Fusidic acid gel based on deep eutectic solvent and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to fusidic acid gel based on a deep eutectic solvent (DES) and a preparation method of the fusidic acid gel. The invention aims to solve the problems that the stability of cream is poor, and the curative effect is poor due to the fact that raw materials exist in a suspension form. According to the invention, a plurality of deep eutectic solvents are firstly screened, and it is accidentally found that DES formed by taking glycerol as a hydrogen bond acceptor and arginine as a hydrogen bond donor has the best dissolution effect on fusidic acid, and the dissolution effect is far better than that of traditional solvents and other types of DES. Based on the discovery, the fusidic acid gel provided by the invention is prepared by taking the preferable DES as a core component, dissolving the medicine at high concentration, and then mixing with a gel matrix for forming. The preparation is simple in preparation process, green and safe, and has the advantages of high stability, efficient in-vitro release, remarkable antibacterial ability and the like.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a fusidic acid gel based on deep eutectic solvent (DES) and its preparation method. Background Technology

[0002] Fusidic acid (FA), also known as fusidic acid or fusidic acid, is a triterpenoid natural product with a steroidal skeleton extracted from the fungus *Fusidium coccineum*. It possesses both antibacterial and immunomodulatory effects. While its chemical structure is similar to cephalosporin P, FA is not a hormone and has no hormonal side effects. In clinical applications, FA is often found in its sodium salt form. It delays bacterial protein synthesis by inhibiting translation elongation factor G (EF-G), effectively inhibiting Gram-positive bacteria such as streptococci and *Staphylococcus aureus*, as well as some Gram-negative bacteria such as *Neisseria*. It exhibits significant inhibitory activity against methicillin-resistant *Staphylococcus aureus*, making it an important treatment option for bacterial skin infections. In recent years, the pharmacological activities of FA and its derivatives have been extensively studied, including anti-inflammatory, immunomodulatory, antitumor, antiviral, drug resistance reversal, and neuroprotective effects.

[0003] Fusidic acid has strong skin penetration, allowing it to penetrate deep into the skin to clear infections. In recent years, fusidic acid cream has been widely used in dermatology and surgery as a topical antibacterial preparation, demonstrating good clinical efficacy and safety. Currently, commercially available fusidic acid creams (such as original products) typically contain 2% fusidic acid. However, due to the limited solubility of fusidic acid itself, there is still room for improvement in the bioavailability of the drug at this concentration. Therefore, there has long been a desire in the field for a technology that can both maintain and improve efficacy while reducing drug dosage, thereby reducing potential systemic absorption risks, skin irritation, and raw material costs. However, existing technologies have not provided an effective solution. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the first objective of this invention is to provide a fusidic acid gel with a significantly lower content of active ingredient than commercially available 2% creams (e.g., only one-quarter, or 0.5%), but which, through innovative DES technology, achieves a faster drug release rate and in vitro antibacterial activity equivalent to the original product.

[0005] Another object of the present invention is to provide a method for preparing the above-mentioned gelling agent, which is simple, green, and suitable for industrial production.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: A fusidic acid gel, by weight percentage, is composed of the following active ingredient and excipients: 0.5%~2% fusidic acid, 10%~40% deep eutectic solvent active ingredient, 0.3%~5% gel matrix, 0.1% preservative, 0.05% disodium edetate (EDTA-2Na), 3% propylene glycol, and the balance being water.

[0007] Furthermore, the fusidic acid gel is composed of the following active pharmaceutical ingredient and excipients by weight percentage: 0.5%~1.5% fusidic acid, 10%~30% deep eutectic solvent active ingredient, 0.3%~1% gel matrix, 0.1% preservative, 0.05% disodium edetate, 3% propylene glycol, and the balance being water.

[0008] Furthermore, the fusidic acid gel is composed of the following active pharmaceutical ingredient and excipients by weight percentage: 0.5% fusidic acid, 20% deep eutectic solvent active ingredient, 1% gel matrix, 0.1% preservative, 0.05% disodium edetate, 3% propylene glycol, and the balance being water.

