KR20020082635A - Composition for prevention and treatment of septic shock comprising lysophosphatidic acid - Google Patents

Abstract

PURPOSE: A therapeutic and preventive composition for septic shock containing lysophosphatidic acid as an effective ingredient is provided which is effective in treatment and prevention of septic shock and remarkably reduces a death rate caused by the disease. CONSTITUTION: The composition for the prevention and treatment of septic shock contains lysophosphatidic acid of formula 1, a pharmaceutically acceptable salt, for example, an inorganic salt such as sodium salt, potassium salt, magnesium salt, calcium salt, and an organic salt such as ammonium salt, a salt of lysine, ethanol amine, N,N-dibenzylethylenediamine, angelic acid, etc.. In formula, R1 is substituted or non-substituted straight or branched C4-30 alkyl.

Description

Composition for preventing and treating septic shock comprising lysophosphatidic acid {COMPOSITION FOR PREVENTION AND TREATMENT OF SEPTIC SHOCK COMPRISING LYSOPHOSPHATIDIC ACID}

The present invention relates to a composition for preventing and treating septic shock, including lysophoshatidic acid or a pharmaceutically acceptable salt thereof.

Septic shock occurs when a host, such as a mammal, reacts excessively to a bacterial infection, resulting in a mortality rate of about 45% of the host. Specifically, this disease occurs because the host reacts excessively to endotoxins of Gram-negative bacteria. Conventionally, antimicrobial agents and steroidal agents have been used to treat septic shock, but the effect is negligible and the mortality rate of the host due to septic shock is still high.

Accordingly, it is an object of the present invention to provide a pharmaceutical composition excellent in the prevention and treatment of septic shock.

In accordance with the above object, the present invention provides a composition for preventing and treating septic shock, including lysophosphatidic acid and its pharmaceutically acceptable salts as an active ingredient.

Hereinafter, the present invention will be described in detail.

Lysophosphatidic acid as an active ingredient of the composition of the present invention is represented by the following formula (1).

Wherein R ₁ is substituted or unsubstituted straight or branched C _4-30 alkyl.

Lysophosphatidic acid is readily available commercially. Lysophosphatidic acid may also be isolated from plants or animals, or may be prepared by synthetic methods well known in the art, such as by using phospholipase A from phosphatidic acid.

Pharmaceutically acceptable salts of lysophosphatidic acid include, for example, inorganic salts such as sodium salts, potassium salts, magnesium salts, calcium salts, and ammonium salts, lysine, ethanolamine, N, N'-dibenzylethylenediamine Organic salts, such as salts with angelic acid, but are not limited thereto.

Lysophosphatidic acid and its pharmaceutically acceptable salts have an excellent prophylactic and therapeutic effect of septic shock, significantly lowering mortality from this disease.

Lysophosphatidic acid is endogenous to the body of mammals, so its safety is proven.

The pharmaceutical compositions of the invention can be formulated in a variety of parenteral or oral dosage forms. Representative of parenteral formulations are injectable formulations, preferably aqueous isotonic solutions or suspensions. In addition, oral administration formulations include, for example, tablets, capsules, and the like, and these formulations may include diluents (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine), bows in addition to the active ingredients. Turbidity such as silica, talc, stearic acid and its magnesium or calcium salts and / or polyethylene glycols. Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine, optionally starch, agar, alginic acid or its Disintegrants or boiling mixtures such as sodium salts and / or absorbents, colorants, flavors, and sweeteners. The formulations may be prepared by conventional mixing, granulating or coating methods.

The pharmaceutical compositions of the present invention may contain sterile and / or adjuvant such as preservatives, stabilizers, hydrating or emulsifying accelerators, salts and / or buffers for the control of osmotic pressure and other therapeutically useful substances, Can be formulated accordingly.

Lysophosphatidic acid and its pharmaceutically acceptable salts as active ingredients of the compositions of the present invention may be used once or several times a day in amounts of 0.1 to 100 mg / kg body weight per day for mammals, including humans. It may be divided by the administration and administered by parenteral or oral route.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are only for illustrating the present invention, and the scope of the present invention is not limited thereto.

Example

Cecal Ligation and Puncture (CLP) Model Test

In order to confirm that lysophosphatidic acid, an active ingredient of the composition of the present invention, has an excellent effect on the prevention and treatment of septic shock, a CLP model (induced peritonitis by artificially ligation and puncture of the caecum causes septic shock Placed animals).

Fifteen ICR mice (weight 25-30 g; MJ Ltd.) were anesthetized with pentobarbital, incised the right side of the abdomen to a length of 1 cm, exposed the cecum, and ligated under the ileocecal valve. Thereafter, the caecum was punctured with 21 gauge needles and the abdomen was resealed to cause septic shock.

After 2 and 4 hours of suture, 5 doses of lysophosphatidic acid (oleoyl-sn-glycerol-3-phosphate; Sigma Co.) dissolved in 10% DMSO solution were administered intraperitoneally to 5 mice. (Group A), another 5 mice were intraperitoneally administered in an amount of 50 mg / kg (Group B), and the other 5 mice were administered only a 10% solution of DMSO (control). The survival rate of ICR mice in group A, group B and control group was examined over time.

The results are shown in Table 1 below.

24 hour survival rate (survival mouse / total mouse) 48 hour survival rate (survival mouse / total mouse) Control 20% (1/5) 0% (0/5) A group 60% (3/5) 40% (2/5) B group 60% (3/5) 40% (2/5)

As can be seen from Table 1, mice in the lysophosphatidic acid-administered group had a much higher survival rate than the mice in the control group. Therefore, it was confirmed that lyphospatidin acid has a prophylactic and therapeutic effect of septic shock.

The composition of the present invention containing lysophosphatidic acid or a pharmaceutically acceptable salt thereof as an active ingredient can effectively prevent and treat septic shock.

Claims (1)

A composition for the prevention and treatment of septic shock, comprising lysophosphatidic acid or a pharmaceutically acceptable salt thereof as an active ingredient.