Relecotinib phosphate cream and preparation method thereof

Abstract

According to the rukotinib phosphate cream and the preparation method thereof provided by the invention, in the preparation process, more sufficient emulsification is carried out by adopting a high-shearing and high-pressure homogenizing mode, so that the prepared cream is fine and smooth in texture, stable in physical property and free of toxic and side effects; the characteristics, the droplet particle size, the dynamic viscosity and the in-vitro release rate of the emulsifiable paste are stable under the accelerated or long-term placement condition, the unstable phenomena of layering, water bleeding and the like of the emulsifiable paste in a short time are avoided, the continuous safety and the curative effect stability of the emulsifiable paste in the using process are ensured, and the preparation method is simple, high in operability and suitable for industrial production. The method is suitable for large-scale industrial production.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a ruxolitinib phosphate cream and a preparation method thereof. BACKGROUND

[0002] Ruxolitinib phosphate is a potent and selective inhibitor of Janus kinases (JAK1 and JAK2), and the targeting of these kinases is associated with the therapeutic benefits of patients with atopic dermatitis (AD). The ruxolitinib phosphate cream is developed by Anacor Company and jointly developed by Incyte and Novartis, and is applied to the short-term and non-persistent chronic treatment of non-segmental vitiligo in non-immunocompromised adults and children aged 12 years and older. The ruxolitinib phosphate cream shows certain curative effect on patients with the above indications, however, it is found that the ruxolitinib phosphate cream shows delamination, water separation and other unstable phenomena in a short time after opening, which may affect the continuous stability of the curative effect in the use process. SUMMARY

[0003] The purpose of the present application is to provide a preparation method of ruxolitinib phosphate cream on the basis of the prior art, which adopts high shear and high pressure homogenization to achieve more sufficient emulsification in the preparation process, so that the prepared cream has fine texture and stable physical properties, and the properties, droplet size, dynamic viscosity and in-vitro release rate are relatively stable under accelerated or long-term storage conditions, thereby avoiding the delamination, water separation and other unstable phenomena of the cream in a short time after opening, ensuring the continuous safety and curative effect stability of the cream in the use process, and the preparation method is simple and has strong operability, and is suitable for large-scale industrial production.

[0004] The second purpose of the present application is to provide a ruxolitinib phosphate cream prepared by the above preparation method.

[0005] The technical solution of the present application is as follows:

[0006] A preparation method of ruxolitinib phosphate cream, comprising the following steps:

[0007] (1) preparing an oil phase: mixing polysorbate 20, dimethicone, medium-chain triglyceride, cetyl alcohol, stearyl alcohol, light liquid paraffin, white vaseline, butylated hydroxytoluene and self-emulsifying glyceryl stearate, melting the obtained mixture at 60-80 DEG C to obtain an oil phase;

[0008] (2) preparing a bacteriostatic phase: mixing methylparaben, propylparaben and propylene glycol, adding xanthan gum to the obtained mixture, and uniformly dispersing to obtain a bacteriostatic phase;

[0009] (3) preparing an aqueous phase: dissolving polyethylene glycol 200, disodium edetate and ruxolitinib phosphate in purified water at 60-80 DEG C to obtain an aqueous phase;

[0010] (4) preparing the initial emulsion: mixing the oil phase in step (1), the bacteriostatic phase in step (2) and the water phase in step (3) at 60-80℃, and subjecting the obtained mixture to high shear emulsification to form an initial emulsion;

[0011] (5) preparing the final emulsion: subjecting the initial emulsion obtained in step (4) to high pressure homogenization to form a final emulsion, adding phenoxyethanol to the obtained final emulsion, stirring uniformly, and cooling to 25-35℃ to obtain the cream;

[0012] The cream is mainly prepared from the following components in parts by weight: 1.5-2.5 parts of luspaterin phosphate, 1-10 parts of polyethylene glycol 200, 0.01-0.1 parts of edetate disodium, 10-30 parts of propylene glycol, 0.05-0.15 parts of methylparaben, 0.01-0.1 parts of propylparaben, 0.1-1 parts of xanthan gum, 1-3 parts of polysorbate 20, 0.5-1.5 parts of dimethicone, 1-10 parts of medium-chain triglyceride, 1-5 parts of cetyl alcohol, 1-3 parts of stearyl alcohol, 1-10 parts of light liquid paraffin, 1-10 parts of white petrolatum, 0.00005-0.0005 parts of butylated hydroxytoluene, 1-5 parts of self-emulsifying glyceryl stearate, and 0.1-1 parts of phenoxyethanol.