[0009] Furthermore, the active ingredient of the deep eutectic solvent is composed of natural amino acids and polyols; the natural amino acids are basic amino acids selected from one or more of arginine, lysine, and histidine; the polyols are selected from one or more of glycerol, propylene glycol, and sorbitol.

[0010] Furthermore, the active ingredient of the deep eutectic solvent is composed of arginine and glycerol; even further, the molar ratio of arginine and glycerol is 1:(2~6); preferably, the active ingredient of the deep eutectic solvent is formed by mixing arginine and glycerol in a molar ratio of 1:4.

[0011] Furthermore, the gel matrix is ​​carbomer (preferably carbomer 980).

[0012] Further, the preservative is methylparaben and / or propylparaben; even further, the preservative is a mixture of methylparaben and propylparaben in a mass ratio of 4:1.

[0013] The present invention also provides a method for preparing the above-mentioned fusidic acid gel, comprising the following steps: (1) Preparation of deep eutectic solvent: Natural amino acids and polyols are mixed, water is added, and the mixture is stirred at 60~90℃ (preferably 70~80℃) until a clear and transparent liquid is formed to obtain deep eutectic solvent; (2) Preparation of drug loading solution: Fusidic acid was added to the deep eutectic solvent obtained in step (1) and stirred at room temperature until completely dissolved to obtain the drug loading solution; (3) Preparation of preservative solution: Mix propylene glycol with preservative and stir at room temperature to disperse it evenly to obtain preservative solution; (4) Preparation of gel matrix solution: The gel matrix is ​​uniformly dispersed in an aqueous solution of disodium edetate at room temperature and stirred to allow it to swell fully, thus obtaining the gel matrix solution; (5) Mixing and molding: Mix the preservative solution from step (3) with the gel matrix solution from step (4), stir until uniform, then add the drug loading solution from step (2), and stir until a uniform gel is formed to obtain the fusidic acid gel.

[0014] Further, in step (1), the effective components of the deep eutectic solvent are composed of arginine and glycerol, with a molar ratio of 1:(2~6) (preferably 1:4), and a water content of 40%.

[0015] This invention provides a fusidic acid gel based on a deep eutectic solvent and its preparation method. The solubility and stability of fusidic acid are significantly improved by DES technology. The prepared gel has excellent in vitro antibacterial activity. The preparation process is simple, the quality is stable, and it is suitable for industrial production. It has broad application prospects in the treatment of skin infections caused by Gram-positive bacteria.

[0016] Compared with the prior art, the present invention has the following advantages and beneficial effects: 1. This invention utilizes arginine-glycerol DES technology to successfully reduce the effective therapeutic concentration of fusidic acid from the industry standard of 2% to 0.5%. In vitro antibacterial experiments have confirmed that the diameter of the antibacterial zone of 0.5% of the gel of this invention is comparable to that of 2% of the commercially available original cream, with no statistically significant difference, achieving a major breakthrough by using a quarter dose to achieve an equivalent antibacterial effect.

[0017] 2. Faster onset of action potential: In vitro release experiments show that the drug release rate and cumulative release amount of 0.5% of the gel of this invention are significantly higher than those of 2% of commercially available creams, indicating that the drug can reach the site of action more quickly and may lead to a faster clinical onset of action.

[0018] 3. Enhanced safety and cost-effectiveness: The significant reduction in drug dosage directly reduces the risks of skin irritation and systemic absorption that may result from high-concentration drugs, while also significantly lowering the cost of raw materials, thus possessing significant clinical and economic value.

[0019] 4. Green and environmentally friendly: The selected DES components (arginine and glycerin) are all natural, non-toxic, and biodegradable pharmaceutical excipients with extremely high safety. Attached Figure Description

[0020] Figure 1 Results of drug dosage screening; Figure 2 Photographs of the gel's appearance; Figure 3: Flow curve of fusidic acid gel in Example 2 of the present invention; Figure 4 Yield stress diagram of fusidic acid gel in Example 2 of the present invention; Figure 5 Frequency scan diagram of fusidic acid gel in Example 2 of this invention. Detailed Implementation

[0021] To better understand the technical solution of this invention, the invention will be further described in detail and completely below with reference to the accompanying drawings and specific embodiments. It should be understood that the described embodiments are merely some embodiments of this invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0022] Unless otherwise specified, the experimental methods used in the following examples are conventional methods; and the materials and reagents used are commercially available unless otherwise specified.

