External instant film containing rucotinib as well as preparation method and application of external instant film

Abstract

The invention discloses an external instant film containing rucotinib as well as a preparation method and application of the external instant film, the external instant film comprises the following raw materials: rucotinib phosphate or pharmaceutically acceptable salt thereof and a film-forming agent in a weight part ratio of 1: (5-20), and the film-forming agent is polyethylene oxide or polyvinyl alcohol. The external instant film disclosed by the invention has the advantages of high drug loading capacity, high dissolution rate, high drug accumulative release amount and high permeation rate, is good in adhesion degree with skin, is not easy to contaminate clothes, and is better in compliance compared with cream or other external dosage forms.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and more specifically, relates to an external fast-dissolving film containing ruxolitinib and a preparation method and application thereof. Background Art

[0002] Ruxolitinib ((R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propionitrile, structural formula Figure 1 (shown) was originally an oral drug for the treatment of myelofibrosis. It is a tyrosine kinase inhibitor, a small molecule inhibitor of protein kinases JAK1 and JAK2, suitable for the treatment of intermediate or high-risk myelofibrosis (PMF), including primary myelofibrosis, myelofibrosis secondary to polycythemia vera (PPV-MF) and myelofibrosis secondary to primary thrombocytosis (PET-MF).

[0003] In September 2021, the U.S. Food and Drug Administration (FDA) approved Incyte Corporation's ruxolitinib cream (trade name Opzelura) for the treatment of moderate atopic dermatitis (AD) and non-segmental vitiligo in patients aged 12 years and above. It is the first and only topical JAK inhibitor approved by the FDA.

[0004] Patent No. CN103002875B discloses a cream formed by an oil-in-water emulsion containing ruxolitinib or a pharmaceutically acceptable salt thereof, and Patent No. CN115702936A prepares a gel containing ruxolitinib, but the penetration rate of the raw material drug of the cream and gel is not high enough. The penetration efficiency of ruxolitinib may be improved by making it into a film, however, there is no relevant report on the external use instant film product of ruxolitinib. Summary of the invention

[0005] Based on this, the purpose of the present invention is to provide an external fast-dissolving film containing ruxolitinib, and a preparation method and application thereof. The present invention utilizes ruxolitinib phosphate or a pharmaceutically acceptable salt thereof and a film-forming agent to prepare an external fast-dissolving film, which has the advantages of high drug loading, fast dissolution rate and high penetration rate.

[0006] The technical solutions for achieving the above-mentioned invention objectives include the following.

[0007] In a first aspect of the present invention, a topical fast-dissolving film containing ruxolitinib is provided, wherein the raw materials include ruxolitinib phosphate or a pharmaceutically acceptable salt thereof and a film-forming agent in a weight ratio of 1:5 to 20, wherein the film-forming agent is polyethylene oxide (PEO) or polyvinyl alcohol (PVA).

[0008] The second aspect of the present invention provides a method for preparing the above-mentioned external fast-dissolving film containing ruxolitinib, comprising the following steps: dissolving a film-forming agent in a first solvent to prepare a solution A; dissolving ruxolitinib phosphate or a pharmaceutically acceptable salt thereof in a second solvent to prepare a solution B; adding solution B to solution A to prepare a solution C; and electrospinning solution C to obtain.

[0009] The third aspect of the present invention provides use of the above-mentioned external fast-dissolving film containing ruxolitinib in the treatment of atopic dermatitis or non-segmental vitiligo.

[0010] The present invention adopts electrostatic spinning technology to mix a specific film-forming agent with ruxolitinib phosphate or a pharmaceutically acceptable salt thereof in a certain proportion, and successfully prepares an external quick-dissolving film. The drug is dispersed in the external quick-dissolving film in an amorphous form, which solves the problem of poor water solubility of ruxolitinib. The external quick-dissolving film of the present invention has the advantages of high drug loading (the maximum drug loading can be 16%), fast dissolution rate, high cumulative drug release, and high permeation rate.

