Combined medicine for treating multiple sclerosis

Abstract

The invention discloses a combined medicine for treating multiple sclerosis. The combined medicine comprises one or more medicines selected from glucocorticoid, teriflunomide, recombinant human beta-1b interferon, fingolimod and alendauzumab, and an NPYY1 receptor agonist. The invention further discloses a combined medicine composed of the NPYY1 receptor stimulant and glucocorticoid for treating acute-stage multiple sclerosis, and a combined medicine composed of the NPYY1 receptor stimulant and fingolimod for treating recurrent and progressive multiple sclerosis. The invention relates to a drug combination for treating recurrent progression type multiple sclerosis and secondary progression type multiple sclerosis, wherein the drug combination comprises an NPYY1 receptor agonist and teriflunomide and / or alendobuzumab. The combined medicine composed of the NPYY1 receptor agonist and the recombinant human beta-1b interferon is used for treating the recurrent progression type multiple sclerosis, and the clinical isolated syndrome of the multiple sclerosis is prompted by nuclear magnetic resonance imaging evidence.

Description

Technical Field

[0001] The present invention belongs to the technical field of biology and new medicine technologies, and particularly relates to a combined drug for treating multiple sclerosis. Background Art

[0002] Multiple sclerosis (MS) is an immune-mediated disease mainly characterized by inflammatory demyelination lesions in the central nervous system (CNS). Its core immune mechanism stems from the loss of self-immune tolerance of T lymphocytes. The immune response mediated by autoreactive lymphocytes attacks myelin sheaths, affecting parts such as the optic nerve, spinal cord, brainstem, and periventricular white matter, resulting in clinical symptoms such as visual abnormalities, limb movement disorders, and ataxia. Currently, the drug treatment for MS mainly targets the regulation of immune responses at different stages of disease progression. For example, hormone shock therapy in the acute phase, and immunotherapies such as β-1b interferon, fingolimod, teriflunomide, and alemtuzumab in the remission phase. Due to the complexity of the MS progression mechanism, current single therapies or combination medications cannot achieve a radical cure. At the same time, existing treatment drugs all have problems of strong side effects and large individual differences, and recurrence and drug resistance are urgent problems to be solved in clinical treatment. For example, the commonly used glucocorticoid shock therapy in the acute phase can widely cause side effects such as electrolyte disorders, abnormal blood sugar, blood pressure, and blood lipids, upper gastrointestinal bleeding, osteoporosis, and femoral head necrosis. Side effects of drugs in the remission phase: fingolimod causes cardiovascular function abnormalities, viral and bacterial infections due to weakened immune surveillance of the body, and depression, etc.; teriflunomide causes diarrhea, vomiting, sparse hair, elevated alanine aminotransferase levels, etc.; β-1b interferon causes flu-like symptoms, leukopenia, and thyroid function abnormalities, etc.

[0003] The Neuropeptide Y (NPY) signal has a wide range of regulatory effects in the immune system. Experimental studies on animal models of MS have shown that exogenous NPY can effectively inhibit disease progression by inhibiting the NPY Y1 receptor and thus reducing the IFN-γ secretion of autoreactive T lymphocytes. At the same time, NPY can inhibit the activation of microglia through the Y1 receptor, reducing the secretion of cytotoxic mediators such as nitric oxide, glutamate, and cytokines, thereby regulating the central inflammatory response in MS animal models. Therefore, in the progression of MS disease, intervening to activate the neuropeptide Y signal has potential immunomodulatory effects. Summary of the Invention

[0004] In order to solve the technical problems existing in the prior art, the present invention aims to provide a combined drug for treating multiple sclerosis.

[0005] The specific technical solution is as follows:

[0006] The present invention provides a combined drug for treating multiple sclerosis, which comprises one or more drugs selected from glucocorticoids, teriflunomide, recombinant human beta-1b interferon, fingolimod, and alemtuzumab, and an NPY Y1 receptor agonist.

[0007] Further, the active ingredients of the combined drug consist of an NPY Y1 receptor agonist and a glucocorticoid.

[0008] Further, the active ingredients of the combined drug consist of an NPY Y1 receptor agonist and fingolimod.

[0009] Further, the active ingredients of the combined drug consist of an NPY Y1 receptor agonist and teriflunomide and / or alemtuzumab.

[0010] Further, the active ingredients of the combined drug consist of an NPY Y1 receptor agonist and recombinant human beta-1b interferon.

[0011] Further, the NPY Y1 receptor agonist is selected from one or more of an NPY natural active peptide molecule (amino acid sequence: YPSKPDNPGEDAPAEDMARYYSALRHYINLITRQRY) and small molecule drugs that can specifically activate the NPY Y1 receptor.

[0012] The present invention provides the use of a combined drug whose active ingredients consist of an NPY Y1 receptor agonist and a glucocorticoid in the preparation of a drug for treating acute-phase multiple sclerosis.

[0013] The present invention provides the use of a combined drug whose active ingredients consist of an NPY Y1 receptor agonist and fingolimod in the preparation of a drug for treating relapsing-remitting multiple sclerosis.

[0014] The present invention provides the use of a combined drug whose active ingredients consist of an NPY Y1 receptor agonist and teriflunomide and / or alemtuzumab in the preparation of a drug for treating relapsing-remitting multiple sclerosis with secondary progressive multiple sclerosis.

[0015] The present invention provides the use of a combined drug whose active ingredients consist of an NPY Y1 receptor agonist and recombinant human beta-1b interferon in the preparation of a drug for treating relapsing-remitting multiple sclerosis with magnetic resonance imaging evidence suggesting clinically isolated syndrome of multiple sclerosis.