[0023] Example 1 The preparation and screening of DES (deep eutectic solvent active component, hereinafter the same, will not be repeated) to select the DES with the best solubility for fusidic acid includes the following steps: Step 1: DES preparation: Mix the components according to the composition and molar ratio of each DES group in Table 1, heat and stir in an 80°C water bath until a clear and transparent liquid is formed, and then cool for later use.

[0024] Step 2, solubility determination (using the equilibrium solubility method): Add excess fusidic acid to each of the above-mentioned DES groups, shake at 25°C for 24 hours, filter, and determine the drug concentration in the filtrate according to the high performance liquid chromatography method of General Chapter 0512 of Part IV of the Chinese Pharmacopoeia 2025.

[0025] Table 1

[0026] As shown in Table 1, arginine-glycerol DES (1:4) has the best solubility for fusidic acid, far exceeding other DESs. Therefore, it was selected as the drug carrier and used in the following examples.

[0027] Examples 2-8 Table 2

[0028] A method for preparing a fusidic acid gel includes the following steps: (1) Mix arginine and glycerol in a molar ratio of 1:4, add purified water to a content of 40% (the mass percentage of purified water in the deep eutectic solvent is 40%), stir at 30 rpm for 40 min at 80 °C to form a clear and transparent liquid, which is the deep eutectic solvent. (2) Add fusidic acid to the deep eutectic solvent obtained in step (1) and stir at 20 rpm for 20 min at room temperature until fusidic acid is completely dissolved to obtain a drug-loaded solution; (3) Mix propylene glycol, methylparaben, and propylparaben, and stir at 20 rpm for 20 min at room temperature to disperse them evenly, so as to obtain a preservative solution; (4) Add disodium edetate to the remaining purified water and stir to dissolve it; add carbomer 980 to the aqueous solution of disodium edetate and stir at 400 rpm for 40 min at room temperature to make the carbomer uniformly dispersed and fully swollen to obtain a gel matrix solution. (5) Mixing and shaping: Mix the preservative solution from step (3) with the gel matrix solution from step (4), stir evenly, then add the drug loading solution from step (2), and stir at 300 rpm for 2 minutes at room temperature until a uniform gel is formed.

[0029] Single-factor examination of prescriptions (1) Screening of Carbomer 980 dosage (Examples 2-4) For gels, the compatibility of the drug with the matrix has a significant impact on the drug loading, stability, and release behavior of the system. Therefore, preliminary screening of matrix types should be conducted before formulation design to determine the basic composition of the gel formulation. Carbomer is a high molecular weight polymer crosslinked with acrylic acid and propylene sucrose. It has a uniform texture, no greasy feel, good coupling effect with skin and mucous membranes, and rapid drug release, and is widely used in the preparation of gels.

[0030] Based on the properties of carbomer, the dosage of carbomer was set to 0.3%, 0.6%, and 1%, respectively. Gels were prepared according to the above preparation process. The dosage of carbomer was screened using appearance, viscosity, and flowability as evaluation indicators.

[0031] (2) Screening of DES dosage (Examples 2, 5, 6) Carbomer aqueous solution is acidic, with a pH of around 3. When neutralized with alkali, the previously coiled molecular chains unfold, increasing the volume and viscosity, eventually forming a colorless, transparent, semi-solid gel at higher concentrations. Due to its alkaline properties, DES (diethylstilbestrol) combines drug solubilization and pH adjustment functions. Based on actual needs, a carbomer gelling agent with an appropriate consistency was selected, and the effect of DES concentration on the gelling agent was investigated. With a fixed carbomer dosage of 1%, three DES concentration levels were set: 10%, 20%, and 30%. The amount of DES used was screened using appearance, uniformity, flowability, viscosity, and spreadability as evaluation indicators.

