Oral gel and application thereof

Abstract

The invention belongs to the field of pharmacy, and particularly relates to oral gel and application thereof. The oral gel provided by the invention comprises nystatin or nysfungin as an active ingredient (API), hydroxyethyl cellulose, sodium carboxymethyl cellulose and optional strawberry essence. The oral gel is used for treating oral candidiasis, can effectively cover the earthy smell of API, and is strong in adhesion, good in coating property, good in palatability and high in stability.

Description

Technical Field

[0001] The invention belongs to the pharmaceutical field, and in particular relates to an oral gel and an application thereof. Background Art

[0002] Oral candidiasis is an acute, subacute or chronic oral mucosal disease caused by infection with Candida species. The occurrence of this disease is a continuous process from Candida colonization, infection to onset, and often occurs in individuals with high-intensity Candida colonization, accompanied by destruction of the physiological barrier of the oral mucosa, or accompanied by underlying diseases and low immune function. In recent years, with the application of broad-spectrum antimicrobial drugs, glucocorticoids, and immunosuppressants, and the widespread development of organ transplantation and tumor treatment, the prevalence of oral candidiasis has been on the rise, becoming the most common infectious disease of the oral mucosa. Oral candidiasis is common in the "young, old, and sick" population, and is also known as "the disease of patients." With the acceleration of the aging process, oral candidiasis will be the focus of prevention and treatment of oral mucosal infectious diseases in the future.

[0003] Topical antifungal drugs are preferred for the treatment of oral candidiasis, among which nystatin is the first-line drug recommended by domestic and international guidelines. As a polyene antifungal drug, nystatin has a strong inhibitory effect on infections caused by Candida albicans. It is not absorbed through the mucosa and is not absorbed by the gastrointestinal tract after oral administration. It has a high safety. Clinicians often choose it as a treatment for thrush (oral fungal infection). Currently, the nystatin preparations that have been marketed for the treatment of thrush mainly include oral tablets, oral suspensions (Mycostatin) and oral gels (Nystaderm Mundgel). However, the currently approved dosage forms of nystatin are not suitable for topical oral administration, especially for young children. For example, oral tablets need to be taken by adults, but young children, especially young children, cannot do so. Oral suspensions need to be taken for a long time, otherwise they are easy to swallow and cannot play a local therapeutic role, and it is difficult for young children to take them for a long time. Oral gel is a more suitable dosage form. It is applied directly to the child's mouth and will not be swallowed quickly. However, currently only Germany has related products (Nystaderm). This product has weak adhesion to the oral mucosa and is easy to fall off after being applied to the lesion site, resulting in a shorter retention time of the drug in the lesion site, which seriously affects the efficacy of the drug.

[0004] On the other hand, nystatin has an extremely bitter and earthy taste. Direct exposure of the drug to the oral cavity may cause nausea and vomiting, which is generally difficult for patients to tolerate. For example, the 2022 edition of the "Guidelines for the Diagnosis and Treatment of Oral Candidiasis (National Health Commission)" mentioned that nystatin has a poor taste when applied topically, and some patients find it difficult to tolerate. Therefore, the taste masking of nystatin is a big challenge. For example, the prescription of the listed product oral gel (Nystaderm Mundgel) contains a large amount of sucrose (accounting for more than 30%) and raspberry flavor, but it only has a certain taste masking effect on the bitterness of nystatin, and the earthy smell is still heavy. There are no suitable solutions for the development of oral preparations for nystatin. At the same time, no existing reports have been found to clearly distinguish between the bitterness and earthy taste masking of nystatin. For example, in patent application CN106324681A, an oral film-forming gel composition is disclosed, which solves the problem of short retention time of water-soluble gel in the oral mucosa, but the taste masking effect of drug-containing preparations is not evaluated. Patent application CN118634191A discloses an oral gel spray composition that improves patient compliance and therapeutic effects, but does not evaluate the taste-masking effect of the drug-containing preparation. The document (DOI: 10.3109 / 03639040903384729) discloses an oral tablet that uses sodium carboxymethylcellulose and hydroxymethylcellulose as thickeners; sorbitol and sodium saccharin as flavoring agents; after clinical taste testing, the tablet is very sweet, but the taste is still poor, and the taste-masking problem has not been completely solved.