[0013] For the present application, in a preferred embodiment, the cream is mainly prepared from the following components in parts by weight: 1.95-2.05 parts of luspaterin phosphate, 6-8 parts of polyethylene glycol 200, 0.04-0.06 parts of edetate disodium, 14-16 parts of propylene glycol, 0.09-0.11 parts of methylparaben, 0.04-0.06 parts of propylparaben, 0.3-0.5 parts of xanthan gum, 1.2-1.3 parts of polysorbate 20, 0.9-1.1 parts of dimethicone, 4-6 parts of medium-chain triglyceride, 2-4 parts of cetyl alcohol, 1.7-1.8 parts of stearyl alcohol, 3-5 parts of light liquid paraffin, 6-8 parts of white petrolatum, 0.0001-0.0003 parts of butylated hydroxytoluene, 2-4 parts of self-emulsifying glyceryl stearate, and 0.4-0.6 parts of phenoxyethanol.

[0014] For the present application, in a more preferred embodiment, the cream is mainly prepared from the following components in parts by weight: 1.98 parts of luspaterin phosphate, 7 parts of polyethylene glycol 200, 0.05 parts of edetate disodium, 15 parts of propylene glycol, 0.1 parts of methylparaben, 0.05 parts of propylparaben, 0.4 parts of xanthan gum, 1.25 parts of polysorbate 20, 1 parts of dimethicone, 5 parts of medium-chain triglyceride, 3 parts of cetyl alcohol, 1.75 parts of stearyl alcohol, 4 parts of light liquid paraffin, 7 parts of white petrolatum, 0.0002 parts of butylated hydroxytoluene, 3 parts of self-emulsifying glyceryl stearate, and 0.5 parts of phenoxyethanol.

[0015] In the present application, in step (5), when high pressure homogenization, the homogenization pressure is 300-900 bar, can but not limited to 300 bar, 400 bar, 500 bar, 600 bar, 700 bar, 800 bar or 900 bar, preferably, the homogenization pressure is 600 bar.

[0016] In step (5), when high pressure homogenization, the homogenization rate is 30-50 Hz, can but not limited to 30 Hz, 35 Hz, 40 Hz, 45 Hz or 50 Hz, preferably, the homogenization rate is 40 Hz.

[0017] In step (5), when high pressure homogenization, the pump speed is 40%-80%, can but not limited to 40%, 50%, 60%, 70% or 80%, preferably, the pump speed is 60%.

[0018] In step (5), when high pressure homogenization, the homogenization times is 2-6 times, can but not limited to 2 times, 3 times, 4 times, 5 times or 6 times, preferably, the homogenization times is 3-4 times.

[0019] In step (5), phenoxyethanol is added to the obtained final milk, stirred uniformly, and cooled to 25-35℃, can but not limited to 25℃, 30℃ or 35℃, preferably, cooled to 30℃.

[0020] In step (5), the stirring rate is 20-60 rpm, preferably 30-40 rpm.

[0021] In the present application, in step (4), when high shear emulsification, the high shear rate is 2000-3500 rpm, can but not limited to 2000 rpm, 2500 rpm, 3000 rpm or 3500 rpm, preferably, the high shear rate is 2500-3000 rpm.

[0022] In step (4), when high shear emulsification, the emulsification time is 20-60 minutes, can but not limited to 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes or 60 minutes, preferably, the emulsification time is 30-40 minutes.

[0023] In step (4), the mixing temperature is 60-80℃, can but not limited to 60℃, 65℃, 70℃, 75℃ or 80℃, preferably, the mixing temperature is 65-75℃, more preferably, the mixing temperature is 70℃.

[0024] In the present application, in step (1), the melting temperature is 60-80℃, can but not limited to 60℃, 65℃, 70℃, 75℃ or 80℃, preferably, the melting temperature is 65-75℃, more preferably, the melting temperature is 70℃.

[0025] In step (1), the melting time is 20-40 minutes.

[0026] In the present application, in step (2), the mixing time is 30-50 minutes; the dispersing time is 5-15 minutes.

[0027] In the present application, in step (3), the dissolving temperature is 60-80℃, which can be but is not limited to 60℃, 65℃, 70℃, 75℃ or 80℃, preferably, the dissolving temperature is 65-75℃, more preferably, the dissolving temperature is 70℃.

[0028] In step (3), the dissolving time is 20-60 minutes.