[0011] The external quick-dissolving film of the present invention dissolves rapidly when in contact with water, has good flexibility, good adhesion to the skin, is not easy to stain clothes, and has better compliance compared to creams or other external dosage forms.

[0012] The external quick-dissolving film of the present invention is easy to use. It only needs to be attached to the skin and gently patted with a small amount of water to completely dissolve, or the sweat secreted by the skin can also quickly dissolve the film. As the water evaporates, the dissolved drug is always in a supersaturated state, and the active ingredients can penetrate into the skin in a short time, thereby increasing the rate of transdermal penetration. At the same time, the required size and shape can be cut according to the size and properties of the skin lesions, thereby ensuring the uniformity of drug administration. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 is the chemical structural formula of ruxolitinib of the present invention.

[0014] Figure 2 This is a micrograph of the external quick-dissolving film of Example 1 of the present invention (*200 times).

[0015] Figure 3 This is a micrograph of the external quick-dissolving film of Example 1 of the present invention (*500 times).

[0016] Figure 4 This is a micrograph of the external quick-dissolving film of Example 2 of the present invention (*200 times).

[0017] Figure 5 This is a micrograph of the external quick-dissolving film of Example 2 of the present invention (*500 times).

[0018] Figure 6 This is the XRPD pattern of the external quick-dissolving film of Example 2 of the present invention.

[0019] Figure 7 This is a Raman scan of the external quick-dissolving film of Example 2 of the present invention.

[0020] Figure 8 The dissolution curves of the external quick-dissolving films of Example 1, Example 2, Comparative Example 1, Comparative Example 2 and Comparative Example 3 of the present invention are shown.

[0021] Fig. 9 The in vitro release diagrams of the external quick-dissolving films of Example 1, Example 2, Comparative Example 1, Comparative Example 2, and Comparative Example 3 of the present invention are shown. DETAILED DESCRIPTION

[0022] In order to facilitate the understanding of the present invention, the present invention will be described more fully below. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0023] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as those commonly understood by those skilled in the art to which the present invention belongs. The terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used in the present invention includes any and all combinations of one or more of the related listed items.

[0024] The experimental methods in the following examples where specific conditions are not specified are generally carried out under conventional conditions, such as those described in Green and Sambrook et al., Molecular Cloning: A Laboratory Manual, 2013, or according to the conditions recommended by the manufacturer. The various commonly used chemical reagents used in the examples are all commercially available products.

[0025] In some embodiments of the present invention, a topical fast-dissolving film containing ruxolitinib is disclosed, wherein the raw materials include ruxolitinib phosphate or a pharmaceutically acceptable salt thereof and a film-forming agent in a weight ratio of 1:5 to 20, wherein the film-forming agent is polyethylene oxide (PEO) or polyvinyl alcohol (PVA).

[0026] In some embodiments, the weight ratio of ruxolitinib phosphate or a pharmaceutically acceptable salt thereof to the film-forming agent is 1:5-15.

[0027] In some embodiments, the weight ratio of ruxolitinib phosphate or a pharmaceutically acceptable salt thereof to the film-forming agent is 1:5-10.

[0028] In some of the embodiments, the raw materials also include a plasticizer, and the plasticizer is one or more of polyethylene glycol (PEG), glycerol, propylene glycol, and sorbitol. The plasticizer can enhance the flexibility of the film and avoid the film from being fragile during use.

[0029] In some embodiments, the weight ratio of the plasticizer to the film-forming agent is 1:2-4.

[0030] In some embodiments, the weight ratio of the plasticizer to the film-forming agent is 1:2-3.

[0031] In some of the embodiments, the raw materials of the external fast-dissolving film containing ruxolitinib include ruxolitinib phosphate or a pharmaceutically acceptable salt thereof, a film-forming agent and a plasticizer; the weight ratio of ruxolitinib phosphate or a pharmaceutically acceptable salt thereof to the film-forming agent is 1:5-10; the weight ratio of the plasticizer to the film-forming agent is 1:2-3; the film-forming agent is polyethylene oxide (PEO) or polyvinyl alcohol (PVA), and the plasticizer is polyethylene glycol (PEG-400).

