Glycyrrhizic acid hydrogels

Description

1 / 24 “GLYCYRRHIZIC ACID HYDROGELS FIELD OF THE INVENTION

[0001] The present invention relates to hydrogel compositions comprising glycyrrhizic acid and analogues thereof, within a specific acidic pH range, and to the use of such compositions in the treatment or prevention of skin and soft tissue infections and for use as a coating to prevent infections in medical devices. BACKGROUND OF THE INVENTION

[0002] Different therapeutic properties of glycyrrhizic acid have been reported: antiviral, anti-inflammatory, antitumor, and hepatoprotective [Azaz & Segal (1980) Pharm Acta Helv. 55, 183-186]. Due to the amphiphilic nature of glycyrrhizic acid, aggregates are formed in aqueous solution, eventually leading to gel formation. The formation of a glycyrrhizic acid hydrogel is related to its acidity and the concentration of glycyrrhizic acid.

[0003] There are different studies available on the antibacterial potential of glycyrrhizic acid in solution - not as a hydrogel - with reported activities against: Staphylococci, Enterococci, Helicobacter pylori, Bacillus subtilis, and Pseudomonas aeruginosa. In contrast, several studies have also reported the lack of activity of glycyrrhizic acid in solution against Escherichia coli, Proteus vulgaris, Candida albicans, and Streptococci. Zhao et al. (2020) [ACS Appl Bio Mater 3,648-653] evaluated the antibacterial activity of a 0.13% by weight glycyrrhizic acid hydrogel in PBS with reported activity against Staphylococcus aureus, but no effect against Escherichia coli.

[0004] US patent 2021 / 0015965 discloses glycyrrhizic acid hydrogels for wound healing. SUMMARY OF THE INVENTION

[0005] The present invention describes methods for increasing the antibacterial / bactericidal activity and spectrum of activity of glycyrrhizic acid hydrogels by lowering the pH of the gel below pH 5.0, more specifically between pH 3.0 and pH 4.85. Petition 870250114133, dated 11 / 12 / 2025, page 12 / 43 2 / 24

[0006] The antibacterial / bactericidal activity resulting from glycyrrhizic acid hydrogels cannot be imitated by reducing the pH of the growth medium or by a comparable concentration of glycyrrhizic acid in solution, i.e., it is not a hydrogel. Therefore, it is the combination of the glycyrrhizic acid hydrogel (and not glycyrrhizic acid in solution) at a given pH that results in the broad and unexpected antibacterial / bactericidal activity of these hydrogels.

[0007] The present invention demonstrates that lowering the pH of the hydrogel increases the antibacterial activity against bacterial strains against which glycyrrhizic acid in solution (with pH 7) is not active. Lowering the pH of the glycyrrhizic acid hydrogel to pH 4.2 already increases the antibacterial activity against Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Streptococcus pyogenes, and Enterococcus faecalis. Further lowering the pH of the glycyrrhizic acid hydrogel to pH 3.8 broadens the spectrum of activity to include Pseudomonas aeruginosa. Finally, lowering the pH of the glycyrrhizic acid hydrogel even further to pH 3 broadens the spectrum of activity of the hydrogel to include Escherichia coli, Klebsiella aerogenes, and Klebsiella pneumoniae. DETAILED DESCRIPTION

[0008] Figure captions

[0009] Figure 1 Decreasing the pH of the GLY hydrogel increases the spectrum of activity.

[0010] Figure 2 Growth inhibitory activity of hydrogel A

[0011] Figure 3 Bactericidal activity of hydrogel A

[0012] Figure 4 Growth inhibitory activity of hydrogel B

[0013] Figure 5 Bactericidal activity of hydrogel B

[0014] Figure 6 Growth inhibitory activity of hydrogel C

[0015] Figure 7 Bactericidal activity of hydrogel C

[0016] The abbreviations in the figures are: GLY: acid Petition 870250114133, dated 11 / 12 / 2025, page 13 / 43 3 / 24 Glycyrrhizic; Hydrogel A: a glycyrrhizic acid hydrogel with a gel pH of 4.2. This hydrogel acidifies the growth medium above the hydrogel (gel surface) to a pH of 5.2; Hydrogel B: a glycyrrhizic acid hydrogel with a gel pH of 4.2. This hydrogel acidifies the growth medium above the hydrogel (gel surface) to a pH of 4.8–5.0 depending on the percentage of glycyrrhizic acid in the hydrogel and the amount of this gel used in the assay; Hydrogel C: a glycyrrhizic acid hydrogel with a gel pH of 3.0. This hydrogel acidifies the growth medium above the hydrogel (gel surface) to a pH of 4.4–4.8 depending on the percentage of glycyrrhizic acid in the hydrogel and the amount of this gel used in the assay.

[0017] Hydrogel: According to the IUPAC golden book, a hydrogel is defined as a gel in which the swelling agent is water with a finite, generally small, yield stress. In the hydrogels of the present invention, a network is formed through physical interaction between molecules, resulting in a thermoreversible network, since the local order regions are thermally reversible. Regarding rheological parameters, this means that the shear storage modulus (G') needs to be greater than the loss modulus (G”). G' is preferably 10 times greater than G”. Rheological measurements are performed on thermally stable hydrogels.

[0018] pH Determination: The pH within the gel phase of a gel-phase hydrogel cannot be determined and is therefore measured in the sol phase. Here, the gel itself becomes a liquid (G'»G”) upon heating the gel above the gel-sol transition temperature, and the pH is measured at that temperature. HYDROGEL

[0019] In a first aspect, the present invention relates to a glycyrrhizic acid hydrogel with a pH between 2.5 and 5.0. The inventors have found that glycyrrhizic acid hydrogels in the specified pH range are more effective against bacterial infections. In particular, glycyrrhizic acid hydrogels in the specified pH range, unlike glycyrrhizic acid hydrogels at different pH levels and unlike solutions containing glycyrrhizic acid. Petition 870250114133, dated 11 / 12 / 2025, page 14 / 43 4 / 24 glycyrrhizic acid has been shown to be effective against a broad spectrum of bacterial infections. In comparison, previous glycyrrhizic acid hydrogels and solutions containing glycyrrhizic acid were known to be effective against certain specific bacteria, while ineffective against many others.

[0020] Furthermore, the applicant found that pH had a significant impact on the rheological properties of the hydrogel. Without delving into theory, it is believed that these rheological differences can be attributed to the extent to which glycyrrhizic acid is protonated. Glycyrrhizin contains three carboxyl groups, which can be protonated or deprotonated depending on the pH, influencing, for example, gel strength and gelation temperature.

