Compendium of the most significant studies with reference to properties, intake, effects.

Barone A, Cristiano MC, Cilurzo F, Locatelli M, Iannotta D, Di Marzio L, Celia C, Paolino D. Ammonium glycyrrhizate skin delivery from ultradeformable liposomes: A novel use as an anti-inflammatory agent in topical drug delivery. Colloids Surf B Biointerfaces. 2020 Sep;193:111152. doi: 10.1016/j.colsurfb.2020.111152.

Abstract. The aim of this work was the synthesis and physicochemical characterization of the ammonium glycyrrhizinate-loaded ultradeformable liposomes, the evaluation of drug release and permeation through stratum corneum and epidermis barrier. The in vivo anti-inflammatory effect of ammonium glycyrrhizinate-loaded ultradeformable liposomes was tested on human healthy volunteers.

Dalimov, D. N., Isaev, Y. T., & Saiitkulov, A. M. (2001). Molecular complexes of ammonium glycyrrhizate with certain medicinal agents and their interferon-inducing activity. Chemistry of natural compounds, 37(2), 151-153.

Abstract. The preparation of molecular complexes of ammonium glycyrrhizate with certain sulfamide preparations, gossypol, analgin, and salsolidine is described. Results from a study of the interferon-inducing activity of the complexes are presented.

Wojciechowski, K., Orczyk, M., Gutberlet, T., & Geue, T. (2016). Complexation of phospholipids and cholesterol by triterpenic saponins in bulk and in monolayers. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1858(2), 363-373.

Abstract. The interactions between three triterpene saponins: α-hederin, hederacoside C and ammonium glycyrrhizate with model lipids: cholesterol and dipalmitoylphosphatidylcholine (DPPC) are described. 

Yakovishin, L. A. (2021, November). Possibility of molecular complexation of ammonium glycyrrhizate with cholesterol in aqueous ethanol. In AIP Conference Proceedings (Vol. 2388, No. 1, p. 040020). AIP Publishing LLC.

Abstract. The 1 : 1 molecular complex of ammonium glycyrrhizate (GC) with cholesterol (Chol) was obtained in 80 % aqueous ethanol. GC is monoammonium salt of glycyrrhizic acid (GA). GA is the dominant triterpene glycoside from licorice roots Glycyrrhiza glabra L. Stability constant of the complex (1.6 ± 0.4) × 105 (mol/L)–1. The complex formation was studied by ATR IR-Fourier spectroscopy. Intermolecular interaction in the complex is carried out by hydrogen bond C=O…H–O and hydrophobic contacts

Mukhopadhyay, M., & Panja, P. (2008). A novel process for extraction of natural sweetener from licorice (Glycyrrhiza glabra) roots. Separation and Purification Technology, 63(3), 539-545.

Abstract. Pressurized hot water extraction (PHWE) is a very useful technique for recovering bioactive molecules from natural materials using subcritical compressed liquid water in the temperature range of 50–150 °C. A novel process has been developed for making a natural sweetener from licorice (Glycyrrhiza glabra) roots involving selective chemical reaction and easy separation, for recovering mono-ammonium glycyrrhizate (MAG) using hot water with dissolved ammonia and pressurized with carbon dioxide. 

.Wojciechowski, K., Orczyk, M., Trapp, M., & Gutberlet, T. (2016). Effect of triterpene and steroid saponins on lecithin bilayers. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 510, 150-158.

Abstract. We describe the effect of four triterpene (α-hederin, hederacoside C, ammonium glycyrrhizate, Quillaja bark saponins (QBS)) and one steroid (digitonin) saponins on lecithin and lecithin-cholesterol (4:1 mol/mol) model bilayers.

Ammonio glicirizzato is a triterpene saponin, the ammonium salt of glycyrrhizic acid, derived from the rhizome and root of Glycyrrhiza glabra L. a plant native to central and south-western Asia that possesses sterols, saponins, flavonoids and triterpenes, bioactive components and from which liquorice is derived.