[0005] TR201407775A2 provides a composition in the form of an adhesive film, which comprises nystatin, at least one corticosteroid and at least one polymer selected from hydroxyethylcellulose and xanthan gum and at least one local anesthetic. The composition is effective for treating oral diseases such as oral candidiasis and aphthous ulcers.

[0006] GB2163649B relates to an antifungal suppository comprising nystatin as an antifungal agent, and a hydrocolloid such as sodium carboxymethylcellulose or hydroxypropylmethylcellulose, and a low melting point suppository base. The antifungal suppository functions by melting at body temperature to release the hydrocolloid and the antifungal agent, adhering to the vaginal membrane so that the antifungal agent is evenly distributed and maintained at the infection site.

[0007] Therefore, it is of great significance to develop a nystatin oral smear preparation with good taste to improve the compliance of clinical medication. In addition, if the adhesion of the preparation to the oral mucosa can be further increased and the retention time of the drug in the lesion site can be prolonged, it will help improve the efficacy of the drug and have significant clinical value for patients. Summary of the invention

[0008] In order to solve the earthy smell problem existing in the prior art, the present invention provides an oral gel, which comprises nystatin or nystatin as an active ingredient (API), hydroxyethyl cellulose (HEC, also known as hydroxyethyl cellulose ether, Natrosol, Natrosol 240JR, Natrosol 250H, Natrosol 250 HHR, Natrosol 250M, NatrosolL 250, Natrosol LR, etc., CAS No. 9004-62-0) and sodium carboxymethyl cellulose (CMC-Na, CAS No. 9004-32-4).

[0009] According to the present invention, HEC may be selected from HEC 250M (molecular weight 720,000), HEC 250G (molecular weight 300,000), HEC HX (molecular weight 1,000,000).

[0010] According to the present invention, hydroxypropyl methylcellulose (HPMC) and acrylic resin are optional but not essential for the oral gel. That is, the oral gel of the present invention may contain HPMC and / or acrylic resin (such as L100-55), or may not contain HPMC and / or acrylic resin.

[0011] According to the present invention, the oral gel further comprises flavor, preferably strawberry flavor or raspberry flavor, more preferably strawberry flavor.

[0012] The concentration of the flavor is usually 0.1-1wt%. The higher the concentration, the stronger the aroma. When it exceeds 1wt%, the aroma is too strong and irritates the nose. Therefore, the concentration of the flavor is preferably such that the oral gel can maintain a light aroma and cover up the unpleasant earthy smell of the API. According to the present invention, the concentration of the flavor in the oral gel is 0.1-0.8wt%, preferably 0.1-0.6wt%, more preferably 0.2-0.5wt%, and most preferably 0.25wt%.

[0013] According to the present invention, in the oral gel, the concentration of HEC is 0.5-5wt%, preferably 1.5-5wt%, more preferably 2-3wt%; the concentration of CMC-Na is 0.15-2wt%, preferably 0.5-2wt%, more preferably 1-2wt%.

[0014] HEC and CMC-Na are gel polymer materials. As the concentration increases, the viscosity increases and the coating property decreases. The sum of the concentrations of the two should not exceed 5wt%, preferably not exceed 4wt%.

[0015] In one aspect, the present invention provides the use of a combination of hydroxyethylcellulose (HEC) and sodium carboxymethylcellulose (CMC-Na) for masking the earthy taste of nystatin or nystatin contained in an oral gel.

[0016] On the other hand, the present invention also provides a method for treating oral candidiasis, comprising administering an effective amount of oral gel to a patient in need thereof, or using the oral gel for treating oral candidiasis, or using the oral gel in preparing a medicament for treating oral candidiasis.

