A preparation method of compound dexamethasone acetate cream

Abstract

The present invention discloses a method for preparing a compound dexamethasone acetate cream, comprising: mixing menthol, camphor, and a crystallization inhibitor to obtain a eutectic solution; the crystallization inhibitor is a mixture of cyclic olefins and unsaturated fatty acids; dexamethasone acetate is added to the eutectic solution, and then mixed with a matrix oil phase and an aqueous phase to obtain the compound dexamethasone acetate cream. The present invention adds a crystallization inhibitor when preparing the menthol and camphor eutectic solution, and the obtained eutectic solution has good homogeneity and is not prone to crystallization. Therefore, the prepared compound dexamethasone acetate cream has stable content of each component and is not prone to granularity at low temperatures, greatly improving production efficiency, product quality stability, and user experience.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, in particular to a method for preparing a compound dexamethasone acetate cream. Background Art

[0002] Compound dexamethasone acetate cream is a topical skin medicine that has significant therapeutic effects on localized pruritus, neurodermatitis, contact dermatitis, seborrheic dermatitis, and chronic eczema. The 2020 edition of the Chinese Pharmacopoeia, Part II, discloses that the prescription composition of compound dexamethasone acetate cream is: 0.75g dexamethasone acetate; 10g camphor; 10g menthol; 1g paraben; appropriate amount of base; appropriate amount of purified water; made into 1000g; the camphor and menthol ingredients provide a cooling sensation and effectively relieve skin itching. However, since camphor and menthol are both highly volatile components, crystalline at room temperature, and extremely difficult to dissolve in water, this physical property increases the difficulty of the pharmaceutical process on the one hand, and on the other hand, it will cause the preparation to crystallize and precipitate under low temperature conditions, resulting in crystalline particles in the ointment, affecting its use and efficacy. Specifically, in the prior art, a liquid phase solution containing camphor and menthol is prepared by using an organic solvent dissolution method or a eutectic method. Liquid mixing is beneficial to improving the compatibility of the components, but the former may lead to the problem of residual organic solvent, while the latter may result in a camphor and menthol eutectic solution with poor stability and easy re-crystallization, thereby affecting the accuracy of the feed ratio and the stability of the product quality.

[0003] In view of this, it is necessary to improve the formula and preparation process of the cream, improve the stability of camphor and menthol in the cream, and improve production efficiency and product quality. Summary of the Invention

[0004] The invention provides a preparation method of a compound dexamethasone acetate cream, aiming to improve the stability of a camphor and menthol eutectic solution, thereby improving the phenomenon of camphor and menthol crystallization occurring in the cream at low temperatures.

[0005] The present invention is achieved in that:

[0006] In a first aspect, the present invention provides a method for preparing a compound dexamethasone acetate cream, comprising the following steps:

[0007] (1) mixing menthol, camphor and a crystallization inhibitor to obtain a eutectic solution; the crystallization inhibitor is a mixture of cyclic olefins and unsaturated fatty acids;

[0008] (2) heating and stirring the oil phase matrix to obtain an oil phase; dissolving a moisturizer, an antibacterial agent, a carbomer, and an emulsifier in pure water to obtain an aqueous phase;

[0009] (3) adding dexamethasone acetate to the eutectic solution to obtain a drug phase mixture; mixing the oil phase and the water phase to obtain a first mixed solution;

[0010] (4) Add the drug phase mixture to the first mixed solution, add a pH adjuster, and stir evenly to obtain a compound dexamethasone acetate cream.

[0011] In some embodiments of the present invention, the cyclic olefin comprises at least one of pinene, limonene, and camphene.

[0012] In some embodiments of the present invention, the unsaturated fatty acid comprises at least one of oleic acid, linoleic acid, and linolenic acid.

[0013] In some embodiments of the present invention, the temperature of the mixing and stirring is 30-40° C., and the pressure is 0.2-0.4 MPa.

[0014] In some embodiments of the present invention, the molar ratio of the cyclic olefin to the fatty acid in the crystallization inhibitor is (1:2) to (3:1).

[0015] In some embodiments of the present invention, the mass of the crystallization inhibitor is 10% to 20% of the total mass of menthol and camphor.

