Anti-epileptic application of brazilin
By using Brazilian hematoxylin as an antiepileptic drug, the problems of poor efficacy and severe side effects of existing drugs have been solved, achieving safe and effective epilepsy treatment.
Patent Information
- Application Number
- CN202311773497.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-22
- Publication Date
- 2026-02-10
AI Technical Summary
Existing antiepileptic drugs are ineffective and have side effects in about one-third of patients, making the search for safer and more effective treatments urgent.
Brazilian hematoxylin was used to prepare an antiepileptic drug with an effective dose of 50 mg/kg, which was used to delay the latency period of epileptic seizures.
Brazilian hematoxylin significantly reduces the biotoxicity of drugs, has fewer side effects, and its efficacy is comparable to that of sodium valproate, but at a lower dosage, providing a new avenue for the treatment of epilepsy.
Smart Images
Figure CN121489934A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of pharmaceutical technology, and in particular to the anti-epileptic use of Brazilian hematoxylin. Background Technology
[0002] Epilepsy is a common neurological disorder affecting more than 70 million people worldwide. It is characterized by a persistent tendency for spontaneous seizures and has numerous neurobiological, cognitive, and sociopsychological consequences. Seizures occur "due to abnormally excessive or synchronized neuronal activity in the brain." Epilepsy is the process by which a non-epileptic brain is transformed into a brain capable of producing spontaneous, recurrent seizures. Epilepsy is a complex disease with multiple risk factors and, in many cases, a strong genetic component. Oxidative stress can trigger neurodegeneration, indirectly inducing seizures. Antiepileptic drugs are the primary treatment, but about one-third of patients develop drug resistance. While surgery is more effective, its cost-effectiveness and low patient acceptance limit its benefits. Currently, antiepileptic drugs are ineffective for about one-third of patients and are accompanied by varying degrees of side effects. Therefore, developing new drugs for treating epilepsy is of great significance. Finding better, more effective drug and non-drug treatments to alleviate and cure the disease is therefore urgent.
[0003] Brazilian hematoxylin, also known as Brazilian redwood, is a legume, mainly distributed in Southeast Asia and the Americas. It is an isoflavone compound extracted from the heartwood of sappanwood or Brazilian wood, with the molecular formula C. 16 H 14 O5, with a molecular weight of 286.28 g / mol, possesses various pharmacological activities, including antibacterial, anti-inflammatory, hypoglycemic, and immunomodulatory effects. Its chemical structure is shown in the figure below. .
[0004] Brazilin has potential applications in oxidative stress, inflammation, antibacterial activity, cancer, diabetes, neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and other pathologies. Pretreatment with 10 µM and 20 µM Brazilin significantly improved the survival rate of H2O2-treated PC12 cells and reduced apoptosis (Wang X, Xiu Z, Du Y, et al. Brazilin Treatment Produces Antidepressant- and Anxiolytic-Like Effects in Mice[J]. Biol Pharm Bull, 2019, 42(8): 1268-1274.). No reports on the antiepileptic effects of Brazilin have been found in the prior art. Summary of the Invention
[0005] The purpose of this invention is to provide an anti-epileptic use of Brazilian hematoxylin. Brazilian hematoxylin is a natural product with high safety and few side effects. Compared with commercially available chemically synthesized anti-epileptic drugs, its biotoxicity is significantly reduced, thus broadening the application scope of Brazilian hematoxylin and providing a new approach to the treatment of epilepsy.
[0006] The technical solution adopted by this invention to solve its technical problem is: Application of Brazilian hematoxylin in the preparation of antiepileptic drugs.
[0007] Brazilian hematoxylin can effectively delay the latency period of epileptic seizures.
[0008] The effective dose of Brazilian hematoxylin is 50 mg / kg.
[0009] An antiepileptic drug comprising a therapeutically effective amount of brassinolide or a pharmaceutically acceptable salt thereof.
[0010] The beneficial effects of this invention are: Brazilian hematoxylin is a natural product with high safety and few side effects. Compared with commercially available chemically synthesized antiepileptic drugs, its biological toxicity is significantly reduced, which broadens the application scope of Brazilian hematoxylin and provides a new approach to the treatment of epilepsy.
[0011] This invention found that 50 mg / kg of Brazilian hematoxylin has an effect comparable to that of sodium valproate, an effective antiepileptic drug already on the market, and the dosage is significantly lower than that of sodium valproate at 200 mg / kg. Attached Figure Description
[0012] Figure 1 This is a diagram showing the effect of Brazilian hematoxylin on the latency period of epileptic seizures: a diagram of the latency period of secondary seizures.
