Application of PDE4D inhibitor in preparation of medicine for treating or preventing oral ulcer
By using the PDE4D inhibitor GSK356278 as a local dosage form, alone or in combination with benzocaine, the problems of large side effects, low compliance and limited efficacy of existing oral ulcer treatments have been solved, achieving safer and more effective ulcer healing.
Patent Information
- Application Number
- CN202511361881.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-23
- Publication Date
- 2025-11-21
AI Technical Summary
Existing treatments for oral ulcers suffer from significant side effects, low patient compliance, and limited efficacy, especially since topical medications have limited efficacy and cannot prevent recurrence.
The PDE4D inhibitor GSK356278 is used as a topical dosage form, such as gel, spray, patch, mouthwash or orally disintegrating tablet, alone or in combination with benzocaine, to promote ulcer healing.
It improves the healing effect of oral ulcers, is simple to operate, has high safety, enhances patient compliance, and avoids the single effect of drugs.
Smart Images
Figure CN120983429A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of pharmaceutical technology, and more specifically to the application of PDE4D inhibitors in the preparation of drugs for the treatment or prevention of oral ulcers. Background Technology
[0002] Oral ulcers are a common oral mucosal disease characterized by painful ulcers on the oral mucosa. It is a global health disorder, with an estimated 39% to 50% of people experiencing recurrent ulcers at some point in their lives. Current treatments include lifestyle modifications, traditional Chinese medicine, systemic drug therapy, and topical treatments. Lifestyle modifications can prevent ulceration by avoiding irritating foods, maintaining good oral hygiene, maintaining a healthy lifestyle, and managing stress. However, these require long-term adherence and have limited effectiveness on existing ulcers. Traditional Chinese medicine, such as watermelon frost, propolis, and herbal mouthwashes, may have the advantage of fewer side effects; however, their mechanisms of action are unclear, efficacy lacks large-scale clinical data support, and quality is difficult to standardize. Systemic drug therapy, such as thalidomide, while effective for severe cases, has serious systemic side effects, limiting its clinical application. Topical drug therapy, such as benzocaine, is convenient, safe, and has low risk. It simply involves applying the medication directly to the affected area and provides rapid pain relief. Its limitations include a single action, inability to prevent recurrence, and the potential for long-term side effects. In summary, health education and lifestyle adjustments alone are slow to take effect and have low patient compliance; traditional Chinese medicine treatments require long-term conditioning and have unclear efficacy evaluations; while topical treatment is the main method for treating oral ulcers. Because topical administration bypasses absorption by internal organs, the drug acts directly on the affected area to achieve a therapeutic effect. Furthermore, even if the dosage is exceeded, it rarely causes serious consequences, and patients tolerate it well. Therefore, developing novel topical medications for combined use with existing topical medications such as benzocaine gel can promote the healing of oral ulcers and provide a safer and more effective treatment method. Summary of the Invention
[0003] The purpose of this invention is to provide the use of PDE4D inhibitors in the preparation of medicaments for the treatment or prevention of oral ulcers.
[0004] The technical problem solved by this invention is achieved by the following technical solution: In a first aspect, the present invention provides the use of a PDE4D inhibitor in the preparation of a medicament for treating or preventing oral ulcers.
[0005] In one or more embodiments of the present invention, the PDE4D inhibitor is used in the preparation of a medicament for treating oral ulcers.
[0006] In one or more embodiments of the present invention, the PDE4D inhibitor is GSK356278.
[0007] In one or more embodiments of the present invention, the GSK356278 is formulated as an oral topical dosage form.
[0008] In one or more embodiments of the present invention, the dosage form of GSK356278 includes GSK356278 gel, GSK356278 spray, GSK356278 patch, GSK356278 mouthwash, or GSK356278 orally disintegrating tablets.
[0009] In one or more embodiments of the present invention, the concentration of GSK356278 in the GSK356278 spray is 1-5 mg / ml.