[0032] In other embodiments of the present invention, a method for preparing the above-mentioned external fast-dissolving film containing ruxolitinib is disclosed, comprising the following steps: dissolving a film-forming agent in a first solvent to prepare a solution A with a film-forming agent concentration of 5 wt% to 25 wt%; dissolving ruxolitinib phosphate or a pharmaceutically acceptable salt thereof in a second solvent to prepare a solution B with a concentration of 8 wt% to 12 wt% of ruxolitinib phosphate or a pharmaceutically acceptable salt thereof; adding solution B to solution A at a volume ratio of 1:9 to 11 to prepare solution C; and electrospinning solution C to obtain.

[0033] In other embodiments of the present invention, a method for preparing the above-mentioned external fast-dissolving film containing ruxolitinib is disclosed, comprising the following steps: dissolving a film-forming agent in a first solvent, and then adding a plasticizer to prepare a solution A with a film-forming agent concentration of 5 wt%~25wt% and a plasticizer concentration of 4 wt%~6 wt%; dissolving ruxolitinib phosphate or a pharmaceutically acceptable salt thereof in a second solvent to prepare a solution B with a concentration of 8 wt%~12 wt% of ruxolitinib phosphate or a pharmaceutically acceptable salt thereof; adding solution B to solution A at a volume ratio of 1:9~11 to prepare solution C; and electrospinning solution C to obtain.

[0034] In some embodiments, the first solvent is one or more of purified water, ethanol (EA), dimethyl sulfoxide (DMSO), and N,N-dimethylformamide (DMF).

[0035] In some embodiments, the second solvent is one or more of purified water, ethanol (EA), methanol (MT), ethylene glycol, butanediol, hexanediol, dimethyl sulfoxide (DMSO), and N,N-dimethylformamide (DMF).

[0036] In other embodiments of the present invention, the use of the above-mentioned external fast-dissolving film containing ruxolitinib in the treatment of atopic dermatitis or non-segmental vitiligo is disclosed.

[0037] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments.

[0038] Example 1 External fast-dissolving film containing ruxolitinib and preparation method thereof

[0039] The external fast-dissolving film of this embodiment is prepared from raw materials including ruxolitinib phosphate and polyethylene oxide.

[0040] The following steps are involved: 1. Dissolve 3g of film-forming agent polyethylene oxide in 42g of pure water to prepare solution A; 2. Dissolve 0.5 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare solution B; 3. Mix solution A and solution B evenly at room temperature to obtain solution C; 4. Use a syringe to take an appropriate amount of solution C and place it in the micro-injection pump, and adjust the flow rate to 0.35ml / h. Turn on the electrospinning machine, adjust the distance between the needle and the roller to 15cm, adjust the positive voltage to 10kV, adjust the negative voltage to -4.5kV, adjust the roller speed to 100rpm, adjust the scanning stroke to 3cm, and collect the filaments with aluminum foil or silicone oil paper. After spinning for 7 hours, a white, smooth and soft film is obtained.

[0041] 5. Use a hole puncher to cut the film into rectangles and put it into aluminum-plastic packaging bags for heat sealing.

[0042] Add an appropriate amount of purified water to the surface dish, preferably enough to just cover the bottom of the surface dish. Take a piece of external instant dissolving film prepared in this example and put it into the surface dish. The film will be completely dissolved within 2 seconds.

[0043] Example 2 External fast-dissolving film containing ruxolitinib and preparation method thereof

[0044] The external fast-dissolving film of this embodiment is prepared from raw materials including ruxolitinib phosphate and polyvinyl alcohol.

