Fluticasone propionate cream and preparation method thereof

Abstract

The invention discloses fluticasone propionate emulsifiable paste and a preparation method thereof. The preparation method of the fluticasone propionate emulsifiable paste comprises the following steps: S1, mixing liquid paraffin, isopropyl myristate and other auxiliaries, and heating to obtain an oil phase; s2, purified water, propylene glycol, disodium hydrogen phosphate dodecahydrate and other auxiliaries are mixed to obtain a water phase; and S3, adding the oil phase into the water phase, adding fluticasone propionate and the like after complete emulsification, uniformly stirring, and standing to obtain the cream. Compared with the prior art, the fluticasone propionate emulsifiable paste prepared by the invention is not easy to layer at high and low temperatures, and the obtained emulsifiable paste has better stability and is very beneficial to transportation, storage and the like of the product.

Description

Technical Field

[0001] The present invention relates to the technical field of topical drugs, and particularly relates to a fluticasone propionate cream and a preparation method thereof. Background Art

[0002] Fluticasone propionate belongs to medium- to high-potency topical glucocorticoid drugs. Its chemical name is (6α,11β,16α,17α)-6,9-difluoro-11-hydroxy-16-methyl-3-oxo-17-(1-oxopropoxy)-androsta-1,4-diene-17-thiocarboxylic acid, S-fluoromethyl ester. This drug is in the form of white or off-white powder, odorless and tasteless. It shows unique properties in terms of solubility. It is extremely soluble in common solvents such as dimethyl sulfoxide and dimethylformamide, can also dissolve in dichloromethane, is slightly soluble in ethanol, and is almost insoluble in water. Fluticasone propionate has strong lipophilicity, which enables it to bind well with human skin tissues and glucocorticoid receptors when used as a topical drug. Fluticasone propionate has powerful anti-inflammatory, anti-allergic and immunosuppressive effects. It can bind to glucocorticoid receptors and inhibit the release of various inflammatory mediators such as histamine and leukotrienes, and can also inhibit the migration and activation of inflammatory cells, thereby reducing the inflammatory response and alleviating allergic symptoms. In clinical applications, it is commonly used for the prophylactic treatment of bronchial asthma. It can be administered by inhalation, directly acting on the airway, reducing airway inflammation, lowering airway hyperresponsiveness, effectively controlling asthma symptoms, and reducing the frequency and severity of asthma attacks. It can also be used for the adjuvant treatment of chronic obstructive pulmonary disease (COPD) to help reduce inflammation and improve lung function. Fluticasone propionate is commonly used topically in the form of creams for the treatment of various skin diseases, such as dermatitis eczema, psoriasis, etc. It can inhibit the chronic allergic inflammatory response of epithelial cells through various action pathways. The nasal spray formulation can be used to treat seasonal allergic rhinitis and perennial allergic rhinitis, can reduce nasal mucosa inflammation, relieve symptoms such as nasal congestion, runny nose, and sneezing, and improve nasal ventilation function.

[0003] Patent CN102885762A proposes a method for preparing fluticasone propionate cream, and the steps are as follows: 1. Preparation of oil phase: Mix 1860 alcohol, liquid paraffin and 20-perchlorethylene glycol and heat them to melt them, and then keep them warm at 75°C for subsequent use. 2. Preparation of water phase: Mix citric acid, sodium citrate, imidazolidinyl urea with purified water and heat them, and keep them warm at 75°C for standby use. 3. Drug dissolution and emulsification: Weigh the propylene glycol solution and heat it to 65°C for insulation, then weigh the fluticasone propionate and add it to the prepared propylene glycol solution, and stir it to dissolve it. Pour the aqueous phase into the oil phase quickly, stir continuously during the pouring process until it is completely emulsified, and then cool the emulsified solution to 65°C while stirring. Finally, add the dissolved fluticasone propionate solution to the above emulsion, stir evenly, and wait for it to cool naturally to room temperature, and then it can be condensed into a cream.

[0004] Patent CN119454579A belongs to the field of topical drug technology. The patent discloses a stable topical drug composition containing fluticasone propionate. Its ingredients include: 0.05% fluticasone propionate, 10.00% propylene glycol, 0.05% triethanolamine, 0.20% imidazolidinyl urea, 0.8%-1.2% carbomer, 5%-20% paraffin, 0.75% polycetomel, 5.00% isopropyl myristate, and the remaining ingredients are purified water. In addition, carbomer is added to the formula of the drug composition to replace the 1860 alcohol in the original formula. In the preparation and optimization process of fluticasone propionate cream, this replacement effectively improves the high temperature stability of the cream. This is because the molecular structure of carbomer can form a more stable interaction with other ingredients in the cream, such as oil phase and water phase molecules. In a high temperature environment, Carbomer can effectively inhibit the excessive aggregation of oil molecules due to thermal motion, while enhancing the stability of the water phase and preventing water from separating from the cream system.