[0017] Although carbomer, xanthan gum, HEC, CMC-Na or a combination thereof are commonly used gel polymer materials, the prior art does not clearly teach the application of the combination of HEC and CMC-Na to the API nystatin, let alone masking the earthy smell of the API.

[0018] The present invention confirms that carbomer, xanthan gum, HEC and CMC-Na alone, as well as the combination of HEC with carbomer and xanthan gum, respectively, cannot mask the earthy smell of API (nystatin).

[0019] The present invention also confirms that the combination of HEC and CMC-Na can significantly mask the earthy smell of API, the combination of HEC and CMC-Na and strawberry flavor can completely mask the earthy smell of API, while raspberry flavor cannot completely mask the earthy smell of API. Without being limited by existing or unknown mechanisms, the inventors speculate that the combination of HEC and CMC-Na has a synergistic effect on masking the earthy smell of API.

[0020] In addition, by optimizing the concentrations of HEC and CMC-Na (e.g., HEC 2-3wt%, and CMC-Na 0.5-2wt% or 1-2wt%), the oral gel of the present invention can mask the earthy smell of API while achieving coating and adhesion comparable to or even better than those of commercially available products.

[0021] Beneficial Effects

[0022] The oral gel of the present invention is used for treating oral candidiasis, can effectively cover up the earthy smell of the active ingredient (API) nystatin or nystatin in the oral gel, and has strong adhesion, good coating property, good palatability and high stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly describe the technical solution of the present invention, a brief introduction will be given below in conjunction with the accompanying drawings. These drawings are only some specific implementation methods recorded in this application, and the present invention includes but is not limited to the following drawings.

[0024] Figure 1 Display the yield stress values ​​of samples from batches with different contents;

[0025] Figure 2 Shows the normal force of samples from batches with different contents;

[0026] Figure 3Shows the coating properties of samples from different batches;

[0027] Figure 4 Display the yield stress values ​​of samples from batches with different contents;

[0028] Figure 5 Shows the normal force of samples from batches with different contents;

[0029] Figure 6 Shows the coating properties of samples from different batches. DETAILED DESCRIPTION

[0030] In order to further understand the present invention, the technical scheme of the present invention will be clearly and completely described below in conjunction with the specific embodiments of the present invention. Obviously, the described embodiments are part of the present invention, not all. Based on the embodiments of the present invention, all variations obtained by those skilled in the art without the need for creative work fall within the scope of protection claimed by the present invention. Unless otherwise specified, the percentages of the present invention are wt%.

[0031] Example 1

[0032] Taste-masking effects of common sweeteners on API

[0033] Prescription design, see Table 1:

[0034] Table 1

[0035]

[0036] Preparation method

[0037] API was mixed with glycerol-water (1:1, M / M) solution, gel polymer, sweetener and antibacterial agent were added to the remaining water to dissolve, pH adjuster was added after the two solutions were mixed evenly, the remaining purified water was added, stirred evenly, and left to swell overnight.

[0038] in conclusion

[0039] Existing sweeteners can mask the bitter taste of nystatin, but they cannot mask the earthy taste either alone or in combination.

[0040] Example 2

[0041] Effect of HEC and CMC-Na on the Taste Masking of API

[0042] For prescription design, see Table 2:

[0043] Table 2

[0044]

[0045] Preparation method

[0046] API was mixed with glycerol-water (1:1, M / M) solution, gel polymer, sweetener and antibacterial agent were added to the remaining water to dissolve, pH adjuster was added after the two solutions were mixed evenly, the remaining purified water was added, stirred evenly, and left to swell overnight.

[0047] See Table 3 for test results.