[0013] Figure 2 This is a diagram showing the effect of Brazilian hematoxylin on the latency period of epileptic seizures: a diagram of the latency period of a fourth-degree seizure.
[0014] Figure 3 This is a diagram showing the effect of Brazilian hematoxylin on the latency period of epileptic seizures: an average seizure severity diagram. Detailed Implementation
[0015] The technical solution of the present invention will be further described in detail below through specific embodiments.
[0016] In this invention, unless otherwise specified, all raw materials and equipment used are commercially available or commonly used in the field. The methods described in the following embodiments are conventional methods in the field, unless otherwise specified.
[0017] Brazilian hematoxylin was purchased from MCE China, while pentylenetetrazol and sodium valproate were purchased from Sigma.
[0018] Example 1: Drug concentration preparation The solvent for Brazilian hematoxylin consisted of 10% anhydrous ethanol and 90% physiological saline. The test drug was prepared into a 5 mg / mL solution using this solvent, with dosages of 12.5 mg / kg, 25 mg / kg, and 50 mg / kg. It was stored at room temperature in a sealed container until use. Pentyltetrazole (PTZ, used to induce seizures) was prepared into a 14 mg / mL solution using physiological saline, with a dosage of 77 mg / kg. Sodium valproate was prepared into a 40 mg / mL solution using physiological saline, with a dosage of 200 mg / kg.
[0019] Test animals: Male ICR mice, 23-25g. Provided by Zhejiang Academy of Medical Sciences. All groups of animals were housed under the same conditions: ambient temperature 23±2℃, relative humidity 50%–60%, with free access to food and water.
[0020] Animal grouping and treatment: Fifteen ICR mice were acclimatized for one week and then randomly divided into five groups of three: PTZ+Pro group (model group, Pro is the solvent: 10% anhydrous ethanol + 90% physiological saline), PTZ+VPA group (sodium valproate positive control group), PTZ+Bra-L group (12.5 mg / kg of brassinolide), PTZ+Bra-M group (25 mg / kg of brassinolide), and PTZ+Bra-H group (50 mg / kg of brassinolide).
[0021] Twenty minutes after intraperitoneal injection of the drug, an acute epilepsy model was established in mice by intraperitoneal injection of 77 mg / kg pentylenetetrazol. The seizure severity of the mice was observed, and the latency of grade II and IV seizures was recorded and statistically analyzed. Grade II and IV seizures are more typical and easier to observe and statistically analyze.
[0022] The epilepsy severity score was assessed using the Racine scale, as follows: Grade 1: Facial clonic contractions, including blinking, whisker twitching, rhythmic chewing, etc.; Grade 2: Grade 1 plus rhythmic head nodding; Grade 3: Grade 2 plus forelimb clonic contractions; Grade 4: Grade 3 plus hindlimb standing; Grade 5: Grade 4 plus falling; Grade 6: Generalized tonic-clonic contractions and death (Van Erum J, Van Dam D, De Deyn PP. PTZ-induced seizures in mice require a revised Racine scale[J]. EpilepsyBehav, 2019, 95: 51-55.).
[0023] result like Figure 1-3 As shown, compared with the model group, the latency of grade II and grade IV epileptic seizures was significantly delayed in the brassin and sodium valproate groups, and the grade of epileptic seizures in mice was significantly reduced. P <0.05, P <0.01 or P <0.001). This indicates that brassinolide can delay the latency of seizures induced by pentylenetetrazol in mice and reduce the severity of seizures. It exhibits a concentration gradient effect in delaying seizures, with 50 mg / kg of brassinolide being the most effective.
[0024] In summary, the present invention provides a novel drug that can effectively delay epileptic seizures—Brazilian hematoxylin, wherein the most preferred dose is 50 mg / kg.
[0025] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the present invention in any way. Other variations and modifications are possible without departing from the technical solutions described in the claims.
Claims
1. The application of Brazilian hematoxylin in the preparation of antiepileptic drugs.
2. The application according to claim 1, characterized in that: Brazilian hematoxylin can effectively delay the latency period of epileptic seizures.
3. The application according to claim 1, characterized in that: The effective dose of Brazilian hematoxylin is 50 mg / kg.
4. An antiepileptic drug, characterized in that: Contains a therapeutically effective amount of brassinolide or a pharmaceutically acceptable salt thereof.