[0016] In some embodiments of the present invention, the oil phase base includes at least one of liquid paraffin, petrolatum, lanolin, cetyl alcohol, stearic acid, palmitic acid, lauric acid, stearyl alcohol and glyceryl stearate.

[0017] In some embodiments of the present invention, the humectant comprises at least one of glycerin, propylene glycol, and butylene glycol.

[0018] In some embodiments of the present invention, the antimicrobial agent comprises at least one of methylparaben, propylparaben, and ethylparaben.

[0019] In some embodiments of the present invention, the emulsifier includes at least one of polyoxyethylene 25 propylene oxide stearate, sodium lauryl sulfate, polyoxyl 40 stearate, polyethylene glycol 400 monostearate, polyethylene glycol 600 monostearate, polyoxyethylene 20 stearate and polyoxypropylene distearate.

[0020] In some embodiments of the present invention, the pH adjuster comprises at least one of sodium bicarbonate and triethanolamine.

[0021] In a second aspect, the present invention provides a compound dexamethasone acetate cream prepared by the preparation method of any embodiment.

[0022] A compound dexamethasone acetate cream is composed of the following raw materials by weight based on a total weight of 1000g: 0.75g of dexamethasone acetate, 10-18g of menthol, 10-18g of camphor, 1-9g of a crystallization inhibitor, 100-160g of an oily phase base, 20-50g of a moisturizer, 1-4g of an antibacterial agent, 2-5g of carbomer, 20-40g of an emulsifier, 1-2g of a pH regulator, and the balance being water.

[0023] The present invention has the following beneficial effects:

[0024] The invention provides a preparation method of a compound dexamethasone acetate cream. According to the invention, a crystallization inhibitor is added when preparing a menthol and camphor eutectic solution. The obtained eutectic solution has good homogeneity and is not prone to crystallization. Therefore, the content of each component in the prepared compound dexamethasone acetate cream is stable, and a granular feeling is not easily generated at low temperatures, thereby greatly improving production efficiency, product quality stability, and usage experience. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 These are optical microscope images of Example 1 before and after the cold resistance test (standing at -20°C for 24 hours), with a scale of 25 μm.

[0026] Figure 2 These are optical microscope images of Example 10 before and after the cold resistance test (standing at -20°C for 24 hours), with a scale of 25 μm. DETAILED DESCRIPTION

[0027] To make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are described clearly and completely below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer are used. Where the manufacturer of the reagents or instruments is not specified, all are conventional products that can be purchased commercially.

[0028] In the description of the embodiments of this application, technical terms such as "first" and "second" are only used to distinguish different objects and cannot be understood as indicating or implying relative importance or implicitly indicating the number, specific order or primary and secondary relationship of the indicated technical features.

[0029] Reference herein to an "embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment may be included in at least one embodiment of the present application. The appearance of the phrase in various places in the specification does not necessarily refer to the same embodiment, nor does it constitute an independent or alternative embodiment that is mutually exclusive with other embodiments.

[0030] In the embodiment of the present application, the term "or / and" is only a description of the association relationship of associated objects, indicating that three relationships may exist. For example, A or / and B can represent three situations: A exists alone, A and B exist at the same time, and B exists alone.

[0031] In addition, the character “ / ” in this article generally indicates that the previous and next related objects are in an “or” relationship.

[0032] In the embodiments of the present application, "multiple" means more than two (including two). Similarly, "multiple groups" means more than two groups (including two groups), and "multi-layer" means more than two layers (including two layers), unless otherwise clearly specified and limited.

[0033] In the embodiments of the present application, “at least one” means one or more than one.

[0034] In the embodiments of the present application, the directions or positional relationships indicated by the technical terms "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", etc. are based on the directions or positional relationships shown in the accompanying drawings and are only for the convenience of describing the embodiments of the present application and simplifying the description. They do not indicate or imply that the devices or components referred to must have a specific direction or be constructed in a specific direction, etc., and should not be understood as limiting the embodiments of the present application. Those skilled in the art can understand the specific meanings of the above terms in the embodiments of the present application according to specific circumstances.

