Application of idebenz in preparation of medicine for treating psoriasis

Abstract

The invention relates to novel medical application of idebenz, in particular to application of idebenz in preparation of medicine for treating psoriasis, a composition and a preparation. The invention aims to provide an application of idebenz in preparation of a medicine for treating psoriasis. The idebenz can contain various dosage forms such as oil, cream, ointment, gel and spray, and is suitable for different diseased regions and patient requirements. By reasonably selecting a pharmaceutically acceptable carrier or excipient, the pharmaceutical composition disclosed by the invention not only can effectively improve the stability and bioavailability of idebenz, but also can remarkably improve the symptoms of psoriasis, reduce inflammatory response and reduce oxidative damage to skin.

Description

Technical Field

[0001] The present invention relates to a new medical application of idebenconazole, and in particular to an application, composition and preparation of idebenconazole in preparing a medicine for treating psoriasis. Background Art

[0002] Psoriasis is a common chronic, inflammatory skin disease that is recurrent and difficult to cure. The pathological characteristics of the disease are excessive proliferation of keratinocytes and abnormal epidermal keratinization, accompanied by activation of the immune system and inflammatory response. Although there are currently a variety of drugs and treatments for psoriasis, due to the complex pathogenesis of psoriasis, existing therapies still have limitations in efficacy, tolerability and safety. Common treatment options such as topical glucocorticoids, immunosuppressants and phototherapy are often accompanied by significant side effects, and long-term use may lead to adverse reactions such as skin atrophy and pigmentation. Therefore, there is an urgent need to find new, safe and effective drugs and compositions for the treatment of psoriasis.

[0003] Idebenone is an organic compound with the molecular formula C 19 H 30 O5 is yellow crystal or crystalline powder, odorless. It is very insoluble in water, very soluble in chloroform, methanol or anhydrous ethanol, soluble in ethyl acetate, and insoluble in n-hexane. It is a kind of intelligence-promoting drug developed and marketed by Takeda Pharmaceutical Co., Ltd. in Japan in 1986. It has an activating effect on mitochondrial function, improves brain function metabolism and brain dysfunction, can increase the utilization rate of glucose in the brain, and promotes ATP generation; it can improve the metabolism of the neurotransmitter 5-hydroxytryptamine in the brain, and has a strong antioxidant and free radical scavenging effect. It is mainly used in the clinic to treat central nervous system degenerative diseases related to oxidative stress, such as Parkinson's disease, Alzheimer's disease, multi-infarct dementia, local cerebral anemia and brain failure, and is also used to treat Friedreich's ataxia.

[0004] In recent years, idebenone, as a powerful antioxidant, has shown potential therapeutic effects in the treatment of various skin diseases. Idebenone can protect cells from damage by inhibiting the production of free radicals and reducing oxidative stress. Studies have shown that idebenone has a significant inhibitory effect on the oxidative stress response of keratinocytes induced by UVB radiation, and can reduce the content of malondialdehyde (MDA) by increasing the activity of superoxide dismutase (SOD) in cells, thereby slowing down the oxidative damage of cells. It can be used in cosmetic formulas and has cosmetic effects such as scavenging free radicals, inhibiting lipid peroxidation, inhibiting inflammation, inhibiting DNA damage, photoprotection, and reducing pigmentation. Summary of the invention

[0005] In order to solve the above technical problems, an object of the present invention is to provide the use of idebenquin in the preparation of a medicament for treating psoriasis. Idebenquin can include a variety of dosage forms such as oils, creams, ointments, gels and sprays, suitable for different lesion sites and patient needs. By reasonably selecting a pharmaceutically acceptable carrier or excipient, the pharmaceutical composition of the present invention can not only effectively improve the stability and bioavailability of idebenquin, but also significantly improve the symptoms of psoriasis, reduce inflammatory reactions, and reduce oxidative damage to the skin.

[0006] In order to achieve the above-mentioned purpose, the present invention adopts the following technical solutions:

[0007] Application of idebenconazole in preparing medicine for treating psoriasis.