[0048] Table 3

[0049]

[0050] in conclusion

[0051] Existing sweeteners alone cannot mask the earthy smell of API. The present invention unexpectedly discovered that the combination of HEC and CMC-Na can effectively mask the earthy smell of API, while HEC alone or in combination with other polymers cannot effectively mask the smell, and the choice of sweetener has nothing to do with it.

[0052] Example 3

[0053] Effects of other polymers used alone or in combination on masking the earthy odor of API

[0054] For the prescription design, see Table 4.

[0055] Table 4

[0056]

[0057] Preparation method

[0058] API was mixed with glycerol-water (1:1, M / M) solution, gel polymer, sweetener and antibacterial agent were added to the remaining water to dissolve, pH adjuster was added after the two solutions were mixed evenly, the remaining purified water was added, stirred evenly, and left to swell overnight.

[0059] in conclusion

[0060] Commonly used gel matrices such as carbomer and xanthan gum, either alone or in combination, as well as CMC-Na alone, cannot mask the earthy smell of the API for nystatin.

[0061] Example 4

[0062] Masking effect of flavors on earthy taste of API

[0063] Although the combination of gel polymers can significantly reduce the earthy smell of API, it cannot completely cover up the taste, so further adding flavors for flavoring is considered.

[0064] For the prescription design, see Table 5.

[0065] Table 5

[0066]

[0067] in conclusion

[0068] Among the existing flavors, strawberry flavor and raspberry flavor can well cover up the earthy smell of API; considering that children are more receptive to the sour and sweet taste of strawberry, strawberry flavor can be used as an object of investigation.

[0069] Example 5

[0070] Effect of different HEC+CMC-Na ratios on gel quality (1)

[0071] Experimental Design

[0072] A combination of HEC 250M and CMC-Na was selected to investigate the gel properties of the gels prepared with different ratios of the two and compared with the marketed product Nystaderm.

[0073] For the prescription design, see Table 6.

[0074] Table 6

[0075]

[0076] Preparation method

[0077] API was mixed with glycerol-water (1:1, M / M) solution, gel polymer, sweetener and antibacterial agent were added to the remaining water to dissolve, pH adjuster was added after the two solutions were mixed evenly, the remaining purified water was added, stirred evenly, and left to swell overnight.

[0078] Test results - Comparison of yield stress values ​​of samples from different batches

[0079] Definition of yield stress value: the stress corresponding to when the sample is deformed by 300%

[0080] Testing equipment: Rheometer HAAKE Mars iQ AIR

[0081] For general external preparation samples, when the sample is squeezed out of the tube, the sample deformation is about 300%. This value can be used to judge the internal structural stability of the sample. The higher the YS value, the better the internal structural stability of the sample.

[0082] The results showed that the internal structure of the gel prepared by HEC+CMC-Na was more stable than that of the gel prepared by HEC alone and the control drug (Nystaderm). Figure 1 ).

[0083] Test results - Comparison of normal force between batches of samples with different contents

[0084] Definition of normal force value: The force perpendicular to the surface of the object points to the surface in contact with the surface of the object, reflecting the mechanical behavior of the gel in the vertical direction during shearing.

[0085] Testing equipment: Rheometer HAAKE Mars iQ AIR

[0086] Place the sample on the sample plate, and after the rotor is in close contact with the sample plate, lift it up and observe the adhesion of the sample; the greater the normal force, the better the adhesion.

[0087] The samples with HEC + CMC-Na combined had greater normal force and better adhesion than those with HEC alone and the control drug Nystaderm ( Figure 2 ).

[0088] Test results - Comparison of coating properties of samples from different batches

[0089] Definition of spreadability: It refers to the property of a liquid or paste-like substance being evenly coated on the surface of a solid substrate (or skin) to form a thin film or coating.

[0090] Testing equipment: Rheometer HAAKE Mars iQ AIR

[0091] The sample was placed in a low shear-high shear, high shear-low shear cycle and the coating properties of the sample were observed. The larger the ΔA, the better the coating properties ( Figure 3 ).