[0021] At a pH below 2.5, glycyrrhizic acid hydrogel becomes brittle even at 37 °C, resulting in a gel that breaks or cracks easily. Furthermore, at lower pH, glycyrrhizin and water must be mixed above the gelling range to obtain a homogeneous gel. As the gelling range increases with temperature and decreasing pH, this results in greater heating and energy requirements. These reasons made working at pH below 2.5 increasingly impractical, as the gel became difficult to produce and apply.

[0022] As the pH increases, the gelation and gel-sol transition temperatures decrease, and the strength and brittleness of the gel decrease. The sensitivity to changes and / or variations in rheological properties in relation to time, temperature, pH, and glycyrrhizic acid concentration during gelation / gel-sol transition increases significantly.

[0023] At pH above 5.0, gelation at room temperature requires increasingly longer periods of time. Although gelation could be accelerated by active cooling, this required more energy and equipment. Furthermore, small deviations in temperature, pH, or glycyrrhizic acid concentration had a large impact on the gel's properties, including gelation times and gel strength. As a result, working with pH above 5.0 quickly became increasingly impractical, as the gel became difficult to use and apply. Petition 870250114133, dated 11 / 12 / 2025, page 15 / 43 5 / 24

[0024] In the claimed ranges, water and glycyrrhizic acid can be mixed in the sol phase, i.e., above the gel-sol transition point, at relatively low temperatures. This is advantageous from an energy and safety standpoint. By cooling the sol phase, a stable and soft hydrogel is rapidly formed, even at room temperature. This allows for the rapid, safe, and relatively easy production and use of the hydrogel. The present application achieves these characteristics by modifying the pH instead of adding additional gelling agents or crosslinking agents. This is particularly advantageous as it reduces compatibility and in vivo degradability problems of the glycyrrhizic acid hydrogel.

[0025] The term “glycyrrhizic acid hydrogel”, as used herein, refers to a glycyrrhizic acid hydrogel, its derivatives and combinations thereof. In a preferred embodiment, the glycyrrhizic acid hydrogel with a pH between 2.5 and 5.0 comprises 2.5 to 25% by weight of a molecule having formula (I) as represented below or a pharmaceutically acceptable salt or solvate thereof:

[0026] where R2 is H or an alkyl chain C1 to C20;

[0027] and R1 is H or a chemical moiety of glucuronic acid represented in formula (II) Petition 870250114133, dated 11 / 12 / 2025, page 16 / 43 6 / 24 (Ϡ) OH OH >— —1η

[0028] wherein n=1 to 10,

[0029] wherein the symbol in formula (II) describes the linkage between the chemical portion comprising glucuronic acid and (I),

[0030] wherein if n=1, the chemical portion of glucuronic acid is a glucuronic acid monomer,

[0031] wherein if n>1, the chemical portion comprising glucuronic acid is an alpha-1,2-linked glucuronic acid oligomer. In a preferred embodiment, R2 is a glucuronic acid moiety and is 2. In a preferred embodiment, R2 is H. In the most preferred embodiment, the molecule of formula (I) is glycyrrhizic acid.

[0032] In a preferred embodiment, the invention provides a glycyrrhizic acid hydrogel comprising 2.5 to 25% by weight of glycyrrhizic acid, a pharmaceutically acceptable salt or solvate thereof, the hydrogel having a pH between 2.5 and 5.0. In another preferred embodiment, the glycyrrhizic acid hydrogel comprises 2.5 to 25% by weight of a pharmaceutically acceptable salt of glycyrrhizic acid. Suitable pharmaceutically acceptable salts may include alkali metal salts, for example, sodium or potassium salts; alkaline earth metal salts, for example, calcium or magnesium salts; and salts formed with suitable organic binders, for example, ammonium salts. More preferably, the glycyrrhizic acid hydrogel comprises 2.5 to 25% by weight of a monoammonium salt of glycyrrhizic acid.

[0033] In a preferred embodiment, the concentration of glycyrrhizic acid, a pharmaceutically acceptable salt or solvate thereof in said glycyrrhizic acid hydrogel is between 2% by weight and 15% by weight, more Petition 870250114133, dated 11 / 12 / 2025, p. 17 / 43 7 / 24 preferably between 2.5 and 15% by weight, more preferably between 2.5 and 12% by weight, more preferably between 2.5 and 10% by weight, more preferably between 2.5 and 9% by weight, more preferably between 3 and 8% by weight, more preferably between 3 and 7% by weight, more preferably between 4 and 7% by weight, more preferably between 4 and 6% by weight, most preferably about 5% by weight. Advantageously, these concentrations of glycyrrhizic acid, a pharmaceutically acceptable salt or solvate thereof in water, in the pH range of 2 to 5 and in the absence of additional gelling agents, result in a hydrogel with a gelling point between 40 and 60 °C. Advantageously, compared to other hydrogels, there is no need for additional gelling agent, as glycyrrhizic acid acts as a gelling agent, thus reducing toxicity and preventing an immune response. Furthermore, it allows the hydrogel to be fully degradable and promotes API-independent formulation by the physician.

[0034] In a preferred embodiment, the hydrogel is antibiotic-free. In a preferred embodiment, the hydrogel is antibacterial-free. In a preferred embodiment, the hydrogel is anesthetic-free. In a preferred embodiment, the hydrogel is free of active pharmaceutical ingredients. In the most preferred embodiment, the hydrogel is free of antibiotics, anesthetics, antibacterials, and active pharmaceutical ingredients. In other words, the hydrogel preferably does not contain any antibiotics, antibacterials, anesthetics, or active pharmaceutical ingredients other than glycyrrhizic acid. In another preferred embodiment, the hydrogel is administered in an antibiotic-free formulation. In another preferred embodiment, the hydrogel is administered in a formulation without other antibacterials. In another preferred embodiment, the hydrogel is administered in an anesthetic-free formulation.In another preferred embodiment, the hydrogel is administered in a formulation without other active pharmaceutical ingredients. In this context, "free of antibiotics, antibacterials, anesthetics, or active pharmaceutical ingredients" refers to any antibiotics, antibacterials, anesthetics, or active pharmaceutical ingredients other than glycyrrhizic acid. In a preferred embodiment, the hydrogel is free of antifungals. In another preferred embodiment, the... Petition 870250114133, dated 11 / 12 / 2025, page 18 / 43 8 / 24 hydrogel is administered in a formulation without other antifungals.

[0035] This is advantageous because it limits interactions between APIs, making it easier for medical professionals to determine treatment while maintaining complete control over each API and its respective dose. Furthermore, many APIs influence the properties of the hydrogel. For example, tertiary amines commonly found in many APIs, such as anesthetics, can increase the gel's hardness and flowability, which in turn affects the hydrogel's effectiveness in treating bacterial infections.