[0008] Furthermore, the present invention also discloses a pharmaceutical composition for treating psoriasis, comprising an effective amount of idebenquinol and a pharmaceutically acceptable carrier or excipient, wherein the concentration of the idebenquinol is in the range of 0.0005umol / L-0.01umol / L.

[0009] Furthermore, the present invention also discloses a preparation for treating psoriasis, which comprises the pharmaceutical composition.

[0010] Preferably, the dosage form of idebenacum is oil, cream, gel, ointment or spray.

[0011] Preferably, the dosage form of idebenkun is an oil preparation, and the carrier or excipient includes one or more of vegetable oil, triglyceride, mineral oil and synthetic ester. More preferably, the vegetable oil is selected from one or more of olive oil, sweet almond oil, coconut oil and sunflower oil; the triglyceride is selected from medium chain triglyceride (MCT); the mineral oil is selected from one or more of vaseline and liquid paraffin; the synthetic ester is selected from one or more of isopropyl isostearate and caprylic / capric triglyceride.

[0012] Preferably, the dosage form of idebenconazole is a cream, and the carrier or excipient includes one or more of an emulsifier, a thickener, a moisturizer and a gel matrix. More preferably, the emulsifier is selected from one or more of stearic acid, polysorbate (Tween), and span; the thickener is selected from one or more of carbomer, xanthan gum, and guar gum; the moisturizer is selected from one or more of propylene glycol, glycerin, and urea; and the gel matrix is ​​selected from one or more of hydroxypropyl methylcellulose (HPMC), carbomer, and hyaluronic acid.

[0013] Preferably, the dosage form of idebenacum is an ointment, and the carrier or excipient includes one or more of vaseline, lanolin and waxes; preferably, the wax is beeswax or microcrystalline wax.

[0014] Preferably, the dosage form of idebenconazole is a spray, and the carrier or excipient includes a solvent and an aerosol propellant; preferably, the solvent is selected from one or two of ethanol and isopropanol; and the aerosol propellant is selected from one or two of dimethyl ether and butane.

[0015] Due to the adoption of the above technical scheme, the present invention has significant antioxidant, anti-inflammatory and keratinocyte hyperproliferation inhibitory effects in the preparation of drugs for treating psoriasis. It can reduce oxidative stress damage by increasing intracellular SOD activity and reducing MDA content. In addition, idebenkun can also inhibit the inflammatory response caused by TNF-α and effectively repair ultraviolet damage. Combined with different carriers or excipients, the permeability and stability of idebenkun preparations are significantly improved, and can be prepared into oils, creams, ointments, gels and sprays to meet different clinical needs and become an effective solution for treating psoriasis. It is mainly reflected in the following aspects:

[0016] 1. Antioxidant effect: Idebencol is a powerful antioxidant that can effectively reduce cell damage caused by oxidative stress. In the pathological mechanism of psoriasis, keratinocytes are affected by oxidative stress, which can cause excessive proliferation and abnormal keratinization. By using Idebencol, the activity of superoxide dismutase (SOD) in cells can be increased, and the content of oxidative damage products such as malondialdehyde (MDA) can be significantly reduced, thereby slowing down the oxidative damage of psoriasis lesion cells and improving the health of skin cells.

[0017] 2. Inhibit excessive proliferation of keratinocytes: Excessive proliferation of keratinocytes in patients with psoriasis is one of the main pathological manifestations of the disease. Idebenone can effectively inhibit the abnormal proliferation of keratinocytes induced by UVB radiation and TNF-α by regulating the oxidative stress response in cells, thereby reducing the formation and development of skin lesions. This effect has important clinical significance for controlling the recurrence and progression of psoriasis.

[0018] 3. Anti-inflammatory effect: Idebenquin can not only reduce oxidative stress damage, but also has anti-inflammatory effects. Studies have shown that Idebenquin can inhibit the inflammatory response caused by TNF-α and reduce the release of inflammatory mediators by regulating the immune system. This anti-inflammatory effect is particularly important for relieving symptoms such as redness, swelling, and increased dandruff in patients with psoriasis, and helps repair and recover the lesion area.