[0029] The technical solution of the present application has the following advantages:

[0030] The present application provides a preparation method of a ripretinib phosphate cream, which adopts high shear and high pressure homogenization to achieve more sufficient emulsification during the preparation process, so that the prepared cream has fine texture and stable physical properties, and the properties, droplet size, dynamic viscosity and in-vitro release rate of the cream are relatively stable under accelerated or long-term storage conditions, avoiding the unstable phenomena such as cream separation and water separation in a short period of time, ensuring the continuous safety and stability of the cream during use, and the preparation method is simple and easy to operate, which is suitable for large-scale industrial production. BRIEF DESCRIPTION OF DRAWINGS

[0031] Figure 1 is the property chart of the opening day of examples and comparative examples; wherein, Figure 1 a in the table is example 1; Figure 1 b in the table is example 1; Figure 1 c in the table is example 1; Figure 1 d in the table is comparative example 1; Figure 1 e in the table is comparative example 2; Figure 1 f in the table is comparative example 3;

[0032] Figure 2 is the property chart of the opening day of examples and comparative examples; wherein, Figure 2 a in the table is example 1; Figure 2 b in the table is example 1; Figure 2 c in the table is example 1; Figure 2 d in the table is comparative example 1; Figure 2 e in the table is comparative example 2; Figure 2 f in the table is comparative example 3;

[0033] Figure 3 is a droplet size plot of Example 1; wherein Figure 3a is the droplet size plot of Example 1 - 0 days; Figure 3b is the droplet size plot of Example 1 - 10 days at 40°C / 75% RH; Figure 3c is the droplet size plot of Example 1 - 30 days at 40°C / 75% RH;

[0034] Figure 4 is a droplet size plot of Example 2; wherein Figure 4a is the droplet size plot of Example 2 - 0 days; Figure 4b is the droplet size plot of Example 2 - 10 days at 40°C / 75% RH; Figure 4c is the droplet size plot of Example 2 - 30 days at 40°C / 75% RH;

[0035] Figure 5 is a droplet size plot of Example 3; wherein Figure 5a is the droplet size plot of Example 3 - 0 days; Figure 5b is the droplet size plot of Example 3 - 10 days at 40°C / 75% RH; Figure 5c is the droplet size plot of Example 3 - 30 days at 40°C / 75% RH;

[0036] Figure 6 is a droplet size plot of Comparative Example 1; wherein Figure 6a is the droplet size plot of Comparative Example 1 - 0 days; Figure 6b is the droplet size plot of Comparative Example 1 - 10 days at 40°C / 75% RH; Figure 6c is the droplet size plot of Comparative Example 1 - 30 days at 40°C / 75% RH;

[0037] Figure 7 is a droplet size plot of Comparative Example 2; wherein Figure 7a is the droplet size plot of Comparative Example 2 - 0 days; Figure 7b is the droplet size plot of Comparative Example 2 - 10 days at 40°C / 75% RH; Figure 7c is the droplet size plot of Comparative Example 2 - 30 days at 40°C / 75% RH;

[0038] Figure 8 is a droplet size plot of Comparative Example 3; wherein Figure 8a is the droplet size plot of Comparative Example 3 - 0 days; Figure 8b is the droplet size plot of Comparative Example 3 - 10 days at 40°C / 75% RH; Figure 8c is the droplet size plot of Comparative Example 3 - 30 days at 40°C / 75% RH;

[0039] Figure 9 is the change in in vitro release rate of Example 1 after 6 months at room temperature;

[0040] Figure 10 is the change in in vitro release rate of Example 2 after 6 months at room temperature;

[0041] Figure 11 is the change in in vitro release rate of Example 3 after 6 months at room temperature;

[0042] Figure 12 is the change in in vitro release rate of Comparative Example 1 after 6 months at room temperature;

[0043] Figure 13 is the change in in vitro release rate of Comparative Example 2 after 6 months at room temperature;

[0044] Figure 14 Variation of in vitro release rate of Comparative Example 1 after being placed at room temperature for 6 months. DETAILED DESCRIPTION

[0045] The present application can be better understood in accordance with the following examples. However, it will be readily apparent to those of ordinary skill in the art that the examples described are for purposes of illustration only and should not be so limited.

[0046] Example 1

[0047] A lucortinib phosphate cream is prepared from the following components by weight, as shown in Table 1.

