Application of C6-C3 derivative in preparation of medicine for treating autoimmune demyelination disease

Abstract

The invention belongs to the technical field of medicines, and discloses application of C6-C3 derivatives in preparation of medicines for treating autoimmune demyelination diseases. The invention particularly relates to application of the isopentenyl-substituted C6-C3 derivative IB as shown in a formula (I) in preparation of drugs for preventing, relieving and / or treating autoimmune demyelination diseases. On a mouse experimental autoimmune encephalomyelitis model, the compound IB shows a good treatment effect, can effectively prevent and treat pathological changes and disease progression of diseases, relieve the severity of the diseases and relieve spinal cord inflammatory cell infiltration and spinal cord demyelination, and provides a new drug and a new structure for clinical treatment. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the use of an isopentenyl-substituted C6-C3 derivative IB in preparing a drug for preventing, alleviating and / or treating autoimmune demyelinating diseases, and belongs to the technical field of medicine. Background Art

[0002] Multiple sclerosis (MS) is a chronic, progressive, immune-mediated, inflammatory demyelinating disease of the central nervous system (CNS). Affecting over two million people worldwide, it poses a serious threat to human health and places a heavy economic burden on society. The pathogenesis of MS is complex, its etiology remains unknown, and it is currently incurable, requiring long-term treatment. MS is characterized by inflammation and demyelination of the brain, spinal cord, and optic nerves. Its clinical manifestations range widely, including muscle weakness, sensory impairment, cognitive impairment, and fatigue. The etiology of MS remains unclear, but it may be associated with multiple factors, including genetics, the environment, and infection. Based on clinical presentation, MS can be categorized into four types: relapsing-remitting, characterized by alternating relapses and remissions without significant disease progression; primary progressive, characterized by progressive worsening after onset; secondary progressive, characterized by a relapsing-remitting onset followed by progressive worsening; and progressive-relapsing, characterized by gradual progression with relapses. Currently, clinical treatment drugs are mostly targeted at patients with relapsing-remitting disease.

[0003] Multiple sclerosis is considered an autoimmune disease, mainly caused by the entry of autoreactive immune cells into the CNS through the blood-brain barrier. Its early lesions are manifested by peripheral immune cell infiltration and blood-brain barrier (BBB) leakage. The cell infiltration is mainly composed of macrophages, CD8 + T cells are second, CD4 + The number of T cells, B cells, and plasma cells is relatively small. The composition of T cells does not change with the progression of the disease, but the relative proportions of B cells and plasma cells increase. Microglia and macrophages remain in a chronically activated state throughout the disease process, forming plaques of myelin and oligodendrocyte loss. As the disease progresses, patients develop focal white matter lesions in the brain. Brain and spinal cord damage is not obvious, but brain atrophy is common, accompanied by ventricular enlargement. Astrocytes form multiple sclerosis-like glial scars in white matter lesions, and demyelination also occurs in the gray matter of the cerebral cortex, nuclei, and spinal cord. However, demyelinated areas of white matter can be partially repaired through remyelination. In addition, the disease process not only affects myelin but also causes degenerative changes in axons and neurons, resulting in irreversible disability in patients.

[0004] Over the past two decades, as our understanding of the pathogenesis of multiple sclerosis has deepened, researchers have developed a variety of drugs targeting specific physiological pathways of the disease. Currently, drugs used to treat multiple sclerosis are mainly divided into five categories: immunomodulators, hormones, monoclonal antibodies, interferons, and neurorepair agents. These drugs can slow disease progression and control symptoms, but they are ineffective in repairing damaged neurons, have no effect on improving patients' functional disabilities, and have serious toxic side effects with long-term use.