[0016] The beneficial effects of the present invention are as follows:

[0017] In the present invention, during the acute-phase treatment and remission-phase treatment of multiple sclerosis, a neuropeptide Y1 receptor agonist is used in combination as an immunomodulatory treatment means, and different combination drugs are used in different disease courses of MS, so as to improve the treatment effect of multiple sclerosis, reduce the recurrence rate and disability progression, and prolong the survival period of patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 : The NPY Y1 receptor agonist is used in combination with existing therapies in different disease courses of MS for the treatment of MS. DETAILED DESCRIPTION OF THE INVENTION

[0019] To better understand the present invention, the present invention will be further described with reference to the following examples and drawings. The examples are for explanation only and do not limit the present invention in any way. In the examples, all original reagent materials are commercially available, and the experimental methods without specific conditions are conventional methods and conventional conditions well known in the art, or the conditions recommended by the instrument manufacturer.

[0020] Example 1

[0021] The NPY Y1 receptor agonists used in the present invention include NPY natural active peptide segment molecules (amino acid sequence: YPSKPDNPGEDAPAEDMARYYSALRHYINLITRQRY), and small molecule drugs that can specifically activate the NPY Y1 receptor, and they all fall within the protection scope of the present invention.

[0022] As Figure 1 shown, the present invention uses the NPY Y1 receptor agonist in combination with existing therapies in different disease courses of MS for the treatment of MS.

[0023] 1. Combination during the acute-phase treatment of MS

[0024] It is combined with glucocorticoid therapy, such as methylprednisolone pulse therapy. It is administered by intravenous drip (natural NPY active peptide) or oral administration (small molecule NPY Y1 receptor agonist), and the drug dose is 0.2 - 1 mg / kg, and the treatment course is 2 weeks.

[0025] 2. Combination during the remission-phase treatment of MS

[0026] It is combined with disease-modifying therapy drugs, such as teriflunomide, recombinant human beta-1b interferon, fingolimod, and alemtuzumab, etc.

[0027] (1) For patients with relapsing-remitting multiple sclerosis (RRMS) who have been diagnosed, fingolimod and a small molecule NPY Y1 receptor agonist can be used in combination for treatment.

[0028] Oral fingolimod, 0.5 mg, once a day; and oral small molecule NPYY1 receptor agonist, dose 0.2 - 1 mg / kg, once a day. Treatment principle: early and long-term.

[0029] (2) For patients with confirmed relapsing - remitting (RRMS) and secondary progressive (SPMS): a) Administer combination therapy of teriflunomide and small molecule NPYY1 receptor agonist; or b) Administer combination therapy of alemtuzumab and small molecule NPYY1 receptor agonist.

[0030] a) Oral teriflunomide, 14 mg, once a day, oral small molecule NPYY1 receptor agonist, dose 0.2 - 1 mg / kg, once a day. Treatment principle: early and long-term.

[0031] b) Intravenous infusion of alemtuzumab at 12 mg / day for 2 courses. First course: 12 mg / day for 5 consecutive days (total dose 60 mg). Second course: 12 months after the first course, administer 12 mg / day for 3 consecutive days (total dose 36 mg); and oral small molecule NPYY1 receptor agonist, dose 0.2 - 1 mg / kg, once a day. Treatment principle: early and long-term.

[0032] (3) For patients with confirmed relapsing - remitting (RRMS) and clinically isolated syndrome with magnetic resonance imaging evidence suggesting MS, combination therapy of recombinant human beta - 1b interferon and small molecule NPYY1 receptor agonist can be administered.

[0033] Subcutaneous injection of recombinant human beta - 1b interferon, recommended dose is 250 μg, once every other day. Starting dose is 62.5 μg, and after every 2 injections, increase by 62.5 μg until the recommended dose. Plus oral small molecule NPYY1 receptor agonist, dose 0.2 - 1 mg / kg, once a day. Treatment principle: early, sequential, and long-term.

[0034] The combination drug therapy in this embodiment has been experimentally verified.

[0035] Obviously, the above - mentioned embodiments are only examples for clear illustration and not limitations on the implementation methods. For those of ordinary skill in the art, other different forms of changes or alterations can be made based on the above description.

Claims

1. A combined medicine for treating multiple sclerosis, characterized in that, The combined drug includes one or more drugs selected from glucocorticoids, teriflunomide, recombinant human beta-1b interferon, fingolimod, and alemtuzumab, and an NPY Y1 receptor agonist.

2. The combined medicine according to claim 1, characterized in that, The active ingredients of the combined drug consist of an NPY Y1 receptor agonist and a glucocorticoid.

3. The combined medicine according to claim 1, characterized in that, The active ingredients of the combined drug consist of an NPY Y1 receptor agonist and fingolimod.

4. The combined medicine according to claim 1, characterized in that, The active ingredients of the combined drug consist of an NPY Y1 receptor agonist and teriflunomide and / or alemtuzumab.

5. The combined medicine according to claim 1, characterized in that, The active ingredients of the combined drug consist of an NPY Y1 receptor agonist and recombinant human beta-1b interferon.

6. The combined medicine according to any one of claims 1-5, characterized in that, The NPY Y1 receptor agonist is selected from one or more of NPY natural active peptide molecules and small molecule drugs that can specifically activate the NPY Y1 receptor.

7. Use of the combined medicine according to claim 2 in the preparation of a medicine for treating acute-phase multiple sclerosis.

8. Use of the combined medicine according to claim 3 in the preparation of a medicine for treating relapsing-remitting multiple sclerosis.

9. Use of the combined medicine according to claim 4 in the preparation of a medicine for treating relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis.

10. Use of the combined medicine according to claim 5 in the preparation of a medicine for treating relapsing-remitting multiple sclerosis, or clinically isolated syndrome of multiple sclerosis with magnetic resonance imaging evidence.

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