Topical rapidly dissolving film containing ruxolitinib, preparation method and application thereof

Abstract

The present invention discloses an externally applied rapid-dissolving film containing ruxolitinib, a preparation method thereof and applications. The raw materials of the externally applied rapid-dissolving film include ruxolitinib phosphate or a pharmaceutically acceptable salt thereof and a film-forming agent in a weight ratio of 1:5 to 20, and the film-forming agent is polyethylene oxide or polyvinyl alcohol. The externally applied rapid-dissolving film of the present invention has the advantages of high drug loading, fast dissolution rate, high cumulative drug release amount, and high penetration rate. It has good adhesion to the skin and is not easy to stain clothes. Compared with cream agents or other external dosage forms, it has better compliance.

Description

Technical Field

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

[0002] Ruxolitinib ((R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, the structural formula is as Figure 1 shown) was initially an oral drug for the treatment of myelofibrosis. It is a tyrosine kinase inhibitor, that is, a small molecule inhibitor of protein kinases JAK1 and JAK2, and is suitable for the treatment of intermediate or high-risk myelofibrosis (primary 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 US 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 12 years of age and older. It is the first and only topically applied JAK inhibitor approved by the FDA.

[0004] Patent No. CN103002875B discloses a cream formed from an oil-in-water emulsion containing ruxolitinib or a pharmaceutically acceptable salt thereof. Patent No. CN115702936A prepared a gel containing ruxolitinib. However, for creams and gels, the penetration rate of the active ingredient is not high enough. Making ruxolitinib into a film may improve its penetration efficiency. However, there is currently no relevant report on externally applied fast-dissolving film products of ruxolitinib. Summary of the Invention

[0005] Based on this, the purpose of the present invention is to provide an externally applied fast-dissolving film containing ruxolitinib, a preparation method thereof, and an application thereof. The present invention uses ruxolitinib phosphate or a pharmaceutically acceptable salt thereof and a film-forming agent to prepare an externally applied 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 invention purposes are as follows.

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

[0008] In the second aspect of the present invention, there is provided a method for preparing the above-mentioned topical fast-dissolving film containing ruxolitinib, which includes the following steps: dissolving the film-forming agent in a first solvent to prepare solution A; dissolving ruxolitinib phosphate or a pharmaceutically acceptable salt thereof in a second solvent to prepare solution B; adding solution B to solution A to prepare solution C; and performing electrospinning on solution C to obtain the film.

[0009] In the third aspect of the present invention, there is provided the use of the above-mentioned topical fast-dissolving film containing ruxolitinib in the treatment of atopic dermatitis or non-segmental vitiligo.

[0010] The present invention adopts the electrospinning technology, and combines a specific film-forming agent with ruxolitinib phosphate or a pharmaceutically acceptable salt thereof in a certain proportion to successfully prepare a topical fast-dissolving film. The drug is dispersed in the topical fast-dissolving film in an amorphous form, solving the problem of poor water solubility of ruxolitinib. The topical fast-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 amount, and high penetration rate.

[0011] The topical fast-dissolving film of the present invention dissolves rapidly in water, has good flexibility, good adhesion to the skin, and is not easy to stain clothes. Compared with cream agents or other topical dosage forms, it has better compliance.

[0012] The topical fast-dissolving film of the present invention is convenient 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, which can make the active ingredient penetrate into the skin in a short time, increasing the transdermal rate. At the same time, according to the size and shape of the skin lesion, the required size and shape can be cut out, ensuring the uniformity of drug administration. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0014] Figure 2 It is the micrograph (*200 times) of the topical fast-dissolving film of Example 1 of the present invention.

[0015] Figure 3 It is the micrograph (*500 times) of the topical fast-dissolving film of Example 1 of the present invention.

[0016] Figure 4 It is the micrograph (*200 times) of the topical fast-dissolving film of Example 2 of the present invention.

[0017] Figure 5 Micrograph (*500x) of the topical fast-dissolving film of Example 2 of the present invention.

[0018] Figure 6 XRPD pattern of the topical fast-dissolving film of Example 2 of the present invention.

[0019] Figure 7 Raman scanning pattern of the topical fast-dissolving film of Example 2 of the present invention.

