Combination medicine containing galanin receptor GAL2R agonist for treating multiple sclerosis

Abstract

The invention discloses a combined medicine for treating multiple sclerosis and containing a galanin receptor GAL2R agonist. The combined medicine comprises one or more medicines selected from glucocorticoid, teriflunomide, recombinant human beta-1b interferon, fingolimod and alendauzumab, and the galanin receptor GAL2R agonist. According to the invention, the galanin receptor GAL2R agonist is used in a combined manner, and different combined medicines are adopted in different disease courses of MS, so that the treatment effect of multiple sclerosis is improved, the recurrence rate and the disability progress are reduced, and the lifetime of a patient is prolonged.

Description

Technical Field

[0001] The present invention belongs to the technical field of biological and new pharmaceutical technologies, and particularly relates to a combined drug for treating multiple sclerosis, which contains a galanin receptor GAL2R agonist. Background Art

[0002] Multiple sclerosis (MS) is an immune-mediated disease mainly characterized by inflammatory demyelinating 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 autoimmune 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 in different stages of disease progression. For example, hormone shock therapy in the acute stage, and immunotherapies such as β-1b interferon, fingolimod, teriflunomide, and alemtuzumab in the remission stage. 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 stage 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 stage: 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 galanin signal has potential immunomodulatory effects. In the animal experimental model study of MS, the expression of galanin in oligodendrocytes increased significantly; and overexpression of galanin in transgenic mice could inhibit disease progression; while loss-of-function mutations of galanin or its receptor GAL2R exacerbated disease progression. Thus, it can be seen that the activation of the galanin signal can be used as a new and potential immunomodulatory means for the treatment of MS. 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, which contains a galanin receptor GAL2R agonist.

[0005] The specific technical solutions are as follows:

[0006] The present invention provides a combined drug for treating multiple sclerosis, which contains a galanin receptor GAL2R agonist. The combined drug includes one or more drugs selected from glucocorticoids, teriflunomide, recombinant human beta-1b interferon, alemtuzumab, and mitoxantrone, and a galanin receptor GAL2R agonist; the galanin receptor GAL2R agonist is selected from one or more of galanin natural active peptide segments and small molecule drugs that can specifically activate the galanin receptor GAL2R..

[0007] Further, the active ingredients of the combined drug are composed of a galanin receptor GAL2R agonist and a glucocorticoid.

[0008] Further, the active ingredients of the combined drug are composed of a galanin receptor GAL2R agonist and teriflunomide.

[0009] Further, the active ingredients of the combined drug are composed of a galanin receptor GAL2R agonist and recombinant human beta-1b interferon.

[0010] Further, the active ingredients of the combined drug are composed of a galanin receptor GAL2R agonist and alemtuzumab.

[0011] Further, the active ingredients of the combined drug are composed of a galanin receptor GAL2R agonist and mitoxantrone.

[0012] The present invention also provides the use of a combined drug composed of a galanin receptor GAL2R agonist and a glucocorticoid in the preparation of a drug for treating acute-phase multiple sclerosis.

[0013] The present invention also provides the use of a combined drug composed of a galanin receptor GAL2R agonist and teriflunomide in the preparation of a drug for treating relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis with relapses.

[0014] The present invention also provides the use of the combined drug composed of a galanin receptor GAL2R agonist and recombinant human beta-1b interferon in the preparation of a drug for treating patients who do not meet the diagnostic criteria for multiple sclerosis but have lesions suggested by magnetic resonance imaging evidence, confirmed relapsing-progressive multiple sclerosis, secondary progressive multiple sclerosis with relapses, or secondary progressive multiple sclerosis without relapses.

[0015] The present invention also provides the use of the combined drug composed of a galanin receptor GAL2R agonist and alemtuzumab in the preparation of a drug for treating confirmed relapsing-progressive multiple sclerosis or secondary progressive multiple sclerosis with relapses;

[0016] Or, a combined drug composed of a galanin receptor GAL2R agonist and mitoxantrone is used in the preparation of a medicament for treating confirmed relapsing - progressive multiple sclerosis, deteriorating relapsing - progressive multiple sclerosis, or secondary progressive multiple sclerosis with relapses.

[0017] The beneficial effects of the present invention are as follows:

[0018] During the acute - phase treatment and remission - phase treatment of multiple sclerosis, the present invention combines the use of a galanin receptor GAL2R agonist, and different combined drugs are used in different disease courses of MS, thereby improving the treatment effect of multiple sclerosis, reducing the relapse rate and disability progression, and prolonging the survival period of patients. Description of the Drawings

[0019] Figure 1 : The galanin receptor GAL2R agonist is used in combination with existing therapies in different disease courses of MS for the treatment of MS. Detailed Embodiments

[0020] To understand the present invention more clearly, the present invention is further described below with reference to the following embodiments and drawings. The embodiments are only for explanation and do not limit the present invention in any way. In the embodiments, all original reagent materials can be obtained commercially. 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.

[0021] The galanin receptor GAL2R agonists used in the present invention include galanin natural active peptide segment molecules (amino acid sequence: GWTLNSAGYLLGPHAVGNHRSFSDKNGLTS), and small - molecule drugs that can specifically activate the galanin receptor GAL2R, and they all fall within the protection scope of the present invention.

[0022] As Figure 1 shown, the present invention uses a galanin receptor GAL2R agonist in combination with existing therapies in different disease courses of MS for the treatment of MS.

