Use of solanesol in preparation of drug for preventing and / or treating dermatitis

Abstract

The present invention relates to the use of solanesol in the preparation of a drug for preventing and / or treating dermatitis. The drug of the present invention may be an oral preparation or a topical preparation, and the effect of the drug is equivalent to the effect of tacrolimus ointment.

Description

Use of solanesol in preparing medicine for preventing and / or treating dermatitis Technical Field

[0001] The present invention belongs to the field of medical technology, and particularly relates to use of solanesol in preparing a medicine for preventing and / or treating dermatitis. Background Art

[0002] Dermatitis refers to inflammation of the skin. It is a general term for inflammatory skin diseases, not a distinct entity, and is clinically common. Its etiology is complex and may be related to contact allergens, genetics, immunity, environmental factors, and abnormal skin barrier function. Clinical manifestations vary, with patients experiencing redness, swelling, dryness, or itching, as well as blistering, exudation, crusting, and scaling. These include contact dermatitis, atopic dermatitis, seborrheic dermatitis, neurodermatitis, and insect bite dermatitis. Currently, a wide range of medications are used clinically to treat dermatitis, with different treatment modalities tailored to the individual symptoms. For patients with localized, mild-to-moderate dermatitis, topical medications are recommended as the primary treatment. Common topical medications include glucocorticoids (TCSs), calcineurin inhibitors (TCIs), and phosphodiesterase-4 (PDE-4) inhibitors. Short-term treatment with TCS for generalized, severe or stubborn skin lesions can effectively control symptoms, but long-term, large-area use of TCS may cause adverse skin and systemic reactions; TCI and PDE-4 can be used to control inflammation and relieve itching in specific areas such as the face, neck, and wrinkles, which has a good therapeutic effect, but some patients will experience adverse reactions such as intolerable burning sensations. For patients with systemic attacks and moderate to severe dermatitis, systemic drugs are used for treatment. These mainly include oral antihistamines, immunosuppressants, systemic glucocorticoids, biologics, and Janus kinase (JAK) inhibitors. Although traditional drugs such as glucocorticoids and immunosuppressants have shown good results in the treatment of dermatitis, they have obvious side effects and cannot be used for a long time. Therefore, there is an urgent need to develop innovative drugs for the treatment of dermatitis.

[0003] Solanesol is an aliphatic terpene alcohol composed of nine isoprene units, primarily found in plants of the Solanaceae family, such as tobacco, tomatoes, and potatoes. Because its long carbon chain makes chemical synthesis of solanesol difficult, it is primarily obtained through extraction from Solanaceae plants. Tobacco is the richest plant source of solanesol. Among tobacco plant organs, leaves have the highest solanesol content, followed by stems and roots. Currently, solanesol is primarily used to synthesize coenzyme Q10, vitamin K2, and the anticancer agent synergist N-solanesoyl-N,N′-bis(3,4-dimethoxybenzyl)ethylenediamine (SDB). Furthermore, micelles derived from solanesol have also been used to deliver hydrophobic drugs. Recent studies have revealed that solanesol possesses antibacterial, antioxidant, and neuroprotective properties, but the targets and mechanisms of action remain largely unexplained. Summary of the Invention

[0004] In order to overcome the defects of the prior art, the applicant has conducted in-depth research and found that oral and topical solanesol can effectively treat dermatitis.

[0005] Therefore, an object of the present invention is to provide a use of solanesol in preparing a medicament for preventing and / or treating dermatitis.

[0006] Preferably, the dermatitis is DNCB sensitization-induced dermatitis, for example, atopic dermatitis or contact dermatitis;

[0007] Preferably, the drug is an oral preparation or an external preparation.

[0008] Preferably, the oral preparation is prepared using carboxymethyl cellulose solution as a matrix;

[0009] Preferably, the oral preparation is prepared using 0.5% carboxymethyl cellulose solution as a matrix;

[0010] Preferably, the concentration of the oral preparation is 0.1 to 100 mg / kg, preferably 1 to 25 mg / kg;

[0011] Preferably, the external preparation is selected from tinctures, ointments, pastes, aerosols, sprays, powders, lotions, rinses, liniments, paints, gels, and patches.