[0036] The pH of the hydrogel can be modified to be within the desired range using any suitable means. In a preferred embodiment, the pH is modified by adding pharmaceutically acceptable pH modifiers. In a preferred embodiment, the pH can be buffered within the desired range. This can be advantageous to ensure that the pH remains within the desired range when the hydrogel is modified and / or applied. Preferably, pharmaceutically acceptable pH modifiers are chosen from pharmaceutically acceptable acids, pharmaceutically acceptable salts, pharmaceutically acceptable bases, and pharmaceutically acceptable buffers. Pharmaceutically acceptable acids include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, acetic acid, maleic acid, fumaric acid, lactic acid, tartaric acid, citric acid, and gluconic acid.Pharmaceutically acceptable salts include: hydrochloride, hydrobromide, sulfate, phosphate, nitrate, acetate, maleate, fumarate, lactate, tartrate, citrate, and gluconate salts. Pharmaceutically acceptable bases include sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, and aqueous ammonia NH4OH. It should be noted that these pH modifiers are used in hydrogels to obtain and / or maintain the pH within the desired range. In other words, these pH modifiers are highly diluted and used in aqueous media. Pharmaceutically acceptable bases are suitable for adjusting the pH as well as buffering the hydrogel at a desired pH; however, it is important to emphasize that the desired pH remains well within the acidic range (i.e., less than 5). The most preferred pH modifiers are chosen from the list of: Petition 870250114133, dated 11 / 12 / 2025, page 19 / 43 9 / 24 HCl, HBr, NaOH, and NH4OH.

[0037] In another preferred embodiment, the present invention provides a glycyrrhizic acid hydrogel consisting essentially of, preferably consisting of:

[0038] - 2.5 to 25% by weight of glycyrrhizic acid, a pharmaceutically acceptable salt or solvate thereof;

[0039] - pharmaceutically acceptable pH modifiers; in an amount such that said hydrogel has a pH between 2.5 and 5.0; and

[0040] - water.

[0041] In another preferred embodiment, the present invention provides a glycyrrhizic acid hydrogel consisting essentially of, preferably consisting of:

[0042] - 2.5 to 25% by weight of glycyrrhizic acid, a pharmaceutically acceptable salt or solvate thereof;

[0043] - pharmaceutically acceptable pH modifiers chosen from: hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, acetic acid, maleic acid, fumic acid, lactic acid, tartaric acid, citric acid, gluconic acid, hydrochloride salts, hydrobromide salts, sulfate salts, phosphate salts, nitrate salts, acetate salts, maleate salts, fumarate salts, lactate salts, tartrate salts, citrate salts, gluconate salts, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide and aqueous ammonia NH4OH; in an amount such that said hydrogel has a pH between 2.5 and 5.0; and

[0044] - water.

[0045] In a preferred embodiment, the concentration of glycyrrhizic acid, a pharmaceutically acceptable salt or solvate thereof in said glycyrrhizic acid hydrogel is between 2% by weight and 25% by weight. More preferably, the concentration of glycyrrhizic acid, a pharmaceutically acceptable salt or solvate thereof is between 2.5% and 25% by weight, most preferably the hydrogel comprises 2.5% to 3%; 2.5% to 3.5%; 2.5% to 4%; 2.5% to 4.5%; 2.5% to 5%; 2.5% to 5.5%; 2.5% to 6%; 2.5% to 6.5%; 2.5% to 7%; 2.5% to 7.5%; 2.5% to 8%; Petition 870250114133, dated 11 / 12 / 2025, p. 20 / 43 10 / 24 2,5% a 8,5%; 2,5% a 9%; 2,5% a 9,5%; 2,5% a 10%; 2,5% a 10,5%; 2,5% a 11%; 2,5% a 11,5%; 2,5% a 12%; 2,5% a 12,5%; 2,5% a 13%; 2,5% a 13,5%; 2,5% a 14%; 2,5% a 14,5%; 2,5% a 15%; 2,5% a 16%; 2,5% a 17%; 2,5% a 18%; 2,5% a 19%; 2,5% a 20%; 2,5% a 21%; 2,5% a 22%; 2,5% a 23%; 2,5% a 24%; 2,5% a 25%; 3% a 3,5%; 3% a 4%; 3% a 4,5%; 3% a 5%; 3% a 5,5%; 3% a 6%; 3% a 6,5%; 3% a 7%; 3% a 7,5%; 3% a 8%; 3% a 8,5%; 3% a 9%; 3% a 9,5%; 3% a 10%; 3% a 10,5%; 3% a 11%; 3% a 11,5%; 3% a 12%; 3% a 12,5%; 3% a 13%; 3% a 13,5%; 3% a 14%; 3% a 14,5%; 3% a 15%; 3% a 16%; 3% a 17%; 3% a 18%; 3% a 19%; 3% a 20%; 3% a 21%; 3% a 22%; 3% a 23%; 3% a 24%; 3% a 25%; 3,5% a 4%; 3,5% a 4,5%; 3,5% a 5%; 3,5% a 5,5%; 3,5% a 6%; 3,5% a 6,5%; 3,5% a 7%; 3,5% a 7,5%; 3,5% a 8%; 3,5% a 8,5%; 3,5% a 9%; 3,5% a 9,5%; 3,5% a 10%; 3,5% a 10,5%; 3,5% a 11%; 3,5% a 11,5%; 3,5% a 12%; 3,5% a 12,5%; 3,5% a 13%; 3,5% a 13,5%; 3,5% a 14%; 3,5% a 14,5%; 3,5% a 15%; 3,5% a 16%; 3,5% a 17%; 3,5% a 18%; 3,5% a 19%; 3,5% a 20%; 3,5% a 21%; 3,5% a 22%; 3,5% a 23%; 3,5% a 24%; 3,5% a 25%; 4% a 4,5%; 4% a 5%; 4% a 5,5%; 4% a 6%; 4% a 6,5%; 4% a 7%; 4% a 7,5%; 4% a 8%; 4% a 8,5%; 4% a 9%; 4% a 9,5%; 4% a 10%; 4% a 10,5%; 4% a 11%; 4% a 11,5%; 4% a 12%; 4% a 12,5%; 4% a 13%; 4% a 13,5%; 4% a 14%; 4% a 14,5%; 4% a 15%; 4% a 16%; 4% a 17%; 4% a 18%; 4% a 19%; 4% a 20%; 4% a 21%; 4% a 22%; 4% a 23%; 4% a 24%; 4% a 25%; 4,5% a 5%; 4,5% a 5,5%; 4,5% a 6%; 4,5% a 6,5%; 4,5% a 7%; 4,5% a 7,5%; 4,5% a 8%; 4,5% a 8,5%; 4,5% a 9%; 4,5% a 9,5%; 4,5% a 10%; 4,5% a 10,5%; 4,5% a 11%; 4,5% a 11,5%; 4,5% a 12%; 4,5% a 12,5%; 4,5% a 13%; 4,5% a 13,5%; 4,5% a 14%; 4,5% a 14,5%; 4,5% a 15%; 4,5% a 16%; 4,5% a 17%; 4,5% a 18%; 4,5% a 19%; 4,5% a 20%; 4,5% a 21%; 4,5% a 22%; 4,5% a 23%; 4,5% a 24%; 4,5% a 25%; 5% a 5,5%; 5% a 6%; 5% a 6,5%; 5% a 7%; 5% a 7,5%; 5% a 8%; 5% a 8,5%; 5% a 9%; 5% a 9,5%; 5% a 10%; 5% a 10,5%; 5% a 11%; 5% a 11,5%; 5% a 12%; 5% a 12,5%; 5% a 13%; 5% a 13,5%; 5% a 14%; 5% a 14,5%; 5% a 15%;5% to 16%; 5% to 17%; 5% to 18%; 5% to 19%; 5% to 20%; 5% to 21%; 5% to 22%; 5% to 23%; 5% to 24%; 5% to 25%; 6% to 7%; 6% to 8%; 6% to 9%; 6% to 10%; 6% to 11%; 6% to 12%; 6% to 13%; 6% to 14%; 6% to 15%; 6% to 16%; 6% to 17%; 6% to 18%; 6% to 19%; 6% to 20%; 6% to 21%; 6% to 22%; 6% to 23%; 6% to 24%; 6% to; Petition 870250114133, dated 11 / 12 / 2025, page 21 / 43 11 / 24 25%; 7% to 8%; 7% to 9%; 7% to 10%; 7% to 11%; 7% to 12%; 7% to 13%; 7% to 14%; 7% to 15%; 7% to 16%; 7% to 17%; 7% to 18%; 7% to 19%; 7% to 20%; 7% to 21%; 7% to 22%; 7% to 23%; 7% to 24%; 7% to 25%; 8% to 9%; 8% to 10%; 8% to 11%; 8% to 12%; 8% to 13%; 8% to 14%; 8% to 15%; 8% to 16%; 8% to 17%; 8% to 18%; 8% to 19%; 8% to 20%; 8% to 21%; 8% to 22%; 8% to 23%; 8% to 24%; 8% to 25%; 9% to 10%; 9% to 11%; 9% to 12%; 9% to 13%; 9% to 14%; 9% to 15%; 9% to 16%; 9% to 17%; 9% to 18%; 9% to 19%; 9% to 20%; 9% to 21%; 9% to 22%; 9% to 23%; 9% to 24%; 9% to 25%; 10% to 12%; 10% to 14%; 10% to 16%; 10% to 18%; 10% to 20%; 10% to 22%; 10% to 25%; 12% to 15%; 12% to 18%; 12% to 21%; 12% to 25%; 14% to 18%; 14% to 21%; 14% to 23%; 14% to 25%; 16% to 19%; 16% to 21%; 16% to 23%; 16% to 25%; or 25% of glycyrrhizic acid, a pharmaceutically acceptable salt or solvate thereof in water. The term “% of a molecule”, as described herein, refers to % by weight or percentage by weight.