[0048] Table 1 Components and amounts

[0049]

[0050] The preparation method of the above cream includes the following steps:

[0051] (1) Prepare the oil phase: mix polysorbate 20, dimethicone, medium-chain triglyceride, cetyl alcohol, stearyl alcohol, light liquid paraffin, white vaseline, butylated hydroxytoluene, and self-emulsifying glyceryl stearate, heat the mixture to 70°C for melting, and the melting time is 20-40 minutes to obtain the oil phase;

[0052] (2) Prepare the bacteriostatic phase: mix methylparaben, propylparaben, and propylene glycol, and the mixing time is 30-50 minutes, add xanthan gum to the mixture, and the dispersion time is 5-15 minutes, and after uniform dispersion, the bacteriostatic phase is obtained;

[0053] (3) Prepare the water phase: dissolve polyethylene glycol 200, disodium edetate, and lucortinib phosphate in purified water at 70°C, and the dissolving time is 20-60 minutes to obtain the water phase;

[0054] (4) Prepare the initial milk: mix the oil phase in step (1), the bacteriostatic phase in step (2), and the water phase in step (3) at 70°C, and the obtained mixture is subjected to high-shear emulsification at a high-shear rate of 3000 rpm for 30 minutes to form the initial milk;

[0055] (5) Prepare the final milk: subject the initial milk obtained in step (4) to high-pressure homogenization at a homogenization pressure of 600 bar, a homogenization rate of 40 Hz, a pump speed of 60%, and 3 times of homogenization to form the final milk, add phenoxyethanol to the obtained final milk, and stir uniformly at 30 rpm, and cool to 30°C to obtain the cream.

[0056] Examples 2-3

[0057] The difference between Example 2 and Example 1 is that the homogenization pressure is 300 bar, and the types and amounts of each component and the preparation method are the same as in Example 1.

[0058] The difference between Example 3 and Example 1 is that the homogenization pressure is 900 bar, and the types and amounts of each component and the preparation method are the same as in Example 1.

[0059] Comparative Examples 1-2

[0060] The difference between Comparative Example 1 and Example 1 is that the homogenization pressure is 200 bar, and the types and amounts of each component and the preparation method are the same as in Example 1.

[0061] The difference between Comparative Example 2 and Example 1 is that the homogenization pressure is 1000 bar, and the types and amounts of each component and the preparation method are the same as in Example 1.

[0062] Comparative Example 3

[0063] The ruxolitinib phosphate cream marketed in Germany, licensed by Incyte Biosciences Distribution B.V., and marketed under the brand name Opzelura, differs primarily in that it uses only high-shear mixing during the emulsification process.

[0064] The stability of the cream prepared according to the present invention (hereinafter referred to as the Examples) and the creams of each comparative example were tested, and the results are as follows:

[0065] 1. Changes in traits

[0066] The properties of the cream were compared between the day of opening and three months after opening. The properties of the cream in the examples and the creams in each comparative example are shown in the figures below. Figure 1 , Figure 2 (All creams were left at room temperature after opening). Creams in Examples 1-3 ( Figure 2 (a-2c) showed no obvious abnormalities in properties, while the creams in comparative examples 1-3 ( Figure 2 Slight stratification and water separation were observed in d-2f, indicating that too low a high-pressure homogenization pressure (Comparative Example 1, 200 bar) or too high a pressure (Comparative Example 2, 1000 bar), as well as no high-pressure homogenization (Comparative Example 3), would affect the physical stability of the cream after opening, and thus affect its continued effectiveness and safety during use; while homogenization at a pressure of 300 bar-900 bar can increase the physical stability of the cream.

[0067] 2. Droplet size testing

[0068] Test instrument: particle size analyzer for external preparation. The droplet size detection results of the cream of Example 1 and each comparative example at 0 day and under 40℃ / 75%RH accelerated condition for different storage time are shown in Figures 3-8.