[0019] 4. Repair UV damage: The skin of psoriasis patients is very sensitive to UV rays, and UV radiation can aggravate the condition. Idebenone can effectively reduce skin damage caused by UVB radiation, repair damaged skin cells, and reduce inflammation and cell damage caused by UV exposure. This allows Idebenone to help reduce the negative effects of external environmental factors on the skin during the treatment of psoriasis. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is a graph showing the results of the cytotoxicity assay of idebenone.

[0021] Figure 2 This is a graph showing the changes in cell proliferation rate after the action of idebenone on the oxidative stress model induced by different doses of UVB.

[0022] Figure 3 This is a graph showing the changes in SOD activity in the oxidative stress model induced by different doses of UVB after treatment with idebenone.

[0023] Figure 4 This is a graph showing the changes in MDA content in the oxidative stress model induced by different doses of UVB after treatment with idebenone.

[0024] Figure 5 This is a diagram comparing the antioxidant capacity and photoaging treatment effects of idebenconazole and the antioxidant coenzyme Q.

[0025] Figure 6 This is a graph showing the changes in cell proliferation rate after idebenone treated the abnormal cell proliferation and inflammatory response model induced by TNF-α.

[0026] Figure 7 This is a picture showing the effect of systemic use of idebenone oil on improving skin lesions in psoriasis mice. DETAILED DESCRIPTION

[0027] The following is a clear and complete description of the technical solutions in the embodiments of the present invention in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] Example 1: Idebenacum oil

[0029] Dissolve idebenkun in 10 μL DMSO mother solution (DMSO mother solution concentration is 6000 mg / mL), and stir slowly until idebenkun is completely dissolved. Then add 190 μL corn oil and mix, continue to stir evenly, and prepare a stable oil, in which idebenkun is 0.005 μmol / L. The oil is stored in a light-proof container to prevent oxidation failure. For patients with psoriasis, apply the above-prepared idebenkun oil externally every day, apply an appropriate amount of the oil to the skin lesions affected by psoriasis, and gently massage until absorbed. After 7 consecutive days of use, the improvement of the skin lesions was observed, and the PASI score decreased significantly, indicating that the idebenkun oil can effectively alleviate the symptoms of patients with psoriasis.

[0030] Example 2: Idebenacum cream

[0031] Dissolve idebenconazole in a small amount of propylene glycol as a drug solution. Take 10% stearic acid and 5% polysorbate (Tween-80) as emulsifiers, heat them to 70°C with 80% purified water, then slowly add the drug solution, emulsify and stir to form a cream base, and idebenconazole is 0.005μmol / L. After the cream is cooled to room temperature, it is packaged and stored. Apply the above-mentioned idebenconazole cream evenly to the psoriasis lesion area twice a day, and gently massage until absorbed. After 10 days of continuous use, the redness and scaling of the skin are significantly reduced, and the inflammatory response is effectively controlled.

[0032] Example 3: Idebenacum Gel

[0033] Dissolve idebenconazole in a small amount of ethanol as a drug solution. Take 1.5% carbomer as a thickener, disperse it in an appropriate amount of purified water, add 0.5% glycerol as a moisturizer, and stir evenly. Then slowly add the drug solution to the carbomer solution, stir evenly, adjust the pH to neutral, and make a transparent gel with idebenconazole at 0.005μmol / L. For patients with psoriasis, apply idebenconazole gel evenly to the damaged skin area once a day. After 14 days of continuous use, the patient's skin lesion area and inflammatory response were significantly reduced, and the skin repair effect was significant.

[0034] Example 4: Idebenacum ointment

[0035] Dissolve idebenac in a small amount of medium-chain triglycerides. Take 50% vaseline, 10% beeswax and 5% lanolin and heat at 70°C until completely dissolved. Then add the idebenac solution to the ointment base, idebenac is 0.005μmol / L, stir evenly, cool to room temperature and package. Apply the above ointment to the patient's psoriasis lesions every day, especially dry and thickened skin areas. After 7 days of continuous use, the patient's skin lesions are significantly reduced in thickness, the skin becomes soft, and the symptoms are effectively improved.