[0023] Explanation of abbreviations in this embodiment:

[0024] RRMS: Relapsing - Remitting Multiple Sclerosis

[0025] SPMS: Secondary Progressive Multiple Sclerosis

[0026] 1. Combination during the acute - phase treatment of MS

[0027] It is combined with glucocorticoid therapy, such as methylprednisolone pulse therapy. It is administered by intravenous drip (galanin natural active peptide) or orally (small - molecule galanin receptor GAL2R agonist), with a drug dose of 0.2 - 1 mg / kg and a treatment course of 2 weeks.

[0028] 2. MS remission treatment combination

[0029] 1) Oral combination with teriflunomide

[0030] Recommendation: This regimen can be used in patients with relapsing MS (relapsing-remitting RRMS patients and secondary progressive SPMS patients with relapses).

[0031] Usage: Oral teriflunomide, 14 mg, once a day, and oral small molecule galanin receptor GAL2R agonist, dose 0.2 - 1 mg / kg, once a day.

[0032] 2) Combination with recombinant human beta-1b interferon

[0033] Recommendation: High-risk CIS patients who may develop MS (not meeting the MS diagnostic criteria but with MRI lesions highly suggestive of MS), or patients with diagnosed RRMS or SPMS still having relapses can be treated with recombinant human beta-1b interferon for injection (Grade I recommendation), or the efficacy of recombinant human beta-1b interferon for injection in clinically relapse-free SPMS patients is unclear (Grade IV recommendation), and this regimen can be used.

[0034] Usage: Subcutaneous injection of recombinant human beta-1b interferon, the recommended dose is 250 μg, once every other day. The starting dose is 62.5 μg, and after every 2 injections, it is increased by 62.5 μg until the recommended dose. Additionally, oral small molecule galanin receptor GAL2R agonist, dose 0.2 - 1 mg / kg, once a day.

[0035] 3) Combination with alemtuzumab

[0036] Recommendation: This regimen can be used in patients with diagnosed relapsing MS (RRMS and SPMS patients with relapses).

[0037] Usage: Alemtuzumab 12 mg / d, intravenous infusion, for 2 courses. The first course of alemtuzumab: 12 mg / d, for 5 consecutive days (total dose 60 mg). The second course: 12 months after the first course, give 12 mg / d, for 3 consecutive days (total dose 36 mg). At the same time, oral small molecule galanin receptor GAL2R agonist, dose 0.2 - 1 mg / kg, once a day.

[0038] 4) Combination with mitoxantrone

[0039] Recommendation: This regimen can be used in patients with diagnosed relapsing MS (RRMS, worsening RRMS, and SPMS patients with relapses).

[0040] Usage: Mitoxantrone 8 - 12 mg / m 2, by intravenous injection, once every 3 months, and the total lifetime cumulative dose is limited to 140 mg / m 2 Below, the course of treatment should not exceed 2 years. At the same time, orally take a small molecule galanin receptor GAL2R agonist at a dose of 0.2 - 1 mg / kg, once a day.

[0041] The combination drug therapy in this embodiment has been experimentally verified.

[0042] Obviously, the above embodiments are only examples for clear illustration and not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to enumerate all implementation manners here. And the obvious changes or modifications derived therefrom are still within the protection scope of the present invention.

Claims

1. A combined drug for treating multiple sclerosis, comprising a galanin receptor GAL2R agonist, characterized in that, The combination drug includes one or more drugs selected from glucocorticoids, teriflunomide, recombinant human beta-1b interferon, alemtuzumab, and mitoxantrone, and a galanin receptor GAL2R agonist; the galanin receptor GAL2R agonist is selected from one or more of galanin natural active peptide molecules and small molecule drugs that can specifically activate the galanin receptor GAL2R..

2. The combined drug according to claim 1, characterized in that, The active ingredients of the combination drug consist of a galanin receptor GAL2R agonist and a glucocorticoid.

3. The combined drug according to claim 1, characterized in that, The active ingredients of the combination drug consist of a galanin receptor GAL2R agonist and teriflunomide.

4. The combined drug according to claim 1, characterized in that, The active ingredients of the combination drug consist of a galanin receptor GAL2R agonist and recombinant human beta-1b interferon.

5. The combined drug according to claim 1, characterized in that, The active ingredients of the combination drug consist of a galanin receptor GAL2R agonist and alemtuzumab.

6. The combined drug according to claim 1, characterized in that, The active ingredients of the combination drug consist of a galanin receptor GAL2R agonist and mitoxantrone.

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

8. Use of the combined drug according to claim 3 in the preparation of a drug for treating relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis with relapses.

9. Use of the combined drug according to claim 4 in the preparation of a drug for treating those who do not meet the diagnostic criteria for multiple sclerosis but have lesions indicated by magnetic resonance imaging evidence, confirmed relapsing-progressive multiple sclerosis, secondary progressive multiple sclerosis with relapses, or secondary progressive multiple sclerosis without relapses.

10. Use of the combined drug according to claim 5 in the preparation of a drug for treating confirmed relapsing-progressive multiple sclerosis or secondary progressive multiple sclerosis with relapses; Or, use of the combined drug according to claim 6 in the preparation of a drug for treating confirmed relapsing-progressive multiple sclerosis, deteriorating relapsing-progressive multiple sclerosis or secondary progressive multiple sclerosis with relapses.

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