[0005] As a product with a mixture of water and oil phases, creams may experience oil-water separation under extreme conditions such as high and low temperatures. High temperature intensifies the thermal motion of molecules, which will weaken the strength of the emulsion film formed by the emulsifier at the oil-water interface. The emulsion film may rupture or increase the pores due to excessive molecular motion, which will reduce the repulsive force between oil droplets and make them easily aggregated, eventually leading to oil-water separation and destroying the stability of the cream. At low temperatures, the water phase is easy to freeze, and the volume of water expands after freezing, which will damage the microstructure of the cream. This may cause the oil droplets in the emulsification system to be squeezed, deformed, aggregated, and even rupture the emulsion film, which will cause the cream to stratify and have uneven properties, affecting its stability. Therefore, improving the stability of fluticasone propionate in extreme environments is of great significance to its storage, transportation and use. Summary of the invention

[0006] In view of the above-mentioned defects of the prior art, the technical problem to be solved by the present invention is to provide a fluticasone propionate cream and a preparation method thereof.

[0007] To achieve the above object, the present invention provides a fluticasone propionate cream, comprising the following components in mass percentage: fluticasone propionate 0.05%, liquid paraffin 41%, isopropyl myristate 7%, cetostearyl alcohol 6%, ceteth-20 2%, propylene glycol 10%, methylparaben 0.17%, propylparaben 0.03%, disodium hydrogen phosphate dodecahydrate 0.15%, citric acid 0.05%, purified water 33.55%.

[0008] A preparation method of a fluticasone propionate cream comprises the following steps:

[0009] S1. Mix liquid paraffin with isopropyl myristate, cetostearyl alcohol, and ceteth-20 according to the formula amount, heat to 70 - 75 °C, and stir evenly to obtain an oil phase;

[0010] S2. Mix purified water, propylene glycol, disodium hydrogen phosphate dodecahydrate, and citric acid according to the formula amount, and stir evenly to obtain an aqueous phase;

[0011] S3. Add the oil phase to the aqueous phase, stir until completely emulsified, then add fluticasone propionate, mix evenly, add methylparaben and propylparaben, stir evenly, and let stand to obtain the cream.

[0012] Since phenomena such as oil-water separation may occur in extreme environments such as high and low temperatures, the present invention provides an alternative solution. Modified xanthan gum is used to replace cetostearyl alcohol as an emulsifying stabilizer. Xanthan gum has good thickening and suspension stability, can increase the viscosity of the cream, helps to maintain the morphological stability of the cream, enables the drug components to be better dispersed in the matrix, prevents precipitation and stratification, and the components are natural and safe. However, xanthan gum is highly water-soluble and belongs to an aqueous-phase thickener, mainly increasing the viscosity of the aqueous phase, which will cause the oil phase to lack structural support. In addition, it has a relatively low thermal transition temperature in aqueous solution. Therefore, the present invention modifies xanthan gum to first make it amphiphilic, and then improves its comprehensive performance by compounding with an acid. By introducing long alkyl chains, it has certain hydrophobicity, so that it can produce hydrophobic association in the solution, increase the solution viscosity, and at the same time enhance the structural support in the oil phase. And its temperature resistance is improved under covalent cross-linking and hydrophobic association.

[0013] Furthermore, the fluticasone propionate cream comprises the following components in mass percentage: fluticasone propionate 0.05%, liquid paraffin 40 - 45%, isopropyl myristate 6 - 10%, modified xanthan gum 0.2 - 1%, cetostearyl alcohol 2 - 5%, propylene glycol 8 - 12%, methylparaben 0.17%, propylparaben 0.03%, disodium hydrogen phosphate dodecahydrate 0.15%, citric acid 0.05%, and purified water 33.55%.

[0014] The preparation method of the modified xanthan gum comprises the following steps:

[0015] X1. Add xanthan gum into water, adjust the pH with an alkali solution, then successively add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide, stir evenly, add 2-aminohexadecanoic acid, stir for 2 - 4 h, then adjust the pH with an alkali solution, and perform dialysis followed by lyophilization for the next step;

[0016] X2. Mix the product from the previous step with an acid in water, stir for 24 - 48 h, and then perform lyophilization to obtain the modified xanthan gum.