[0005] The experimentally allergic encephalomyelitis (EAE) model is a classic animal model of multiple sclerosis. Myelin autoantigens specifically activate brain helper T cells, leading to inflammatory infiltration and demyelination in the central nervous system. Its biochemical, immunological, and pathological features closely resemble those of multiple sclerosis. Furthermore, EAE in rats and mice serves as an ideal animal model for studying autoimmune demyelinating diseases, including experimental autoimmune encephalomyelitis, neuroencephalomyelitis optica, and acute disseminated encephalomyelitis. Its clinical, pathological, immunological, and biochemical characteristics closely resemble those of human demyelinating diseases, leading to its widespread application.

[0006] The compound IB [6-allyl-6-(3-methylbut-2-en-1-yl)benzo[d][1,3]dioxol-5(6H)-one] of the present invention is an isopentenyl-substituted C6-C3 derivative with a molecular formula of C 15 H 18 O3. This compound was isolated from various Illicium plants (Journal of Asian Natural Products Research, 2009, 11, 1056-1061; Phytochemistry, 2011, 72, 115-125; Phytochemistry, 2013, 86, 176-183; Planta Medica, 73, 372-375; Fitoterapia, 2015, 107, 22-28). To date, no biological activity has been reported.

[0007] The compound IB [6-allyl-6-(3-methylbut-2-en-1-yl)benzo[d][1,3]dioxol-5(6H)-one] described herein is isolated and prepared from the roots, stem bark, or branches and leaves of the plant Illicium brevistylum ACsmith using various chromatographic separation techniques. The invention primarily relates to the preparation of pharmaceuticals and drug combinations using this compound, and its clinical application in the preparation of drugs for the prevention, alleviation, and / or treatment of autoimmune demyelinating diseases. Currently, there are no reports, either domestically or internationally, of this compound exerting a direct or indirect effect on autoimmune demyelinating diseases. Summary of the Invention

[0008] The technical problem to be solved by the present invention is to provide the use of compound IB[6-allyl-6-(3-methylbut-2-en-1-yl)benzo[d][1,3]dioxol-5(6H)-one] in the preparation of drugs for preventing, alleviating and / or treating autoimmune demyelinating diseases.

[0009] In order to solve the technical problems of the present invention, the present invention provides the following technical solutions:

[0010] The first aspect of the technical solution of the present invention is to provide the use of the compound IB [6-allyl-6-(3-methylbut-2-en-1-yl)benzo[d][1,3]dioxol-5(6H)-one] as shown in formula (I) in the preparation of a drug for preventing, alleviating and / or treating autoimmune demyelinating diseases.

[0011]

[0012] The autoimmune demyelinating diseases include, but are not limited to, demyelinating autoimmune diseases of the central nervous system (CNS) such as multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), acute disseminated encephalomyelitis, leukoencephalitis and transverse myelitis; and demyelinating autoimmune diseases affecting the peripheral nervous system such as acute inflammatory demyelinating polyneuropathy (AIDP; Guillain-Barré syndrome), chronic inflammatory demyelinating polyneuropathy, anti-MAG peripheral neuropathy, Motor and Sensory Neuropathy (HMSN), Hereditary Sensorimotor Neuropathy (HSMN), Peroneal Muscular Atrophy (CMS), and other autoimmune diseases. Atrophy), Charcot-Marie-Tooth Disease, etc.

[0013] The multiple sclerosis includes relapsing-remitting multiple sclerosis, primary progressive multiple sclerosis, secondary progressive multiple sclerosis and progressive relapsing multiple sclerosis.

[0014] An EAE model was established using female C57BL / 6J mice. The effects of Compound IB on the animal disease scores were examined. Limb strength and treatment outcomes were assessed using suspension grading and suspension duration tests. H&E and LFB staining were used to assess Compound IB's improvement in inflammatory cell infiltration and demyelination in the spinal cord of the experimental animals. This data suggests the potential use of Compound IB in the development of drugs for the prevention, alleviation, and / or treatment of autoimmune demyelinating diseases.