[0036] Example 5: Idebenkun Spray

[0037] Dissolve idebenconazole in ethanol and add an appropriate amount of isopropanol as a cosolvent. Then add the solution to a mixture of aerosol propellants dimethyl ether and butane, stir evenly, and put it into an aerosol can to make a spray. The idebenconazole concentration is 0.005 μmol / L. For large areas of psoriasis lesions, use the spray to spray evenly and pat gently until the drug is absorbed. After 10 consecutive days of use twice a day, the area of ​​lesions has been significantly reduced and the inflammation has been effectively relieved.

[0038] Experimental Example 1 Study on the Antioxidant Effect of Idebenone on HaCaT Cells

[0039] 1. Cell culture

[0040] HaCaT cells (human keratinocytes) were cultured in DMEM medium containing 10% fetal bovine serum and 1% penicillin / streptomycin at 37°C in an incubator with 5% CO2. After the cells grew to 80-90% confluence, they were digested with trypsin and subcultured.

[0041] 2. CCK-8 cell proliferation activity assay

[0042] Cell seeding: HaCaT cells were seeded in 96-well plates at a density of 1×104 cells / well and cultured for 24 hours.

[0043] Idebenone treatment: Idebenone solutions of different concentrations (0.001 μmol / L, 0.005 μmol / L, 0.01 μmol / L, 0.05 μmol / L) were added to the cells to set up a blank control group for 24 hours.

[0044] CCK-8 assay: After treatment, add 10 μL of CCK-8 reagent and continue incubation for 2 hours. Use an ELISA reader to measure the absorbance at a wavelength of 450 nm and calculate the cell proliferation rate.

[0045] 3. Establishment of oxidative stress model and idebenone treatment

[0046] UVB irradiation: HaCaT cells were exposed to different doses of UVB radiation (10 mJ / cm2, 20 mJ / cm2, 30 mJ / cm2) to establish an oxidative stress model.

[0047] Idebenone intervention: Immediately after UVB irradiation, different concentrations of idebenone (0.001 μmol / L, 0.005 μmol / L, 0.01 μmol / L) were added to treat the cells for 24 h to observe its antioxidant effect.

[0048] 4. SOD activity detection

[0049] The activity of superoxide dismutase (SOD) in HaCaT cells was detected using a SOD kit. After UVB treatment, the cell lysate was collected and tested according to the kit instructions to determine the intracellular SOD activity and evaluate the protective effect of idebenone on cellular oxidative stress.

[0050] 5. MDA content detection

[0051] The malondialdehyde (MDA) kit was used to detect the MDA content in HaCaT cells. After UVB treatment, the cell lysate was collected and the intracellular MDA level was detected according to the kit instructions. The MDA content reflects the degree of intracellular lipid peroxidation and thus evaluates the antioxidant effect of idebenone.

[0052] 6. Data Analysis

[0053] One-way ANOVA was used to evaluate the statistical differences among different experimental groups. The experimental results were expressed as mean ± standard error (SEM), and the significance level was set at P < 0.05.

[0054] like Figure 1 As shown, the cytotoxicity of idebenone was determined as follows: Figure 1 (A) Changes in cell proliferation rate after the action of idebenone in different concentration gradient groups on HaCaT cells; Figure 1 (B) Changes in cell proliferation rate after the action of idebenone in a medium and small concentration range on HaCaT cells. One-way ANOVA was used to evaluate the statistical significance between groups. ns indicates no significance, * indicates P < 0.05, ** indicates P < 0.01, and *** P < 0.001. Data are expressed as mean ± SEM.

[0055] The results of CCK-8 experiments showed that when the dose of idebenone was 1-5 μmol / L, all dose groups had no significant inhibitory effect on the proliferation of HaCaT cells, indicating that idebenone had no obvious toxic side effects on HaCaT cells.

[0056] like Figure 2 As shown, the changes in cell proliferation rate after idebenone acted on the oxidative stress model induced by different doses of UVB: Figure 2 (A) Changes in cell proliferation after 10mJ / cm2 UVB irradiation; Figure 2 Middle (B) Changes in cell proliferation after 20mJ / cm2 UVB irradiation; Figure 2 (C) Changes in cell proliferation after 30 mJ / cm2 UVB irradiation. One-way ANOVA was used to evaluate the statistical significance between groups. ns indicates no significance, * indicates p<0.05, ** indicates P<0.01, and ***P<0.001. Data are presented as mean ± SEM

[0057] The results of CCK-8 experiments showed that different doses of UVB radiation could inhibit HaCaT cell viability and proliferation to varying degrees. When the UVB radiation dose was 30mJ / cm2, the relative viability of cells had significantly decreased, about 60% of the blank control group. As the concentration of idebenone decreased, the cell survival rate continued to increase. 0.005μmol / L idebenone was effective for 30mJ / cm 2 The damaged cells caused by ultraviolet rays have reached the optimal repair effect.