[0092] The samples with HEC + CMC-Na combined had better coating properties than those with HEC alone and the control drug Nystaderm.

[0093] Experimental summary

[0094] The gel matrix combination of HEC + CMC-Na had better gel characteristics.

[0095] Example 6

[0096] Effect of different HEC+CMC-Na ratios on gel quality (2)

[0097] Experimental Design

[0098] A combination of HEC 250M and CMC-Na was selected to investigate the gel properties of the gels prepared with different ratios of the two and compared with the marketed product Nystaderm.

[0099] For prescription design, see Table 7.

[0100] Table 7

[0101]

[0102] Preparation method

[0103] API was mixed with glycerol-water (1:1, M / M) solution, gel polymer, sweetener and antibacterial agent were added to the remaining water to dissolve, pH adjuster was added after the two solutions were mixed evenly, the remaining purified water was added, stirred evenly, and left to swell overnight.

[0104] Test results - Comparison of yield stress values ​​of samples from different batches

[0105] Definition of yield stress value: the stress corresponding to when the sample is deformed by 300%

[0106] Testing equipment: Rheometer HAAKE Mars iQ AIR

[0107] For general external preparation samples, when the sample is squeezed out of the tube, the sample deformation is about 300%. This value can be used to judge the internal structural stability of the sample. The higher the YS value, the better the internal structural stability of the sample.

[0108] The results suggest that the combination of HEC 3% + CMCNa 2% is better than the combination of HEC 3% + CMCNa 1%, and these two combinations are far superior to other combinations, including commercially available products ( Figure 4 ).

[0109] Test results - Comparison of normal force between batches of samples with different contents

[0110] Definition of normal force value: The force perpendicular to the surface of the object points to the surface in contact with the surface of the object, reflecting the mechanical behavior of the gel in the vertical direction during shearing.

[0111] Testing equipment: Rheometer HAAKE Mars iQ AIR

[0112] Place the sample on the sample plate, and after the rotor is in close contact with the sample plate, lift it up and observe the adhesion of the sample; the greater the normal force, the better the adhesion.

[0113] The normal force of HEC + CMC-Na combination was better than that of the control drug Nystaderm, and the higher the dosage, the greater the normal force ( Figure 5 ).

[0114] Test results - Comparison of coating properties of samples from different batches

[0115] Definition of spreadability: It refers to the property of a liquid or paste-like substance being evenly coated on the surface of a solid substrate (or skin) to form a thin film or coating.

[0116] Testing equipment: Rheometer HAAKE Mars iQ AIR

[0117] The sample was placed in low shear-high shear, high shear-low shear cycle conditions, and the coating properties of the sample were observed. The larger the ΔA, the better the coating properties.

[0118] in conclusion

[0119] The coating properties of HEC + CMC-Na combined use were better than those of the control drug Nystaderm, and the coating properties of HEC 2% + CMC-Na2% were the best ( Figure 6 ).

[0120] Example 7

[0121] The best ratio of HEC+CMC-Na combined taste masking

[0122] Experimental Design

[0123] The optimized combination of HEC 250M and CMC-Na was selected to investigate the taste differences of the gels prepared with different proportions of the two.

[0124] For prescription design, see Table 8.

[0125] Table 8

[0126]

[0127] Preparation method

[0128] API was mixed with glycerol-water (1:1, M / M) solution, gel polymer, sweetener and antibacterial agent were added to the remaining water to dissolve, pH adjuster was added after the two solutions were mixed evenly, the remaining purified water was added, stirred evenly, and left to swell overnight.

[0129] Scoring criteria

[0130] Ten healthy volunteers took each prescription gel with a quantitative spoon and applied it in the mouth. They rated the mouthfeel, smoothness of application, and the time the gel stayed in the mouth.

[0131] in conclusion

[0132] The three prescriptions in Table 8 have a significantly better taste than the commercially available products, and their spreadability and adhesion are at least comparable to or even better than the commercially available products.