[0012] Preferably, the external preparation is an ointment.

[0013] Preferably, the ointment has the following formula: 0.1-10 g of solanesol, 12 ml of olive oil, 3 g of cetyl alcohol, 4 ml of polysorbate 80, 5 g of glyceryl monostearate, 3 ml of silicone oil, 1.5 g of lanolin, 5 ml of glycerol, and 66 ml of water.

[0014] Preferably, the ointment has the following formula: 0.2-5 g of solanesol, 12 ml of olive oil, 3 g of cetyl alcohol, 4 ml of polysorbate 80, 5 g of glyceryl monostearate, 3 ml of silicone oil, 1.5 g of lanolin, 5 ml of glycerol, and 66 ml of water.

[0015] Preferably, the ointment has the following formula: 1 g of solanesol, 12 ml of olive oil, 3 g of cetyl alcohol, 4 ml of polysorbate 80, 5 g of glyceryl monostearate, 3 ml of silicone oil, 1.5 g of lanolin, 5 ml of glycerol, and 66 ml of water.

[0016] The present invention relates to the use of solanesol in preparing a medicament for preventing and / or treating dermatitis, particularly dermatitis induced by DNCB sensitization, such as contact dermatitis and atopic dermatitis. The medicament of the present invention can be an oral preparation or a topical preparation, and its efficacy is comparable to that of tacrolimus ointment.

[0017] The solanesol of the invention has wide sources, is safe and effective, low in price and has a clear mechanism. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 shows that oral administration of solanesol alleviates ear inflammation in DNCB-sensitized dermatitis mice (**P<0.01): (A) Dynamic monitoring of ear thickness in dermatitis mice; (B) Measurement of ear thickness in dermatitis mice on day 21; (C) Observation of ear inflammation in dermatitis mice on day 21;

[0019] Figure 2 shows that topical solanesol alleviates ear inflammation in DNCB-sensitized dermatitis mice (**P<0.01): (A) Dynamic monitoring of ear thickness in dermatitis mice; (B) Measurement of ear thickness in dermatitis mice on day 21; (C) Observation of the inflammatory status of the ears in dermatitis mice on day 21. DETAILED DESCRIPTION

[0020] The present invention is described below with reference to specific examples. Those skilled in the art will appreciate that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention in any way.

[0021] Example 1: Effect of Solanesol in Treating Dermatitis

[0022] 1. Research Plan

[0023] 1.1 Experimental animals

[0024] Eight-week-old SPF C57BL / 6J male mice (Animal Ethics Approval No. LA2022125, Biomedical Ethics Committee of Peking University) were purchased from Weitong Lihua (Experimental Animal Production License No. SCXK (Beijing) 2021-0013). Mice were randomly grouped and housed in standardized individually ventilated cages (temperature 25°C, relative humidity 45-65%, 12-h light / dark cycle) with ample standardized chow and water.

[0025] 1.2 Establishment of a DNCB-sensitized dermatitis mouse model

[0026] Acetone and olive oil were mixed in a volume ratio of 3:1 to prepare a matrix, and 1% and 0.5% DNCB solutions were prepared using this matrix. Mice were housed in a clean-grade environment with a constant temperature and humidity and randomly assigned to groups using a random number table. For the DNCB-induced ear dermatitis model in mice, 20 μl of a 1% DNCB solution in acetone and olive oil were applied to the outer skin of both ears on days 1, 3, and 5 of week 1, respectively, for initial sensitization. Starting in week 2, mice were re-sensitized by applying 20 μl of a 0.5% DNCB solution in acetone and olive oil to the sensitized area on both ears every three days. Drug treatment was continued daily until day 21. The control group received an equal amount of acetone and olive oil matrix applied at the same time. Photos were taken and ear thickness was measured twice weekly at the same interval using a vernier caliper.