[0058] like Figure 3 As shown, the changes of SOD activity after idebenone on the oxidative stress model induced by different doses of UVB: Figure 3 (A) Changes in SOD activity after 10mJ / cm2 UVB irradiation; Figure 3 Middle (B) Changes in SOD activity after 20mJ / cm2 UVB irradiation; Figure 3 (C) Changes in SOD activity after 30 mJ / cm2 UVB irradiation. One-way ANOVA was used to evaluate the statistical significance between groups. ns indicates no significance, * indicates P<0.05, ** indicates P<0.01, and ***P<0.001. Data are presented as mean ± SEM.

[0059] The results of the superoxide reactive oxygen species (SOD) assay showed that different doses of UVB radiation could inhibit the viability of HaCaT cells to varying degrees, resulting in a decrease in SOD content. 0.005μmol / L, 0.001μmol / L, and 0.05μmol / L idebenone could increase the activity of SOD in cells and reduce the content of MDA to resist UVB-induced cell oxidative damage.

[0060] like Figure 4 As shown, the changes of MDA content after idebenone in the oxidative stress model induced by different doses of UVB: Figure 4 (A) Changes in MDA content after 10mJ / cm2 UVB irradiation; Figure 4 (B) Changes in MDA content after 20mJ / cm2 UVB irradiation; Figure 4 (C) Changes in MDA content after 30 mJ / cm2 UVB irradiation. One-way ANOVA was used to evaluate the statistical significance between groups. ns indicates no significance, * indicates P<0.05, ** indicates P<0.01, and ***P<0.001. Data are presented as mean ± SEM.

[0061] The results of MDA experiments showed that different doses of UVB radiation could inhibit HaCaT cell viability to varying degrees, resulting in an increase in MDA content. 0.005μmol / L, 0.001μmol / L, and 0.05μmol / L idebenone could reduce the MDA content to resist UVB-induced cell oxidative damage.

[0062] Experimental Example 2 Comparison of Antioxidant Capacity and Photoaging Effects of Idebenkun and Antioxidant Coenzyme Q

[0063] HaCaT human keratinocytes were cultured in DMEM medium containing 10% fetal bovine serum and 1% penicillin / streptomycin at 37°C and 5% CO2. When the cells were 80-90% confluent, they were passaged. The cells were exposed to UVB radiation of 10mJ / cm2 and 30mJ / cm2. The irradiation time was set according to the experimental requirements to establish a cell photoaging model. After irradiation, the survival of the treated cells was observed under a microscope. By comparing the effects of the two antioxidants in alleviating the symptoms of cell photoaging, the differences between idebenconazole and coenzyme Q in the treatment of photoaging were evaluated.

[0064] like Figure 5 As shown in the results, the antioxidant capacity of idebenacum is lower than that of coenzyme Q; the effect of idebenacum in treating photoaging is better than that of coenzyme Q.

[0065] Experimental Example 3 Study on the inhibitory effect of idebenacum on keratinocyte proliferation and anti-inflammatory effect

[0066] 1. Cell culture

[0067] HaCaT human keratinocytes were cultured in DMEM medium containing 10% fetal bovine serum and 1% penicillin / streptomycin at 37°C and 5% CO 2 . After the cells reached 80-90% fusion, they were passaged for experimental use.

[0068] 2. Cell proliferation assay

[0069] Cell seeding: HaCaT cells were seeded in 96-well plates at a density of 1×104 cells / well and cultured for 24 hours.

[0070] Cell proliferation inhibition experiment: Add different concentrations (such as 0.001 μmol / L, 0.005 μmol / L, 0.01 μmol / L) of idebenconazole solution to the cells and compare with the untreated group (blank control group), and set up a positive control group (for example, using common anti-proliferative drugs).