[0133] Example 8

[0134] Stability of oral gels

[0135] For prescription design, see Table 9.

[0136] Table 9

[0137]

[0138] (1) Preparation of gel matrix

[0139] Set the water pot temperature to 75±5℃, add about 90.38% of the prescribed amount of purified water into the water pot, then add the prescribed amount of methylparaben and propylparaben, and stir in the main tank of the vacuum emulsifying mixer. The fast stirring frequency is 300 Hz (100~700 Hz), and the slow stirring frequency is set to 25Hz (20~30Hz). Stir for about 30 minutes. After methylparaben and propylparaben are completely dissolved, stop heating; after the temperature of the main tank cools to below 30℃, continue to add the prescribed amount of stevioside, dipotassium hydrogen phosphate, and potassium dihydrogen phosphate, and stir until completely dissolved; then add sodium carboxymethyl cellulose and hydroxyethyl cellulose in turn, and continue stirring until completely swollen. The fast stirring speed is 1000HZ (500~1200HZ) for 120 minutes, and the slow stirring speed is 25HZ (20~30HZ) for 120 minutes.

[0140] (2) Preparation of drug solution

[0141] Add glycerol and an equal amount of purified water (about 5.1% of the prescribed purified water volume) into a beaker, stir (stirring speed: 50~500rpm) evenly, then add API, continue stirring, and set aside after fully moistening.

[0142] (3) Preparation of gel samples

[0143] Pour the liquid medicine in the beaker into the main pot containing the gel matrix (rinse the beaker with the remaining purified water once and then transfer it to the main pot), then add the prescribed amount of strawberry essence, set the slow stirring speed to 20±5 Hz, do not turn on the fast stirring, and stir for at least 10 hours until the product is completely gelled.

[0144] (4) Sample filling

[0145] The gel sample was filled into an aluminum medicinal ointment tube, sealed at the end and set aside.

[0146] (5) Stability test

[0147] pH determination method:

[0148] Take 0.5 g of gel sample, add 2.5 g of purified water, stir evenly, and measure the pH value with a pH meter.

[0149] Content determination method: Determine by referring to high performance liquid chromatography (Chinese Pharmacopoeia 2020 Edition, Part IV, General Rules 0512).

[0150] Chromatographic conditions: octadecylsilane bonded silica gel was used as filler (Agilent, OmniSpher 150 mm×4.6 mm, 5 μm or equivalent chromatographic column); pH 6.0 phosphate buffer solution (0.4 g of disodium hydrogen phosphate dihydrate and 1.4 g of sodium dihydrogen phosphate (dihydrate) were dissolved in 1000 mL of water. The pH value was adjusted to 6.0 with 8.5% phosphoric acid, filtered, and degassed) was used as mobile phase A, methanol was used as mobile phase B, and isocratic elution was performed according to mobile phase A: mobile phase B = 35:65 (V:V), and the running time was 30 min. The flow rate was 0.8 mL per minute; the detection wavelength was 305 nm; the column temperature was 30 °C, and the sample tray temperature was 4 °C.

[0151] Solution preparation:

[0152] Reference solution: Take about 10 mg of nystatin standard, weigh accurately, place in a 100 mL volumetric flask, add about 40 mL of N,N-dimethylformamide, sonicate for 2 min to dissolve, add about 10 mL of mobile phase A, and make up to the mark with methanol, shake well, and the solution is ready.

[0153] Test solution: Take about 300 mg of the test sample, accurately weigh it, place it in a 50 mL volumetric flask, add about 5 mL of mobile phase A, vortex for 5 min until the sample is completely dispersed, add about 20 mL of N,N-dimethylformamide, wait until the temperature reaches room temperature, dilute to the scale with methanol, shake well, and filter through a 0.45 μm nylon filter membrane to obtain the solution.