[0035] The present invention adds a crystallization inhibitor when preparing a menthol and camphor eutectic solution, so that the obtained eutectic solution has good homogeneity and is not prone to crystallization. Therefore, the content of each component in the prepared compound dexamethasone acetate cream is stable, and it is not prone to granularity at low temperatures, thereby greatly improving production efficiency, product quality stability, and usage experience.

[0036] Specifically, the crystallization inhibitor is a mixture of cyclic olefins and unsaturated fatty acids. Since the cyclic olefins have a structure similar to that of menthol and camphor, they hinder the orderly arrangement of menthol and camphor molecules, thereby inhibiting the formation of crystal nuclei and crystallization. Furthermore, the addition of unsaturated fatty acids with a melting point lower than room temperature has, on the one hand, a solubilizing effect on menthol and camphor, inhibiting the crystallization of the two. On the other hand, the unsaturated fatty acids contain both carboxyl groups and alkenyl groups. The carboxyl groups can combine with the hydroxyl groups of menthol and the ketone groups of camphor through hydrophilic effects, while the alkenyl groups can combine with the cyclic olefins through hydrophobic effects, thereby improving the compatibility of the components and preventing phase separation, thereby improving the compatibility of menthol and camphor in the liquid phase and inhibiting their crystallization. Since the eutectic solution of menthol and camphor provided by the present invention has good stability and is difficult to crystallize, the phenomenon of crystals adhering to the wall does not occur during the preparation process, thereby greatly improving production efficiency. At the same time, the stability of the component content is also ensured, thereby improving the stability of product quality. Furthermore, the compound dexamethasone acetate cream prepared by the present invention does not crystallize or have a granular feel at low temperatures, and thus has a good feel during use.

[0037] The following is a specific embodiment to further illustrate the solution of the present invention.

[0038] Example 1

[0039] A method for preparing a compound dexamethasone acetate cream comprises the following steps:

[0040] (1) Menthol, camphor, and crystallization inhibitor were added into a reactor according to the formula, the temperature was set to 30°C, the pressure was controlled to 0.3 MPa, and the mixture was stirred until completely melted to obtain a eutectic solution, which was kept warm for later use.

[0041] The crystallization inhibitor is a mixture of α-pinene and oleic acid in a molar ratio of 1:1.

[0042] (2) Mixing the oil phase matrix and heating it to 70°C and stirring to obtain the oil phase, which is then kept warm for later use; adding the carbomer into pure water, heating it to 60°C and stirring to swell it, then adding the moisturizer, antibacterial agent, and emulsifier, and stirring and maintaining the temperature to uniformly disperse them to obtain the water phase, which is then kept warm for later use;

[0043] Among them, the oil phase matrix is ​​a mixture of liquid paraffin, cetyl alcohol and glyceryl stearate in a mass ratio of 2:1:1; the moisturizer is glycerin, the antibacterial agent is ethyl hydroxybenzoate, and the emulsifier is polyethylene glycol 400 monostearate.

[0044] (3) Dexamethasone acetate was added to the eutectic solution, heated to 60°C, controlled at a pressure of 0.2 MPa, and stirred to obtain a drug phase mixture; the oil phase and the aqueous phase were mixed, kept warm and homogenized under vacuum conditions (vacuum degree of -0.09 MPa) for 8 minutes at a speed of 6000 rpm to obtain a first mixed solution, which was then cooled to 50°C for use;

[0045] (4) adding the drug phase mixture to the first mixed solution, homogenizing at 6000 rpm for 2 min, and adding a pH regulator to adjust the pH to 6.7 to obtain a compound dexamethasone acetate cream;

[0046] Wherein, the pH adjuster is sodium bicarbonate.

[0047] A compound dexamethasone acetate cream is composed of the following raw materials by weight based on a total weight of 1000 g: 0.75 g of dexamethasone acetate, 10 g of menthol, 10 g of camphor, 3 g of a crystallization inhibitor, 130 g of an oily phase base, 30 g of a moisturizer, 1.5 g of an antibacterial agent, 3 g of carbomer, 30 g of an emulsifier, 1.4 g of a pH regulator, and the balance being water.

[0048] Example 2

[0049] A method for preparing a compound dexamethasone acetate cream comprises the following steps:

[0050] (1) Menthol, camphor, and crystallization inhibitor were added into a reactor according to the formula, the temperature was set to 40°C, the pressure was controlled to 0.2 MPa, and the mixture was stirred until completely melted to obtain a eutectic solution, which was kept warm for later use.