[0045] The following steps are involved: 1. Dissolve 9.5g of film-forming agent polyvinyl alcohol (model: 17-88) in 35.5g of pure water to prepare solution A; 2. Dissolve 0.5 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare solution B; 3. Mix solution A and solution B evenly at room temperature to obtain solution C; 4. Use a syringe to take an appropriate amount of solution C and place it in the micro-injection pump, and adjust the flow rate to 0.4ml / h. Turn on the electrospinning machine, adjust the distance between the needle and the roller to 12cm, adjust the positive voltage to 10kV, adjust the negative voltage to -4kV, adjust the roller speed to 100rpm, adjust the scanning stroke to 3cm, and collect the filaments with aluminum foil or silicone oil paper. After spinning for 8 hours, a white, smooth and soft film is obtained.

[0046] 5. Use a hole puncher to cut the film into rectangles and put it into aluminum-plastic packaging bags for heat sealing.

[0047] Add an appropriate amount of purified water to the surface dish, the amount of water should just cover the bottom of the surface dish, take a piece of The external quick-dissolving film prepared in the example was placed in a watch glass, and the film was completely dissolved within 2 seconds.

[0048] Example 3 External fast-dissolving film containing ruxolitinib and preparation method thereof

[0049] The external fast-dissolving film of this comparative example is prepared from raw materials including ruxolitinib phosphate, polyethylene oxide and polyethylene glycol 400.

[0050] The following steps are involved: 1. Dissolve 5g of film-forming agent polyethylene oxide in 37.5g of pure water, add 2.5g of polyethylene glycol 400 (plasticizer) to prepare solution A; 2. Dissolve 0.5 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare solution B; 3. Mix solution A and solution B evenly at room temperature to obtain solution C; 4. Use a syringe to take an appropriate amount of solution C and place it in a micro-injection pump, and adjust the flow rate to 0.3 ml / h. Turn on the electrospinning machine, adjust the distance between the needle and the roller to 10 cm, adjust the positive voltage to 8 kV, adjust the negative voltage to -4 kV, adjust the roller speed to 100 rpm, adjust the scanning stroke to 3 cm, and collect the filaments with aluminum foil or silicone oil paper. After spinning for 6 hours, a white, smooth and soft film is obtained.

[0051] 5. Use a hole puncher to cut the film into rectangles and put it into aluminum-plastic packaging bags for heat sealing.

[0052] Add an appropriate amount of purified water to the surface dish, preferably enough to just cover the bottom of the surface dish. Take a piece of external instant dissolving film prepared in this example and put it into the surface dish. The film will be completely dissolved within 2 seconds.

[0053] Comparative Example 1 External quick-dissolving film containing ruxolitinib and preparation method thereof

[0054] The external quick-dissolving film of this comparative example is prepared from raw materials including ruxolitinib phosphate, hydroxypropyl methylcellulose and polyvinyl pyrrolidone.

[0055] The following steps are involved: 1. Dissolve 5 g of film-forming agent hydroxypropyl methylcellulose and 2.5 g of polyvinyl pyrrolidone in 37.5 g of pure water to prepare solution A; 2. Dissolve 0.5 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare solution B; 3. Mix solution A and solution B evenly at room temperature to obtain solution C; 4. Use a syringe to take an appropriate amount of solution C and place it in a micro-injection pump, and adjust the flow rate to 0.35 ml / h. Turn on the electrospinning machine, adjust the distance between the needle and the roller to 10 cm, adjust the positive voltage to 8 kV, adjust the negative voltage to -4 kV, adjust the roller speed to 100 rpm, adjust the scanning stroke to 3 cm, and collect the filaments with aluminum foil or silicone oil paper. After spinning for 6 hours, a white, smooth and soft film is obtained.

[0056] 5. Use a hole puncher to cut the film into rectangles and put it into aluminum-plastic packaging bags for heat sealing.