[0071] CCK-8 detection of cell proliferation: After 24 hours of treatment, CCK-8 reagent was added and incubated for 2 hours. The absorbance was measured at a wavelength of 450 nm using an ELISA reader to evaluate the effects of different concentrations of idebenconazole on the proliferation of HaCaT cells.

[0072] 3. Research model of anti-inflammatory effect

[0073] Inflammation induction: Tumor necrosis factor-α (TNF-α, concentration of 10 ng / mL) was used to induce inflammatory response in HaCaT cells to establish a cell inflammation model. TNF-α was added to the culture medium to treat the cells for 24 hours, and the occurrence of cell inflammation response was observed.

[0074] Idebenquinone treatment: After TNF-α induction, different concentrations of idebenquinone (such as 0.001 μmol / L, 0.005 μmol / L, 0.01 μmol / L) were added to treat the cells for 24 hours, and an untreated TNF-α model group and a normal control group were established to evaluate the anti-inflammatory effect of idebenquinone.

[0075] 4. Detection of inflammation-related cytokines

[0076] ELISA test: ELISA kits were used to detect the levels of inflammation-related cytokines in the culture supernatant, such as IL-6, IL-1β, and TNF-α. The anti-inflammatory effect of idebenkun was evaluated by comparing the TNF-α model group with the idebenkun-treated group.

[0077] mRNA expression detection: Total RNA of treated cells was extracted, and reverse transcription PCR (RT-PCR) was used to detect the mRNA expression levels of inflammation-related genes (such as IL-6, IL-1β, TNF-α), and further analyze the inhibitory effect of idebenac on inflammation at the gene expression level.

[0078] 5. Comprehensive analysis of cell proliferation and inflammation

[0079] Cell viability assay: CCK-8 method was used to detect the effect of idebenconazole on cell proliferation while inhibiting inflammation. The effect of idebenconazole at different concentrations was evaluated by comparing the data with the control group and TNF-α treatment group.

[0080] Changes in inflammatory mediators: The changes in cytokines in each group were recorded, and statistical analysis was performed to determine the effect of idebenconazole in inhibiting keratinocyte proliferation and alleviating inflammatory responses.

[0081] 6. Statistical analysis

[0082] One-way ANOVA was used to evaluate the statistical differences among the experimental groups. The experimental results were expressed as mean ± standard error (SEM), and the significance level was set at P < 0.05.

[0083] like Figure 6 As shown, the changes in cell proliferation rate after idebenone induced abnormal cell proliferation and inflammatory response model in TNF-α: One-way ANOVA was used to evaluate the statistical significance between groups, ns indicates no significance, * indicates P<0.05, ** indicates P<0.01, ***P<0.001. Data are expressed as mean ± SEM.

[0084] Experimental Example 4 Study on the Systemic Use of Idebenacum Oil to Improve Psoriasis Lesions in Mice

[0085] 1. Establishment of animal model

[0086] Experimental animals: Healthy male BALB / c mice (6-8 weeks old, weighing about 20-25 g) were selected and divided into three groups (at least 8 mice in each group): a psoriasis model group, an idebenkon oil treatment group, and a control group.

[0087] Psoriasis model establishment: 5% Imiquimod cream was applied topically on the back of mice, about 70 mg per mouse per day for 7 consecutive days to induce psoriasis-like skin lesions. After the model was established, psoriasis symptoms such as erythema, scaling and skin thickening appeared on the back skin of the mice.

[0088] 2. Drug treatment

[0089] Preparation of idebenacum oil: Prepare idebenacum oil with a concentration of 0.005 μmol / L, Example 1.

[0090] Treatment method: The mice in the psoriasis model group were not treated with any drugs. The mice in the idebenkun treatment group were treated with 1.5 g / kg / day of idebenkun oil orally for 7 consecutive days after the topical application of imiquimod cream. The mice in the control group were treated orally with a blank vehicle equal to the amount of idebenkun oil.

