Tris-Buffered Saline / Tween 20) and blocked with TBS / T containing 5% (w / v) skim milk for 1 hour at room temperature. (1: 1000 dilution, Abcam, USA) overnight at 4 ° C and then incubated with HRP (horseradish peroxidase-conjugated secondary antibody) iNtRON Biotechnology, Korea). Each band was evaluated by density measurement with ImageQuant ^TM TL (Amersham Biosciences / GE Healthcare, USA).

As a result, it was confirmed that the concentration of HMGB-1 decreased after administration of zeniprin in sera from mice with CLP-induced sepsis. Thus, it can be seen that the genitin inhibits the production of inflammatory cytokines in CLP-induced sepsis, thereby suppressing hyperphagia (Fig. 6). These results suggest that the Jenin fins of the present invention can treat or prevent sepsis.

2-3. Serum ALT , AST , LDH , BUN  And Creatinine  Analysis of organ damage index by activity analysis

After the administration of CLP, physiological saline or zeniprin (2.5 mg / kg), which is a preparation solvent, was administered. Blood was collected at 1, 3, 6, 12, 24, and 48 hours after administration and sera were separated from the serum, and alanine aminotransferase (ALT) and aspartate aminotransferase (BUN) and creatinine levels in the blood were measured to determine the degree of damage to the renal function. The levels of urea nitrogen (BUN) and creatinine in the blood were measured by measuring the AST , And the degree of damage of cardiac function was evaluated by measuring lactate dehydrigenase (LDH) (Life Science, 79 (21), 2010-2016, 2006).

As a result, it was confirmed that ALT, AST, BUN, creatinine and LDH concentrations were decreased after administration of zeniprin in sera from mice with CLP-induced sepsis (FIGS. 7 to 11). These results suggest that zenith inhibition of hepatic, renal and cardiac function through inhibition of serum ALT, AST, BUN, creatinine and LDH levels in sepsis induced by CLP, And the like.

Claims (7)

Genipin, geniposide, derivatives thereof, genipiodisic acid, penta-acetyl geniposide, 6a-hydroxygeniposide, 6b-hydroxypiperidine, A pharmaceutical composition for preventing or treating septicemia comprising 6b-methoxygeniposide, 6b-methoxygeniposide, 6b-methoxygeniposide, 6b-methoxygeniposide and 6b-methoxygeniposide.
delete The pharmaceutical composition for preventing or treating septicemia according to claim 1, which is characterized by inhibiting organs damage due to sepsis.
The pharmaceutical composition for preventing or treating sepsis according to claim 3, wherein the organs are any one or more of liver, kidney and heart.
The pharmaceutical composition according to any one of claims 1, 3 and 4, wherein the composition further comprises a pharmaceutically acceptable carrier, excipient or diluent.
The composition according to any one of claims 1, 3, and 4, wherein the composition is formulated or used together with a medicament selected from the group consisting of an anti-inflammatory agent, an analgesic agent, a blood coagulation inhibitor, an antibiotic, an antibacterial agent and an antiallergic agent Or a pharmaceutically acceptable salt thereof.
Genipin, geniposide, derivatives thereof, genipiodisic acid, penta-acetyl geniposide, 6a-hydroxygeniposide, 6b-hydroxypiperidine, A composition for improving septicemia comprising 6b-dhydroxygeniposide, 6a-methoxygeniposide or 6b-methoxygeniposide.

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