[0032] Table 3: Evaluation Criteria for Uniformity, Flowability, Viscosity, and Spreadability

[0033] (3) Screening of drug dosage (Examples 2, 7, 8) The drug loading capacity of gels is one of the important factors affecting drug release and efficacy. Therefore, this invention explores the effect of drug loading capacity on the release of fusidic acid gel. Through in vitro release studies, the effects of different drug contents (0.5%, 1.0%, and 1.5%) on the release behavior of fusidic acid gel were investigated, providing a key basis for determining the core formulation and screening the most promising drug concentration for subsequent pharmacodynamic experiments.

[0034] Drug release experiments were conducted using a transdermal diffusion cell. A mixed solution of PBS buffer (pH 6.8), sodium dodecyl sulfate, and isopropanol (79.5:0.5:20, mass ratio) was used as the release medium. An artificial membrane (0.45 μm x 25 mm) was placed in the release medium and immersed at 32°C for 30 min. After immersion, the membrane was blotted dry with filter paper. The artificial membrane was then laid flat between the supply and receiving cells. Each drug-loaded gel was then placed flat in the supply cell (n = 3). The temperature was set at 32°C, and the stirring speed at 600 rpm. 1 mL samples were taken at 60, 120, 240, 360, 540, and 720 min, and an equal volume of fresh medium was added. Fusidic acid content was determined by high-performance liquid chromatography (HPLC) according to General Chapter 0512 of the 2025 edition of the Chinese Pharmacopoeia, Part IV. The results were recorded, and the cumulative release of fusidic acid in each gel formulation was calculated.

[0035] Results of Single-Factor Study of Prescriptions (1) Screening results of carbomer 980 dosage Table 4

[0036] As shown in Table 4, when the content of Carbomer 980 is 1%, the fluidity and viscosity of the gel are at a medium level. Therefore, 1% Carbomer 980 is selected as the gel matrix.

[0037] (2) Screening results of DES dosage Table 5

[0038] Table 5 presents the effect of DES content on formulation performance. The results show that when the DES content is 20%, the formulation is colorless and transparent, the system is uniform, and the spreadability is good. It performs well in terms of appearance, uniformity, and spreadability. Compared with DES contents of 10% (milky white, uneven) and 30% (low flowability, difficult to spread), 20% DES has a greater advantage in formulation molding performance and may be a more suitable DES addition ratio, which can be used as a reference for subsequent research or application.

[0039] (3) Screening results of drug dosage The results of the drug dosage screening are shown below. Figure 1 In in vitro release experiments, the cumulative release curves of fusidic acid gel at different drug concentrations (0.5%, 1%, and 1.5%) were compared with those of commercially available 2% fusidic acid cream (Lisidin, batch number D01178). The results showed that the release behavior of 0.5% fusidic acid gel was most similar to that of the commercially available 2% cream, exhibiting consistent release trends at the same time points, and the cumulative release amount remained within a reasonable range. Furthermore, the 0.5% concentration, while ensuring release efficiency, can reduce raw material costs and potentially mitigate the irritation risks associated with higher concentrations. Therefore, considering release performance, economy, and safety, selecting 0.5% as the formulation development concentration is both reasonable and feasible.

[0040] Example 9 This example is used to evaluate the quality of the gel prepared in Example 2.

[0041] 1. Appearance Visually, fusidic acid gel is a colorless, transparent, semi-solid. Figure 2 .

[0042] 2. pH Referring to the pH determination method in General Chapter 0631 of the 2025 edition of the Chinese Pharmacopoeia: 1g of fusidic acid gel was weighed into a beaker, 30g of purified water was added, the mixture was stirred evenly, and sonicated for 30 minutes. The pH value was then measured using a pH meter. The prepared fusidic acid gel had a pH of 7.01, which meets the requirements for dermatological use.

[0043] 3. Content determination The fusidic acid content was determined using an Inertsil ODS-3V (4.6 mm × 150 mm, 5 μm) column as the stationary phase; the mobile phase was methanol-acetonitrile-0.05 mol / L phosphoric acid aqueous solution (10:50:40, v / v / v); the flow rate was 1.8 mL / min; and the detection wavelength was 235 nm. The results of the determination of the labeled fusidic acid content in three batches of fusidic acid gel are shown in Table 6. The results showed that the average labeled fusidic acid content was 98.3%, and the RSD was 1.48%.