[0017] Preferably, the concentration of the xanthan gum in water is 0.1 - 0.5%.

[0018] Preferably, the mass ratio of the xanthan gum to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and 2-aminohexadecanoic acid is 1:1 - 1.5:0.6 - 0.9:1 - 3.

[0019] Preferably, the pH adjustment range is 5 - 6.

[0020] Preferably, the mass ratio of the product from the previous step to the acid and water is 1:1 - 2:50 - 100.

[0021] Preferably, the acid is one of chlorogenic acid, gallic acid, or tannic acid.

[0022] More preferably, the preparation method of the modified xanthan gum comprises the following steps:

[0023] X1. Add xanthan gum into water with a concentration of 0.1 - 0.5%, add sodium hydroxide solution to adjust the pH to 5 - 6, then successively add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide, stir evenly, add 2-aminohexadecanoic acid, the mass ratio of the xanthan gum to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and 2-aminohexadecanoic acid is 1:1 - 1.5:0.6 - 0.9:1 - 3, stir for 2 - 4 h, then add an alkali solution to adjust the pH to 5 - 6, perform dialysis, and then perform lyophilization for the next step;

[0024] X2. Mix the product of the previous step with an acid in water at a mass ratio of 1:1 to 2:50 to 100, stir for 24 to 48 h, and then freeze-dry to obtain the modified xanthan gum.

[0025] Further, the preparation method of the fluticasone propionate cream includes the following steps:

[0026] S1. Mix liquid paraffin with isopropyl myristate and cetostearyl alcohol in accordance with the formula amounts, heat to 70 - 75 °C, and stir evenly to obtain an oil phase;

[0027] S2. Mix purified water, propylene glycol, modified xanthan gum, disodium hydrogen phosphate dodecahydrate, and citric acid in accordance with the formula amounts, and stir evenly to obtain an aqueous phase;

[0028] S3. Add the oil phase to the aqueous phase, stir until completely emulsified, then add fluticasone propionate, mix evenly, add methylparaben and propylparaben, stir evenly, and let stand to obtain the cream.

[0029] Advantages of the present invention:

[0030] 1. Compared with the prior art, the fluticasone propionate cream prepared by the present invention has better stability, is not prone to layering and deterioration under extreme conditions, which is very beneficial for the transportation, storage, etc. of the product.

[0031] 4. By modifying xanthan gum, the present invention first endows it with amphiphilicity, then improves its comprehensive performance by compounding with an acid, and makes it have certain hydrophobicity by introducing long alkyl chains, so that it can produce hydrophobic association in the solution, increase the solution viscosity, and at the same time improve the structural support in the oil phase. Moreover, under the action of covalent crosslinking and hydrophobic association, its heat resistance is improved, and its application to the fluticasone propionate cream makes the stability better. Specific embodiments

[0032] Example 1

[0033] A preparation method of a fluticasone propionate cream includes the following steps, in parts by weight:

[0034] S1. Mix 41 parts of liquid paraffin with 7 parts of isopropyl myristate, 6 parts of cetostearyl alcohol, and 2 parts of cetostearyl polyoxyethylene ether, heat to 72 °C, and stir evenly to obtain an oil phase;

[0035] S2. Mix 33.55 parts of purified water, 10 parts of propylene glycol, 0.15 parts of disodium hydrogen phosphate dodecahydrate, and 0.05 parts of citric acid, and stir evenly to obtain an aqueous phase;

[0036] S3. Add the oil phase to the water phase, stir until completely emulsified, then add 0.05 parts of fluticasone propionate, mix evenly, add 0.17 parts of methylparaben and 0.03 parts of propylparaben, stir evenly, and let stand to obtain the cream.

[0037] Example 2

[0038] A method for preparing fluticasone propionate cream, comprising the following steps, by weight:

[0039] S1. Mix 44 parts of liquid paraffin, 6.37 parts of isopropyl myristate, and 5 parts of polyethylene glycol cetostearyl ether, heat to 72 °C, and stir evenly to obtain the oil phase;

[0040] S2. Mix 33.55 parts of purified water, 10 parts of propylene glycol, 0.6 parts of modified xanthan gum, 0.15 parts of disodium hydrogen phosphate dodecahydrate, and 0.05 parts of citric acid, and stir evenly to obtain the water phase;

[0041] S3. Add the oil phase to the water phase, stir until completely emulsified, then add 0.05 parts of fluticasone propionate, mix evenly, add 0.17 parts of methylparaben and 0.03 parts of propylparaben, stir evenly, and let stand to obtain the cream.