[0091] 3. PASI score assessment

[0092] Skin lesion scoring: The Psoriasis Area and Severity Index (PASI) was used for scoring, which was mainly based on the erythema, scaling, and skin thickening of the back skin of the mice. Each symptom was scored from 0 to 4 points, and the higher the score, the more severe the symptom. Scores were performed before and after treatment to observe the improvement of psoriasis lesions by idebenconazole.

[0093] 4. Pathological analysis

[0094] Tissue sample collection: After the treatment, the mice were euthanized and their back skin tissue samples were taken, fixed and sliced.

[0095] Pathological staining: Use hematoxylin-eosin staining (H&E staining) to stain skin tissue sections to observe the pathological changes of psoriasis lesions, such as excessive proliferation of keratinocytes, epidermal thickening, and inflammatory cell infiltration.

[0096] Microscopic observation: The pathological characteristics of the skin tissue of each group of mice were observed and recorded under a microscope, and the differences between the idebenconazole-treated group and the model group were compared.

[0097] like Figure 7As shown in the study, the systemic use of idebenacum oil improved the skin lesions of psoriasis mice: Figure 7 Middle (A) Changes in the skin lesions on the back of mice after daily application of 70 mg / d imiquimod cream for 7 days, with a PASI score of 4 points; Figure 7 Middle (B) After daily application of 70 mg / d imiquimod cream and oral administration of 1.5 g / kg idebenone oil for 7 days, the changes in the skin lesions on the back of mice were observed, with a PASI score of 2.5 points; Figure 7 Middle (C) Pathology of imiquimod psoriasis model mice; Figure 7 Middle (D) Pathology of mice after idebenone treatment.

[0098] The above is a description of the embodiments of the present invention. Through the above description of the disclosed embodiments, professionals and technicians in the field can implement or use the present invention. Various modifications to these embodiments will be apparent to professionals and technicians in the field. The general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown in this article, but will conform to the widest range consistent with the principles and novelties disclosed herein.

Claims

1. The use of idebenconazole in the preparation of medicines for treating psoriasis.

2. A pharmaceutical composition for treating psoriasis, characterized in that: The composition comprises an effective amount of idebenquinol and a pharmaceutically acceptable carrier or excipient, wherein the concentration of the idebenquinol is in the range of 0.0005umol / L-0.01umol / L.

3. A preparation for treating psoriasis, characterized in that: The preparation comprises the pharmaceutical composition according to claim 2.

4. The preparation according to claim 3, characterized in that The dosage form of the idebenconazole is oil, cream, gel, ointment or spray.

5. The preparation according to claim 3, characterized in that The dosage form of idebenconazole is an oily agent, and the carrier or excipient includes one or more of DMSO, vegetable oil, triglyceride, mineral oil and synthetic esters.

6. The preparation according to claim 5, characterized in that The vegetable oil is selected from one or more of olive oil, sweet almond oil, coconut oil, and sunflower oil; the triglyceride is medium-chain triglyceride (MCT); the mineral oil is selected from one or more of vaseline and liquid paraffin; the synthetic ester is selected from one or more of isopropyl isostearate and caprylic / capric triglyceride.

7. The preparation according to claim 3, characterized in that The dosage form of idebenconazole is a cream, and the carrier or excipient includes one or more of an emulsifier, a thickener, a moisturizer and a gel matrix.

8. The preparation according to claim 7, characterized in that The emulsifier is selected from one or more of stearic acid, polysorbate (Tween), and span; the thickener is selected from one or more of carbomer, xanthan gum, and guar gum; the humectant is selected from one or more of propylene glycol, glycerin, and urea; and the gel matrix is ​​selected from one or more of hydroxypropyl methylcellulose (HPMC), carbomer, and hyaluronic acid.

9. The preparation according to claim 3, characterized in that The dosage form of idebenconazole is an ointment, and the carrier or excipient includes one or more of vaseline, lanolin and waxes; preferably, the wax is beeswax or microcrystalline wax.

10. The preparation according to claim 3, characterized in that The dosage form of idebenconazole is a spray, and the carrier or excipient includes a solvent and an aerosol propellant; preferably, the solvent is selected from one or two of ethanol and isopropanol; and the aerosol propellant is selected from one or two of dimethyl ether and butane.

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