[0015] The second aspect of the technical solution of the present invention is to provide a pharmaceutical composition for use in preparing a drug for preventing, alleviating and / or treating autoimmune demyelinating diseases, characterized in that the pharmaceutical composition contains an effective dose of compound IB as represented by formula (I) and a pharmaceutical excipient.

[0016]

[0017] The pharmaceutical composition contains Compound IB as the active pharmaceutical ingredient and other active ingredients. The pharmaceutical composition can be in the following dosage forms: solution, suspension, lyophilized powder injection, emulsion, pill, capsule, powder, controlled-release formulation, sustained-release formulation, and microsomal delivery system. Pharmaceutical excipients include starch, dextrin, sodium polymethylcellulose, magnesium stearate, and talc. The product is selected from pharmaceuticals and health supplements.

[0018] The present invention also relates to the use of a pharmaceutical composition containing Compound IB of the present invention as an active ingredient for preventing, alleviating, and / or treating autoimmune demyelinating diseases. Such pharmaceutical compositions can be prepared according to methods known in the art. The compounds of the present invention can be combined with one or more pharmaceutically acceptable solid or liquid excipients and / or adjuvants to form any dosage form suitable for human or animal use.

[0019] The compounds of the present invention or pharmaceutical compositions containing the same can be administered in unit dosage forms, and the routes of administration can be enteral or parenteral, such as oral, intravenous, intramuscular, subcutaneous, nasal, oral mucosa, eyes, lungs and respiratory tract, skin, vagina, rectum, etc. The dosage form can be a liquid dosage form, a solid dosage form, or a semisolid dosage form. Liquid dosage forms can be solutions (including true solutions and colloidal solutions), emulsions (including o / w types, w / o types, and multiple emulsions), suspensions, injections (including aqueous injections, powder injections, and infusions), eye drops, nasal drops, lotions, and liniments; solid dosage forms can be tablets (including ordinary tablets, enteric-coated tablets, lozenges, dispersible tablets, chewable tablets, effervescent tablets, orally disintegrating tablets), capsules (including hard capsules, soft capsules, and enteric-coated capsules), granules, powders, micropills, dropping pills, suppositories, films, patches, aerosols (powders), sprays, etc.; semisolid dosage forms can be ointments, gels, pastes, etc. The compound of the present invention can be prepared into common preparations, sustained-release preparations, controlled-release preparations, targeted preparations and various microparticle delivery systems.

[0020] In order to prepare the compound of the present invention into tablets, various excipients well known in the art can be widely used, including diluents, binders, wetting agents, disintegrants, lubricants, and glidants. Diluents can be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, etc.; wetting agents can be water, ethanol, isopropyl alcohol, etc.; binders can be starch slurry, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, acacia slurry, gelatin slurry, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, carbomer, polyvinyl pyrrolidone, polyethylene glycol, etc.; disintegrants can be dry starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, sodium bicarbonate and citric acid, polyoxyethylene sorbitan fatty acid ester, sodium lauryl sulfate, etc.; lubricants and glidants can be talc, silicon dioxide, stearate, tartaric acid, liquid paraffin, polyethylene glycol, etc. Tablets can also be further prepared as coated tablets, such as sugar-coated tablets, film-coated tablets, enteric-coated tablets, or bilayer and multilayer tablets. To prepare the dosing unit as a capsule, the active ingredient compound of the present invention can be mixed with a diluent and a glidant, and the mixture can be directly placed in a hard or soft capsule. Alternatively, the active ingredient compound of the present invention can be first prepared into granules or pellets with a diluent, a binder, and a disintegrant, and then placed in a hard or soft capsule. The diluents, binders, wetting agents, disintegrants, and glidants used to prepare tablets of the compound of the present invention can also be used to prepare capsules of the compound of the present invention. To prepare the compound of the present invention as an injection, water, ethanol, isopropanol, propylene glycol, or mixtures thereof can be used as solvents, and appropriate amounts of solubilizers, cosolvents, pH adjusters, and osmotic pressure regulators commonly used in the art can be added. Solubilizers or cosolvents may include poloxamer, lecithin, hydroxypropyl-β-cyclodextrin, etc.; pH adjusters may include phosphates, acetates, hydrochloric acid, sodium hydroxide, etc.; osmotic pressure regulators may include sodium chloride, mannitol, glucose, phosphates, acetates, etc. For the preparation of lyophilized powder injections, mannitol, glucose, etc. may also be added as support agents. Furthermore, colorants, preservatives, fragrances, flavorings, or other additives may be added to the pharmaceutical preparations, if desired. To achieve the intended use and enhance the therapeutic effect, the drugs or pharmaceutical compositions of the present invention may be administered using any known method.

