Acute Respiratory Distress Syndrome Therapeutic Agent

Abstract

An agent for treating acute respiratory distress syndrome includes, as an active ingredient, a lecithinized superoxide dismutase represented by the general formula (I):SOD′(Q-B)m  (I)(wherein, SOD′ represents a residue of a superoxide dismutase; Q represents a chemical crosslinking; B represents a residue of lysolecithin, in which a hydrogen atom of a hydroxyl group is removed from the lysolecithin having the hydroxyl group at the 2-position of glycerol; and m is the average number of bonds of the lysolecithin relative to one molecule of the superoxide dismutase and represents an integer of 1 or more).

Description

TECHNICAL FIELD[0001]The present invention relates to an agent for treating acute respiratory distress syndrome, and specifically, to an agent for treating acute respiratory distress syndrome that contains lecithinized superoxide dismutase (hereinafter may be referred to as “PC-SOD”) as an active ingredient.BACKGROUND ART[0002]Acute respiratory distress syndrome (ARDS) (hereinafter may be referred to as “ARDS”) is designated as “Kyuusei kokyuu sokuhaku shokogun” or “Kyuusei kokyuu kyuuhaku shokogun” in Japanese. This syndrome is one of the main causes of death among patients during intensive care and is a disease of great significance for public health. The annual number of ARDS patients has reached 200,000 in the United States. A reliable method for treating this disease has not been established yet and currently the mortality rate of ARDS is fairly high (40 to 50%).[0003]ARDS is a fatal clinical syndrome defined by edema, acute hypoxic respiratory failure with cardiac filling pres...

AI Technical Summary

Benefits of technology

The present invention introduces an agent that uses PC-SOD as its main ingredient to treat acute respiratory distress syndrome (ARDS). This agent can successfully treat edema, tissue injury, and inflammation in the lung and other organs that were previously unresponsive to steroids and sivelestat. This new treatment option offers hope for better outcomes in treating ARDS and VILI.

Problems solved by technology

A reliable method for treating this disease has not been established yet and currently the mortality rate of ARDS is fairly high (40 to 50%).

The injury of an epithelium and an endothelium also induces serious inflammatory response (for example, recruitment and activation of a leukocyte and production of an inflammatory cytokine precursor), increases vascular permeability (edema), and activates a coagulation system in all tissues as well as in the lung, resulting in a multifunctional failure.

Since the lung is an organ through which blood circulating within a body always passes, the lung is susceptible to influence of the blood.

This leads to an increase in vascular permeability and bloody exudate fills the interstitium and even the inside of the pulmonary alveolus.

Because of ventilation-perfusion mismatch and increased dead space, exhalation of CO2 requires more ventilation than usual.

However, reduction of lung compliance (lung consolidation) is caused in the early stage by the pulmonary alveolus filled with the exudate and in the late stage by the lung that underwent fibrosis, and consequently, mechanical ventilation at a high pressure becomes necessary.

However, ventilation becomes poor in many areas of the lung in ARDS and therefore capillaries in these areas constrict to cause pulmonary hypertension.

Recently, a steroid has been used for treating ARDS, however, the effect thereof has not been proved yet.

Although other various therapeutic approaches such as administration of a β-adrenergic agonist, activated protein C, or a statin drug are under investigation, the effects thereof are very restricted.

Furthermore, although a mechanical ventilator (MV: mechanical ventilation) (hereinafter may be referred to as “MV”) is important for critical care for an ARDS patient, MV involves a high tidal volume and repeated gas flow by forced ventilation, causing ventilator-induced lung injury (VILI).

For this reason, MV with a low tidal volume is clinically recommended; however, a recent research states that even MV with a low tidal volume causes VILI and alveolar injury.

Therefore, it is also an important issue to suppress not only ARDS but also VILI for increasing the survival rate of ARDS patients.

The mechanical ventilator also stimulates production of reactive oxygen species by extending the lung tissue excessively.

However, the clinical effect of sivelestat is not necessarily satisfactory.

This suggests that this is because sivelestat is not directly effective in suppressing ROS production and therefore indicates that treatment of a tissue injury mediated by ROS in ARDS cannot be achieved clinically by sivelestat.

However, the clinical application was unsuccessful since this Cu / Zn SOD has low tissue affinity and low stability in blood plasma.

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