[0046] In a preferred embodiment, the glycyrrhizic acid hydrogel has a temperature below 40 °C. That is, the glycyrrhizic acid hydrogel is a stable hydrogel at temperatures below 40 °C. In a preferred embodiment, the glycyrrhizic acid hydrogel has a gelling point above 40 °C. In a preferred embodiment, the glycyrrhizic acid hydrogel has a gel-sol transition point above 40 °C. It is highly preferable that the gel-sol transition point of the hydrogel be above the body temperature of the mammal to be treated for the wound; otherwise, the hydrogel will become liquid when applied to the wound. The present application shows that the hydrogel form has significant beneficial effects for use in the treatment or prevention of bacterial infections compared to a liquid form.For example, the gelling point for the 2.5% glycyrrhizic acid hydrogel was determined to be 40°C in the experimental setup of the examples of the present invention, while the gelling point for the 5% glycyrrhizic acid hydrogel was determined to be 45°C under those experimental conditions.

[0047] The “gelling point” or “gelling temperature” as used herein is defined as the temperature at which the modulus of Petition 870250114133, dated 11 / 12 / 2025, page 22 / 43 12 / 24 elasticity G' becomes greater than the loss modulus G'', measured during cooling at a rate of 0.01 °C / s. The “gel-sol transition point” or “gel-sol transition temperature” is defined as the temperature at which the loss modulus G” becomes greater than the elasticity modulus G', measured during heating at a rate of 0.01 °C / s.

[0048] The gelation and gel-sol transition of glycyrrhizic acid hydrogels exhibit hysteresis, therefore the gelation point and gel-sol transition point and the gel-sol transition point are not a single value. The “gelation range” or “gel-sol transition range” as used herein is the range defined by the gelation point and the gel-sol transition point; both measured with a temperature sweep of 0.01 °C / s.

[0049] Preferably, the gelation and gel-sol transition range lies entirely above the body temperature of the mammal to be treated, more preferably above 40 °C. In a further preferred embodiment, the gel-sol transition range lies entirely between 40 and 70 °C, more preferably between 40 and 60 °C, and most preferably between 40 and 50 °C. The minimum temperature of 40 °C is beneficial to ensure that the hydrogel remains a hydrogel, which is highly desirable for its antibacterial and healing functions. The maximum temperature is beneficial to allow for easy, safe, and energy-efficient processing of the hydrogel in its sol phase. TREATMENT

[0050] In a second aspect, the present invention provides a glycyrrhizic acid hydrogel as a broad-spectrum hydrogel composition for use in the treatment or prevention of infections, preferably skin and soft tissue infections. In a preferred embodiment, the present invention provides a glycyrrhizic acid hydrogel with a pH below 5.0, for use in the treatment or prevention of an infection, preferably a bacterial infection. In a more preferred embodiment, the invention provides a glycyrrhizic acid hydrogel comprising 2.5 to 25% by weight of glycyrrhizic acid, a pharmaceutically acceptable salt or solvate thereof, the hydrogel having a pH between 2.5 and 5.0, for Petition 870250114133, dated 11 / 12 / 2025, page 23 / 43 13 / 24 use in the treatment or prevention of a bacterial infection. In a preferred embodiment, the invention relates to a hydrogel composition for use in the treatment or prevention of infections in humans or animals, more preferably in humans.