[0044] Table 6

[0045] 4. Rheological analysis 4.1 Flow curve Using a Thermo Fisher Scientific MARS40 rheometer, with parallel plate clamps (1.00 mm spacing) of 20 mm diameter and at 25.00 °C, shear rates ranging from 0.001 to 1000 s⁻¹ were measured on the gel. -1 The flow curves were tested to record the changes in shear stress and viscosity, thereby clarifying its shear rheological behavior.

[0046] from Figure 3 As can be seen, with increasing shear rate, shear stress gradually increases and tends to stabilize; while viscosity decreases significantly with increasing shear rate, exhibiting shear-thinning rheological properties. This property causes the viscosity of fusidic acid gel to decrease and its fluidity to increase during application (due to shearing), facilitating uniform application; after shearing stops, the viscosity can recover to some extent, ensuring the gel's retention on the skin surface, which is beneficial for transdermal absorption and drug efficacy. Its rheological behavior is well-suited to the ease of use and efficacy of the formulation.

[0047] 4.2 Yield Stress Thermo Fisher Scientific MARS40 rheometer was used with a parallel plate fixture with a diameter of 20 mm (plate spacing set to 1.00 mm) to perform strain scanning tests on the sample at 25.00℃ and an angular frequency of 1.752 Hz (strain range 0.001%~1000%) to determine the linear viscoelastic region of the gel.

[0048] Figure 4 The amplitude scan curves of the fusidic acid gel show the storage modulus (G', red), loss modulus (G'', blue), and loss tangent (tanδ, purple) as a function of strain. The variation pattern of G' is as follows: In the low strain stage (linear viscoelastic region), G' is always higher than G'' and the two remain stable, indicating that the gel is mainly elastic and structurally stable; when the strain exceeds the "End of LVR" critical value, G' decreases, G'' first increases and then decreases, and tan(δ) increases significantly, indicating that the gel changes from elastic to viscous, which meets the application requirements of "easy flow and easy spread" under the action of external force during application.

[0049] 4.3 Frequency Scan Using a Thermo Fisher Scientific MARS40 rheometer, with a parallel plate clamp of 20 mm diameter (plate spacing 1.00 mm), at 25.00℃, and with a fixed strain in the linear viscoelastic region, the sample was subjected to frequency scanning tests ranging from 0.100 to 46.42 rad / s to determine its viscoelastic proportion and shear rheological properties.

[0050] from Figure 5 As can be seen, the storage modulus (G') remains relatively stable with increasing angular frequency, indicating that the gel's elastic structure is stable over a wide frequency range. The loss modulus (G'') shows a slow upward trend, indicating that viscous energy dissipation increases slightly with increasing frequency. The complex viscosity, however, decreases significantly with increasing frequency. These rheological characteristics demonstrate that fusidic acid gel has good frequency stability. Under different external force frequencies (such as different operating rates during application), it can maintain relatively stable viscoelastic properties, possessing both sufficient elasticity to maintain structural integrity and moderate viscosity to ensure smoothness and spreadability during use. Its frequency response characteristics are well-suited to the actual application scenarios of the formulation.

[0051] Example 10 Test sample group: Fusidic acid gel prepared in Example 2.

[0052] Control group: Fusidic acid cream (Lisidin, batch number D01178).

[0053] Evaluation team: 10 healthy adults. No skin diseases and no history of allergies to the test ingredients.

[0054] Evaluation Method: A blinded sensory evaluation method was used. Samples were randomly numbered (e.g., A, B), and neither the evaluators nor the statisticians knew the specific identities of the samples. Specific criteria are shown in Table 7. Table 7

[0055] Experimental Procedure: The experiment was conducted in a temperature- and humidity-controlled room (e.g., 22±2℃, 50±10% RH). Each volunteer tested different samples on different areas of the same arm (or symmetrical areas of the left and right arms), with sufficient spacing (e.g., 5cm) and washing intervals between samples. Volunteers independently scored each indicator for each sample according to the above criteria. All scoring data were recorded, and the results are shown in Table 8 below.

