Application of peimine in preparation of medicine for treating multiple sclerosis
By using fritillarin as a drug component, the preparation of drugs for the prevention and treatment of multiple sclerosis has been solved, and the problem of lack of effective drugs in the prior art has been achieved, and the effective prevention and treatment of multiple sclerosis has been achieved, with high Clinical value and economic benefits, but dosage needs to be optimized to reduce toxicity.
Patent Information
- Application Number
- CN202310709126.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-06-15
- Publication Date
- 2024-12-17
AI Technical Summary
The prior art has not yet found effective methods to prevent and treat multiple sclerosis. Traditional Chinese medicine has advantages in this field, but there is a lack of new drugs to prevent and treat injuries.
Fritillarin as a pharmaceutical ingredient is used to prevent and treat multiple sclerosis by preparing drugs or drug preparations, including improving neurological damage, reducing morbidity and blocking the incidence of EAE in multiple sclerosis models.
Fritillaria can effectively block the incidence of EAE in multiple sclerosis model, improve neurological damage, and reduce the incidence of multiple sclerosis. It has high clinical value and economic benefits, but the dose needs to be further optimized to reduce drug toxicity.
Smart Images
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Abstract
Description
Technical Field
[0001] The invention belongs to the field of medicine, and particularly relates to the application of fritillary hormone A in preparing a drug for treating multiple sclerosis. Background Art
[0002] Multiple sclerosis is an inflammatory demyelinating neurodegenerative disease of the central nervous system that occurs most often in young people. Its etiology remains unknown, but is generally believed to be related to the environment, viral infection, and autoimmunity.
[0003] There is no good method for the treatment of multiple sclerosis. Practice has shown that traditional Chinese medicine has certain advantages in the treatment of multiple sclerosis. It can effectively improve the clinical symptoms of patients, relieve relapses, reduce the number of attacks, regulate their immune function, and promote axon and myelin repair. Therefore, it is very necessary to find new drugs to prevent and treat multiple sclerosis damage.
[0004] Experimental autoimmune encephalomyelitis (EAE) is an internationally recognized animal model for studying multiple sclerosis, which can fully reflect the pathogenesis and therapeutic effects of multiple sclerosis.
[0005] Fritillaria suturalensis structural formula:
[0006]
[0007] Fritillaria sutchuenensis is one of the main active ingredients of Fritillaria sutchuenensis and belongs to the alkaloid class of substances. Studies have shown that Fritillaria sutchuenensis has significant anti-inflammatory effects. However, there are currently no reports on the use of Fritillaria sutchuenensis in the prevention and / or treatment of multiple sclerosis. Summary of the invention
[0008] The invention aims to provide a new medicinal use of fritillaria aviculare.
[0009] The new use of the medicine of Fritillaria cirrhosae provided by the present invention is its use in preparing products for preventing and / or treating multiple sclerosis.
[0010] The prevention and / or treatment of multiple sclerosis is embodied in at least one of the following aspects:
[0011] (a1) Improve neurological function damage caused by multiple sclerosis;
[0012] (a2) reducing the incidence of multiple sclerosis or blocking the onset of multiple sclerosis;
[0013] (a3) Blocking the onset of EAE, a multiple sclerosis model.
[0014] The present invention also provides a new medicinal use of Fritillaria suturalensis A, which is at least one of the following (b1)-(b4):
[0015] (b1) prevention and / or treatment of multiple sclerosis;
[0016] (b2) Improve neurological function damage caused by multiple sclerosis;
[0017] (b3) reducing the incidence of multiple sclerosis or blocking the onset of multiple sclerosis;
[0018] (b4) Blocking the onset of EAE, a multiple sclerosis model.
[0019] The present invention also claims a product.
[0020] The product claimed in the present invention has an active ingredient of Fritillaria sutchuenensis; the product has any of the following uses:
[0021] (c1) prevention and / or treatment of multiple sclerosis;
[0022] (c2) Improve neurological function damage caused by multiple sclerosis;
[0023] (c3) reducing the incidence of multiple sclerosis or blocking the onset of multiple sclerosis;
[0024] (c4) Blocking the onset of EAE, a multiple sclerosis model.
[0025] In the present invention, the product may be a medicine or a pharmaceutical preparation.
[0026] In the present invention, the multiple sclerosis includes: primary progressive multiple sclerosis, secondary progressive multiple sclerosis and relapsing-remitting multiple sclerosis.