[0069] Figures 3a-3c The droplet size of the cream of Example 1 is shown in the micro-characteristics figures of 0 day storage, 10 days storage under 40℃ / 75%RH and 30 days storage under 40℃ / 75%RH respectively, with a magnification of 200x; Figures 4a-4c The droplet size of the cream of Example 2 is shown in the micro-characteristics figures of 0 day storage, 10 days storage under 40℃ / 75%RH and 30 days storage under 40℃ / 75%RH respectively, with a magnification of 200x; Figures 5a-5c The droplet size of the cream of Example 3 is shown in the micro-characteristics figures of 0 day storage, 10 days storage under 40℃ / 75%RH and 30 days storage under 40℃ / 75%RH respectively, with a magnification of 200x; Figures 6a-6c The droplet size of the cream of Comparative Example 1 is shown in the micro-characteristics figures of 0 day storage, 10 days storage under 40℃ / 75%RH and 30 days storage under 40℃ / 75%RH respectively, with a magnification of 200x; Figures 7a-7c The droplet size of the cream of Comparative Example 2 is shown in the micro-characteristics figures of 0 day storage, 10 days storage under 40℃ / 75%RH and 30 days storage under 40℃ / 75%RH respectively, with a magnification of 200x; Figures 8a-8c The droplet size of the cream of Comparative Example 3 is shown in the micro-characteristics figures of 0 day storage, 10 days storage under 40℃ / 75%RH and 30 days storage under 40℃ / 75%RH respectively, with a magnification of 200x; As can be seen from Figures 3-8, the droplet size of the cream of Examples 1-3 is small and does not change significantly, while the droplet size of the cream of Comparative Examples 1-3 has a tendency to aggregate and increase, indicating that too small (Comparative Example 1, 200 bar) or too large (Comparative Example 2, 1000 bar) high-pressure homogenization pressure and no high-pressure homogenization (Comparative Example 3) can significantly aggregate and increase the droplet size of the cream, thereby increasing the risk of cream separation, water separation and the like; while homogenization under a homogenization pressure of 300 bar-900 bar can relatively stabilize the droplet size of the cream, thereby increasing the physical stability of the cream.

[0070] 3. Dynamic viscosity detection

[0071] Test instrument: rheometer. Parameters: PP25 rotor, test temperature 25.00±1.00℃, shear rate 0.1-1001 / s; log collection 120s, a total of 31 time points. The dynamic viscosity detection results of the cream of Example and each comparative example at 0 day and under 40℃ / 75%RH accelerated condition for 1 month at low, medium and high shear rates are shown in Table 2:

[0072] Table 2 Results of dynamic viscosity test

[0073]

[0074] At day 0, the dynamic viscosity of the creams in each example and the comparative examples was similar at different shear rates within the range of 0.1 to 100 1 / s. After being placed at 40°C / 75% RH for a period of time, the dynamic viscosity of the creams in comparative examples 1-3 decreased significantly at each shear rate, while the dynamic viscosity of the creams in examples 1-3 remained relatively stable. This indicates that too low a high-pressure homogenization pressure (comparative example 1, 200 bar) or too high a pressure (comparative example 2, 1000 bar), as well as not performing high-pressure homogenization (comparative example 3), would cause significant changes in the dynamic viscosity of the cream. Homogenization under a pressure of 300 bar to 900 bar can keep the dynamic viscosity of the cream relatively stable, indicating good physical stability.

[0075] 4. In vitro release test (IVRT)

[0076] Experimental instruments: Automated sampling transdermal diffusion system, high performance liquid chromatograph. Experimental method: Receiving medium: physiological saline; Artificial membrane: 0.45μm PTFE hydrophilic membrane; Dosage: 0.32-0.33g; Rotation speed: 600rpm; Test time: 6h, with samples taken at 0.5, 1, 2, 3, 4, and 6h for analysis.

[0077] from Figures 9-14 As can be seen, after 6 months of storage, the in vitro release rate of creams 1-3 in Examples 1-3 showed no significant difference compared to day 0. However, after 6 months of storage under the same conditions, the in vitro release rate of creams in Comparative Examples 1-3 slowed down slightly. This indicates that excessively low (Comparative Example 1, 200 bar) or excessively high (Comparative Example 2, 1000 bar) high-pressure homogenization, as well as the absence of high-pressure homogenization (Comparative Example 3), will slow down the in vitro release rate of the cream after a period of storage, thus affecting the cream's continued effectiveness. Homogenization at a pressure of 300-900 bar can keep the in vitro release rate of the cream relatively stable, ensuring its continued effectiveness.