[0021] Beneficial technical effects

[0022] 1. The isopentenyl-substituted C6-C3 derivatives of the present invention can prevent, alleviate and / or treat autoimmune demyelinating diseases, and provide a new structural type of drug selection for the clinical treatment of autoimmune demyelinating diseases.

[0023] 2. The isopentenyl-substituted C6-C3 derivatives of the present invention can be administered orally, achieving therapeutic and preventive effects with a small dosage. They are safe and reliable, and have significant advantages for development as pharmaceuticals. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Flow chart of extraction and separation of compound IB

[0025] Figure 2 Effect of Compound IB on Body Weight in EAE Mice. In this experiment, the body weight of mice in the EAE model group was significantly lower than that of the normal group after onset of disease. After drug administration, the body weight of the Compound IB-treated group increased significantly compared to the model group in the later stages of drug administration.

[0026] Figure 3 Effect of Compound IB on Disease Scores in Experimental Autoimmune Encephalomyelitis (EAE) Mice. In this experiment, the disease scores of mice in the EAE model group were significantly higher than those in the control group after onset of the disease. Following administration of Compound IB, the mice in the group receiving Compound IB showed overall relief of symptoms and significantly lower disease scores than those in the EAE model group, demonstrating a significant improvement in disease scores and confirming that Compound IB significantly improves the neurological function of EAE mice.

[0027] Figure 4 Effect of Compound IB on the Hanging Time of EAE Mice. In this experiment, compared with the normal control group, the EAE model group mice significantly decreased their hanging time on the wire mesh. Compound IB was able to prolong this time, confirming that Compound IB treatment significantly improved the motor function of EAE mice. ###P<0.001 vs. the normal control group, ***P<0.001 vs. the EAE model group.

[0028] Figure 5 Effect of Compound IB on the Hanging Score of EAE Mice. In this experiment, the Hanging Score of EAE model mice was significantly lower after onset of disease compared to the normal control group. Following administration, the Hanging Score of EAE mice in the Compound IB-treated group was significantly higher than that of the EAE model group. ###P<0.001 vs. the normal control group; **P<0.01 vs. the EAE model group.

[0029] Figure 6 Effect of Compound IB on Inflammatory Cell Infiltration in the Spinal Cord of EAE Mice. In this experiment, compared with the normal control group, the spinal cord inflammatory cell infiltration of EAE model mice was significantly higher. Compound IB could significantly inhibit the infiltration of inflammatory cells in the spinal cord of EAE mice.

[0030] Figure 7Effect of Compound IB on spinal cord demyelination in EAE mice. In this experiment, Luxol Fast Blue (LFB) staining revealed larger demyelination lesions in the spinal cord of EAE mice compared to the normal control group. Compound IB reduced the white matter area of the spinal cord in EAE mice, effectively improving demyelination. DETAILED DESCRIPTION

[0031] The pharmacological effects of Compound IB in preventing, alleviating and / or treating autoimmune demyelinating diseases will be further described below in conjunction with the present invention.

[0032] The following examples illustrate the present invention in more detail but are not intended to limit the present invention in any way.