[0057] Add an appropriate amount of purified water to the surface dish, preferably enough to just cover the bottom of the surface dish. Take a piece of external instant dissolving film prepared in this comparative example and put it into the surface dish. The film will be completely dissolved within 2 seconds.

[0058] Comparative Example 2 External quick-dissolving film containing ruxolitinib and preparation method thereof

[0059] The external quick-dissolving film of this comparative example is prepared from raw materials including ruxolitinib phosphate, hypromellose and polyethylene glycol 400.

[0060] The following steps are involved: 1. Dissolve 5 g of film-forming agent hydroxypropyl methylcellulose in 37.5 g of pure water, add 2.5 g of polyethylene glycol 400 (plasticizer) to prepare solution A; 2. Dissolve 0.5 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare solution B; 3. Mix solution A and solution B evenly at room temperature to obtain solution C; 4. Use a syringe to take an appropriate amount of solution C and place it in a micro-injection pump, and adjust the flow rate to 0.3 ml / h. Turn on the electrospinning machine, adjust the distance between the needle and the roller to 10 cm, adjust the positive voltage to 8 kV, adjust the negative voltage to -4 kV, adjust the roller speed to 100 rpm, adjust the scanning stroke to 3 cm, and collect the filaments with aluminum foil or silicone oil paper. After spinning for 6 hours, a white, smooth and soft film is obtained.

[0061] 5. Use a hole puncher to cut the film into rectangles and put it into aluminum-plastic packaging bags for heat sealing.

[0062] Add an appropriate amount of purified water to the surface dish, preferably enough to just cover the bottom of the surface dish. Take a piece of external instant dissolving film prepared in this comparative example and put it into the surface dish. The film will be completely dissolved within 2 seconds.

[0063] Comparative Example 3 External quick-dissolving film containing ruxolitinib and preparation method thereof

[0064] The external quick-dissolving film of this comparative example is prepared from raw materials including ruxolitinib phosphate and hypromellose.

[0065] The following steps are involved: 1. Dissolve 0.25 g of ruxolitinib phosphate in 24.75 g of anhydrous ethanol to prepare solution A; 2. Dissolve 4.75 g of the film-forming agent, hydroxypropyl methylcellulose, in 20 g of anhydrous ethanol to prepare solution B; 3. Mix solution A and solution B evenly at room temperature to obtain solution C; 4. Use a syringe to take an appropriate amount of solution C and place it in the micro-injection pump, and adjust the flow rate to 0.3ml / h. Turn on the electrospinning machine, adjust the distance between the needle and the roller to 10cm, adjust the positive voltage to 8kV, adjust the negative voltage to -3.5kV, adjust the roller speed to 100rpm, adjust the scanning stroke to 3cm, and collect the filaments with aluminum foil or silicone oil paper. After spinning for 7 hours, a white, smooth and soft film is obtained.

[0066] 5. Use a hole puncher to cut the film into rectangles and put it into aluminum-plastic packaging bags for heat sealing.

[0067] Add an appropriate amount of purified water to the surface dish, preferably enough to just cover the bottom of the surface dish. Take a piece of external instant dissolving film prepared in this comparative example and put it into the surface dish. The film will be completely dissolved within 2 seconds.

[0068] Comparative Example 4

[0069] The external fast-dissolving film of this comparative example is prepared from raw materials including ruxolitinib phosphate and polyvinyl alcohol.

[0070] The following steps are involved: 1. Dissolve 7g of film-forming agent polyvinyl alcohol (model: 17-88) in 35.5g of pure water to prepare solution A; 2. Dissolve 3 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare solution B; 3. Mix solution A and solution B evenly at room temperature to obtain solution C; 4. Use a syringe to take an appropriate amount of solution C and place it in a micro-injection pump, and adjust the flow rate to 0.4 ml / h. Turn on the electrospinning machine, adjust the distance between the needle and the roller to 12 cm, adjust the positive voltage to 10 kV, adjust the negative voltage to -4 kV, adjust the roller speed to 100 rpm, adjust the scanning stroke to 3 cm, and collect the filaments with aluminum foil or silicone oil paper. After spinning for 8 hours, a white film is obtained.