[0020] Figure 8 Dissolution curves of the topical fast-dissolving films of Example 1, Example 2, Comparative Example 1, Comparative Example 2, and Comparative Example 3 of the present invention.

[0021] Figure 9 In vitro release profiles of the topical fast-dissolving films of Example 1, Example 2, Comparative Example 1, Comparative Example 2, and Comparative Example 3 of the present invention. Detailed implementation manners

[0022] For ease of understanding the present invention, the present invention will be described more comprehensively below. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, these embodiments are provided 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 commonly understood by those skilled in the technical field 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 without specific conditions noted in the following examples are generally in accordance with conventional conditions, such as those described in Green and Sambrook et al., Molecular Cloning: A Laboratory Manual, 2013, or in accordance with the conditions recommended by the manufacturer. All common chemical reagents used in the examples are commercially available products.

[0025] In some embodiments of the present invention, a topical fast-dissolving film containing ruxolitinib phosphate is disclosed, and its 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, and 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 to 15.

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

[0028] In some of these embodiments, the raw materials further 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 phenomenon of brittleness during use.

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

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

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

[0032] In some other embodiments of the present invention, a preparation method of the above-mentioned externally applied instant-dissolving film containing ruxolitinib is disclosed, including the following steps: dissolving the 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 its pharmaceutically acceptable salt in a second solvent to prepare a solution B with a concentration of ruxolitinib phosphate or its pharmaceutically acceptable salt of 8 wt% to 12 wt%; adding solution B to solution A according to a volume ratio of 1:9 to 11 to prepare a solution C; and performing electrospinning on solution C to obtain the product.

[0033] In some other embodiments of the present invention, a preparation method of the above-mentioned externally applied instant-dissolving film containing ruxolitinib is disclosed, including the following steps: dissolving the 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% to 25 wt% and a plasticizer concentration of 4 wt% to 6 wt%; dissolving ruxolitinib phosphate or its pharmaceutically acceptable salt in a second solvent to prepare a solution B with a concentration of ruxolitinib phosphate or its pharmaceutically acceptable salt of 8 wt% to 12 wt%; adding solution B to solution A according to a volume ratio of 1:9 to 11 to prepare a solution C; and performing electrospinning on solution C to obtain the product.

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

[0035] In some of these 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 some other embodiments of the present invention, the application of the above-mentioned topical fast-dissolving film containing ruxolitinib in the treatment of atopic dermatitis or non-segmental vitiligo is disclosed.

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

[0038] Example 1 Topical Fast-Dissolving Film Containing Ruxolitinib and Its Preparation Method

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

[0040] It includes the following steps:

[0041] 1. Dissolve 3 g of the film-forming agent polyethylene oxide in 42 g of pure water to prepare Solution A;

[0042] 2. Dissolve 0.5 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare Solution B;

[0043] 3. Mix Solution A and Solution B evenly at room temperature to obtain Solution C;

[0044] 4. Take an appropriate amount of Solution C with a syringe and place it on a micro-injection pump, and adjust the flow rate to 0.35 ml / h. Turn on the electrospinning machine and adjust the distance between the needle and the roller to 15 cm, adjust the positive voltage to 10 kV, adjust the negative voltage to -4.5 kV, adjust the roller speed to 100 rpm, adjust the scanning stroke to 3 cm, collect the fiber with aluminum foil paper or silicone oil paper, and after electrospinning for 7 hours, obtain a white, smooth and soft film.

[0045] 5. Cut the film into rectangles with a punch and pack it into an aluminum-plastic packaging bag for heat sealing.

[0046] Add an appropriate amount of purified water to a petri dish, and the amount of water should be just enough to cover the bottom of the petri dish. Take a piece of the topical fast-dissolving film prepared in this example and put it into the petri dish, and the film will completely dissolve within 2 s.

[0047] Example 2 Topical Fast-Dissolving Film Containing Ruxolitinib and Its Preparation Method

[0048] The topical fast-dissolving film of this example is prepared from raw materials including ruxolitinib phosphate and polyvinyl alcohol.

[0049] It includes the following steps:

[0050] 1. Dissolve 9.5 g of the film-forming agent polyvinyl alcohol (model: 17-88) in 35.5 g of pure water to prepare solution A;

[0051] 2. Dissolve 0.5 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare solution B;

[0052] 3. Mix solution A and solution B evenly at room temperature to obtain solution C;

[0053] 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, collect the fiber with aluminum foil or silicone oil paper, and after spinning for 8 hours, obtain a white, smooth and soft film.