[0051] In a further aspect, the present invention provides a method of treating or preventing a bacterial infection in an individual, comprising the step of administering an effective amount of glycyrrhizic acid hydrogel of the first or second aspect. In a preferred embodiment, the present invention provides a method of treating or preventing a bacterial infection in an individual, comprising the step of administering an effective amount of glycyrrhizic acid hydrogel, a pharmaceutically acceptable salt or solvate thereof, having a pH between 2.5 and 5.0.

[0052] The applicant surprisingly discovered that acidification of a glycyrrhizic acid hydrogel increases the spectrum of activity of said gel against bacterial infection, in addition to modifying the rheological properties of the gel.

[0053] In a preferred embodiment, the glycyrrhizic acid hydrogel has a pH less than 5.0, more preferably a pH less than 4.9, more preferably a pH less than 4.8, more preferably a pH less than 4.85, more preferably a pH less than 4.8, more preferably a pH less than 4.75, more preferably a pH less than 4.7, more preferably a pH less than 4.6, more preferably a pH less than 4.5, more preferably a pH less than 4.4, more preferably a pH less than 4.3, more preferably a pH less than 4.2, more preferably a pH less than 4.0, more preferably a pH less than 3.9, more preferably a pH less than 3.8, more preferably a pH less than 3.7, more preferably a pH less than 3.6, more preferably a pH less than 3.5, more preferably a pH less than 3.4, more preferably a pH lower than 3.3, more preferably a pH lower than 3.2. Petition 870250114133, dated 11 / 12 / 2025, page 24 / 43 14 / 24

[0054] Preferably, the glycyrrhizic acid hydrogel has a pH of at least 1.0, more preferably a pH of at least 2.0, more preferably a pH of at least 2.1, more preferably a pH of at least 2.2, more preferably a pH of at least 2.3, more preferably a pH of at least 2.4, more preferably a pH of at least 2.5, more preferably a pH of at least 2.6, more preferably a pH of at least 2.7, more preferably a pH of at least 2.8, more preferably a pH of at least 2.9, more preferably a pH of at least 3.0, more preferably a pH of at least 3.1, more preferably a pH of at least 3.2.

[0055] In a preferred embodiment, the glycyrrhizic acid hydrogel has a pH between 1.0 and 5.0, more preferably a pH between 2.0 and 5.0, more preferably a pH between 2.5 and 5.0, more preferably a pH between 2.6 and 4.9, more preferably a pH between 2.7 and 4.8, more preferably a pH between 2.8 and 4.8, more preferably a pH between 2.8 and 4.5, more preferably a pH between 2.8 and 4.2, more preferably a pH between 2.8 and 4.0, more preferably a pH between 2.8 and 3.9.

[0056] The applicant surprisingly found that the claimed pH window increases the effectiveness of a glycyrrhizic acid hydrogel against bacterial infections. Furthermore, instead of being effective only against specific bacterial infections outside the preferred pH range, a broad spectrum of antibacterial activity was achieved. This is advantageous as it allows the use of glycyrrhizic acid hydrogel against a wider range of bacterial infections, as well as allowing the use of glycyrrhizic acid hydrogel as a first treatment without or before testing which bacteria are causing the infection.

[0057] In another preferred embodiment, the glycyrrhizic acid hydrogel has a pH between 4.0 and 4.4, more preferably a pH between 4.1 and 4.3, most preferably a pH of about 4.2. In a further preference, this hydrogel is for use in the treatment or prevention of a bacterial infection, wherein the bacterial infection is MRSA, Staphylococcus epidermidis, Petition 870250114133, dated 11 / 12 / 2025, p. 25 / 43 15 / 24 Acinetobacter baumannii, E. faecalis, or S. pyogenes. More preferentially, the bacterial infection is MRSA, Acinetobacter baumannii, and Streptococcus pyogenes. This specific pH range was considered the most effective against bacterial infections of MRSA, Acinetobacter baumannii, and Streptococcus pyogenes. Furthermore, this pH range was considered very effective against bacterial infection by MRSA, Acinetobacter baumannii, and Streptococcus pyogenes.

[0058] In another preferred embodiment, the glycyrrhizic acid hydrogel has a pH between 3.6 and 4.0, more preferably a pH between 3.7 and 3.7, most preferably a pH of about 3.8. In a further preference, this hydrogel is for use in the treatment or prevention of a bacterial infection, wherein the bacterial infection is Pseudomonas aeruginosa. This specific pH range was considered the most effective against a Pseudomonas aeruginosa bacterial infection.

[0059] In another preferred embodiment, the glycyrrhizic acid hydrogel has a pH between 2.8 and 3.2, more preferably a pH between 2.9 and 3.2, most preferably a pH of about 3. In a further preference, this hydrogel is for use in the treatment or prevention of a bacterial infection, wherein the bacterial infection is of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Klebsiella aerogenes or Enterococcus faecalis. More preferably, this hydrogel is for use in the treatment or prevention of a bacterial infection wherein the bacterial infection is of Escherichia coli, Klebsiella pneumoniae or Klebsiella aerogenes. This specific pH range has been found to be the most effective against a bacterial infection of Escherichia coli, Klebsiella pneumoniae or Klebsiella aerogenes.Furthermore, this pH range has been found to be very effective against bacterial infection by Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Klebsiella aerogenes, or Enterococcus faecalis.

[0060] In one preferred embodiment, the hydrogel is for topical use. In another preferred embodiment, the hydrogel is for use in the treatment or prevention of a bacterial infection, the hydrogel being for topical use. In yet another preferred embodiment, the hydrogel is for topical use on wounds. Petition 870250114133, dated 11 / 12 / 2025, page 26 / 43 16 / 24 Chronic. The term "chronic wound" refers to a wound that has not healed. Wounds that do not heal within 6 weeks, for example, are considered chronic. Chronic wounds include, for example, pressure ulcers, bedsores, diabetic ulcers, including diabetic foot and leg ulcers, slow-healing or non-healing venous ulcers, venous stasis ulcers, arterial ulcers, vasculitic ulcers, burn ulcers, trauma-induced ulcers, infectious ulcers, mixed ulcers, and pyoderma gangrenosum. A chronic wound can be an arterial ulcer, which comprises ulcerations resulting from complete or partial arterial blockage. A chronic wound can also be a venous or venous stasis ulcer, which comprises ulcerations resulting from venous valve malfunction and associated vascular disease. Bacterial infections commonly occur in chronic wounds, as they provide suitable entry and growth sites for bacteria.The glycyrrhizic acid hydrogel of the present invention can be advantageously used to treat or prevent bacterial infections in a broad spectrum of bacteria.