[0033] Example 1: Isolation and structural characterization of compound IB

[0034] 5 kg of Illicium brevistylum ACsmith roots were crushed and extracted with 95% ethanol under reflux three times for 2 hours each time. The extract was concentrated under reduced pressure to yield 215 g of an extract. This extract was chromatographed on a silica gel column using petroleum ether, dichloromethane, ethyl acetate, and methanol, yielding 0.2 g of a petroleum ether fraction, 36.6 g of a dichloromethane fraction (including 15 g of the D1 component), 30.7 g of an ethyl acetate fraction, and 118 g of a methanol fraction. The D1 component was then chromatographed on a silica gel column using a petroleum ether-ethyl acetate gradient (100:1-8:1) to yield six fractions, D1E1-D1E6. The D1E1 component (7 g) was further subjected to silica gel column chromatography with a gradient elution of petroleum ether-ethyl acetate (100:1-40:1) to obtain eight components, namely D1E1a1, D1E1a2, D1E1b1, D1E1b2, D1E1b3, D1E1c1, D1E1c2, and D1E1. The component D1E1c1 (0.754 g) rich in compound IB was subjected to reverse phase C18 preparative liquid chromatography (Shimadzu LC-6AD chromatograph; YMC-pack ODS-A column, 250×20 mm, 5 μm; 60% acetonitrile as mobile phase; flow rate 5 ml / min) to obtain compound IB (0.6 g). The extraction and separation flow chart is shown in the attached figure. Figure 1 shown.

[0035] Structure and identification of compound IB

[0036]

[0037] Physicochemical properties and NMR spectral data of compound IB

[0038] Colorless oil, ESI-MS m / z 247[M+H]+ ; 1 H NMR and 13 C NMR spectral data are shown in Table 1.

[0039] Table 1 Compound IB 1 H NMR (500 MHz) and 13 C NMR (125 MHz) spectral data (acetone-d6)

[0040]

[0041] Example 2: Effect of Compound IB on the Behavior of EAE Mice

[0042] 2.1 Establishment of the experimental autoimmune encephalomyelitis mouse model and drug administration

[0043] Experimental Principle

[0044] C57BL / 6J mice were treated with MOG 35-55 Induced EAE model.

[0045] Experimental methods

[0046] Female C57BL / 6J mice, 6 weeks old, weighing 16-18 g, were subcutaneously injected with MOG after 3-5 days of adaptive feeding. 35-55 An experimental autoimmune encephalomyelitis (EAE) model was established by injecting 300 μg of pertussis toxin and 400 ng of pertussis toxin into the tail vein. A normal control group was also established. Eleven days after modeling, the animals developed varying degrees of limb paralysis, confirming the successful establishment of the experimental autoimmune encephalomyelitis model in mice.

[0047] After immunization, female C57BL / 6 mice were randomly divided into two groups: an EAE control group and an EAE group treated with 30 mg / kg compound IB. After grouping, mice were gavage-administered once daily. The normal control group and the EAE model group were given the same volume of solvent control (0.5% sodium carboxymethylcellulose solution). Compound IB was administered continuously from the date of immunization until day 28 of modeling. Disease scores were measured daily, and animal deaths were recorded. The hanging grade of the animals was measured on days 7, 14, 21, and 28 after immunization, and the hanging time of the animals on the wire mesh was measured on day 28.

[0048] Experimental results

[0049] On the 11th day after immunization, the animals began to become ill, with weight loss and decreased neurological function scores.

[0050] 2.2 Effect of compound IB on body weight of EAE mice

[0051] Experimental methods

[0052] Body weight is an important indicator of an animal's energy balance and growth. In this experiment, we observed and recorded the animals' activity, hair growth, and other general conditions daily, and monitored their body weight daily.

[0053] Experimental results

[0054] In this experiment, the weight of mice in the EAE model group was significantly lower than that in the normal group after the onset of the disease. However, after administration, the weight of mice in the compound IB treatment group increased significantly compared with the model group in the later period of administration, confirming that compound IB has the effect of improving weight loss. Figure 2 .