[0056] Table 8: Sensory characteristics evaluation results of the formulation (n=10, mean ± SD)

[0057] As shown in Table 8, the appearance uniformity and application smoothness scores of the two samples are quite similar. However, the "post-application refreshing score" of the fusidic acid gel prepared in this invention is significantly higher than that of commercially available creams. This demonstrates that the gel formulation of this invention has a better application experience and skin feel, and is expected to improve patient medication compliance.

[0058] Example 11 The stability of the fusidic acid gel prepared in Example 2 compared with the commercially available cream (Lisdin, batch number D01178) was tested by rheological analysis.

[0059] Using a Thermo Fisher Scientific MARS40 rheometer and a parallel plate fixture with a diameter of 20 mm (plate spacing set to 1.00 mm), strain scanning tests were performed on the samples at 25.00℃ and an angular frequency of 1.752 Hz (strain range 0.001%~1000%) to determine the linear viscoelastic region of the gel.

[0060] Table 9

[0061] The yield value of the fusidic acid gel of the present invention is stable with time and temperature. As can be seen from the yield value changes in Table 9, the fusidic acid gel prepared in Example 2 exhibits better stability: at room temperature, the initial yield value of the gel is 24.23. After 1 month, 2 months and 3 months of storage, the value only fluctuates slightly to 24.12, 24.06 and 23.24, and remains at a high and stable level. Even in a high-temperature environment of 40°C, although its yield value decreases slightly with time, the overall change is gradual (21.36 after 1 month, 20.44 after 2 months and 18.14 after 3 months), without drastic fluctuations.

[0062] The stability of the cream is significantly worse: at room temperature, its initial yield value of 5.99 continued to decline to 3.32, 2.56 and 2.34 within 1-3 months, showing a gradual decline trend; under high temperature conditions, the yield value fluctuated even more, rising rapidly from 12.21 in 1 month to 19.64 in 2 months and 31.35 in 3 months, making it difficult to guarantee stability.

[0063] In summary, the yield value of gels changes more gradually and controllably, whether stored at room temperature for a long time or under high temperature conditions. This means that the stability of its physical state and performance is significantly better than that of creams, and it can maintain a stable effect under different conditions.

[0064] Example 12 This example is used to compare the antibacterial efficacy of the fusidic acid gel prepared in Example 2 with that of a commercially available cream.

[0065] I. Experimental Methods Test strain: Staphylococcus aureus (ATCC 29213) Test samples: Fusidic acid gel prepared in Example 2 and commercially available fusidic acid cream (Lisidic acid, batch number D01178, containing 2% fusidic acid).

[0066] Preparation of fusidic acid gel solution: Weigh 2 g of fusidic acid gel agent, add it to 100 mL of water, dissolve and disperse it completely, filter it through a 0.22 μm microporous membrane for sterilization, and store the resulting solution at 4℃ for later use (the preparation method of blank gel matrix solution is the same).

[0067] Preparation of fusidic acid cream solution: Weigh 2 g of fusidic acid cream, dissolve and disperse it in an aqueous solution containing 1% DMSO (volume percentage), then filter it through a 0.22 μm microporous membrane for sterilization, and store the resulting solution at 4℃ for later use.

[0068] LB solid medium: Weigh 10g tryptone, 5g yeast extract, 10g sodium chloride, and 15g agar powder, add 1L deionized water, adjust the pH to 7.2-7.4, autoclave at 121℃ for 20 min, cool and store at 4℃ for later use.

