A medicament for treating psoriasis

Abstract

The present invention relates to a medicament for the treatment of psoriasis. In particular, the present invention provides the use of uridine 5'-diphosphate for the manufacture of a composition for the prevention and / or treatment of psoriasis.

Description

Technical Field

[0001] This invention relates to the field of pharmaceuticals, and more specifically, to a medicine for treating psoriasis. Background Technology

[0002] Psoriasis is considered a genetically related inflammatory skin disease characterized by scaly, erythematous plaques or patches, often accompanied by itching, and can be associated with various systemic diseases. The underlying causes and mechanisms of psoriasis are not fully understood. Under the influence of genetic factors and environmental stimuli, immune cells and their secreted inflammatory cytokines accumulate in large numbers within the epidermal layer of the skin, creating an inflammatory environment. Simultaneously, keratinocytes in the skin also proliferate excessively and differentiate abnormally. Although psoriasis is not a fatal disease, patients experience significant suffering, and the disease negatively impacts their physical and mental well-being. However, current treatments can only alleviate skin lesions and symptoms for a limited time, and cannot cure psoriasis. Therefore, developing more effective treatment methods is crucial. Thus, there is a need in this field to develop an effective drug for treating psoriasis. Summary of the Invention

[0003] The purpose of this invention is to address the shortcomings of the prior art by providing the use of uridine 5'-bisphosphate in the effective treatment of psoriasis.

[0004] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0005] The first aspect of the present invention provides the use of uridine 5'-bisphosphate for preparing a composition for the prevention and / or treatment of psoriasis.

[0006] Preferably, the composition is a pharmaceutical composition.

[0007] Preferably, the composition further includes a pharmaceutically acceptable carrier.

[0008] Preferably, the dosage form of the composition is a solid dosage form, a liquid dosage form, or a semi-solid dosage form.

[0009] Preferably, the dosage form of the composition is an oral preparation, a topical preparation, or an injectable preparation.

[0010] Preferably, the dosage form of the composition is a topical skin preparation.

[0011] Preferably, the topical skin preparation is a skin cream or ointment.

[0012] Preferably, the dosage form of the composition is a tablet, injection, infusion, cream, gel, solution, microsphere, or film.

[0013] Preferably, the content of uridine 5'-bisphosphate is 0.1-99.9 wt%, more preferably 1-99 wt%, more preferably 10-90 wt%, more preferably 20-80 wt%, more preferably 30-70 wt%, more preferably 30-60 wt%, based on the weight of the composition.

[0014] Preferably, uridine 5'-bisphosphate is the only active ingredient in the composition.

[0015] Preferably, the composition further includes other active ingredients for the prevention and / or treatment of psoriasis.

[0016] Preferably, the psoriasis is human psoriasis.

[0017] A second aspect of the present invention provides a method for preventing and / or treating psoriasis, the method comprising the step of administering uridine 5'-bisphosphate to a desired subject, thereby preventing and / or treating psoriasis.

[0018] Preferably, the object is a person.

[0019] Within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below can be combined with each other to form new or preferred technical solutions. Attached Figure Description

[0020] Figure 1To investigate the significant reduction of psoriatic inflammation in an imiquimod-induced psoriasis-like mouse model after administration of uridine 5'-bisphosphate (UDP). (A) Photographs of mouse skin lesions show that in the imiquimod-induced psoriasis-like mouse model, administration of 5 mg / kg or 10 mg / kg uridine 5'-bisphosphate (UDP) significantly reduced erythema, infiltration, and scaling compared to imiquimod-induced psoriasis-like mice; with 10 mg / kg uridine 5'-bisphosphate (UDP) showing a more significant improvement. (B) Immunohistochemical staining results show that in the imiquimod-induced psoriasis-like mouse model, administration of 5 mg / kg or 10 mg / kg uridine 5'-bisphosphate (UDP) significantly reduced epidermal thickness and significantly improved inflammatory cell infiltration compared to imiquimod-induced psoriasis-like mice; with 10 mg / kg uridine 5'-bisphosphate (UDP) showing a more significant improvement. (C) The results of the psoriasis plaque severity scoring show that in the imiquimod-induced psoriasis-like mouse model, the application of 5 mg / kg or 10 mg / kg uridine 5'-bisphosphate (UDP) significantly reduced the severity of the disease compared to imiquimod-induced psoriasis-like mice, with 10 mg / kg uridine 5'-bisphosphate (UDP) showing a more significant improvement. (D) The results of mouse body weight measurement show that in the imiquimod-induced psoriasis-like mouse model, the application of 5 mg / kg or 10 mg / kg uridine 5'-bisphosphate (UDP) significantly improved the weight loss compared to imiquimod-induced psoriasis-like mice.