[0055] 2.3 Effect of compound IB on disease scores in EAE mice

[0056] Experimental methods

[0057] The experimental mice were scored for disease every day after modeling, and the scoring criteria were as follows:

[0058] 0 points: normal mouse; 0.5 points: tail weakness; 1 point: complete tail paralysis; 1.5 points: weakness of one hind limb; 2 points: weakness of both hind limbs; 2.5 points: paralysis of one hind limb and weakness of the other hind limb; 3 points: paralysis of both hind limbs; 3.5 points: partial weakness of the forelimbs; 4 points: partial paralysis of the forelimbs; 4.5 points: complete paralysis of the forelimbs; 5 points: death.

[0059] Experimental results

[0060] In this experiment, the disease scores of mice in the EAE model group were significantly higher than those in the normal control group after the onset of the disease. After administration, the overall symptoms of mice in the compound IB-administered group were alleviated, and the disease scores were significantly lower than those in the EAE model group, showing a significant improvement in the disease scores, confirming that compound IB has a significant improvement effect on the neurological function of EAE mice. Figure 3 .

[0061] 2.3 Effect of compound IB on the hanging time of EAE mice

[0062] Experimental methods

[0063] On the 28th day after modeling, the time it took for mice to fall from the 180° wire mesh was measured, and a time greater than 120 s was counted as 120 s.

[0064] Experimental results

[0065] In this experiment, compared with the normal control group, the EAE model group mice's hanging time on the wire mesh was significantly reduced. Compound IB can prolong the hanging time of EAE mice, confirming that Compound IB treatment has a significant and considerable improvement effect on the motor function of EAE mice. Figure 4 And Table 2.

[0066] Table 2 Effect of compound IB on the hanging time of MOG-induced EAE mice

[0067]

[0068] Mean±SEM (n=8).

[0069] ###P<0.001 vs. normal control group, ***P<0.001 vs. EAE model group.

[0070] 2.4 Effect of Compound IB on the Hanging Grading of EAE Mice

[0071] Experimental methods

[0072] On days 7, 14, 21, and 28 after modeling, the mice's front paws were suspended on a balance rope 30 cm above the ground. The mice's limb suspension status on the balance rope was observed and scored according to the following grading criteria: 5 points: grasping the rope and being able to pull with the hind limbs, with the tail tightly wrapped around the rope; 4 points: grasping the rope and being able to pull with the hind limbs, with the tail raised but unable to wrap around the rope; 3 points: grasping the rope and being able to pull with the hind limbs, with the tail drooping; 2 points: lifting the hind limbs, grasping the rope but unable to pull; 1 point: lifting the hind limbs, but unable to grasp the rope; 0 points: unable to lift the hind limbs.

[0073] Experimental results

[0074] In this experiment, compared with the normal control group, the hanging score of EAE model mice was significantly reduced after the onset of the disease. After administration, the hanging score of EAE mice in the compound IB administration group was significantly increased compared with the EAE model group, confirming that compound IB can significantly improve the hanging behavior of EAE mice. Figure 5 And Table 3.

[0075] Table 3 Effects of Compound IB on the hanging grade of MOG-induced EAE mice

[0076]

[0077] Mean±SEM (n=8).

[0078] ###P<0.001vs. normal control group; **P<0.01vs. EAE model group.

[0079] Example 3: Effects of Compound IB on Inflammatory Cell Infiltration and Demyelination in the Spinal Cord of EAE Model Mice 3.1 Establishment of EAE Mouse Model and Administration

[0080] The experimental principle, experimental method and experimental results are the same as those in Example 2.1.