The name describes the structure of the molecule:

• Ammonium is a cation derived from ammonia. In this context, it serves as the ionic part that makes the molecule water-soluble.
• Glycyrrhizate comes from the licorice root, from which it is extracted. Glycyrrhizate has emollient and soothing properties and is often used in cosmetics and skincare products for its beneficial properties.

Raw Materials Used in Production.

• Licorice root (Glycyrrhiza glabra) is the main raw material from which glycyrrhizic acid is extracted.
• Ammonia is used to convert glycyrrhizic acid into its ammonium salt.

Step-by-step Summary of Industrial Production Process.

• Extraction. Glycyrrhizic acid is extracted from the licorice root using solvents.
• Neutralization. The glycyrrhizic acid is then neutralized with ammonia to form ammonium glycyrrhizate salt.
• Purification. The solution is then purified to remove impurities.
• Drying. The ammonium glycyrrhizate salt is dried to get a solid form.

It occurs as white granules or white powder with an intense sweet flavour. Slightly soluble in water, sparingly soluble in anhydrous ethanol, practically insoluble in acetone.

What it is used for and where

Food

About 200 times sweeter than sucrose, it is used as a low-calorie sweetener in food additives such as biscuits, canned meat, flavourings, confectionery, cold fruit and beverages. Flavouring.

Medical and Pharmaceutical

Saponins are biotensioactive glycosides (biological cleaning agents) produced by numerous organisms, mainly plants (1). In this study, the correlation between certain triterpene saponins, including Ammonium glycyrrhizate and cholesterol was investigated (2). 

As a derivative of the plant Glycyrrhiza glabra L., Ammonium glycyrrhizate has anti-inflammatory and anti-allergic properties similar to corticosteroids (3).

Moderate chronic or acute exposure to glycyrrhizinic acid, Ammonium glycyrrhizate and their metabolites has been shown to cause transient systemic changes, including increased potassium excretion, sodium and water retention, increased body weight, alkalosis, and suppression of the renin-angiotensis-aldosterone system. Ammonium glycyrrhizate had no treatment-related effects in motor function tests. In a study of 39 healthy volunteers, a no-effect level of 2 mg/kg/day was determined for glycyrrhizate administered orally for 8 weeks. Clinical tests in seven normal individuals treated with oral ammonium glycyrrhizate at 6 g/day for 3 days revealed a reduction in renal and thermal excretion of Na+ and K+, but carbohydrate and protein metabolism was not affected. Neither glycyrrhizic acid, ammonium glycyrrhizate nor 5% potassium glycyrrhizate proved to be phototoxic or photosensitising agents (4).

Sweetener in medicinal tablets.

Cosmetics

Fragrance. It plays a very important role in the formulation of cosmetic products as it provides the possibility of enhancing, masking or adding fragrance to the final product, increasing its marketability. It is able to create a perceptible pleasant odour, masking a bad smell. The consumer always expects to find a pleasant or distinctive scent in a cosmetic product. 

Flavoring agent. The purpose of this ingredient is to modify the solution to impart a certain flavour. Natural flavouring extracts are rather expensive, so the cosmetic and pharmaceutical industries resort to synthesised substances that have sensory characteristics mostly similar to natural flavourings or are naturally equivalent. This ingredient is isolated through chemical processes or is synthesised from chemicals. It is also referred to as Aroma.

Skin conditioning agent - Miscellaneous.  This ingredient has the task of modifying and improving the condition of the skin when it is damaged or dry, reducing flaking and restoring its elasticity.

Whitening agent, can moderately inhibit melanin activity, accelerates skin absorption, protective agent.