[0021] Figure 2 To investigate the significant decrease in the proportion of Ki67-positive epidermal proliferation markers after application of uridine 5'-bisphosphate (UDP) in an imiquimod-induced psoriasis-like mouse model. (A) Immunofluorescence staining shows that the expression of Ki67, a marker of epidermal proliferation, was significantly reduced in imiquimod-induced psoriasis-like mouse models after application of 10 mg / kg uridine 5'-bisphosphate (UDP) compared to imiquimod-induced psoriasis-like mice alone; (B) Statistical analysis of the proportion of Ki67-positive cells in the immunofluorescence staining in Figure (A) shows that the proportion of Ki67-positive cells was significantly reduced in imiquimod-induced psoriasis-like mouse models after application of 10 mg / kg uridine 5'-bisphosphate (UDP) compared to imiquimod-induced psoriasis-like mouse models alone. The proportion of Ki67 positive cells, a marker of epidermal proliferation, was significantly reduced in imiquimod-induced psoriasis-like mice; (C) shows that the levels of inflammatory factors IL-17A, IL-23, IL-22, and IFN-γ in the skin lesions of imiquimod-induced psoriasis-like mice were significantly reduced after administration of 10 mg / kg uridine 5'-bisphosphate (UDP) compared to those induced by imiquimod alone. Detailed Implementation

[0022] This invention is the first to unexpectedly discover that uridine 5'-bisphosphate has the effect of preventing and treating psoriasis.

[0023] the term

[0024] As used herein, the terms “comprising,” “including,” and “containing” are used interchangeably and include not only open-ended definitions but also semi-closed and closed definitions. In other words, the terms include “consisting of” and “substantially consisting of”.

[0025] As used in this article, the English name for uridine 5'-diphosphate is Uridine-5'-diphosphate, and its structural formula is as follows:

[0026]

[0027] In this invention, the term "prevention" refers to a method of preventing the onset of a disease and / or its accompanying symptoms or protecting a subject from acquiring a disease. As used herein, "prevention" also includes delaying the onset of a disease and / or its accompanying symptoms and reducing the subject's risk of contracting the disease.

[0028] In this invention, the term "treatment" includes delaying and stopping the progression of a disease, or eliminating the disease, without requiring 100% inhibition, eradication, and reversal.

[0029] use

[0030] This invention provides the use of uridine 5'-bisphosphate for preparing compositions for the prevention and / or treatment of psoriasis.

[0031] In a preferred embodiment of the invention, the content of uridine 5'-bisphosphate is 0.1-99.9 wt%, more preferably 1-99 wt%, more preferably 10-90 wt%, more preferably 20-80 wt%, more preferably 30-70 wt%, more preferably 30-60 wt%, based on the weight of the composition.

[0032] In a preferred embodiment of the present invention, uridine 5'-bisphosphate is the only active ingredient in the composition.

[0033] In a preferred embodiment of the invention, the composition further includes other active ingredients for the prevention and / or treatment of psoriasis.

[0034] A second aspect of the present invention provides a method for preventing and / or treating psoriasis, the method comprising the step of administering uridine 5'-bisphosphate to a desired subject, thereby preventing and / or treating psoriasis.

[0035] Preferably, the object is a person.

[0036] Composition

[0037] The compositions described in this invention are preferably pharmaceutical compositions, and may include pharmaceutically acceptable carriers.

[0038] As used in this article, "pharmaceutically acceptable carrier" refers to one or more compatible solid, semi-solid, liquid, or gel fillers that are suitable for human or animal use and must have sufficient purity and sufficiently low toxicity. "Compatibility" refers to the ability of the components and active ingredients in a drug, as well as the interactions between them, to not significantly reduce its efficacy.

[0039] It should be understood that there are no particular limitations on the pharmaceutically acceptable carriers described in this invention. Commonly used materials in the art can be selected, or they can be prepared using conventional methods or purchased from the market. Examples of pharmaceutically acceptable carriers include cellulose and its derivatives (such as methylcellulose, ethylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, etc.), gelatin, talc, solid lubricants (such as stearic acid, magnesium stearate), calcium sulfate, vegetable oils (such as soybean oil, sesame oil, peanut oil, olive oil, etc.), polyols (such as propylene glycol, glycerin, mannitol, sorbitol, etc.), emulsifiers (such as Tween), wetting agents (such as sodium dodecyl sulfate), buffers, chelating agents, thickeners, pH adjusters, transdermal penetration enhancers, colorants, flavoring agents, stabilizers, antioxidants, preservatives, antibacterial agents, pyrogen-free water, etc.

[0040] In a preferred embodiment of the present invention, the dosage form of the composition is a solid dosage form, a liquid dosage form, or a semi-solid dosage form.

[0041] In a preferred embodiment of the present invention, the dosage form of the composition is an oral formulation, a topical formulation, or an injectable formulation.

[0042] In a preferred embodiment of the present invention, the dosage form of the composition is a tablet, injection, infusion, ointment, gel, solution, microsphere or film.

[0043] Preferably, the dosage form of the composition is a topical skin preparation. For example, the topical skin preparation is a skin cream or lotion.