[0078] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications may still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions may be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing ruxolitinib phosphate cream, characterized in that, Includes the following steps: (1) Preparation of oil phase: Polysorbate 20, dimethicone, medium-chain triglycerides, cetyl alcohol, octadecanol, light liquid paraffin, white petrolatum, butylated hydroxytoluene and self-emulsifying glyceryl stearate are mixed and the resulting mixture is heated to 60-80℃ to melt it to obtain the oil phase; (2) Preparation of antibacterial phase: Mix methylparaben, propylparaben and propylene glycol, add xanthan gum to the mixture, and disperse evenly to obtain the antibacterial phase; (3) Preparation of aqueous phase: Dissolve polyethylene glycol 200, disodium edetate and ruxolitinib phosphate in purified water at 60-80℃ to obtain aqueous phase; (4) Preparation of colostrum: The oil phase in step (1), the antibacterial phase in step (2) and the aqueous phase in step (3) are mixed at 60-80℃, and the resulting mixture is emulsified under high shear to form colostrum; (5) Preparation of final emulsion: The initial emulsion obtained in step (4) is homogenized under high pressure to form a final emulsion. Phenoxyethanol is added to the final emulsion, stirred evenly, and cooled to 25-35℃ to obtain an ointment. The cream is mainly composed of the following components in parts by weight: 1.5-2.5 parts ruxolitinib phosphate, 1-10 parts polyethylene glycol 200, 0.01-0.1 parts disodium edetate, 10-30 parts propylene glycol, 0.05-0.15 parts methylparaben, 0.01-0.1 parts propylparaben, 0.1-1 parts xanthan gum, 1-3 parts polysorbate 20, 0.5-1.5 parts dimethicone, 1-10 parts medium-chain triglycerides, 1-5 parts cetyl alcohol, 1-3 parts octadecyl alcohol, 1-10 parts light liquid paraffin, 1-10 parts white petrolatum, 0.00005-0.0005 parts butylated hydroxytoluene, 1-5 parts self-emulsifying glyceryl stearate, and 0.1-1 parts phenoxyethanol.

2. The preparation method according to claim 1, characterized in that, In step (5), during high-pressure homogenization, the homogenization pressure is 300-900 bar; the homogenization rate is 30-50 Hz; the pump speed is 40%-80%; the number of homogenization cycles is 2-6; and the temperature is cooled to 30°C.

3. The preparation method according to claim 2, characterized in that, In step (5), during high-pressure homogenization, the homogenization pressure is 600 bar; the homogenization rate is 40 Hz; the pump speed is 60%; and the number of homogenization cycles is 3-4.

4. The preparation method according to claim 1, characterized in that, In step (4), during high-shear emulsification, the high-shear rate is 2000-3500 rpm, preferably 2500-3000 rpm; the emulsification time is 20-60 minutes, preferably 30-40 minutes.

5. The preparation method according to claim 1, characterized in that, The cream is mainly composed of the following components in parts by weight: 1.95-2.05 parts ruxolitinib phosphate, 200 parts polyethylene glycol. 6-8 parts, disodium edetate 0.04-0.06 parts, propylene glycol 14-16 parts, methylparaben 0.09-0.11 parts, propylparaben 0.04-0.06 parts, xanthan gum 0.3-0.5 parts, polysorbate 201.2-1.3 parts, dimethicone 0.9-1.1 parts, medium-chain triglycerides 4-6 parts, cetyl alcohol 2-4 parts, octadecyl alcohol 1.7-1.8 parts, light liquid paraffin 3-5 parts, white petrolatum 6-8 parts, butylated hydroxytoluene 0.0001-0.0003 parts, self-emulsifying glyceryl stearate 2-4 parts, phenoxyethanol 0.4-0.6 parts; preferably, ruxolitinib phosphate 1.98 parts, polyethylene glycol 200 7 parts, disodium edetate 0.05 parts, propylene glycol 15 parts, methylparaben 0.1 parts, propylparaben 0.05 parts, xanthan gum 0.4 parts, polysorbate 201.25 parts, dimethicone 1 part, medium-chain triglycerides 5 parts, cetyl alcohol 3 parts, octadecyl alcohol 1.75 parts, light liquid paraffin 4 parts, white petrolatum 7 parts, butylated hydroxytoluene 0.0002 parts, self-emulsifying glyceryl stearate 3 parts, phenoxyethanol 0.5 parts.

6. The preparation method according to claim 1, characterized in that, In step (1), the melting temperature is 65-75℃, preferably 70℃; the melting time is 20-40 minutes.

7. The preparation method according to claim 1, characterized in that, In step (2), the mixing time is 30-50 minutes; the dispersion time is 5-15 minutes.

8. The preparation method according to claim 1, characterized in that, In step (3), the dissolution temperature is 65-75℃, preferably 70℃; the dissolution time is 20-60 minutes.

9. The preparation method according to claim 1, characterized in that, In step (4), the mixing temperature is 65-75℃, preferably 70℃.

10. The preparation method according to claim 1, characterized in that, In step (5), the stirring rate is 20-60 rpm, preferably 30-40 rpm.

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