[0061] In another preferred embodiment, the hydrogel is for internal use. In another preferred embodiment, the hydrogel is for use in the treatment or prevention of bacterial infection, the hydrogel being for internal use.

[0062] In another preferred embodiment, the hydrogel is applied as a coating on a medical device. In another preferred embodiment, the hydrogel is for use in the treatment or prevention of a bacterial infection, wherein the hydrogel is applied as a coating on a medical device.

[0063] An unlimited list of conditions and bacteria to be treated with the hydrogels of the present invention is listed in Table 1. TABLE 1 EXAMPLES OF ETIOLOGICAL RISK FACTORS FOR SKIN AND SOFT TISSUE INFECTIONS AND THEIR ASSOCIATED BACTERIAL CAUSES Petition 870250114133, dated 11 / 12 / 2025, page 27 / 43 17 / 24 Risk Factor | Associated Etiological Pathogen | Diabetes mellitus | Staphylococci, Group B streptococci, Acinetobacter rheumanoli, Escherichia coli | Cirrhosis | Klebsiella pneumoniae, Klebsiella aerogneiss, Escherichia coli, Acinetobacter baumannii | Neutropenia | Pseudomonas aeruginosa | Hot tub / sponge exposure | Pseudomonas aeruginosa | Intravenous drug abuse | Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa EXAMPLES EXAMPLE 1: LOWERING THE pH OF GLYCYRRHIZAL ACID HYDROGEL INCREASES THE SPECTRUM OF ACTIVITY.

[0064] The circles in Figure 1 represent the number of pathogens (9 tested in total) whose growth is completely inhibited by the specific hydrogel (defined according to the concentration of glycyrrhizic acid and the pH of the gel surface). The size of the circle is proportional to the number of pathogens whose growth is completely inhibited. The concentration of glycyrrhizic acid is calculated based on the percentage of glycyrrhizic acid in the gel and the amount of gel used in the assay. Note that the pH on the gel surface is lower than the initial pH of the growth medium on top of the gel due to the acidifying effect of the hydrogel. This pH difference depends on the pH of the hydrogel, the percentage of glycyrrhizic acid in the hydrogel, and the amount of hydrogel used. The different hydrogels are indicated by colors: white circles represent hydrogel A, gray circles represent hydrogel B, and black circles represent hydrogel C.The two gray dots at pH 7.0 on the graph represent the (lack of) activity of glycyrrhizic acid in solution. Of all nine pathogens tested, only Streptococcus pyogenes was inhibited by 50 mg / mL of glycyrrhizic acid in solution.

[0065] The black triangle at pH 6.5 in the graph represents the Petition 870250114133, dated 11 / 12 / 2025, page 28 / 43 18 / 24 activity of the hydrogel prepared as described in (Zhao et al. (2020) cited above). Here, the hydrogel from Zhao et al. was prepared according to the authors' instructions and the pH measurement was performed as detailed in the methods and materials of the present invention. EXAMPLE 2: LOWERING THE pH OF GLYCYRRHIZAL ACID HYDROGEL INCREASES ANTIBACTERIAL ACTIVITY.

[0066] The table below summarizes the antibacterial effect (no effect, bacteriostatic, bactericidal) of glycyrrhizic acid hydrogels on different pathogens tested. TABLE 2 OVERVIEW OF THE ANTIBACTERIAL EFFECT (NO EFFECT, BACTERIOSTATIC, BACTERICIDAL) OF GLYCYRRHIZAL ACID HYDROGELS ON DIFFERENT PATHOGENS TESTED. GLYem solution Hydrogel A Hydrogel B Hydrogel C MRSA No effect Bactericidal Bactericidal Bactericidal S. epidermidis No effect Bacteriostatic Bactericidal Bactericidal A. baumannii No effect Bactericidal Bactericidal Bactericidal P. aeruginosa No effect No effect Bacteriostatic Bactericidal E. coli No effect No effect No effect Bactericidal (>50mg / mL) K. pneumoniae No effect No effect No effect Bactericidal (>50mg / mL) K. aerogenes No effect No effect No effect Bactericidal (>50mg / mL) Streptococcus Bacteriostatic Bactericidal Bactericidal Bactericidal Enterococcus No effect Bacteriostatic Bacteriostatic Bactericidal EXAMPLE 3: GROWTH INHIBITING ACTIVITY OF HYDROGEL A

[0067] Hydrogel A shows greater growth inhibitory activity against MRSA, Staphylococcus epidermidis, Acinetobacter baumannii, E. Petition 870250114133, dated 11 / 12 / 2025, p. 29 / 43 19 / 24 faecalis and S. pyogenes, compared to the lack / limited growth inhibition activity of glycyrrhizic acid in solution or at the corresponding pH associated with environmental acidification caused by glycyrrhizic acid hydrogels.

[0068] The growth-inhibiting effect of 25 mg / mL glycyrrhizic acid in solution and 0.5 mL / mL of 5% by weight hydrogel A, corresponding to a total of 25 mg / mL glycyrrhizic acid in the system, is shown in gray bars with circles. Both are compared to suitable controls (shown in white bars with squares), i.e., pH-adjusted growth media that are associated with the acidifying effect of glycyrrhizic acid in solution (pH 7.4) and hydrogel A (pH 5.2) but without the presence of glycyrrhizic acid in solution or hydrogel A, respectively. ns: p>0.05, * p < 0.05, ** p < 0.01, **** p < 0.0001. EXAMPLE 4: BACTERICIDAL ACTIVITY OF HYDROGEL A

[0069] Hydrogel A shows bactericidal activity against MRSA, Acinetobacter baumannii and Streptococcus pyogenes.

[0070] Bactericidal activity is defined as a 3 LOG reduction compared to the inoculum (black bars). The bactericidal effect of 0.5 mL / mL of 5% by weight hydrogel A (shown in gray bars with circles) is compared to the pH-adjusted growth medium (pH 5.2) which is associated with the acidifying effect of hydrogel A (shown in white bars with squares). ns: p>0.05, **** p < 0.0001. EXAMPLE 5: GROWTH-INHIBITING ACTIVITY OF HYDROGEL B

[0071] Hydrogel B shows greater growth-inhibiting activity against Pseudomonas aeruginosa, compared to the lack / limited growth-inhibiting activity of glycyrrhizic acid in solution or at the corresponding pH associated with the acidification of the environment caused by glycyrrhizic acid hydrogels.