[0154] Potency determination method, refer to USP <81> ANTIBIOTIC-MICROBIAL ASSAYS Cylinder-PlateAssay, the specific steps are as follows:

[0155] (1) Preparation of bacterial culture medium

[0156] Add 1 mL of test bacteria suspension to every 100 mL of culture medium (temperature not higher than 45°C), shake well and set aside.

[0157] (2) Double disc preparation

[0158] Take a sterile plate and place it on a horizontal table. Add 16 mL of bacterial culture medium to each plate. After cooling, place 6 steel tubes at equal distances using a steel tube placer and cover them with sterile ceramic lids for later use.

[0159] (3) Sample addition

[0160] ① Standard curve double disc: Take a double disc and drip 300uL of standard solution alternately, drip standard solution S3 into 3 steel tubes and drip standard solution S1 into the other 3, prepare at least 3 double discs (usually 3~5) in parallel, which is the S1 concentration double disc. Prepare S2, S4, S5 concentration double discs in the same way.

[0161] ② Double disc for test sample: Take a double disc and alternately add 300 μL of standard solution and test sample solution. Add standard solution S3 to 3 steel tubes and add test sample solution U3 to the other 3. Prepare at least 3 double discs (usually 3 to 5) in parallel, which is the double disc for test sample.

[0162] (4) Cultivation

[0163] Incubate the double dish at 29-31°C for 16-18 hours.

[0164] (5) Calculation

[0165] Take the double disc after incubation, remove the steel tube, and place it on the inhibition zone measuring instrument to measure the diameter of each inhibition zone, calculate the average diameter of the inhibition zone of all S3, and correct the average diameter of the inhibition zone of S1, S2, S4, and S5. Use the natural logarithm of the concentration of each standard solution as the horizontal axis and the corrected inhibition zone diameter as the vertical axis to make a standard curve, and directly bring the test sample inhibition zone into the curve to calculate the test sample concentration.

[0166] See Table 10 for stability results.

[0167] Table 10

[0168]

[0169] Note: In the table, M stands for month and ND stands for not determined.

[0170] The data showed that there was no significant change in the pH value of the accelerated and long-term 6M samples; there was no significant difference in the content of the three parts of the sample (i.e. front, middle and back), and no obvious stratification occurred; the content and potency IU were both within the qualified range, indicating that the preparation had good stability.

Claims

1. An oral gel comprising nystatin or nystatin as active ingredients, hydroxyethylcellulose (HEC) and carboxymethylcellulose sodium (CMC-Na).

2. The oral gel according to claim 1, wherein the concentration of HEC is 0.5-5wt%, and the concentration of CMC-Na is 0.15-2wt%.

3. The oral gel according to claim 2, wherein the concentration of HEC is 1.5-5wt%, and the concentration of CMC-Na is 0.5-2wt%.

4. The oral gel according to claim 3, wherein the concentration of HEC is 2-3 wt %, and the concentration of CMC-Na is 1-2 wt %.

5. The oral gel according to any one of claims 1 to 4, further comprising a flavor selected from strawberry flavor and / or raspberry flavor. The oral gel according to claim 5 , wherein the flavor is strawberry flavor.

7. The oral gel according to claim 5, wherein the concentration of the flavor is 0.1-0.8 wt%.

8. The oral gel according to claim 5, wherein the concentration of the flavor is 0.1-0.6 wt%.

9. The oral gel according to claim 5, wherein the concentration of the flavor is 0.2-0.5 wt%.

10. The oral gel according to claim 1, wherein the sum of the concentrations of HEC and CMC-Na does not exceed 5 wt%.

11. The oral gel according to claim 10, wherein the sum of the concentrations of HEC and CMC-Na does not exceed 4 wt%.

12. Use of a combination of hydroxyethylcellulose and sodium carboxymethylcellulose for suppressing the earthy taste of nystatin or nystatin contained in an oral gel.

13. Use of the oral gel according to any one of claims 1 to 11 in the preparation of a medicament for treating oral candidiasis.

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