[0069] Inhibition zone assay: The in vitro antibacterial effect of the self-made fusidic acid gel against Staphylococcus aureus (ATCC 29213) was evaluated using the Kirby-Bauer disk diffusion method and compared with that of the original fusidic acid cream. The procedure is briefly as follows: Use a sterile cotton swab to apply a 1×10⁻⁶ g / L fusidic acid gel. 8A CFU / mL bacterial suspension was thoroughly spread in a petri dish containing LB solid medium using a zigzag pattern. The dish was rotated 60° and then zigzag-streaked again, repeated three times until the entire dish was covered. Then, sterile blank paper discs were placed in agar plates using sterile forceps. 20 μL of the following test samples were added to the paper discs: fusidic acid gel solution, fusidic acid cream solution (positive control), blank gel matrix solution (negative control one), and cream solvent (1% DMSO solution, negative control two). After the paper discs were allowed to air dry, they were gently pressed onto the surface of the LB solid medium containing the inoculated bacterial suspension. The plates were incubated at 37°C for 16–24 h, and the diameter of the inhibition zone for each group was measured and recorded.

[0070] II. Experimental Results Table 10: Antibacterial effects of different fusidic acid preparations against Staphylococcus aureus

[0071] Note: "—" indicates the absence of an inhibition zone.

[0072] As shown in Table 10, the diameter of the inhibition zone of the fusidic acid gel prepared in this invention against Staphylococcus aureus is significantly larger than that of commercially available creams, indicating that it has stronger in vitro antibacterial activity.

Claims

1. A fusidic acid gelling agent, characterized in that, By weight percentage, it consists of the following active pharmaceutical ingredient and excipients: fusidic acid 0.5%~2%, deep eutectic solvent active ingredient 10%~40%, gel matrix 0.3%~5%, preservative 0.1%, disodium edetate 0.05%, propylene glycol 3%, and the balance being water.

2. The fusidic acid gelling agent according to claim 1, characterized in that, By weight percentage, it consists of the following active pharmaceutical ingredient and excipients: fusidic acid 0.5%~1.5%, deep eutectic solvent active ingredient 10%~30%, gel matrix 0.3%~1%, preservative 0.1%, disodium edetate 0.05%, propylene glycol 3%, and the balance being water.

3. The fusidic acid gelling agent according to claim 2, characterized in that, By weight percentage, it consists of the following active pharmaceutical ingredient and excipients: 0.5% fusidic acid, 20% deep eutectic solvent active ingredient, 1% gel matrix, 0.1% preservative, 0.05% disodium edetate, 3% propylene glycol, and the balance being water.

4. The fusidic acid gelling agent according to any one of claims 1-3, characterized in that, The active ingredient of the deep eutectic solvent is composed of natural amino acids and polyols; the natural amino acids are basic amino acids selected from one or more of arginine, lysine, and histidine; the polyols are selected from one or more of glycerol, propylene glycol, and sorbitol.

5. The fusidic acid gelling agent according to claim 4, characterized in that, The active ingredient of the deep eutectic solvent is composed of arginine and glycerol; the molar ratio of arginine to glycerol is 1:(2~6).

6. The fusidic acid gelling agent according to claim 5, characterized in that, The molar ratio of arginine to glycerol is 1:

4.

7. The fusidic acid gelling agent according to any one of claims 1-3, characterized in that, The gel matrix is ​​carbomer.

8. The fusidic acid gelling agent according to any one of claims 1-3, characterized in that, The preservative is methylparaben and / or propylparaben.

9. A method for preparing the fusidic acid gelling agent according to any one of claims 1-3, comprising the following steps: (1) Preparation of deep eutectic solvent: Add water to the effective components of deep eutectic solvent and stir at 60~90℃ until a clear and transparent liquid is formed to obtain deep eutectic solvent; (2) Preparation of drug loading solution: Fusidic acid was added to the deep eutectic solvent obtained in step (1) and stirred at room temperature until completely dissolved to obtain the drug loading solution; (3) Preparation of preservative solution: Mix propylene glycol with preservative and stir at room temperature to disperse it evenly to obtain preservative solution; (4) Preparation of gel matrix solution: The gel matrix is ​​uniformly dispersed in an aqueous solution of disodium edetate at room temperature and stirred to allow it to swell fully, thus obtaining the gel matrix solution; (5) Mixing and molding: Mix the preservative solution from step (3) with the gel matrix solution from step (4), stir until uniform, then add the drug loading solution from step (2), and stir until a uniform gel is formed to obtain the fusidic acid gel.

10. The preparation method according to claim 9, characterized in that, In step (1), the water content of the deep eutectic solvent is 40%.

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