[0044] The pharmaceutical formulation should be matched with the route of administration. The pharmaceutical products of this invention can also be used with other synergistic therapeutic agents (including before, during, or after administration). When using the pharmaceutical product or formulation, a safe and effective amount of the drug is administered to the desired subject (e.g., human or non-human mammal), typically at least about 10 micrograms per kilogram of body weight, and in most cases not exceeding about 8 milligrams per kilogram of body weight; preferably, this dose is about 10 micrograms per kilogram of body weight to about 1 milligram per kilogram of body weight. Of course, the specific dosage should also consider factors such as the route of administration and the patient's health condition, which are within the scope of a skilled physician's expertise.

[0045] The main superior technical effects of this invention include:

[0046] This invention is the first unexpected discovery that uridine 5'-bisphosphate has an excellent therapeutic effect on psoriasis.

[0047] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that the following specific embodiments are based on the present technical solution and provide detailed implementation methods and specific operation processes, but the scope of protection of the present invention is not limited to these embodiments.

[0048] Example 1 investigates the therapeutic effect of uridine 5'-bisphosphate (UDP) on psoriasis.

[0049] A psoriasis model induced by imiquimod (IMQ) was established in mice: The backs of mice were shaved, with an area approximately 2.5cm × 2.5cm in size. 5% imiquimod cream was applied topically at a dose of 62.5mg once daily for 6 consecutive days. Uric acid 5'-bisphosphate (UDP) was applied topically on the day before modeling, and on days 1, 2, 4, and 6, at a dose of 5mg / kg or 10mg / kg. Healthy mice that did not undergo any imiquimod modeling or drug administration were selected as the control group. The severity of the disease was assessed using a psoriasis plaque severity score (erythema, 0–4 points; infiltration, 0–4 points; scaling, 0–4 points; total 12 points). Epidermal thickness was measured and inflammatory cell infiltration was assessed using H&E staining. The expression of inflammatory factors that play a major role in the pathogenesis of psoriasis, such as IL-17A, IL-23, IL-22, and IFN–γ, was detected at the lesions using quantitative real-time PCR. The expression of the proliferation and differentiation marker Ki67 at the lesions was detected using immunofluorescence staining.

[0050] The therapeutic effects of uridine 5'-bisphosphate (UDP) on psoriasis are as follows: Figure 1 and Figure 2 As shown. Figure 1 and Figure 2The results showed that imiquimod-induced mice (IMQ group) exhibited greater epidermal thickness and immune cell infiltration, increased expression of several pro-inflammatory cytokines, and elevated markers of keratinocyte proliferation and differentiation compared to the control group, indicating the successful induction of the imiquimod-induced psoriasis model. However, compared to the imiquimod-induced psoriasis model alone, topical application of uridine 5'-bisphosphate (UDP) during the imiquimod-induced psoriasis model construction process significantly improved psoriasis-like inflammation and disease severity in mice. This was mainly manifested in a significant improvement in the characteristic psoriasis skin manifestations of erythema, infiltration, and scaling; a significant decrease in epidermal thickness at the lesion site; a significant improvement in immune cell infiltration; a significant decrease in the expression of pro-inflammatory cytokines and markers of cell proliferation and differentiation; and a significant improvement in the degree of weight loss in mice. Therefore, uridine 5'-bisphosphate (UDP) has excellent therapeutic effects on psoriasis-like inflammation in mice. Therefore, topical uridine 5'-bisphosphate (UDP) can effectively treat psoriasis, effectively improve the epidermal thickness and immune cell infiltration at the lesion site, reduce the degree of erythema, infiltration and scaling at the lesion site, and effectively inhibit the expression of pro-inflammatory cytokines and cell proliferation and differentiation markers that lead to the occurrence and aggravation of the disease, thereby improving the quality of life and physical and mental health of psoriasis patients.

[0051] The above description is merely a preferred embodiment of the present invention and does not limit the implementation and protection scope of the present invention. Those skilled in the art should realize that any equivalent substitutions and obvious changes made based on the description and illustrations of the present invention should be included within the protection scope of the present invention.

Claims

1. The use of uridine 5'-bisphosphate, characterized in that, Used to prepare a composition for the prevention and / or treatment of psoriasis vulgaris; the dosage form of the composition is a topical skin preparation.

2. The use as described in claim 1, characterized in that, The composition is a pharmaceutical composition.

3. The use as described in claim 1, characterized in that, The composition also includes a pharmaceutically acceptable carrier.

4. The use as described in claim 1, characterized in that, The dosage form of the composition is a solid dosage form, a liquid dosage form, or a semi-solid dosage form.

5. The use as described in claim 1, characterized in that, The aforementioned topical skin preparation is a skin cream.

6. The use as described in claim 1, characterized in that, The dosage form of the composition is a cream, gel, solution, or film.

7. The use as described in claim 1, characterized in that, The composition also includes other active ingredients for the prevention and / or treatment of psoriasis.

8. The use as described in claim 1, characterized in that, The characteristic skin manifestations of psoriasis are erythema, infiltration, and scaling; the treatment of psoriasis includes improving the severity of erythema, infiltration, and scaling.

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