[0081] 3.2 Effect of compound IB on inflammatory cell infiltration in the spinal cord of EAE mice

[0082] Experimental methods

[0083] On day 28 after modeling, three mice from each group were anesthetized with 4% tribromoethanol. The mice were first perfused with normal saline until the liver turned pale, followed by perfusion with 4% paraformaldehyde until the limbs became rigid. The animals were decapitated, and the lumbar enlargement of the spinal cord was fixed in 4% paraformaldehyde. Paraffin sections were prepared from the lumbar enlargement of the spinal cord and stained with hematoxylin and eosin (H&E) to observe inflammatory cell infiltration in the spinal cord.

[0084] Experimental results

[0085] In this experiment, compared with the normal control group, the spinal cord inflammatory cell infiltration of EAE model mice was significant. Treatment with 30mg / kg of compound IB significantly inhibited the infiltration of inflammatory cells in the spinal cord of EAE mice, and the pathological changes such as fibrosis and vacuolation caused by the inflammatory infiltration were significantly improved, confirming that compound IB can significantly improve the infiltration of inflammatory cells in the spinal cord of EAE mice. Figure 6 .

[0086] 3.3 Effect of compound IB on demyelination in the spinal cord of EAE mice

[0087] Experimental methods

[0088] On day 28 after modeling, three mice from each group were anesthetized with 4% tribromoethanol. The animals were first perfused with normal saline until the liver turned pale, followed by perfusion with 4% paraformaldehyde until the limbs became rigid. The animals were decapitated, and the lumbar enlargement of the spinal cord was fixed in 4% paraformaldehyde. Paraffin sections were prepared from the lumbar enlargement and stained with Fast Blue (LFB) to observe demyelination within the spinal cord.

[0089] Experimental results

[0090] In this experiment, after LFB staining, the spinal cord of EAE model mice showed larger demyelination lesions compared with the normal control group. 30mg / kg of compound IB can reduce the white area of the spinal cord white matter of EAE mice and effectively improve the demyelination condition. Figure 7 .

Claims

1. Use of a C6-C3 derivative IB as represented by formula (I) in the preparation of a drug for preventing, alleviating and / or treating autoimmune demyelinating diseases; 2. The use according to claim 1, characterized in that The autoimmune demyelinating diseases include demyelinating autoimmune diseases of the central nervous system, demyelinating autoimmune diseases affecting the peripheral nervous system, chronic inflammatory demyelinating polyneuropathy, anti-MAG peripheral neuropathy, motor and sensory neuropathy, genetic sensorimotor neuropathy, Charcot-Marie-Tooth disease, and Charcot-Marie-Tooth disease.

3. The use according to claim 2, characterized in that The demyelinating autoimmune diseases affecting the peripheral nervous system include acute inflammatory demyelinating polyneuropathy; the demyelinating autoimmune diseases of the central nervous system include multiple sclerosis, neuromyelitis optica spectrum disorder, acute disseminated encephalomyelitis, leukoencephalitis and transverse myelitis.

4. The use according to claim 3, characterized in that The multiple sclerosis includes relapsing-remitting multiple sclerosis, primary progressive multiple sclerosis, secondary progressive multiple sclerosis and progressive relapsing multiple sclerosis.

5. Use of a pharmaceutical composition for preventing, alleviating and / or treating autoimmune demyelinating diseases, characterized in that: The pharmaceutical composition contains an effective dose of compound IB as represented by formula (I), and optionally a pharmaceutically acceptable excipient.

6. Use according to claim 5, characterized in that The pharmaceutical composition contains not only compound IB as a pharmaceutically active ingredient, but also other active ingredients.

7. The use according to any one of claims 5 to 6, characterized in that The pharmaceutical composition includes the following dosage forms: solution, suspension, freeze-dried powder injection, emulsion, pill, capsule, powder, controlled release, sustained release preparation and microsome delivery system.

8. The use according to claim 5, characterized in that The pharmaceutical excipients include starch, dextrin, polymethylcellulose sodium, magnesium stearate and talc.

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