[0042] The preparation method of the modified xanthan gum comprises the following steps:

[0043] X1. Add xanthan gum to water with a concentration of 0.25%, add 0.5 mol / L sodium hydroxide solution to adjust the pH to 5.5, then add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide in sequence, stir evenly, add 2-aminohexadecanoic acid, and the mass ratio of xanthan gum to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and 2-aminohexadecanoic acid is 1:1.2:0.72:2. Stir for 4 h, then add 0.5 mol / L sodium hydroxide solution to adjust the pH to 6, dialyze, and freeze-dry for the next step;

[0044] X2. Mix the product of the previous step with chlorogenic acid in water with a mass ratio of 1:1.5:80, stir for 36 h, and then freeze-dry to obtain the modified xanthan gum.

[0045] Example 3

[0046] It is basically the same as Example 1, and the only difference is that chlorogenic acid is replaced by gallic acid.

[0047] Example 4

[0048] It is basically the same as Example 1, and the only difference is that chlorogenic acid is replaced by tannic acid.

[0049] Control Example 1

[0050] A preparation method of fluticasone propionate cream, comprising the following steps, by weight:

[0051] S1. Mix 44 parts of liquid paraffin, 6.37 parts of isopropyl myristate, and 5 parts of polyethylene glycol cetostearyl ether, heat to 72 °C, and stir evenly to obtain an oil phase;

[0052] S2. Mix 33.55 parts of purified water, 10 parts of propylene glycol, 0.6 part of xanthan gum, 0.15 part of disodium hydrogen phosphate dodecahydrate, and 0.05 part of citric acid, and stir evenly to obtain an aqueous phase;

[0053] S3. Add the oil phase to the aqueous phase, stir until completely emulsified, then add 0.05 part of fluticasone propionate, mix evenly, add 0.17 part of methylparaben and 0.03 part of propylparaben, stir evenly, and let stand to obtain the cream.

[0054] Control Example 2

[0055] A preparation method of fluticasone propionate cream, comprising the following steps, by weight:

[0056] S1. Mix 44 parts of liquid paraffin, 6.37 parts of isopropyl myristate, and 5 parts of polyethylene glycol cetostearyl ether, heat to 72 °C, and stir evenly to obtain an oil phase;

[0057] S2. Mix 33.55 parts of purified water, 10 parts of propylene glycol, 0.6 part of modified xanthan gum, 0.15 part of disodium hydrogen phosphate dodecahydrate, and 0.05 part of citric acid, and stir evenly to obtain an aqueous phase;

[0058] S3. Add the oil phase to the aqueous phase, stir until completely emulsified, then add 0.05 part of fluticasone propionate, mix evenly, add 0.17 part of methylparaben and 0.03 part of propylparaben, stir evenly, and let stand to obtain the cream.

[0059] The preparation method of the modified xanthan gum comprises the following steps:

[0060] Add xanthan gum to water with a concentration of 0.25%, add 0.5 mol / L sodium hydroxide solution to adjust the pH to 5.5, then successively add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide, stir evenly, add 2-aminohexadecanoic acid, and the mass ratio of xanthan gum to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and 2-aminohexadecanoic acid is 1:1.2:0.72:2. Stir for 4 h, then add 0.5 mol / L sodium hydroxide solution to adjust the pH to 6, dialyze, and freeze-dry to obtain the modified xanthan gum.

[0061] Control Example 3

[0062] A preparation method of fluticasone propionate cream, comprising the following steps, by weight:

[0063] S1. Mix 44 parts of liquid paraffin, 6.37 parts of isopropyl myristate, and 5 parts of polyethylene glycol cetostearyl ether, heat to 72 °C, and stir evenly to obtain an oil phase;

[0064] S2. Mix 33.55 parts of purified water, 10 parts of propylene glycol, 0.6 part of modified xanthan gum, 0.15 part of disodium hydrogen phosphate dodecahydrate, and 0.05 part of citric acid, and stir evenly to obtain an aqueous phase;

[0065] S3. Add the oil phase to the aqueous phase, stir until completely emulsified, then add 0.05 part of fluticasone propionate, mix evenly, add 0.17 part of methylparaben and 0.03 part of propylparaben, stir evenly, and let stand to obtain the cream.

