Edaravone dextroborneol transdermal patch and preparation method thereof
By preparing edaravone dexborneol transdermal patches, the stability and ease of use issues of concentrated edaravone dexborneol injection solutions were resolved, achieving stable drug release and improved patient compliance. These patches are suitable for room temperature storage and long-term administration.
Patent Information
- Application Number
- CN202511477077.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-16
- Publication Date
- 2025-11-25
AI Technical Summary
The existing concentrated solution of edaravone dexborneol for injection has poor stability, requires low-temperature storage, has high storage costs, is used frequently, has poor patient compliance, and has large fluctuations in blood drug concentration, making it difficult to achieve a stable and convenient dosing regimen.
The transdermal patch using edaravone and dexborneol contains dexborneol, edaravone, disodium EDTA (an antioxidant), vitamin E succinate, azone (a penetration enhancer), and propylene glycol. It is prepared through a specific process to form a transdermal patch with good stability and sustained-release effect.
It achieves significant improvements in the stability and drug release of edaravone dexborneol, is suitable for room temperature storage, reduces storage costs, is suitable for patients who need to extend the dosing interval, and maintains an effective blood drug concentration for more than 1 day.
Smart Images
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Abstract
Description
Technical Field
[0001] This invention relates to the field of pharmaceutical technology, and in particular to an edaravone dexborneol transdermal patch and its preparation method. Background Technology
[0002] Edaravone is an organic compound mainly used as a free radical scavenger. Clinical studies suggest that N-acetylaspartic acid (NAA) is a specific marker of surviving nerve cells, and its content decreases sharply in the early stages of cerebral infarction.
[0003] Dextroborneol is a nonsteroidal anti-inflammatory drug (NSAID) primarily used to relieve mild to moderate pain and reduce fever. Its mechanism of action involves inhibiting cyclooxygenase (COX) activity and reducing prostaglandin synthesis, thereby exerting anti-inflammatory, analgesic, and antipyretic effects. Clinically, it is commonly used for short-term treatment of symptoms such as arthritis, headache, toothache, and muscle aches.
[0004] Edaravone and dexborneol concentrated injection solution is a compound preparation composed of edaravone and dexborneol in a 4:1 ratio. It exerts its brain cell protective effect through a dual mechanism of scavenging free radicals and inhibiting inflammatory responses. It can be used to improve neurological symptoms, activities of daily living, and functional impairments caused by acute cerebral infarction.
[0005] Currently, edaravone dexborneol concentrated solution for injection suffers from problems such as poor stability, the need for low-temperature storage, high storage costs, and frequent use. Furthermore, it requires administration by professional medical personnel, as ordinary patients cannot administer it themselves; additionally, the twice-daily intravenous infusion for 14 days leads to poor patient compliance and significant fluctuations in blood drug concentration, potentially causing peak-and-trough effects. Therefore, there is a need for a formulation with better stability and easier use. Summary of the Invention
[0006] Based on the technical problems existing in the background art, the present invention proposes an edaravone dexborneol transdermal patch and its preparation method. The edaravone dexborneol transdermal patch of the present invention shows significant advantages in transdermal performance, drug stability and skin compatibility, and is particularly suitable for sustained-release transdermal drug delivery of edaravone and dexborneol.
[0007] This invention proposes an edaravone dexborneol transdermal patch, the raw materials of which include, by weight: 1 part dexborneol, 3.8-4.2 parts edaravone, 1.8-3.2 parts antioxidant, 1.2-1.8 parts encapsulating agent, 50-55 parts pressure-sensitive adhesive, and 4-6 parts penetration enhancer;
[0008] The antioxidant is a combination of disodium ethylenediaminetetraacetate and vitamin E succinate.
[0009] The penetration enhancer is a combination of azone and propylene glycol.
[0010] Preferably, the inclusion agent is β-cyclodextrin.
[0011] Preferably, the pressure-sensitive adhesive is a silicone-based pressure-sensitive adhesive.
[0012] Preferably, the weight ratio of disodium ethylenediaminetetraacetate and vitamin E succinate is 1.5-2.5:0.3-0.7.
[0013] Preferably, the weight ratio of azone to propylene glycol is 1:0.8-1.2.
[0014] Preferably, the raw materials include, by weight: 1 part dextroborneol, 4 parts edaravone, 2.5 parts antioxidant, 1.5 parts encapsulating agent, 52.5 parts pressure-sensitive adhesive, and 5 parts penetration enhancer.