[0071] When the film was cut into rectangles with a puncher, it was found that the film was obviously broken during punching. Therefore, the film prepared in this comparative example (the weight ratio of ruxolitinib phosphate to polyvinyl alcohol was 3:7) had poor softness and did not meet the performance requirements of external quick-dissolving films.

[0072] Comparative Example 5

[0073] The external fast-dissolving film of this comparative example is prepared from raw materials including ruxolitinib phosphate and polyvinyl alcohol.

[0074] The following steps are involved: 1. Dissolve 12 g of film-forming agent polyvinyl alcohol (model: 17-88) in 35.5 g of pure water to prepare solution A; 2. Dissolve 3 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare solution B; 3. Mix solution A and solution B evenly at room temperature to obtain solution C; 4. Use a syringe to take an appropriate amount of solution C and place it in a micro-injection pump, and adjust the flow rate to 0.4 ml / h. Turn on the electrospinning machine, adjust the distance between the needle and the roller to 12 cm, adjust the positive voltage to 10 kV, adjust the negative voltage to -4 kV, adjust the roller speed to 100 rpm, adjust the scanning stroke to 3 cm, and collect the filaments with aluminum foil or silicone oil paper. After spinning for 8 hours, a white film is obtained.

[0075] When the film was cut into rectangles with a puncher, it was found that the film was obviously broken during punching. Therefore, the film prepared in this comparative example (the weight ratio of ruxolitinib phosphate to polyvinyl alcohol was 1:4) had poor softness and did not meet the performance requirements of external quick-dissolving films.

[0076] Test Example Performance of external fast-dissolving film containing ruxolitinib

[0077] 1. Microscopic observation According to the first method of Part IV 0982 of the 2020 edition of the Chinese Pharmacopoeia, the external quick-dissolving films prepared in Example 1 and Example 2 were observed under a microscope at 200 times and 500 times magnification, respectively. The results are as follows: Figure 2~Figure 5 As shown, under microscopic observation, the filaments in the external instant dissolving film are dense and uniform.

[0078] 2. Physical properties characterization The thickness of the external instant dissolving films prepared in Example 1, Example 2, Comparative Example 1 and Comparative Example 3 was measured by a thickness meter. The results are shown in Table 1. The thickness of the external instant dissolving films prepared by different film-forming agents was above 10 μm.

[0079]

[0080] The external quick-dissolving film prepared in Example 2 was subjected to X-ray powder diffraction (the spectrum is as follows Figure 6 ) and Raman scanning (spectrum as shown Figure 7 shown), from Figure 6~Figure 7 It can be seen that in the external fast-dissolving film containing ruxolitinib prepared by the present invention, the drug ingredient ruxolitinib is amorphous.

[0081] 3. Dissolution curve The dissolution of the external instant dissolving films prepared in Example 1 to Example 2 and Comparative Example 1 to Comparative Example 3 was tested using the second method of Part 4, 0931, of the 2020 edition of the Chinese Pharmacopoeia. The results are as follows: Figure 8 As shown. The results showed that compared with ruxolitinib phosphate (API), the dissolution rate of the topical fast-dissolving film prepared by electrospinning using polyethylene oxide (PEO) or polyvinyl alcohol (PVA) as a film-forming agent was significantly improved. However, the dissolution rate of the topical fast-dissolving film prepared by electrospinning using hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC) or polyvinyl pyrrolidone (PVP) as a film-forming agent was not significantly improved.