[0010] Medications targeting genetic factors can effectively supplement existing treatments for oral ulcers. Meanwhile, the PDE4D inhibitor GSK356278 spray can be administered directly to the affected area, is easy to use, and can be used in combination with other topical medications to promote ulcer healing.
[0011] A second aspect of the present invention provides the use of a pharmaceutical combination or composition in the preparation of a medicament for treating or preventing oral ulcers, said pharmaceutical combination or composition comprising: The aforementioned PDE4D inhibitors; and benzocaine.
[0012] The present invention has the following beneficial effects: The PDE4D inhibitor spray provided by the present invention can promote the healing of oral ulcers as a treatment solution, and is simple and safe to use. Its combined effect with existing topical treatment drugs avoids single-effect treatment and improves patient compliance. Attached Figure Description
[0013] Figure 1 The experimental procedure is as described in Example 1.
[0014] Figure 2 The image shows the lesion diameter of oral ulcers in mice after 4 days of treatment with GSK356278 monotherapy in Example 1.
[0015] Figure 3 This is a representative image of oral ulcers on day 5 of GSK356278 monotherapy in Example 2.
[0016] Figure 4 The experimental procedure for Example 2 is as follows.
[0017] Figure 5 The lesion diameter of oral ulcers in mice after 5 days of combined treatment with GSK356278 and benzocaine.
[0018] Figure 6This is a representative image of an oral ulcer after 5 days of combined treatment with GSK356278 and benzocaine.
[0019] Unless otherwise stated, the terms used in the specification and claims have the following meanings.
[0020] As described in this invention, the term "prevention" refers to preventing the occurrence of disease and / or preventing the recurrence of disease. Detailed Implementation
[0021] This specification provides a detailed description of specific embodiments. Those skilled in the art should recognize that the following embodiments are exemplary and should not be construed as limiting the invention. For those skilled in the art, various improvements and modifications can be made to the invention without departing from its principles; such improvements and modifications also fall within the scope of protection of the claims. The beneficial effects of the invention are illustrated below through specific examples.
[0022] Example 1 GSK356278 monotherapy for oral ulcers
[0023] 1. Experimental Design (1) Mice were anesthetized by intraperitoneal injection of sodium pentobarbital (50 mg / kg), and then 4 mm filter paper soaked in 50% acetic acid was placed on the surface of the tongue for 1 minute. Ulcers were successfully formed in mice 24 hours later.
[0024] (2) GSK356278 was dissolved in dimethyl sulfoxide (DMSO) to prepare solutions with concentrations of 0, 1, and 3 mg / mL, and sonicated to ensure complete dissolution. A spray device was used with a spray volume of 150 µL per application to precisely control the drug dosage. After establishing the oral ulcer model, the drug (1 and 3 mg / mL) or the control (DMSO) was administered for four consecutive days.
[0025] (3) After establishing an oral ulcer model and administering drugs (1 and 3 mg / ml) or a control group (DMSO), three consecutive images were taken of each group of mice. Images with no glare, clear focus, and precise focal length were selected for analysis. The images were processed and the average area of the ulcers was measured using image analysis software.
[0026] Figure 1 This is the experimental procedure for this scheme.
[0027] 2. Experimental Results Figure 2 The figure shows the lesion diameter of oral ulcers in mice 4 days after treatment with GSK356278 monotherapy. As can be seen from the figure, the lesion diameter of oral ulcers in mice treated with GSK356278 monotherapy was significantly smaller than that in the control group, and this relationship was dose-dependent.
[0028] Figure 3 These are representative images of oral ulcers after 5 days of GSK356278 monotherapy. Control group (DMSO): Large ulcers with significant inflammatory infiltration. GSK356278 treatment group (3mg / ml): Significantly reduced ulcer area, with visible new epithelial tissue coverage indicating a clear healing trend.