[0015] The present invention also proposes a method for preparing the above-mentioned edaravone dexborneol transdermal patch, comprising the following steps: mixing edaravone with an aqueous solution of disodium ethylenediaminetetraacetate to obtain solution 1; mixing dexborneol with an aqueous encapsulating agent to encapsulate the edaravone to obtain solution 2; homogenizing pressure-sensitive adhesive, solution 1, solution 2, penetration enhancer, vitamin E succinate and organic solvent in an inert gas atmosphere to obtain an adhesive solution; forming a film with the adhesive solution and drying it to obtain the edaravone dexborneol transdermal patch.
[0016] Preferably, the organic solvent is ethanol.
[0017] Preferably, the weight ratio of pressure-sensitive adhesive to organic solvent is 50-55:30-40.
[0018] Preferably, the mass fraction of the aqueous solution of disodium ethylenediaminetetraacetate is 0.05-0.15 wt%.
[0019] Preferably, the inclusion agent aqueous solution is a saturated inclusion agent aqueous solution.
[0020] Preferably, it is dried at 40-65°C.
[0021] Preferably, the film thickness of the adhesive film is 280-320 μm.
[0022] The above-mentioned edaravone and dexborneol transdermal patches can be cut into 5cm×5cm square patches, with a drug content of 58-62mg edaravone and 13-17mg dexborneol per patch.
[0023] This invention uses disodium ethylenediaminetetraacetate and vitamin E succinate in an appropriate ratio to give the edaravone dexborneol transdermal patch good stability, avoiding the instability of edaravone and dexborneol and the lower solution stability of the former. Furthermore, the use of azone and propylene glycol in an appropriate ratio gives the edaravone dexborneol transdermal patch good release effect, allowing for continuous drug release for more than one day, significantly improving the convenience of the formulation and clinical efficacy.
[0024] This invention can be stored at room temperature, reducing storage costs; and it has a suitable sustained-release effect, making it suitable for ischemic stroke patients who need extended dosing intervals, and can maintain an effective blood drug concentration for more than one day. Detailed Implementation
[0025] The technical solution of the present invention will now be described in detail through specific embodiments.
[0026] Examples 1-3
[0027] Prepare edaravone dexborneol transdermal patches according to the formulation in Table 1.
[0028] Table 1 Formulations of Examples 1-3
[0029]
[0030]
[0031] The preparation methods of Examples 1-3 above are the same, including the following steps:
[0032] Edaravone was mixed with a 0.1 wt% aqueous solution of disodium ethylenediaminetetraacetate and ground for 30 min to obtain solution 1.
[0033] Dextromethorphanol was mixed with a saturated β-cyclodextrin aqueous solution and stirred for 1 hour to achieve inclusion (the inclusion rate was measured to be ≥90%), resulting in solution 2.
[0034] Under nitrogen protection, pressure-sensitive adhesive, azone, propylene glycol, vitamin E succinate and ethanol were mixed and then added to solution 1 and solution 2. The mixture was stirred and homogenized at 2000 rpm for 15 min to obtain an adhesive solution. The adhesive solution was coated onto a film-coating paper to obtain a wet film with a thickness of 280-320 μm. The film was dried at 60℃ for 20 min and cut into 5cm×5cm square patches to obtain edaravone dexborneol transdermal patches.
[0035] The edaravone dexborneol transdermal patches from Examples 1-3 were tested for their performance and stability. The results are shown in Table 2.
[0036] Table 2 Detection results of Examples 1-3
[0037]
[0038]
[0039] As can be seen from Table 2, the edaravone dexborneol transdermal patches of Examples 1-3 have good stability, can continuously release drugs for more than 1 day, do not irritate the skin, and have moderate peel strength.
[0040] Comparative Examples 1-3
[0041] The disodium ethylenediaminetetraacetate was replaced sequentially with vitamin E succinate, sodium bisulfite, and sodium metabisulfite, with the other steps remaining the same as in Example 1.
[0042] Comparative Examples 4-6
[0043] The vitamin E succinate was replaced sequentially with disodium ethylenediaminetetraacetate, sodium bisulfite, and sodium metabisulfite, with the other steps remaining the same as in Example 1.
[0044] Comparative Examples 7-9
[0045] Replace azone with propylene glycol, oleic acid, and clove volatile oil in sequence, otherwise the same as in Example 1.