[0051] The crystallization inhibitor is a mixture of limonene and linoleic acid in a molar ratio of 1:1.

[0052] (2) Mixing the oil phase matrix and heating it to 70°C and stirring to obtain the oil phase, which is then kept warm for later use; adding the carbomer into pure water, heating it to 60°C and stirring to swell it, then adding the moisturizer, antibacterial agent, and emulsifier, and stirring and maintaining the temperature to uniformly disperse them to obtain the water phase, which is then kept warm for later use;

[0053] Among them, the oil phase matrix is ​​a mixture of white petrolatum, cetyl alcohol, stearyl alcohol, and mono- and distearic glyceryl in a mass ratio of 3:9:1:4; the moisturizer is 1,3-propylene glycol, the antibacterial agent is ethyl hydroxybenzoate, and the emulsifier is polyoxyl 40 stearate.

[0054] (3) Dexamethasone acetate was added to the eutectic solution, heated to 60°C, controlled at a pressure of 0.2 MPa, and stirred to obtain a drug phase mixture; the oil phase and the aqueous phase were mixed, kept warm and homogenized under vacuum conditions (vacuum degree of -0.09 MPa) for 8 minutes at a speed of 6000 rpm to obtain a first mixed solution, which was then cooled to 50°C for use;

[0055] (4) adding the drug phase mixture to the first mixed solution, homogenizing at 6000 rpm for 2 min, and adding a pH regulator to adjust the pH to 6.5 to obtain a compound dexamethasone acetate cream;

[0056] Wherein, the pH adjuster is sodium bicarbonate.

[0057] A compound dexamethasone acetate cream is composed of the following raw materials by weight based on a total weight of 1000 g: 0.75 g of dexamethasone acetate, 18 g of menthol, 18 g of camphor, 3.6 g of a crystallization inhibitor, 100 g of an oily phase base, 20 g of a moisturizer, 2 g of an antibacterial agent, 5 g of carbomer, 20 g of an emulsifier, 1.2 g of a pH regulator, and the balance being water.

[0058] Example 3

[0059] A method for preparing a compound dexamethasone acetate cream comprises the following steps:

[0060] (1) Menthol, camphor, and crystallization inhibitor were added into a reactor according to the formula, the temperature was set to 35°C, the pressure was controlled to 0.4 MPa, and the mixture was stirred until completely melted to obtain a eutectic solution, which was kept warm for later use.

[0061] The crystallization inhibitor is a mixture of camphene and linolenic acid in a molar ratio of 3:1.

[0062] (2) Mixing the oil phase matrix and heating it to 70°C and stirring to obtain the oil phase, which is then kept warm for later use; adding the carbomer into pure water, heating it to 60°C and stirring to swell it, then adding the moisturizer, antibacterial agent, and emulsifier, and stirring and maintaining the temperature to uniformly disperse them to obtain the water phase, which is then kept warm for later use;

[0063] Among them, the oil phase matrix is ​​a mixture of lanolin, white petrolatum and stearic acid in a mass ratio of 1:3:8; the moisturizer is a mixture of 1,4-butylene glycol and glycerol in a mass ratio of 1:2, the antibacterial agent is ethyl hydroxybenzoate, and the emulsifier is a mixture of polyoxyethylene 20 stearate and polyethylene glycol 600 monostearate in a mass ratio of 3:2.

[0064] (3) Dexamethasone acetate was added to the eutectic solution, heated to 60°C, controlled at a pressure of 0.2 MPa, and stirred to obtain a drug phase mixture; the oil phase and the aqueous phase were mixed, kept warm and homogenized under vacuum conditions (vacuum degree of -0.09 MPa) for 8 minutes at a speed of 6000 rpm to obtain a first mixed solution, which was then cooled to 50°C for use;

[0065] (4) adding the drug phase mixture to the first mixed solution, homogenizing at 6000 rpm for 2 min, and adding a pH regulator to adjust the pH to 7.1 to obtain a compound dexamethasone acetate cream;

[0066] Wherein, the pH adjuster is sodium bicarbonate.