[0027] In the present invention, the multiple sclerosis includes: acute multiple sclerosis and chronic progressive multiple sclerosis.
[0028] The product of the present invention may contain, in addition to fritillary hormone, a suitable carrier or excipient, and other effective ingredients that play a synergistic role. The carrier includes conventional diluents, excipients, fillers, adhesives, wetting agents, disintegrants, absorption promoters, surfactants, adsorption carriers, lubricants, etc. in the pharmaceutical field. The above-mentioned medicine can be made into various forms such as injection, tablet, powder, granule, capsule, oral liquid, ointment, cream, etc.; the above-mentioned various dosage forms of medicine can be prepared according to conventional methods in the pharmaceutical field.
[0029] The above drugs can be introduced into the body such as muscle, intradermal, subcutaneous, intravenous, mucosal tissue by injection, spray, nasal drops, eye drops, penetration, absorption, physical or chemical mediation methods; or introduced into the body after being mixed or wrapped with other substances.
[0030] Fritillaria is one of the commonly used traditional Chinese medicines in clinical practice. Fritillaria extract is a representative monomer active drug of Fritillaria extract. This study found that Fritillaria extract can block the onset of EAE, a multiple sclerosis model. This discovery can make up for the shortcomings of modern medicine in the treatment of multiple sclerosis and has high clinical value and economic benefits. BRIEF DESCRIPTION OF THE DRAWINGS
[0031] Figure 1 The neurological function scores of mice in each group were scored;
[0032] Figure 2 H&E staining pathological changes of mice in each group;
[0033] Figure 3 The figures are the pathological changes of LFB staining in mice in each group. DETAILED DESCRIPTION
[0034] The present invention is further described below in conjunction with specific examples, but the present invention is not limited to the following examples. The methods described are conventional methods unless otherwise specified. The raw materials described can be obtained from public commercial channels unless otherwise specified.
[0035] Embodiment 1,
[0036] Establishment of EAE mouse animal model and grouping: 60 SPF C57BL / 6 female mice, 6-8 weeks old, weighing 18-22 g, were randomly divided into 4 groups (n=15 in each group): normal control group, model group, fingolimod group and fingolimod group.
[0037] EAE model preparation: 0.2 ml of MOG was injected subcutaneously at 4 points on both sides of the back of the mouse. 35-55 Emulsion (MOG 35-55 50μg, complete Freund's adjuvant 100μl, inactivated Mycobacterium tuberculosis 2mg / ml). Model animals were intraperitoneally injected with 500ng of pertussis toxin on the day of immunization and 48h later. The normal control group was replaced with normal saline. On the day of modeling, the normal control group and model group were given 0.2ml of normal saline by gavage, and the fritillary linalool group was given 10mg / kg by gavage. The fingolimod group began to be administered (FTY720, 0.3mg / kg) when the EAE mice developed 50% of the disease (day 11). The animals were killed after 35 days; the administration time was 9:00-11:00 am every day.
[0038] Neurobehavioral observation: including the incubation period of animal disease, clinical symptoms and signs, weight changes, morbidity and mortality, etc., and the neurological symptoms of EAE mice were graded and scored according to the universal 0-5 standard: 0 normal mice; 0.5 partial loss of tail tension; 1 paralysis of the tail; 2 moderate weakness of the hind limbs; 2.5 severe weakness of the hind limbs; 3 partial paralysis of the hind limbs; 3.5 complete paralysis of the hind limbs; 4 hind limb paralysis and partial paralysis of the forelimbs; 4.5 complete paralysis of all four limbs or dying. Mice at level 5 died. No score was calculated on the day of death.
[0039] result:
[0040] 1. Changes in morbidity, mortality and incubation period of mice
[0041] The mice in the model group began to develop the disease on the 9th day after immunization, with an incidence rate of 86.7%. Eight mice in the Fritillaria susceptor group died without developing the disease before death, and the remaining seven mice also did not develop the disease. See Table 1.
[0042] In the table below, the incubation period refers to the average time from mouse modeling to onset of disease.