[0046] Comparative Examples 10-12
[0047] Propylene glycol was replaced in sequence with azone, oleic acid, and clove volatile oil, and the rest was the same as in Example 1.
[0048] Comparative Example 13
[0049] Replace the silicone pressure-sensitive adhesive with polyacrylate pressure-sensitive adhesive, otherwise the same as in Example 1.
[0050] The edaravone dexborneol transdermal patches of Comparative Examples 1-13 were tested and compared with those of Example 1. The results are shown in Table 3.
[0051] Table 3 shows the test results of Comparative Examples 1-13.
[0052]
[0053]
[0054] As can be seen from Example 1 and Comparative Examples 1-6, edaravone dexborneol transdermal patches only exhibit good stability when ethylenediaminetetraacetic acid disodium salt and vitamin E succinate work together as antioxidants.
[0055] As can be seen from Example 1 and Comparative Examples 7-12, edaravone dexborneol transdermal patches can only maintain a good transdermal rate when azone and propylene glycol are combined, so that the transdermal patches can maintain an effective blood drug concentration for more than 1 day.
[0056] As can be seen from Example 1 and Comparative Example 13, the silicone pressure-sensitive adhesive matrix, in combination with azone and propylene glycol, can maintain good drug release performance and has good skin compatibility; while the polyacrylate pressure-sensitive adhesive has poor drug release performance and skin compatibility.
[0057] The edaravone and dexborneol transdermal patch of the present invention exhibits significant advantages in transdermal performance, drug stability and skin compatibility, and is particularly suitable for sustained-release transdermal administration of edaravone and dexborneol.
[0058] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.
Claims
1. An edaravone dexborneol transdermal patch, characterized in that, Its raw materials, by weight, include: 1 part dextroborneol, 3.8-4.2 parts edaravone, 1.8-3.2 parts antioxidant, 1.2-1.8 parts encapsulating agent, 50-55 parts pressure-sensitive adhesive, and 4-6 parts penetration enhancer; The antioxidant is a combination of disodium ethylenediaminetetraacetate and vitamin E succinate. The penetration enhancer is a combination of azone and propylene glycol.
2. The edaravone dexborneol transdermal patch according to claim 1, characterized in that, The inclusion agent is β-cyclodextrin.
3. The edaravone dexborneol transdermal patch according to claim 1 or 2, characterized in that, The pressure-sensitive adhesive is a silicone-based pressure-sensitive adhesive.
4. The edaravone dexborneol transdermal patch according to any one of claims 1-3, characterized in that, The weight ratio of disodium ethylenediaminetetraacetate and vitamin E succinate is 1.5-2.5:0.3-0.
7.
5. The edaravone dexborneol transdermal patch according to any one of claims 1-4, characterized in that, The weight ratio of azone to propylene glycol is 1:0.8-1.
2.
6. The edaravone dexborneol transdermal patch according to any one of claims 1-5, characterized in that, Its raw materials, by weight, include: 1 part dextroborneol, 4 parts edaravone, 2.5 parts antioxidant, 1.5 parts encapsulating agent, 52.5 parts pressure-sensitive adhesive, and 5 parts penetration enhancer.
7. A method for preparing the edaravone dexborneol transdermal patch as described in any one of claims 1-6, characterized in that, The process includes the following steps: mixing edaravone with an aqueous solution of disodium EDTA to obtain solution 1; mixing dexborneol with an aqueous encapsulating agent to obtain solution 2; homogenizing pressure-sensitive adhesive, solution 1, solution 2, penetration enhancer, vitamin E succinate, and organic solvent in an inert gas atmosphere to obtain a gel; forming a film with the gel and drying it to obtain an edaravone dexborneol transdermal patch.
8. The method for preparing the edaravone dexborneol transdermal patch according to claim 7, characterized in that, The organic solvent is ethanol; preferably, the weight ratio of pressure-sensitive adhesive to organic solvent is 50-55:30-40.
9. The method for preparing the edaravone dexborneol transdermal patch according to claim 7 or 8, characterized in that, The mass fraction of the aqueous solution of disodium ethylenediaminetetraacetate is 0.05-0.15 wt%; preferably, the inclusion agent aqueous solution is a saturated inclusion agent aqueous solution.
10. The method for preparing the edaravone dexborneol transdermal patch according to any one of claims 7-9, characterized in that, Dry at 40-65℃; preferably, the film thickness of the adhesive film is 280-320μm.