[0054] 5. Use a hole punch to cut the film into a rectangle and pack it into an aluminum-plastic packaging bag for heat sealing.

[0055] Add an appropriate amount of purified water to a petri dish, and the amount of water should be just enough to cover the bottom of the petri dish. Take a piece of the

[0056] externally applied instant-dissolving film prepared in this example, put it into the petri dish, and the film completely dissolves within 2 s.

[0057] Example 3 Externally Applied Instant-Dissolving Film Containing Ruxolitinib and Its Preparation Method

[0058] The externally applied instant-dissolving film of this comparative example is prepared from raw materials including ruxolitinib phosphate, polyethylene oxide, and polyethylene glycol 400.

[0059] Including the following steps:

[0060] 1. Dissolve 5 g of the film-forming agent polyethylene oxide in 37.5 g of pure water, and add 2.5 g of polyethylene glycol 400 (plasticizer) to prepare solution A;

[0061] 2. Dissolve 0.5 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare solution B;

[0062] 3. Mix solution A and solution B evenly at room temperature to obtain solution C;

[0063] 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, collect the fiber with aluminum foil or silicone oil paper, and after spinning for 6 hours, obtain a white, smooth and soft film.

[0064] 5. Cut the film into a rectangle with a hole puncher and load it into an aluminum-plastic packaging bag for heat sealing.

[0065] Add an appropriate amount of purified water to a petri dish, and the amount of water should be just enough to cover the bottom of the petri dish. Take an external instant film prepared in this example and put it into the petri dish. The film completely dissolves within 2 s.

[0066] Comparative Example 1 External instant film containing ruxolitinib and its preparation method

[0067] The external instant film of this comparative example is prepared from raw materials including ruxolitinib phosphate, hypromellose, and polyvinylpyrrolidone.

[0068] Including the following steps:

[0069] 1. Dissolve 5 g of the film-forming agent hypromellose and 2.5 g of polyvinylpyrrolidone in 37.5 g of pure water to prepare Solution A;

[0070] 2. Dissolve 0.5 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare Solution B;

[0071] 3. Mix Solution A and Solution B evenly at room temperature to obtain Solution C;

[0072] 4. Take an appropriate amount of Solution C with a syringe and place it on a micro-injection pump, and adjust the flow rate to 0.35 ml / h. Turn on the electrospinning machine and 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 fibers with aluminum foil or silicone oil paper. After electrospinning for 6 hours, a white, smooth and soft film is obtained.

[0073] 5. Cut the film into a rectangle with a hole puncher and load it into an aluminum-plastic packaging bag for heat sealing.

[0074] Add an appropriate amount of purified water to a petri dish, and the amount of water should be just enough to cover the bottom of the petri dish. Take an external instant film prepared in this comparative example and put it into the petri dish. The film completely dissolves within 2 s.

[0075] Comparative Example 2 External instant film containing ruxolitinib and its preparation method

[0076] The external instant film of this comparative example is prepared from raw materials including ruxolitinib phosphate, hypromellose, and polyethylene glycol 400.

[0077] Including the following steps:

[0078] 1. Dissolve 5 g of the film-forming agent hypromellose in 37.5 g of pure water, and add 2.5 g of polyethylene glycol 400 (plasticizer) to prepare Solution A;

[0079] 2. Dissolve 0.5 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare Solution B;

[0080] 3. Mix Solution A and Solution B evenly at room temperature to obtain Solution C;

[0081] 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, collect the fiber with aluminum foil or silicone oil paper, and after electrospinning for 6 hours, obtain a white, smooth and soft film.

[0082] 5. Use a punch to cut the film into a rectangle and pack it in an aluminum-plastic packaging bag for heat sealing.

[0083] Add an appropriate amount of purified water to a petri dish, and the amount of water should be just enough to cover the bottom of the petri dish. Take an externally applied instant film prepared in this comparative example and put it into the petri dish. The film completely dissolves within 2 s.