[0066] The preparation method of the modified xanthan gum comprises the following steps:

[0067] Add xanthan gum to water with a concentration of 0.25%, adjust the pH to 5.5 with 0.5 mol / L sodium hydroxide solution, then successively add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide, stir evenly, add cysteine, and the mass ratio of xanthan gum to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and cysteine is 1:1.2:0.72:2. Stir for 4 h, then adjust the pH to 6 with 0.5 mol / L sodium hydroxide solution, dialyze, and freeze-dry to obtain the modified xanthan gum.

[0068] Test Example 1

[0069] Sample the creams prepared in the examples and control examples to test their stability. Place them at 5 °C and 50 °C for 10 days respectively, and observe the changes in their properties before and after.

[0070] Table 1

[0071]

[0072] As can be seen from Table 1, the cream in Example 1 has a stratification phenomenon under long-term extreme conditions. This is because high temperature intensifies the molecular thermal motion, which will weaken the strength of the emulsion film formed by the emulsifier at the oil-water interface. The emulsion film may be broken or the pores may be enlarged due to the excessively violent molecular motion, which reduces the repulsion between the oil droplets and makes them easily aggregated, eventually leading to oil-water separation and destroying the stability of the cream. At low temperatures, the water phase is easy to freeze, and the volume expands after the water freezes, which will damage the microstructure of the cream. This may cause the oil droplets in the emulsification system to be squeezed, deformed, aggregated, and even rupture the emulsion film, thereby causing the cream to have problems such as stratification and uneven properties, affecting its stability. In Examples 2 to 4, cetostearyl alcohol is replaced with modified xanthan gum. The pseudoplasticity of xanthan gum maintains the viscosity of the water phase at low temperatures, preventing ice crystals from forming and destroying the emulsified structure. The long-chain alkyl group can enhance the low-temperature fluidity of the oil phase and avoid the hardening of the texture caused by lipid crystallization. At the same time, the long alkyl chain enhances the rigidity of the interface film at high temperatures and prevents the aggregation of emulsion droplets due to the intensification of Brownian motion. The addition of acid can inhibit the oxidation reaction accelerated by high temperature and protect fluticasone propionate and oil components (such as liquid paraffin) from being oxidized and rancidified. This leads to higher stability.

[0073] Test Example 2

[0074] The creams obtained in the embodiments of the present invention and the control examples were stored at 35°C and 65% RH for 12 months. According to the determination method under the related substances of fluticasone propionate in Part II of the 2020 edition of the Chinese Pharmacopoeia, the related substances (total impurities) of the retained samples were determined after 0 month, 3 months, 6 months, 9 months and 12 months, respectively. See the table below for details.

[0075] Table 2

[0076]

[0077]

[0078] Fluticasone propionate is a glucocorticoid derivative, which contains ester bonds and fluorine atoms in its structure. The ester bonds are easily hydrolyzed under high temperature, high humidity or alkaline conditions to generate free fluticasone, resulting in reduced activity. The double bonds and hydroxyl groups in the molecule may be oxidized and degraded under light or metal ion catalysis. Ultraviolet light can also trigger photolysis reactions, leading to deterioration.

[0079] As can be seen from Table 2, the creams in Examples 2 to 4 have higher stability compared to Example 1. This shows that replacing cetearyl alcohol with modified xanthan gum can better extend the shelf life. This may be because xanthan gum has good thickening and suspension stability, which can increase the viscosity of the cream, help maintain the morphological stability of the cream, enable the drug components to be better dispersed in the matrix, prevent precipitation and layering. By modifying xanthan gum, first making it amphiphilic, and then improving its comprehensive performance by compounding with an acid. By introducing long alkyl chains, it has certain hydrophobicity, so that it can produce hydrophobic association in the solution, increase the solution viscosity, and at the same time enhance the structural support in the oil phase. And under the action of covalent crosslinking and hydrophobic association, its heat resistance is improved. Therefore, the cream can also maintain long-term stability and is not easily deteriorated under high-temperature acceleration.

[0080] Comparing between Examples 2 to 4, the stability of Example 4 is the best. This may be because tannic acid has more phenolic hydroxyl groups and a conjugated system, which enhances its antioxidant ability. Gallic acid has relatively weak antioxidant performance as a monomer with three hydroxyl groups. Chlorogenic acid has relatively weak activity due to the dispersion of hydroxyl groups and structural limitations.