[0067] A compound dexamethasone acetate cream is composed of the following raw materials by weight based on a total weight of 1000 g: 0.75 g of dexamethasone acetate, 18 g of menthol, 15 g of camphor, 8.6 g of a crystallization inhibitor, 160 g of an oily phase base, 50 g of a moisturizer, 3.2 g of an antibacterial agent, 2 g of carbomer, 40 g of an emulsifier, 1.8 g of a pH regulator, and the balance being water.

[0068] Example 4

[0069] The difference from Example 1 is that the pressure in step (1) is 0.2 MPa.

[0070] Example 5

[0071] The difference from Example 1 is that the pressure in step (1) is 0.4 MPa.

[0072] Example 6

[0073] The difference from Example 1 is that the mass of the crystallization inhibitor is 10% of the total mass of menthol and camphor, that is, a compound dexamethasone acetate cream, based on a total weight of 1000 g, is composed of the following raw materials by weight: dexamethasone acetate 0.75 g, menthol 10 g, camphor 10 g, crystallization inhibitor 2 g, oil phase base 130 g, moisturizer 30 g, antibacterial agent 1.5 g, carbomer 3 g, emulsifier 30 g, pH regulator 1.4 g, and the balance is water.

[0074] Example 7

[0075] The difference from Example 1 is that the mass of the crystallization inhibitor is 20% of the total mass of menthol and camphor, that is, a compound dexamethasone acetate cream, based on a total weight of 1000 g, is composed of the following raw materials by weight: dexamethasone acetate 0.75 g, menthol 10 g, camphor 10 g, crystallization inhibitor 4 g, oil phase base 130 g, moisturizer 30 g, antibacterial agent 1.5 g, carbomer 3 g, emulsifier 30 g, pH regulator 1.4 g, and the balance is water.

[0076] Example 8

[0077] The difference from Example 1 is that the crystallization inhibitor is a mixture of α-pinene and linoleic acid in a molar ratio of 2:1.

[0078] Example 9

[0079] The difference from Example 1 is that the crystallization inhibitor is a mixture of limonene and oleic acid in a molar ratio of 1:2.

[0080] Example 10

[0081] The difference from Example 1 is that the eutectic solution is prepared under normal pressure and sealed and stirred.

[0082] Comparative Example 1

[0083] The difference from Example 1 is that the crystallization inhibitor is α-pinene.

[0084] Comparative Example 2

[0085] The difference from Example 1 is that the crystallization inhibitor is oleic acid.

[0086] Comparative Example 3

[0087] The difference from Example 1 is that no crystallization inhibitor was added.

[0088] The physical properties of the products of the examples and comparative examples were tested using the following test methods:

[0089] (1) Eutectic stability test: The uniformity of the eutectic prepared in each specific embodiment after standing (25°C, 75% RH) for several times (1h, 10h, 24h) was determined by gas chromatograph. Samples were taken from the liquid surface and liquid bottom of the sealed tank containing the eutectic and the camphor and menthol contents were determined. The uniformity was evaluated by the content difference between the liquid surface and the liquid bottom. The camphor and menthol contents were tested according to the camphor and menthol content test method described in the "Compound Dexamethasone Acetate Cream" in the "Chinese Pharmacopoeia 2020 Edition·Part II". The content difference between the liquid surface and the liquid bottom was measured by the coefficient of variation (RSD value, = sample standard deviation ÷ mean) of the liquid surface content and the liquid bottom content. The results are shown in Table 1.

[0090] Table 1: Coefficient of variation of liquid surface content and liquid bottom content

[0091]

[0092] As can be seen from the data in Table 1, the difference in menthol and camphor content between the surface and bottom of the eutectic prepared by the present invention after standing is smaller than that in the comparative example, indicating higher homogeneity. This indicates that the addition of a crystallization inhibitor improves the compatibility and dispersibility of the phases, thereby inhibiting the crystallization of menthol and camphor. A comparison of Example 1 and Comparative Examples 1-3 shows that while the effect of containing only cyclic olefins or unsaturated fatty acids in the eutectic is not as good as containing both, adding only a cyclic olefin or unsaturated fatty acid solution also helps improve the homogeneity of the eutectic compared to not adding a crystallization inhibitor.