[0084] Comparative Example 3 Externally applied instant film containing ruxolitinib and its preparation method

[0085] The externally applied instant film of this comparative example is prepared from raw materials including ruxolitinib phosphate and hypromellose.

[0086] It includes the following steps:

[0087] 1. Dissolve 0.25 g of ruxolitinib phosphate in 24.75 g of absolute ethanol to prepare Solution A;

[0088] 2. Dissolve 4.75 g of the film-forming agent hypromellose in 20 g of absolute ethanol to prepare Solution B;

[0089] 3. Mix Solution A and Solution B evenly at room temperature to obtain Solution C;

[0090] 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 -3.5 kV, adjust the roller speed to 100 rpm, adjust the scanning stroke to 3 cm, collect the fiber with aluminum foil or silicone oil paper, and after electrospinning for 7 hours, obtain a white, smooth and soft film.

[0091] 5. Use a punch to cut the film into a rectangle and pack it in an aluminum-plastic packaging bag for heat sealing.

[0092] Add an appropriate amount of purified water to a petri dish, and the amount of water should be just enough to cover the bottom of the petri dish. Take an externally applied instant film prepared in this comparative example and put it into the petri dish. The film completely dissolves within 2 s.

[0093] Comparative Example 4

[0094] The external-use instant film of this comparative example is prepared from raw materials including ruxolitinib phosphate and polyvinyl alcohol.

[0095] It includes the following steps:

[0096] 1. Dissolve 7 g of the film-forming agent polyvinyl alcohol (model: 17-88) in 35.5 g of pure water to prepare Solution A;

[0097] 2. Dissolve 3 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare Solution B;

[0098] 3. Mix Solution A and Solution B evenly at room temperature to obtain Solution C;

[0099] 4. Take an appropriate amount of Solution C with a syringe and place it on 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, collect the filaments with aluminum foil or silicone oil paper, and after electrospinning for 8 hours, obtain a white film.

[0100] When using a hole punch to cut the film into a rectangle, it was found that the film was significantly fragmented during punching. Therefore, the film prepared in this comparative example (the weight ratio of ruxolitinib phosphate to polyvinyl alcohol is 3:7) has poor flexibility and does not meet the performance requirements of the external-use instant film.

[0101] Comparative Example 5

[0102] The external-use instant film of this comparative example is prepared from raw materials including ruxolitinib phosphate and polyvinyl alcohol.

[0103] It includes the following steps:

[0104] 1. Dissolve 12 g of the film-forming agent polyvinyl alcohol (model: 17-88) in 35.5 g of pure water to prepare Solution A;

[0105] 2. Dissolve 3 g of ruxolitinib phosphate in 4.5 g of dimethyl sulfoxide to prepare Solution B;

[0106] 3. Mix Solution A and Solution B evenly at room temperature to obtain Solution C;

[0107] 4. Take an appropriate amount of Solution C with a syringe and place it on 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, collect the filaments with aluminum foil or silicone oil paper, and after electrospinning for 8 hours, obtain a white film.

[0108] When cutting the film into a rectangle with a hole punch, it was found that the film was significantly fragmented during punching. Therefore, the film prepared in this comparative example (the weight ratio of ruxolitinib phosphate to polyvinyl alcohol is 1:4) has poor flexibility and does not meet the performance requirements of the external soluble film.

[0109] Test Example Performance of the External Soluble Film Containing Ruxolitinib

[0110] 1. Microscopic Observation

[0111] According to the first method of 0982 in the fourth part of the Chinese Pharmacopoeia 2020 edition, the external soluble films prepared in Example 1 and Example 2 were magnified 200 times and 500 times respectively for microscopic observation. The results are as Figures 2 to 5 shown. Under microscopic observation, the filaments in the external soluble film are dense and uniform.

[0112] 2. Physical Property Characterization

[0113] The thickness of the external soluble films prepared in Example 1, Example 2, Comparative Example 1 and Comparative Example 3 was measured by a thickness gauge. The results are shown in Table 1. The thickness of the external soluble films prepared with different film-forming agents is above 10 μm.

[0114]

[0115] The external soluble film prepared in Example 2 was subjected to X-ray powder diffraction (the spectrum is as Figure 6 shown) and Raman scanning (the spectrum is as Figure 7 shown). It can be seen from Figures 6 to 7 that in the external soluble film containing ruxolitinib prepared by the present invention, the drug component ruxolitinib is amorphous.