[0082] 4. In vitro release rate The Franz diffusion cell method was used to perform in vitro release testing on the external quick-dissolving films prepared in Example 1 to Example 2 and Comparative Example 1 to Comparative Example 3, and the cumulative release amounts were compared with those of ruxolitinib cream (commercially available, with the same active ingredient content in the sample amount). The in vitro release profiles were as follows: Fig. 9 As shown. The results show that compared with the commercially available ruxolitinib cream, the cumulative release amount of the external quick-dissolving film of Examples 1-2 and Comparative Examples 1-3 is significantly increased, and the release rate is significantly accelerated. At the same time, the release rate of the external quick-dissolving film prepared by electrospinning using polyethylene oxide (PEO) or polyvinyl alcohol (PVA) as a film-forming agent is also significantly faster than the release rate of the external quick-dissolving film prepared by electrospinning using hydroxypropyl methylcellulose (HPMC) and / or polyvinyl pyrrolidone (PVP) as a film-forming agent.

[0083] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0084] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A topical quick-dissolving film containing ruxolitinib, characterized in that: The raw materials include ruxolitinib phosphate or a pharmaceutically acceptable salt thereof and a film-forming agent in a weight ratio of 1:5-20, and the film-forming agent is polyethylene oxide or polyvinyl alcohol.

2. The external fast-dissolving film containing ruxolitinib according to claim 1, characterized in that The weight ratio of the ruxolitinib phosphate or a pharmaceutically acceptable salt thereof to the film-forming agent is 1:5-15.

3. The external fast-dissolving film containing ruxolitinib according to claim 2, characterized in that The weight ratio of the ruxolitinib phosphate or a pharmaceutically acceptable salt thereof to the film-forming agent is 1:5-10.

4. The external fast-dissolving film containing ruxolitinib according to any one of claims 1 to 3, characterized in that The raw materials also include a plasticizer, and the plasticizer is one or more of polyethylene glycol, glycerol, propylene glycol, and sorbitol.

5. The external fast-dissolving film containing ruxolitinib according to claim 4, characterized in that The weight ratio of the plasticizer to the film-forming agent is 1:2-4; preferably, the weight ratio of the plasticizer to the film-forming agent is 1:2-3.

6. The external fast-dissolving film containing ruxolitinib according to claim 1, characterized in that The external fast-dissolving film containing ruxolitinib comprises raw materials including ruxolitinib phosphate or a pharmaceutically acceptable salt thereof, a film-forming agent and a plasticizer; the weight ratio of the ruxolitinib phosphate or a pharmaceutically acceptable salt thereof to the film-forming agent is 1:5-10; the weight ratio of the plasticizer to the film-forming agent is 1:2-3; the film-forming agent is polyethylene oxide or polyvinyl alcohol, and the plasticizer is polyethylene glycol 400.

7. The method for preparing the external fast-dissolving film containing ruxolitinib according to any one of claims 1 to 5, characterized in that: The following steps are involved: The film-forming agent is dissolved in a first solvent to prepare a solution A; ruxolitinib phosphate or a pharmaceutically acceptable salt thereof is dissolved in a second solvent to prepare a solution B; the solution B is added to the solution A to prepare a solution C; and the solution C is subjected to electrostatic spinning to obtain the product.

8. The method for preparing the external fast-dissolving film containing ruxolitinib according to claim 6, characterized in that: The following steps are involved: The film-forming agent is dissolved in a first solvent, and a plasticizer is added to prepare a solution A; ruxolitinib phosphate or a pharmaceutically acceptable salt thereof is dissolved in a second solvent to prepare a solution B; solution B is added to solution A to prepare a solution C; and solution C is subjected to electrostatic spinning to obtain the product.

9. The method for preparing the external fast-dissolving film containing ruxolitinib according to claim 7 or 8, characterized in that: The first solvent is one or more of purified water, ethanol, dimethyl sulfoxide, and N,N-dimethylformamide; the second solvent is one or more of purified water, ethanol, methanol, ethylene glycol, butanediol, hexanediol, dimethyl sulfoxide, and N,N-dimethylformamide.

10. Use of the external fast-dissolving film containing ruxolitinib according to any one of claims 1 to 6 in the treatment of atopic dermatitis or non-segmental vitiligo.

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