[0072] The growth-inhibiting effect of 25 mg / mL glycyrrhizic acid in solution and 0.5 mL / mL of 5% by weight hydrogel B, Petition 870250114133, dated 11 / 12 / 2025, pages 30 / 43 20 / 24, corresponding to a total of 25 mg / mL of glycyrrhizic acid in the system, are shown in gray bars with circles. Both are compared to suitable controls (shown in white bars with squares), i.e., pH-adjusted growth media that are associated with the acidifying effect of glycyrrhizic acid solution (pH 7.4) and hydrogel B (pH 5), but without the presence of glycyrrhizic acid solution or hydrogel B, respectively. ns: p > 0.05, **** p < 0.0001. EXAMPLE 6: THE BACTERICIDAL ACTIVITY OF HYDROGEL B SHOWS

[0073] Hydrogel B exhibits bactericidal activity against Staphylococcus epidermidis.

[0074] Bactericidal activity is defined as a 3 LOG reduction compared to the inoculum (black bars). The bactericidal effect of 0.5 mL / mL of 5% by weight hydrogel B (shown in gray bars with circles) is compared to the pH-adjusted growth medium (pH 5) which is associated with the acidifying effect of hydrogel B (shown in white bars with squares). **** p < 0.0001. EXAMPLE 7: GROWTH INHIBITING ACTIVITY OF HYDROGEL C.

[0075] Hydrogel C shows greater growth-inhibiting activity against Escherichia coli, Klebsiella pneumoniae, and Klebsiella aerogenes, compared to the lack / limited growth-inhibiting activity of glycyrrhizic acid in solution or at the corresponding pH associated with environmental acidification caused by glycyrrhizic acid hydrogels.

[0076] The growth-inhibiting effect of 50 mg / mL glycyrrhizic acid in solution and 0.5 mL / mL of 10% by weight hydrogel C, corresponding to a total of 50 mg / mL of glycyrrhizic acid in the system, is shown in gray bars with circles. Both are compared to suitable controls (shown in white bars with squares), i.e., pH-adjusted growth media that are associated with the acidifying effect of glycyrrhizic acid in solution (pH 7.4) and hydrogel C (pH 4.6), but without the presence of acid. Petition 870250114133, dated 11 / 12 / 2025, pages 31 / 43 21 / 24 glycyrrhizic acid in solution or hydrogel C, respectively. ns: p > 0.05, **** p < 0.0001. EXAMPLE 8: BACTERICIDAL ACTIVITY OF HYDROGEL C

[0077] Hydrogel C exhibits bactericidal activity against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Klebsiella aerogenes, and Enterococcus faecalis.

[0078] Bactericidal activity is defined as a 3 LOG reduction compared to the inoculum (black bars). The bactericidal effect of 0.5 mL / mL of 10% by weight hydrogel C (shown in gray bars with circles) is compared to the pH-adjusted growth medium (pH 4.6) which is associated with the acidifying effect of hydrogel C (shown in white bars with squares). **** p < 0.0001. EXAMPLES 9: MATERIALS AND METHODS STRAINS AND CHEMICAL PRODUCTS

[0079] Escherichia coli UTI89, Pseudomonas aeruginosa LMG9009, Staphylococcus aureus ATCC6538, Klebsiella pneumoniae ATCC13883, Klebsiella aerogenes ATCC13048, Acinetobacter baumannii RD5SR3, Enterococcus faecalis LMG8148, Streptococcus pyogenes LMG 14237, as well as clinical isolates of Staphylococcus epidermidis and methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients with osteomyelitis were used. Before the experiments, all strains, except S. pyogenes, were inoculated into lysogeny broth (LB) and incubated overnight at 37 °C (200 rpm). Nocturnal cultures of S. pyogenes were grown microaerophilically in brain-heart infusion broth (BHI). Subsequently, the bacteria were normalized to approximately 5*10⁵ CFU mL⁻¹.

[0080] Lysogeny broth (LB; 10 g L-1 NaCl, 10 g L-1 Tryptone, 5 g L-1 Yeast Extract) was used to create overnight cultures (ONC). Mueller Hinton broth (MHB; 21 g L-1 MHB) was used for minimum inhibitory concentration (MIC) assays for all strains except S. pyogenes. For this strain, BHI was used. If LB agar, BHI agar, or MHB agar was required, 15 g L-1 of bacteriological agar was added. Batches of MHB or BHI with pH Petition 870250114133, dated 11 / 12 / 2025, pages 32 / 43 22 / 24 variable were made by adding HCl or NaOH to acidify or alkalize the medium to the desired pH value, respectively.

[0081] Three different formulations of glycyrrhizic acid hydrogels were made in dH2O: (i) Hydrogel C with pH=3, (ii) Hydrogel B with pH=3.8, and (iii) Hydrogel A with pH=4.2. The pH was measured at 70 °C and varied using HCl or NaOH to acidify or alkalize the formulation to the desired pH value. In addition, different concentration batches (mass by volume) were used for the hydrogels: 2.5%, 5%, 7.5%, 10%, 15%, and 20%. Glycyrrhizic acid solution – not a hydrogel – was prepared at pH 7.4. EVALUATION OF GROWTH INHIBITION

[0082] To determine the growth-inhibiting activity of glycyrrhizic acid in solution, 100 μL of different 1:2 dilutions of a 100 mg / mL glycyrrhizic acid stock solution in MHB were added to the wells of a 96-well microtiter plate, after which 100 μL of a 5*105CFU mL-1 bacterial suspension in MHB was added to each well.

[0083] To determine the growth-inhibiting activity of glycyrrhizic acid hydrogels, the hydrogel was liquefied by heating to 70 °C. When liquid, varying volumes of the liquid hydrogel (80 μL to 160 μL) were pipetted into a 96-well microtiter plate. After the hydrogel solidified, 120 μL of a 5*10⁵ CFU mL⁻¹ bacterial suspension in MHB was added to the hydrogel.

[0084] To prevent evaporation, the plates were sealed with a membrane (Greiner Bio-one NV). After 24 hours of incubation (37 °C, 200 rpm), the OD595 was measured and the relative OD595 was calculated by dividing the OD595 by the average OD595 of the growth control (= cell growth in MHB without glycyrrhizic acid). EVALUATION OF BIOCIDAL ACTIVITY

[0085] To determine the biocidal activity of glycyrrhizic acid in solution and in hydrogel, at the end of the growth inhibition assay (see above), after incubation, 100 μL of the medium on the hydrogel were diluted 10 Petition 870250114133, dated 11 / 12 / 2025, pages 33 / 43 23 / 24 times in phosphate-buffered saline (PBS; 1.24 g L-1K2HPO4, 0.39 g L-1KH2PO4, 8.8 g L-1NaCl) and seeded onto MHB agar plates by spreading 100 μL of the dilution. After overnight incubation at 37 °C, colonies were counted and colony-forming units were determined. Rheological evaluation

[0086] The rheological properties of glycyrrhizic acid hydrogels in the pH range of 2 to 5 were evaluated during time, strain, frequency, and temperature sweeps in a stress-controlled rheometer. In addition, DSC measurements were performed.