[0043] Table 1 Changes in morbidity, mortality and incubation period of mice
[0044]
[0045] 2. Changes in neurological function scores of mice
[0046] The mice became ill from the 9th day of modeling, and the incidence rate of the model group was 86.7%. After the onset of EAE mice, the mice were listless, the fur luster decreased, the food and water intake decreased, the tail was paralyzed, and the hind limbs were paralyzed, and finally the forelimbs were paralyzed. When the mice in the fingolimod group were 50% ill (the 11th day, 7 mice were ill), FTY720 was used for gavage, and the incidence rate was 80.0%. As the gavage time increased, the neurological function scores of the mice in the fingolimod group showed a gradual downward trend. The Fritillaria suturing group began to be gavaged on the day of immunization (day 0). After gavage for 5 days, the spirit was depressed, the food and water intake decreased. At the peak of the model group (day 17), the model group had an incidence rate of 86.7%, and the Fritillaria suturing group had an incidence rate of 0%, and there was no death. However, as the administration time of Fritillaria suturing increased, 8 mice died from the 23rd to 35th day of immunization, and the 8 mice that died had no signs of illness before death. The remaining 7 mice showed no signs of disease when samples were collected on the 35th day. Figure 1 .
[0047] 3. Pathological changes of mice by H&E staining
[0048] H&E results showed that the spinal cord of EAE mice in the model group had obvious inflammatory cell infiltration. After intervention with fingolimod or fritillary glycosides, the inflammatory cell infiltration of the spinal cord of EAE mice was significantly reduced, and nuclear condensation and nuclear fragmentation were also significantly reduced. Figure 2 .
[0049] 4. Pathological changes of mouse LFB staining
[0050] LFB staining showed that the spinal cord staining of EAE mice in the model group was significantly reduced, indicating spinal cord demyelination. After intervention with fingolimod or fritillary lin A, LFB staining of the spinal cord of EAE mice increased significantly, indicating that demyelination was alleviated. Both have myelin protective effects. Figure 3 .
[0051] discuss:
[0052] Fritillaria is one of the commonly used traditional Chinese medicines in clinical practice. Fritillaria extract is a representative monomer active drug of Fritillaria extract. This study found that Fritillaria extract can block the onset of EAE, a multiple sclerosis model. At the same time, it is worth noting that the drug dose used in this study was relatively high, which can lead to the death of EAE mice. This shows that Fritillaria extract can block the onset of EAE mice, but it also has the toxic effects of the drug. The next step is to find a suitable dose of Fritillaria extract to intervene in EAE, in order to block the onset of EAE and reduce the toxic effects of the drug. This can make up for the shortcomings of modern medicine in the treatment of multiple sclerosis and has high clinical value and economic benefits.
Claims
1. Application of Fritillaria cirrhosae in the preparation of products for preventing and / or treating multiple sclerosis.
2. The use according to claim 1, characterized in that: The prevention and / or treatment of multiple sclerosis is embodied in at least one of the following aspects: (a1) Improve neurological function damage caused by multiple sclerosis; (a2) reducing the incidence of multiple sclerosis or blocking the onset of multiple sclerosis; (a3) Blocking the onset of EAE, a multiple sclerosis model.
3. The use according to claim 1 or 2, characterized in that: The product is a drug or a drug preparation.
4. The application of Fritillaria cirrhosae A is at least one of the following (b1)-(b4): (b1) prevention and / or treatment of multiple sclerosis; (b2) Improve neurological function damage caused by multiple sclerosis; (b3) reducing the incidence of multiple sclerosis or blocking the onset of multiple sclerosis; (b4) Blocking the onset of EAE, a multiple sclerosis model.
5. The use according to any one of claims 1 to 4, characterized in that: The multiple sclerosis includes primary progressive multiple sclerosis, secondary progressive multiple sclerosis and relapsing-remitting multiple sclerosis.
6. The use according to any one of claims 1 to 4, characterized in that: The multiple sclerosis includes: acute multiple sclerosis and chronic progressive multiple sclerosis.
7. A product, the active ingredient of which is Fritillaria cirrhosae; the product has any of the following uses: (c1) prevention and / or treatment of multiple sclerosis; (c2) Improve neurological function damage caused by multiple sclerosis; (c3) reducing the incidence of multiple sclerosis or blocking the onset of multiple sclerosis; (c4) Blocking the onset of EAE, a multiple sclerosis model.
8. The use according to claim 7, characterized in that: The product is a drug or a drug preparation.
9. The product according to claim 7 or 8, characterized in that: The multiple sclerosis includes primary progressive multiple sclerosis, secondary progressive multiple sclerosis and relapsing-remitting multiple sclerosis.
10. The product according to claim 7 or 8, characterized in that: The multiple sclerosis includes: acute multiple sclerosis and chronic progressive multiple sclerosis.