阅读说明：本技术 艾拉莫德在制备治疗系统性硬化症的药物中的用途 (Use of Iguratimod in preparation of medicine for treating systemic sclerosis ) 是由 沈力冲 严青然 李�瑞 陈晓翔 于 2019-10-16 设计创作，主要内容包括：本发明提供了艾拉莫德在制备治疗系统性硬化症的药物中的用途,本发明发现将艾拉莫德制备成外用剂型,通过局部涂抹可以软化硬化的皮肤的应用潜能。通过实验证明,局部或全身应用艾拉莫德,可以显著抑制参与纤维化的重要转录因子EGR1,从而导致促纤维化细胞因子TGFβ的表达量减少或下游信号减弱,从而抑制系统性硬化症的进展。采用艾拉莫德二甲基亚砜溶液局部涂抹给药,也能有效减轻和治愈实验性硬皮病皮肤纤维化。(The invention provides application of Iguratimod in preparation of a medicament for treating systemic sclerosis, and the application potential of the Iguratimod in preparation of an external preparation form and capable of softening hardened skin through local application is discovered. Experiments prove that by applying iguratimod locally or systemically, important transcription factor EGR1 involved in fibrosis can be obviously inhibited, so that the expression level of the cell factor TGF beta promoting fibrosis is reduced or downstream signals are weakened, and the progress of systemic sclerosis is inhibited. The Iguratimod dimethyl sulfoxide solution is locally applied, so that experimental scleroderma skin fibrosis can be effectively relieved and cured.)

1. Use of Iguratimod in the manufacture of a medicament for the treatment of systemic sclerosis.

2. The use of claim 1, wherein: the drug dosage form of the Iguratimod is liniment.

3. The use of claim 1, wherein: dissolving Iguratimod in dimethyl sulfoxide to ensure that the mass percentage concentration of the Iguratimod in the medicament is 2 percent.

4. A medicament for the treatment of systemic sclerosis, characterized by: the drug consists of Iguratimod and dimethyl sulfoxide, wherein the mass percentage concentration of the Iguratimod in the drug is 2%.

Technical Field

The invention belongs to the field of biomedicine, and relates to a medicament for treating systemic sclerosis, in particular to application of Iguratimod in preparing a medicament for treating systemic sclerosis.

Background

Systemic sclerosis (SSc) is a rare autoimmune disease in which multiple system organs are involved, which is refractory. Its etiology and pathogenesis are unknown, clinical manifestations are complex and various, and it is characterized by localized or diffuse skin thickening and fibrosis, and can also affect the general diseases of digestive tract, heart, lung, kidney and other internal organs.

The existing treatment means such as the application of glucocorticoid hormone and immunosuppressant have weak or unknown curative effect on blocking the progress of the disease, and even increase the probability of inducing the renal crisis of scleroderma. And the systemic application of the medicines has large side effect and is difficult to tolerate by some patients. Therefore, the research on the medicine with good treatment effect and small side effect on the disease has important clinical significance.

Iguratimod is a new drug for treating rheumatoid arthritis. Clinical studies and applications show that it has comparable efficacy to methotrexate in patients with rheumatoid arthritis with minimal side effects.

Disclosure of Invention

The invention aims to provide a new application of Iguratimod, and the application aims to solve the technical problem that the effect of the medicament for treating scleroderma in the prior art is poor or the side effect is overlarge.

The invention provides application of Iguratimod in preparing a medicament for treating systemic sclerosis.

Further, the drug dosage form of the Iguratimod is liniment.

Further, the Iguratimod is dissolved in the dimethyl sulfoxide, so that the mass percentage concentration of the Iguratimod in the medicament is 2%.

The invention also provides a medicament for treating systemic sclerosis, which consists of Iguratimod and dimethyl sulfoxide, wherein the mass percentage concentration of the Iguratimod in the medicament is 2%.

Specifically, the Iguratimod is a bulk drug, is a commercially available drug, and has a chemical structural formula as follows:

the medicine adopted in the experiment of the invention is purchased from Nanjing Xiihuangyo pharmaceutical industry group Co.

The inventor finds that the Iguratimod can obviously inhibit the expression level of a transcription factor Egr-1 at a cellular level. Egr-1 is a transcription factor closely associated with fibrosis and is significantly highly expressed in the hardened skin tissue of patients with diffuse systemic sclerosis. And the change of the gene expression profile presented by the fibroblast over-expressing the transcription factor is very similar to the change of the gene expression profile presented by the hardened skin tissue of the diffuse systemic sclerosis patient relative to the normal human skin tissue. Therefore, the inventor speculates that the medicine has potential effect of treating systemic sclerosis, and verifies the potential effect in vitro experiments and several animal models of systemic sclerosis.

Experiments prove that by applying iguratimod locally or systemically, important transcription factor EGR1 involved in fibrosis can be obviously inhibited, so that the expression level of the cell factor TGF beta promoting fibrosis is reduced or downstream signals are weakened, and the progress of systemic sclerosis is inhibited. The Iguratimod dimethyl sulfoxide solution is locally applied, so that skin fibrosis caused by experimental scleroderma can be effectively relieved and cured.

Compared with the prior art, the invention has the advantages of positive and obvious technical effect. According to the invention, the Iguratimod is applied to the treatment of the systemic sclerosis internationally, and the curative effect of the Iguratimod on the local skin sclerosis of the experimental animal through local skin smearing is innovatively verified. The invention provides a basis for the development of a new medicine for treating systemic sclerosis and the research and development of a new Iguratimod dosage form.

Drawings

FIG. 1 shows that Iguratimod inhibits the expression of healthy adult skin fibroblast Egr-1 induced by TGF- β.

Figure 2 shows that iguratimod inhibits TGF- β -induced activation of primary fibroblasts and collagen synthesis in healthy adult skin.

Figure 3 shows that intragastric gavage or topical application of Iguratimod is effective in treating bleomycin-induced skin fibrosis.

FIG. 4 shows that intragastric gavage or topical application of Iguratimod inhibits the TGF- β -Egr-1 loop in mice.

FIG. 5 shows a topical skin application of Iguratimod

Figure 6 shows the degree of skin fibrosis in subjects treated with iguratimod.

FIG. 7 shows the expression of dermal fibroblasts Egr-1 and TGF-. beta.in the Iguratimod-treated and empty vector-treated SSc patients.

FIG. 8 shows the expression levels of Egr-1 and TGF- β immunohistochemical staining of skin tissue after Iguratimod treatment of skin fibroblasts Egr-1 and TGF- β.

Detailed Description