[0087] It was discovered that the strength of hydrogels decreases with increasing pH. At pH 3.00 or less, microcracks begin to form within the material. This resulted in a hard, but increasingly brittle hydrogel. The differences in rheological properties between 20 °C and 37 °C at pH 3 were small. Gelation begins almost instantaneously, and the modules reach a stable state in less than 5 minutes.

[0088] Furthermore, the mixture of glycyrrhizic acid and water rapidly forms an impermeable gel, making it impossible for the mixture to gel completely. To obtain a homogeneous gel, the mixture must be heated above its gel-sol transition temperature and properly mixed in the sol phase. As the gelation temperature and the gel-sol transition temperature increase with decreasing pH, a lower pH results in greater heating requirements. These reasons made it impractical to work with a hydrogel with a pH below 2.5.

[0089] As the pH increases, the hydrogels become softer and less brittle. Furthermore, the samples take longer to gel. In other words, it takes longer for the modules to reach a steady state with increasing pH. The gelation temperature decreases with increasing pH. At a pH above 5.35 and a glycyrrhizin concentration of 10% by weight, the gelation temperature is below room temperature. The gels are relatively frequency-independent at each pH. Petition 870250114133, dated 11 / 12 / 2025, pages 34 / 43 24 / 24

[0090] At pH near 5 and above, the effects of temperature and time on gel formation become increasingly significant. For example, at a glycyrrhizin (monoammonium) concentration of 10% by weight in water, pH adjusted with HCl and NH4OH, there is a huge difference in the moduli and gelation time between pH 4.70 and pH 4.85 at 20 °C. Although both pHs result in a soft hydrogel at steady state, reaching a G' of 100 Pa takes 5 minutes and 30 seconds at a pH of 4.70. Reaching the same G' of 100 Pa takes 75 minutes at pH 4.85.

[0091] Due to the drastic increase in gelation times, as well as the gel's sensitivity to differences in pH, temperature, and glycyrrhizic acid concentration, the use of glycyrrhizic acid hydrogels at pH above 5 becomes increasingly impractical. Gelation can be accelerated by cooling, but this increases the equipment and energy requirements for preparation. Furthermore, this has been found to exacerbate high-temperature sensitivity problems when the hydrogel is applied to a wound. The rapid and substantial decrease in gel strength due to increased temperature has resulted in difficult handling. Petition 870250114133, dated 11 / 12 / 2025, pp. 35 / 43

Claims

1 / 3 CLAIMS 1. Glycyrrhizic acid hydrogel, characterized in that it has a pH between 2.5 and 5.0, for use in the treatment or prevention of a bacterial infection.

2. Glycyrrhizic acid hydrogel for use according to claim 1, wherein the hydrogel is characterized by having a pH between 2.8 and 4.

2.

3. Hydrogel, according to claim 1, characterized in that it is for use in the treatment or prevention of a bacterial infection, wherein the hydrogel has a pH between 4.0 and 4.4, or has a pH between 4.1 and 4.3, or has a pH of 4.

2.

4. Hydrogel, according to claim 2, characterized in that it is for use in the treatment or prevention of a bacterial infection, wherein the bacterial infection is MRSA, Staphylococcus epidermidis, Acinetobacter baumannii, E. faecalis or S. pyogenes.

5. Hydrogel, according to claim 2, characterized in that it is for use in the treatment or prevention of a bacterial infection, wherein the bacterial infection is MRSA, Acinetobacter baumannii and Streptococcus pyogenes.

6. Hydrogel, according to claim 1, characterized in that it is for use in the treatment or prevention of a bacterial infection, wherein the hydrogel has a pH between 3.6 and 4.0, or has a pH between 3.7 and 3.9, or has a pH of 3.

8.

7. Hydrogel, according to claim 5, characterized in that it is for use in the treatment or prevention of a bacterial infection, wherein the bacterial infection is Pseudomonas aeruginosa.

8. Hydrogel, according to claim 1, characterized in that it is for use in the treatment or prevention of a bacterial infection, wherein the hydrogel has a pH between 2.8 and 3.2 or has a pH between 2.9 and 3.1 or has a pH of 3. Petition 870250094011, dated 10 / 14 / 2025, pp. 88 / 92 2 / 3 9. Hydrogel, according to claim 7, characterized in that it is for use in the treatment or prevention of a bacterial infection, wherein the bacterial infection is Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Klebsiella aerogenes or Enterococcus faecalis.

10. Hydrogel, according to claim 7, characterized in that it is for use in the treatment or prevention of a bacterial infection where the bacterial infection is Escherichia coli, Klebsiella pneumoniae or Klebsiella aerogenes.

11. Hydrogel, according to any one of claims 1 to 9, characterized in that it is for use in the treatment or prevention of a bacterial infection, wherein the hydrogel is for topical use.

12. Hydrogel, according to claim 6, characterized in that it is for use in the treatment or prevention of a bacterial infection, wherein the hydrogel is for internal use.

13. Hydrogel, according to any one of claims 1 to 11, characterized in that it is for use in the treatment or prevention of a bacterial infection, wherein the hydrogel is applied as a coating on a medical device.

14. Hydrogel for use according to any one of claims 1 to 12, characterized in that the hydrogel is administered in a formulation without antibacterial agents, more preferably without antibiotics.

15. Hydrogel for use according to any one of claims 1 to 14, characterized in that the concentration of glycyrrhizic acid, a pharmaceutically acceptable salt or solvate thereof, in said hydrogel is between 2% by weight and 25% by weight.

16. Pharmaceutical composition, characterized in that it is of hydrogel, as defined in any one of claims 1 to 15.

17. Pharmaceutical composition according to claim 16, characterized in that said pharmaceutical composition is free from other antibacterial and antifungal agents.

18. A method for treating or preventing a bacterial infection in an individual, characterized by the fact that it comprises the step of administering an effective amount of glycyrrhizic acid hydrogel, a pharmaceutically acceptable salt or solvate thereof, with a pH between 2.5 and 5.

0. Petition 870250094011, dated 10 / 14 / 2025, pp. 90 / 92

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