Ammonium glycyrrhizate studies 

Typical commercial product characteristics Ammonium glycyrrhizate

Appearance	White powder
Boiling Point	971.4ºC at 760mmHg
Melting Point	209ºC
Flash Point	288.1ºC
Density	1.43g/cm3
PSA	272.70000
LogP	0.32860
Refraction Index	49° (C=1.5, EtOH)
Loss on Drying	≤4.0%
Residue on Ignition	≤5.0%
Heavy Metals	<10ppm
As	<1ppm
Total Plate	<1000cfu/g
Yeast & Mold	<100cfu/g
Safety

• Molecular Formula    C₄₂H₆₅NO₁₆
• Molecular Weight   839.973
• CAS   53956-04-0
• UNII    3VRD35U26C
• EC Number   258-887-7
• DSSTox Substance ID  DTXSID2041204
• IUPAC  (2S,3S,4S,5R,6R)-6-[(2S,3R,4S,5S,6S)-2-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxy-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-6-carboxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid;azane
• InChI=1S/C42H62O16.H3N/c1-37(2)21-8-11-42(7)31(20(43)16-18-19-17-39(4,36(53)54)13-12-38(19,3)14-15-41(18,42)6)40(21,5)10-9-22(37)55-35-30(26(47)25(46)29(57-35)33(51)52)58-34-27(48)23(44)24(45)28(56-34)32(49)50;/h16,19,21-31,34-35,44-48H,8-15,17H2,1-7H3,(H,49,50)(H,51,52)(H,53,54);1H3/t19-,21-,22-,23-,24-,25-,26-,27+,28-,29-,30+,31+,34-,35-,38+,39-,40-,41+,42+;/m0./s1 
• InChl Key      ILRKKHJEINIICQ-OOFFSTKBSA-N
• SMILES   CC1(C2CCC3(C(C2(CCC1OC4C(C(C(C(O4)C(=O)O)O)O)OC5C(C(C(C(O5)C(=O)O)O)O)O)C)C(=O)C=C6C3(CCC7(C6CC(CC7)(C)C(=O)O)C)C)C)C.N
• MDL number: MFCD00167400
• PubChem Substance ID 329830953
• ChEBI  81864
• FEMA   2528  
• RTECS   LZ6500000

Synonyms

• Monoammonium glycyrrhizinate
• Glycamil
• Glycyrram
• Ammoniated glycyrrhizin
• Monoammonium glycyrrhizate
• EINECS 258-887-7
• alpha-D-Glucopyranosiduronic acid, (3-beta,20-beta)-20-carboxy-11-oxo-30-norolean-12-en-3-yl 2-O-beta-D-glucopyranuronosyl-, ammoniate
• Glycyrrhizic acid, ammonium salt
• Monoammoniumglycyrrhizinate
• (2S,3S,4S,5R,6R)-6-[(2S,3R,4S,5S,6S)-2-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxy-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-6-carboxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid; azane
• alpha-D-Glucopyranosiduronic acid, (3beta,20beta)-20-carboxy-11-oxo-30-norolean-12-en-3-yl 2-O-beta-D-glucopyranuronosyl-, ammonium salt (1:1)

References____________________________________________________________

(1) Wojciechowski K, Orczyk M, Gutberlet T, Geue T. Complexation of phospholipids and cholesterol by triterpenic saponins in bulk and in monolayers. Biochim Biophys Acta. 2016 Feb;1858(2):363-73. doi: 10.1016/j.bbamem.2015.12.001.

(2) Complexation of phospholipids and cholesterol by triterpenic saponins in bulk and in monolayers.
Wojciechowski K, Orczyk M, Gutberlet T, Geue T.
Biochim Biophys Acta. 2016 Feb;1858(2):363-73. doi: 10.1016/j.bbamem.2015.12.001. 

(3) Barone A, Cristiano MC, Cilurzo F, Locatelli M, Iannotta D, Di Marzio L, Celia C, Paolino D. Ammonium glycyrrhizate skin delivery from ultradeformable liposomes: A novel use as an anti-inflammatory agent in topical drug delivery. Colloids Surf B Biointerfaces. 2020 Sep;193:111152. doi: 10.1016/j.colsurfb.2020.111152. 

(4) Final report on the safety assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate.
Cosmetic Ingredient Review Expert Panel.
Int J Toxicol. 2007;26 Suppl 2:79-112. Review.