[0116] 3. Dissolution Curve

[0117] Using the second method of 0931 in the fourth part of the Chinese Pharmacopoeia 2020 edition, the dissolution of the external soluble films prepared in Example 1 to Example 2, Comparative Example 1 to Comparative Example 3 was detected. The results are as Figure 8 shown. The results show that compared with ruxolitinib phosphate (API), the dissolution rate of the external soluble film prepared by electrospinning using polyethylene oxide (PEO) or polyvinyl alcohol (PVA) as a film-forming agent is significantly improved. However, for the external soluble film prepared by electrospinning using hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC) or polyvinylpyrrolidone (PVP) etc. as a film-forming agent, the dissolution rate is not improved much.

[0118] 4. In Vitro Release Rate

[0119] Using the Franz diffusion cell method, the in vitro release of the fast-dissolving topical films prepared in Examples 1 to 2 and Comparative Examples 1 to 3 was detected, and the cumulative release was compared with that of ruxolitinib cream (commercially available, with the same content of active ingredient in the sample loading). The in vitro release profiles are shown respectively as Figure 9 follows. The results showed that the cumulative release of the fast-dissolving topical films in Examples 1 to 2 and Comparative Examples 1 to 3 was significantly increased compared with the commercially available ruxolitinib cream, and the release rate was significantly accelerated. At the same time, the release rate of the fast-dissolving topical films prepared by electrospinning using polyethylene oxide (PEO) or polyvinyl alcohol (PVA) as the film-forming agent was also significantly faster than that of the fast-dissolving topical films prepared by electrospinning using hydroxypropyl methylcellulose (HPMC) and / or polyvinylpyrrolidone (PVP) as the film-forming agent.

[0120] The technical features of the above-described embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope described in this specification.

[0121] The above-described embodiments merely represent several implementation manners of the present invention. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can be made, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the present invention patent shall be subject to the appended claims.

Claims

1. An externally-applied instant dissolving film containing ruxolitinib, characterized in that, Its raw materials include ruxolitinib phosphate or its pharmaceutically acceptable salt and a film-forming agent in a weight ratio of 1:5 to 20, and the film-forming agent is polyethylene oxide or polyvinyl alcohol.

2. The externally-applied fast-dissolving film containing ruxolitinib according to claim 1, wherein The weight ratio of the ruxolitinib phosphate or its pharmaceutically acceptable salt to the film-forming agent is 1:5 to 15.

3. The externally-applied rapid-dissolving film containing ruxolitinib according to claim 2, wherein The weight ratio of the ruxolitinib phosphate or its pharmaceutically acceptable salt to the film-forming agent is 1:5 to 10.

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

5. The externally-applied fast-dissolving film containing ruxolitinib according to claim 4, wherein The weight ratio of the plasticizer to the film-forming agent is 1:2 to 4.

6. The externally-applied instant dissolving film containing ruxolitinib according to claim 5, characterized in that, The weight ratio of the plasticizer to the film-forming agent is 1:2 to 3.

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

8. The preparation method of the topical fast-dissolving film containing ruxolitinib according to any one of claims 1 to 3, characterized in that, It includes the following steps: Dissolve the film-forming agent in a first solvent to form solution A; dissolve ruxolitinib phosphate or its pharmaceutically acceptable salt in a second solvent to form solution B; add solution B to solution A to form solution C; perform electrospinning on solution C to obtain the product.

9. The preparation method of the topical fast-dissolving film containing ruxolitinib according to claim 8, wherein It includes the following steps: Dissolve the film-forming agent in a first solvent, and then add the plasticizer to form solution A; dissolve ruxolitinib phosphate or its pharmaceutically acceptable salt in a second solvent to form solution B; add solution B to solution A to form solution C; perform electrospinning on solution C to obtain the product.

10. The preparation method of the topical fast-dissolving film containing ruxolitinib according to claim 8 or 9, 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, butylene glycol, hexylene glycol, dimethyl sulfoxide, and N,N-dimethylformamide.

11. Use of the externally-applied fast-dissolving film containing ruxolitinib according to any one of claims 1 to 7 in the preparation of a drug for treating atopic dermatitis or non-segmental vitiligo.

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