[0029] In summary, this study established an acetic acid-induced mouse tongue ulcer model. On the fourth day after treatment, ulcer diameter was measured to assess ulcer damage, revealing that treatment significantly promoted ulcer healing. This effect also exhibited a dose-dependent effect.
[0030] Example 2 GSK356278 in combination with benzocaine for the treatment of oral ulcers
[0031] To further evaluate whether GSK356278 has a synergistic effect with existing treatments, a concentration of 3 mg / ml of GSK356278 was used in combination with benzocaine gel, a drug that relieves oral ulcer pain by numbing nerve endings.
[0032] 1. Experimental Design (1) Mice were anesthetized by intraperitoneal injection of sodium pentobarbital (50 mg / kg), and then 4 mm filter paper soaked in 50% acetic acid was placed on the surface of the tongue for 1 minute. Ulcers were successfully formed in mice 24 hours later.
[0033] (2) GSK356278 was dissolved in dimethyl sulfoxide (DMSO) to prepare a solution with a concentration of 3 mg / mL, and sonicated to ensure complete dissolution. A spray device was used, with each spray volume of 150 µL to precisely control the drug dosage. After establishing the oral ulcer model, the drug (3 mg / mL + 0.02 g benzocaine gel) or the control (0.02 g benzocaine gel) was administered for four consecutive days.
[0034] (3) After establishing an oral ulcer model and administering either the drug (3 mg / mL + 0.02 g benzocaine gel) or the control group (0.02 g benzocaine gel), three consecutive images were taken of each group of mice. Images with no glare, clear focus, and precise focal length were selected for analysis. The images were processed and the average area of the ulcers was measured using image analysis software.
[0035] Figure 4 This is the experimental procedure for this scheme.
[0036] 2. Experimental Results Figure 5The figure shows the ulcer diameter of oral ulcers in mice after 5 days of combined treatment with GSK356278 and benzocaine. As can be seen from the figure, the combined treatment group had smaller oral ulcer areas.
[0037] Figure 6 These are representative images of oral ulcers after 5 days of combined treatment with GSK356278 and benzocaine. Compared with the control group, the combined treatment group showed a significant reduction in ulcer area, substantial subsidence of redness and swelling, and epithelial tissue covering the base and edges of the ulcer, indicating near healing.
[0038] In summary, combination therapy resulted in more significant improvements in weight recovery and ulcer healing compared to monotherapy. The combination therapy group also exhibited smaller ulcer areas and better healing outcomes compared to the monotherapy group. These findings suggest that medications targeting genetic factors can effectively complement existing ulcer treatment methods.
[0039] This invention specification provides a detailed description of specific embodiments. Those skilled in the art should recognize that the above embodiments are exemplary and should not be construed as limiting the invention. For those skilled in the art, various improvements and modifications can be made to the invention without departing from its principles, and the resulting technical solutions also fall within the scope of protection of the claims of this invention.
Claims
1. Use of a PDE4D inhibitor for the manufacture of a medicament for the treatment or prevention of oral ulceration.
2. Use according to claim 1, characterized in that, the PDE4D inhibitor for the manufacture of a medicament for the treatment of oral ulceration.
3. Use according to claim 1 or 2, characterized in that, the PDE4D inhibitor is GSK356278.
4. Use according to claim 3, characterized in that, the GSK356278 is formulated in a buccal topical dosage form.
5. Use according to claim 4, characterized in that, the dosage form of the GSK356278 includes GSK356278 gel, GSK356278 spray, GSK356278 film, GSK356278 mouth rinse or GSK356278 buccal disintegrating tablet.
6. Use according to claim 4, characterized in that, the concentration of GSK356278 in the GSK356278 spray is 1-5 mg / ml.
7. Use of a pharmaceutical combination or a pharmaceutical composition for the manufacture of a medicament for the treatment or prevention of oral ulceration, characterized in that, the pharmaceutical combination or pharmaceutical composition comprises: the PDE4D inhibitor of any one of claims 1-6; and benzocaine.