[0027] 1.3 Grouping and Dosing

[0028] 1) Drug Preparation: 1, 5, and 25 mg / kg of solanesol were prepared using a 0.5% carboxymethylcellulose solution as a base for oral administration. 12 ml of olive oil, 3 g of hexadecanol, 4 ml of polysorbate 80, 5 g of glyceryl monostearate, 3 ml of silicone oil, 1.5 g of lanolin, 5 ml of glycerol, and 66 ml of water were dissolved at 75°C and stirred evenly with a magnetic stirrer. Using this base, 0.2 w / w%, 1 w / w%, and 5 w / w% solanesol ointments were prepared. The ointments were then drawn into a 1 ml syringe and slowly cooled to a paste for topical administration. 0.03% tacrolimus ointment was heated until melted and drawn into a 1 ml syringe, slowly cooled to a paste.

[0029] 2) Study on Oral Solanesol Therapy in a DNCB Mouse Ear Model: 30 C57BL / 6J mice were randomly divided into a blank control group, a model group, a 1 mg / kg, a 5 mg / kg, and a 25 mg / kg Solanesol treatment group (n=6 mice in each group). Starting from the second week, the control group was gavaged with 0.5% carboxymethylcellulose solution at the same time daily, while each treatment group received oral administration based on mouse weight at the same time daily.

[0030] 3) Study of topical solanesol treatment in a DNCB-induced mouse ear model: 30 mice were randomly divided into a blank control group, a model group, a 0.2 w / w% solanesol treatment group, a 1 w / w% solanesol treatment group, a 5 w / w% solanesol treatment group, and a 0.03 w / w% tacrolimus treatment group (5 mice per group). Starting from the second week, the control group received a 12.5 μl base ointment (i.e., a base-only ointment without solanesol) applied daily to the dorsal ears of both mice. The remaining treatment groups, according to their respective names, received a 12.5 μl application of either solanesol ointment or tacrolimus ointment daily to the dorsal ears of both mice.

[0031] 2. Experimental results

[0032] 2.1 Oral administration of solanesol in the treatment of dermatitis mouse model

[0033] The results of oral solanesol treatment of a dermatitis mouse model are shown in Figure 1. After DNCB induction, the ear thickened significantly compared to the blank group (Figure 1A). Symptoms of ear skin dermatitis manifest as ear swelling and thickening, which can serve as an important indicator of the severity of dermatitis. After three weeks of DNCB induction and drug treatment (Figures 1B, C), the ear thickening in the dermatitis model group was significantly greater than that in the blank group, with a statistically significant difference (P < 0.01). This manifested as a significant inflammatory reaction in the ear skin, with significant ear redness and swelling, erythema, papules, and lesions, and scales, blood crusts, and pigmentation visible in the lesions. After treatment with various concentrations of solanesol, ear thickness decreased, with statistically significant differences (P < 0.01). The phenotype of ear skin dermatitis in mice was alleviated, inflammation subsided, and ear redness and swelling were significantly improved, as well as symptoms such as erythema and scales.

[0034] 2.2 Topical application of solanesol in the treatment of dermatitis mouse model

[0035] The mouse model of dermatitis treated with topical solanesol is shown in Figure 2. After sensitization with DNCB, the ears of each model group showed significant thickening (Figure 2A). After a total of 21 days of DNCB sensitization and drug treatment (Figures 2B and C), the ears of the model group mice were significantly thickened compared with the blank group mice, with a statistically significant difference (P < 0.01). The ear phenotype showed a significant inflammatory reaction, with obvious dermatitis symptoms such as redness, swelling, and skin lesions, indicating that the disease model was successful. After treatment with various concentrations of solanesol, ear thickness was significantly reduced, with statistically significant differences (P < 0.01), the inflammatory reaction was restrained, and phenotypes such as redness, swelling, and skin lesions were alleviated. There was no statistical difference between low and medium doses of solanesol ointment and 0.03% tacrolimus ointment (P < 0.05), and the phenotypes also showed the same therapeutic effect, indicating that topical solanesol has the same therapeutic effect as 0.03% tacrolimus ointment in treating dermatitis. The results showed that topical solanesol can treat dermatitis, with the optimal dose being 1% solanesol ointment, and has the same efficacy as known drugs with clear therapeutic effects on dermatitis.

