Glycyrrhizic acid API Manufacturers

General Description:

Glycyrrhizic acid, identified by CAS number 1405-86-3, is a notable compound with significant therapeutic applications. Glycyrrhizic acid is extracted from the root of the licorice plant; _Glycyrrhiza glabra_. It is a triterpene glycoside with glycyrrhetinic acid that possesses a wide range of pharmacological and biological activities. When extracted from the plant, it can be obtained in the form of ammonium glycyrrhizin and mono-ammonium glycyrrhizin. Glycyrrhizic acid has been developed in Japan and China as a hepatoprotective drug in cases of chronic hepatitis. From January 2014, glycyrrhizic acid as part of the licorice extract was approved by the FDA as an existing food sweetener. It was approved by Health Canada to be used in over-the-counter products but all the products are currently on the status canceled post marketed.

Indications:

This drug is primarily indicated for: Glycyrrhizic acid is widely applied in foods as a natural sweetener. As a therapeutic agent, is has been used in a vast variety of formulations as it is reported to be anti-inflammatory, anti-ulcer, anti-allergic, antioxidant, anti-tumor, anti-diabetic and hepatoprotective. Due to this properties, its indications have been: treatment of premenstrual syndrome, treatment of viral infections, anti-lipidemic and antihyperglycemic. It is also known to be used as a remedy for peptic ulcer and other stomach diseases. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Glycyrrhizic acid undergoes metabolic processing primarily in: When orally administered, glycyrrhizic acid is almost completely hydrolyzed by intestinal bacteria for the formation of glycyrrhetinic acid, which is an active metabolite and can enter systemic circulation, and two molecules of glucuronic acid. This metabolite is transported and taken in the liver for its metabolization to form glucuronide and sulfate conjugates. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Glycyrrhizic acid are crucial for its therapeutic efficacy: Glycyrrhizic acid is mainly absorbed after presystemic hydrolysis and formation of glycyrrhetinic acid. Therefore, after oral administration of a dose of 100 mg of glycyrrhizic acid, this major metabolite appears in plasma in a concentration of 200 ng/ml while glycyrrhizic acid cannot be found. The finding of a minimal amount of glycyrrhizic acid in urine suggests the existence of a partial absorption in the gastrointestinal tract. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Glycyrrhizic acid is an important consideration for its dosing schedule: Depending on the dose, the second elimination phase in humans has a half-life of 3.5 hours. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Glycyrrhizic acid exhibits a strong affinity for binding with plasma proteins: Glycyrrhizic acid does not bind to any plasma proteins as it is not absorbed systemically. On the other hand, its main active metabolite, glycyrrhetinic acid presents a very large binding to serum proteins such as albumin. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Glycyrrhizic acid from the body primarily occurs through: Glycyrrhizic acid presents a biphasic elimination from the central compartment with a dose-dependent second elimination phase. The majority of the administered dose is eliminated by the bile in which glycyrrhizic acid can be eliminated unchanged and undergoes enterohepatic cycling. On the other hand, the major metabolite, glycyrrhetinic acid, forms glucuronide and sulfate conjugates. These conjugates are efficiently transported into the bile and duodenum where commensal bacteria hydrolizes the conjugate for the formation of glycyrrhetinic acid and further reabsorption. This reabsorption behavior seems to be related to the activity of 3-alpha-hydroxysteroid dehydrogenase which transports very efficiently the metabolite from the plasma to the bile. About 1.1-2.5% of the administered dose of glycyrrhizic acid can be found in urine which corresponds to the minimal cycling and reabsorption of this compound. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Glycyrrhizic acid is distributed throughout the body with a volume of distribution of: The apparent volume of distribution of glycyrrhizic acid either in the central compartment and in steady-state are in the range of 37-64 ml/kg and 59-98 ml/kg, respectively. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Glycyrrhizic acid is a critical factor in determining its safe and effective dosage: The constant reabsorption of glycyrrhetic acid in the duodenum causes a delay in the terminal plasma clearance. The reported total body clearance of glycyrrhizic acid is reported to be in the range of 16-25 ml.kg/h. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Glycyrrhizic acid exerts its therapeutic effects through: Glycyrrhizic acid was reported to present antiallergic, antiviral and anti-inflammatory activities as well as improvements in glucose tolerance. The effect of glycyrrhizic acid in metabolic syndrome generates a significant decrease in blood glucose, fasting blood glucose and mean serum insulin concentration. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Glycyrrhizic acid functions by: Glycyrrhizic acid can be found in the alpha and beta forms. The alpha form is predominant in the liver and duodenum and thus, it is thought that the anti-inflammatory liver effect of this drug are mainly due to the action of this isomer. Glycyrrhizic acid anti-inflammatory effect is generated via suppression of TNF alpha and caspase 3. It also inhibits the translocation of NFkB into the nuclei and conjugates free radicals. Some studies have shown a glycyrrhizic-driven inhibition of CD4+ T cell proliferation via JNK, ERK and PI3K/AKT. The antiviral activity of glycyrrhizic acid includes the inhibition of viral replication and immune regulation. The antiviral activity of glycyrrhizic acid seems to be of a broad spectrum and be able to cover several different viral types such as vaccinia virus, herpes simplex virus, Newcastle disease virus and vesicular stomatitis virus. The effect of glycyrrhizic acid on metabolism is thought to be related to its inhibitory activity towards 11-beta-hydroxysteroid dehydrogenase type 1 which in turn decreases the activity of hexose-6-phosphate dehydrogenase. On the other hand, some studies have shown a potential lipoprotein lipase induction in non-hepatic tissues and thus it is suggested to enhance dyslipidemic conditions. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Glycyrrhizic acid belongs to the class of organic compounds known as triterpene saponins. These are glycosylated derivatives of triterpene sapogenins. The sapogenin moiety backbone is usually based on the oleanane, ursane, taraxastane, bauerane, lanostane, lupeol, lupane, dammarane, cycloartane, friedelane, hopane, 9b,19-cyclo-lanostane, cycloartane, or cycloartanol skeleton, classified under the direct parent group Triterpene saponins. This compound is a part of the Organic compounds, falling under the Lipids and lipid-like molecules superclass, and categorized within the Prenol lipids class, specifically within the Terpene glycosides subclass.

Categories:

Glycyrrhizic acid is categorized under the following therapeutic classes: Alimentary Tract and Metabolism, Anti-Inflammatory Agents, Bile and Liver Therapy, BSEP/ABCB11 Substrates, Liver Therapy, Liver Therapy, Lipotropics, Pentacyclic Triterpenes, Terpenes, Triterpenes. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Glycyrrhizic acid include:

• Water Solubility: Easily soluble in hot water
• Melting Point: 220 ºC (Decomposes at 200 ºC)
• Boiling Point: Decomposes at 200 ºC
• logP: 2.8