Pharmacodynamics

Mechanism of Action

Anti-inflammatory effect

1) Inhibition of enzymes in arachidonic acid metabolic system

Glycyrrhizic acid directly binds to phospholipase A2, the initial enzyme in the arachidonic acid metabolic system, and lipoxygenase, an enzyme to produce the inflammatory chemical mediators. Glycyrrhizic acid selectively inhibits the activation by phosphorylation of these enzymes.

2) Anti-allergic effect

This product has antiallergic activities as shown by the inhibition of Arthus reaction and Shwartzman reaction both in rabbits. Against the activities of cortisone, this product increases the stress reaction inhibitory effect, antagonizes the anti-granulation effect and thymic atrophy inducing effect, but does not affect the anti-exudation effect.

Immuno-response modulating effect

In an in vitro experimental system, glycyrrhizic acid has proved to exhibit:

1. T-cell activation controlling effect
2. Interferon- γ inducing effect

• NK-cell activating effect

1. Extrathymic T lymphatic cell differentiation potentiating effect, etc.

 

3) Experimentally-induced hepatocytes injury inhibiting effect

In an in vitro experimental system using the primary culture of rat hepatocytes, glycyrrhizic acid has proved to inhibit hepatocyte injury induced by carbon tetrachloride.

4) Hepatocyte proliferative effect

In an in vitro experimental system using the primary culture of rat hepatocytes, glycyrrhizic acid and glycyrrhetinic acid have proved to promote proliferation of primary cultured rat hepatocytes.

5) Viral growth inhibiting or inactivating effect

In MHV (mouse hepatitis virus) infection experiments in mice, prolongation of the survivable days was observed after administration of this product. In an experiment to inhibit the vaccinia virus infection in rabbits, eruption of papules was inhibited. Also in vitro experimental systems, growth inhibition and inactivation have been shown in herpes virus etc.

6) Others

Glycine and L-Cysteine hydrochloride have an inhibitory or suppressive activity against manifestation of pseudoaldosteronism which is caused by abnormal electrolyte metabolism after long-term administration of glycyrrhizic acid in large amount.

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Clinical Studies

1. Double-blind Comparative Trial in Chronic Hepatitis

At 36 institutions in Japan, a double-blind comparative trial was conducted in 133 chronic hepatitis patients, where a daily dose of 40mL of this product was intravenously administered consecutively for one month. The results were as follows;

The medicated group was superior in efficacy to the placebo group and in the biochemical parameters of liver function tests, AST (GOT), ALT (GPT) and y-GTP levels improved with statistical significance.

Medication	Effective rate (%)
	Effective or more	Fairly effective or more
Medicated group	25.4% (17/67)	68.7% (46/67)
Placebo group	9.1% (6/66)	27.3% (18/66)

2. Comparative Studies with Different Doses on Chronic Hepatitis and Hepatic Cirrhosis

At 11 institutions in Japan, 178 chronic hepatitis and hepatic cirrhosis patients received intravenous administration of 40 mL/day of this product for 3 weeks. 93 patients without improvement of ALT (GPT) levels down to <1.5 times upper limit of normal at 2-week point were enrolled into a comparative dose study and allocated to a group with continuous dose of 40mL and another group with increased dose of 100mL. The results showed that the ALT (GPT) levels of 100mL-dose group improved significantly compared to the 40mL-dose group. Thus, the administration of increased dose of 100mL was recognized to be effective in case where 40mL was insufficient to lower ALT (GPT) levels.

Dosage	Effective rate (%)
	Effective or more
40mL-dose group	25.5% (12/47)
100mL-dose group	50.0% (23/46)

3. General Clinical Studies

The table summarizes the efficacy data of clinical trials on 59 chronic hepatitis patients who received 60mL of this product for 4 weeks.

Diseases	Effective rate (%)
	Effective or more
Chronic hepatitis	81.4% (48/59)

In another trial where 100mL of this product was administered for 8 weeks in chronic hepatitis patients, good correlation was observed between the improvement of hepatic function and that of liver histology.