Claims

1. Use of solanesol in preparing a medicament for preventing and / or treating dermatitis.

2. The use according to claim 1, characterized in that The dermatitis is DNCB sensitization-induced dermatitis, for example, atopic dermatitis or contact dermatitis.

3. The use according to claim 1 or 2, characterized in that The medicine is an oral preparation or an external preparation.

4. The use according to claim 3, characterized in that The oral preparation is a preparation prepared by using carboxymethyl cellulose solution as a matrix.

5. The use according to claim 4, characterized in that The oral preparation is a preparation prepared by using 0.5% carboxymethyl cellulose solution as a base.

6. The use according to any one of claims 3 to 5, characterized in that The concentration of the oral preparation is 0.1-100 mg / kg, preferably 1-25 mg / kg.

7. The use according to claim 3, characterized in that: The topical preparation is selected from tinctures, ointments, pastes, aerosols, sprays, powders, lotions, rinses, liniments, paints, gels, and patches; Preferably, the external preparation is an ointment.

8. The use according to claim 7, characterized in that The ointment has a formula as follows: 0.1-10 g of solanesol, 12 ml of olive oil, 3 g of hexadecanol, 4 ml of polysorbate 80, 5 g of glyceryl monostearate, 3 ml of silicone oil, 1.5 g of lanolin, 5 ml of glycerol, and 66 ml of water.

9. The use according to claim 7, characterized in that: The ointment has a formula as follows: 0.2-5 g of solanesol, 12 ml of olive oil, 3 g of hexadecanol, 4 ml of polysorbate 80, 5 g of glyceryl monostearate, 3 ml of silicone oil, 1.5 g of lanolin, 5 ml of glycerol, and 66 ml of water.

10. The use according to claim 7, characterized in that The ointment has a formula as follows: 1 g of solanesol, 12 ml of olive oil, 3 g of hexadecanol, 4 ml of polysorbate 80, 5 g of glyceryl monostearate, 3 ml of silicone oil, 1.5 g of lanolin, 5 ml of glycerol, and 66 ml of water.

11. A method for preventing and / or treating dermatitis, comprising the step of administering a therapeutically effective amount of solanesol or a medicament comprising solanesol to a patient in need thereof.

12. The method according to claim 11, characterized in that The dermatitis is DNCB sensitization-induced dermatitis, for example, atopic dermatitis or contact dermatitis.

13. The method according to claim 11 or 12, characterized in that: The medicament containing solanesol is an oral preparation or an external preparation.

14. The method according to claim 13, characterized in that The oral preparation is a preparation prepared by using carboxymethyl cellulose solution as a matrix.

15. The method according to claim 14, characterized in that The oral preparation is a preparation prepared by using 0.5% carboxymethyl cellulose solution as a base.

16. The method according to any one of claims 13 to 15, characterized in that The concentration of the oral preparation is 0.1-100 mg / kg, preferably 1-25 mg / kg.

17. The method according to claim 13, characterized in that The topical preparation is selected from tincture, ointment, paste, aerosol, spray, powder, lotion, rinse, liniment, paint, gel, patch; Preferably, the external preparation is an ointment.

18. The method according to claim 17, characterized in that The ointment has a formula as follows: 0.1-10 g of solanesol, 12 ml of olive oil, 3 g of hexadecanol, 4 ml of polysorbate 80, 5 g of glyceryl monostearate, 3 ml of silicone oil, 1.5 g of lanolin, 5 ml of glycerol, and 66 ml of water.

19. The method according to claim 17, characterized in that The ointment has a formula as follows: 0.2-5 g of solanesol, 12 ml of olive oil, 3 g of hexadecanol, 4 ml of polysorbate 80, 5 g of glyceryl monostearate, 3 ml of silicone oil, 1.5 g of lanolin, 5 ml of glycerol, and 66 ml of water.

20. The method according to claim 17, characterized in that The ointment has a formula as follows: 1 g of solanesol, 12 ml of olive oil, 3 g of hexadecanol, 4 ml of polysorbate 80, 5 g of glyceryl monostearate, 3 ml of silicone oil, 1.5 g of lanolin, 5 ml of glycerol, and 66 ml of water.

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