[0093] (2) Temperature stability test of the ointment: The stability of the ointment at low and high temperatures was evaluated by observation. The specific steps are as follows: ① Place the cream in a sealed bottle and place it at 60°C for 24 hours and -20°C for 24 hours respectively; ② Observe whether the cream has stratification or obvious particles and describe them; ③ Observe the size of the crystal particles in the cream using an optical microscope, and randomly select 5 areas for observation and record. The results are shown in Table 2.

[0094] Table 2

[0095]

[0096] As can be seen from the data in Table 2, the creams prepared in Examples 1 to 10 of the present invention all have good cold resistance, no particulate matter appears in the low temperature test, and the particle size of the crystalline particles obtained by microscopic observation is small, indicating that the compatibility of the components in the compound dexamethasone acetate ointment provided by the present invention is increased, and the crystallization and precipitation of the oil-soluble components therein are suppressed.

[0097] Figure 1 and 2Optical micrographs of Example 1 and Example 10 before and after a cold resistance test (standing at -20°C for 24 hours) are shown. As can be seen from the figures, the particle size and number of precipitated crystals in Example 10 after the cold resistance test are larger than those in Example 1, indicating that applying appropriate pressure during eutectic preparation is beneficial for obtaining a eutectic that is less prone to crystallization and more uniform.

[0098] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A method for preparing a compound dexamethasone acetate cream, characterized in that: The steps include: (1) mixing menthol, camphor and a crystallization inhibitor to obtain a eutectic solution; the crystallization inhibitor is a mixture of cyclic olefins and unsaturated fatty acids; (2) heating and stirring the oil phase matrix to obtain an oil phase; dissolving a moisturizer, an antibacterial agent, a carbomer, and an emulsifier in pure water to obtain an aqueous phase; (3) adding dexamethasone acetate to the eutectic solution to obtain a drug phase mixture; mixing the oil phase and the aqueous phase to obtain a first mixed solution; (4) adding the drug phase mixture to the first mixed solution, adding a pH adjuster, and stirring evenly to obtain a compound dexamethasone acetate cream; The cyclic olefin comprises at least one of pinene, limonene and camphene; The unsaturated fatty acid comprises at least one of oleic acid, linoleic acid and linolenic acid; The molar ratio of the cyclic olefin to the fatty acid in the crystallization inhibitor is (1:2) to (3:1); The mass of the crystallization inhibitor is 10% to 20% of the total mass of the menthol and the camphor.

2. The preparation method of compound dexamethasone acetate cream according to claim 1, wherein The mixing and stirring in step (1) is carried out at a temperature of 30 to 40° C. and a pressure of 0.2 to 0.4 MPa.

3. The preparation method of compound dexamethasone acetate cream according to claim 1, wherein The oil phase matrix includes at least one of liquid paraffin, vaseline, lanolin, cetyl alcohol, stearic acid, palmitic acid, lauric acid, stearyl alcohol and glyceryl stearate; and / or, the moisturizing agent comprises at least one of glycerin, propylene glycol and butylene glycol; and / or, the antibacterial agent comprises at least one of methylparaben, propylparaben and ethylparaben; and / or, the emulsifier comprises at least one of polyoxyethylene 25 propylene oxide stearate, sodium lauryl sulfate, polyoxyalkyl 40 stearate, polyethylene glycol 400 monostearate, polyethylene glycol 600 monostearate, polyoxyethylene 20 stearate and polyoxypropylene distearate; And / or, the pH adjuster includes at least one of sodium bicarbonate and triethanolamine.

4. A compound dexamethasone acetate cream, characterized in that, The compound dexamethasone acetate cream is prepared according to the preparation method according to any one of claims 1 to 3.

5. The compound dexamethasone acetate cream according to claim 4, wherein Based on a total weight of 1000g, the compound dexamethasone acetate cream is composed of the following raw materials by weight: 0.75g of dexamethasone acetate, 10-18g of menthol, 10-18g of camphor, 1-9g of a crystallization inhibitor, 100-160g of an oil phase base, 20-50g of a moisturizer, 1-4g of an antibacterial agent, 2-5g of carbomer, 20-40g of an emulsifier, 1-2g of a pH regulator, and the balance being water.

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