[0081] Comparing Example 4 with the control example, it can be seen that when xanthan gum is not modified, it will greatly affect the stability of the product. Xanthan gum has good water solubility and belongs to a water-phase thickener, mainly improving the viscosity of the water phase, which will cause the oil phase to lack structural support. In addition, it has a relatively low thermal transition temperature in aqueous solution. Without using acid compounding, the stability will also be reduced, which shows that the acid plays an important antioxidant role.

[0082] The preferred specific embodiments of the present invention have been described in detail above. It should be understood that those of ordinary skill in the art can make many modifications and variations according to the concept of the present invention without creative work. Therefore, all technical solutions that can be obtained by those skilled in the art in the technical field of the present invention based on the concept of the present invention through logical analysis, reasoning or limited experiments on the basis of the prior art should be within the protection scope determined by the claims.

Claims

1. A fluticasone propionate cream, characterized in that, It comprises components in the following mass percentages: fluticasone propionate 0.05%, liquid paraffin 41%, isopropyl myristate 7%, cetearyl alcohol 6%, ceteth-20 2%, propylene glycol 10%, methylparaben 0.17%, propylparaben 0.03%, disodium hydrogen phosphate dodecahydrate 0.15%, citric acid 0.05%, purified water 33.55%.

2. The preparation method of the fluticasone propionate cream according to claim 1, wherein, It comprises the following steps: S1. Mix liquid paraffin with isopropyl myristate, cetearyl alcohol, and ceteth-20 according to the formula amounts, heat to 70 - 75°C, and stir evenly to obtain an oil phase; S2. Mix purified water, propylene glycol, disodium hydrogen phosphate dodecahydrate, and citric acid according to the formula amounts, and stir evenly to obtain an aqueous phase; S3. Add the oil phase to the aqueous phase, stir until completely emulsified, then add fluticasone propionate, mix evenly, add methylparaben and propylparaben, stir evenly, and let it stand to obtain a cream.

3. The fluticasone propionate cream according to claim 1, wherein It comprises components in the following mass percentages: fluticasone propionate 0.05%, liquid paraffin 40 - 45%, isopropyl myristate 6 - 10%, modified xanthan gum 0.2 - 1%, ceteth-20 2 - 5%, propylene glycol 8 - 12%, methylparaben 0.17%, propylparaben 0.03%, disodium hydrogen phosphate dodecahydrate 0.15%, citric acid 0.05%, purified water 33.55%.

4. The fluticasone propionate cream according to claim 2, wherein The preparation method of the said modified xanthan gum comprises the following steps: X1. Add xanthan gum to water, adjust the pH with an alkali solution, then successively add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide, stir evenly, add 2-aminohexadecanoic acid, stir for 2 - 4 h, then adjust the pH with an alkali solution, dialyze, and freeze-dry for the next step; X2. Mix the product from the previous step with an acid in water, stir for 24 - 48 h, and then freeze-dry to obtain the modified xanthan gum.

5. The fluticasone propionate cream according to claim 4, wherein, The concentration of the said xanthan gum in water is 0.1 - 0.5%.

6. The fluticasone propionate cream according to claim 4, wherein The mass ratio of the said xanthan gum to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and 2-aminohexadecanoic acid is 1:1 - 1.5:0.6 - 0.9:1 - 3.

7. The fluticasone propionate cream according to claim 4, wherein The range of pH adjustment is 5 - 6.

8. The fluticasone propionate cream according to claim 4, characterized in that, The mass ratio of the product from the previous step to the acid and water is 1:1 - 2:50 - 100.

9. The fluticasone propionate cream according to claim 4, wherein The said acid is one of chlorogenic acid, gallic acid, or tannic acid.

10. The preparation method of the fluticasone propionate cream according to any one of claims 3 to 9, characterized in that, It comprises the following steps: S1. Mix liquid paraffin with isopropyl myristate and ceteth-20 according to the formula amounts, heat to 70 - 75°C, and stir evenly to obtain an oil phase; S2. Mix purified water, propylene glycol, modified xanthan gum, disodium hydrogen phosphate dodecahydrate, and citric acid according to the formula amounts, and stir evenly to obtain an aqueous phase; S3. Add the oil phase to the aqueous phase, stir until completely emulsified, then add fluticasone propionate, mix evenly, add methylparaben and propylparaben, stir evenly, and let it stand to obtain a cream.

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