Traditional Chinese medicine composition for treating or / and preventing infantile febrile convulsion as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention provides a traditional Chinese medicine composition for treating or / and preventing infantile febrile convulsion as well as a preparation method and application thereof, and belongs to the field of traditional Chinese medicines. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 8-12 parts of stiff silkworm, 8-12 parts of rhizoma typhonii, 12-20 parts of gastrodia elata and 8-12 parts of scorpion. The invention further provides a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition is used for treating or / and preventing infantile febrile convulsion, epilepsy and dizziness, the medicine effect is definite, the convulsion latency time can be remarkably prolonged, the convulsion duration time can be shortened, the spleen and stomach functions can be enhanced, the high-temperature resistance and non-convulsion capacity can be effectively improved, the effect can still be maintained after medicine withdrawal, and the medicine compatibility is used to play a synergistic effect.

Description

Technical Field

[0001] The invention relates to a traditional Chinese medicine composition for treating and / or preventing convulsions, belonging to the field of traditional Chinese medicine. Background Art

[0002] Convulsion, also known as convulsion, is a clinical symptom characterized by rhythmic limb movements and coma. It is a common acute and severe disease in childhood and can be caused by a variety of reasons, including infectious and non-infectious diseases. Convulsions may be associated with potential life-threatening risks, especially long-term convulsions or status epilepticus may cause permanent neurological damage. Depending on whether it is accompanied by fever, convulsions can be divided into two major categories: infectious and non-infectious. Common convulsions caused by infectious diseases include intracranial infections such as meningitis and encephalitis, as well as febrile convulsions. Non-infectious causes include water and electrolyte imbalances, hypoglycemia, drug poisoning, food poisoning, genetic metabolic diseases, brain trauma, etc.

[0003] Traditional Chinese Medicine (TCM) provides symptomatic treatment. Convulsions fall under the category of "convulsions" in TCM. TCM uses a variety of methods to treat convulsions, primarily based on the principle of syndrome differentiation and treatment, determining the treatment plan based on the patient's specific symptoms and constitution. Syndrome differentiation and treatment: When treating convulsions, TCM adopts different treatment methods depending on the cause and symptoms. For example, for convulsions caused by exogenous wind pathogens, the treatment principle may be to dispel wind and relieve exterior symptoms, and clear heat and detoxify. TCM uses specific herbal formulas to treat convulsions, such as modified Yinqiao Powder, modified Qingwen Baidu Drink, and modified Lingjiao Gou Teng Decoction. These formulas may contain herbs such as honeysuckle, forsythia, gypsum, coptis root, and scutellaria.

[0004] Ministry-issued standard Z6-90 WS3-B-1158-92 discloses Jinsudan: 200g of Arisaema ciliata, 100g of fried silkworm, 100g of bleached scorpion, 100g of processed aconite root, 100g of calcined ochre, 2g of musk, 200g of Gastrodia elata (fried with ginger juice), 3g of borneol, and 200g of processed frankincense. [Preparation] Finely grind the above nine ingredients, musk and borneol. Grind the remaining seven ingredients, including Arisaema ciliata, into a fine powder, sieve, mix, and make into pills with water. First, take some of the fine powder of Arisaema ciliata and other ingredients to separate the mother and child. Apply the fine powder of musk and borneol to the inner layer, then apply the remaining powder to the outer layer. Dry at low temperature to obtain the product. Its main functions and indications are to dispel wind and resolve phlegm, calm convulsions, and quench wind. It is used for convulsions caused by wind and phlegm in children. Pediatric wind-phlegm convulsions and pediatric febrile convulsions are two different diseases. Although they may both present as convulsions, there are significant differences in etiology, pathogenesis, clinical manifestations and treatment. Pediatric wind-phlegm convulsions are mostly related to internal obstruction of phlegm-dampness and internal movement of liver wind. Traditional Chinese medicine believes that phlegm-dampness blocks the meridians, leading to poor circulation of qi and blood and internal movement of liver wind, which in turn triggers convulsions. Internal obstruction of phlegm-dampness and internal movement of liver wind cause wind-phlegm to disturb the clear orifices, leading to muscle twitching and impaired consciousness. In terms of clinical manifestations, pediatric wind-phlegm convulsions are mostly manifested as limb convulsions, foaming at the mouth, phlegm sounds in the throat, and unconsciousness, which may be accompanied by fever, cough, and excessive sputum. Treatment focuses on clearing heat, resolving phlegm, calming the nerves, and extinguishing wind. Commonly used Chinese medicines include Arisaema consanguineum, Bombyx batryticatus, and Scorpion. Chinese medicine preparations such as Jinsudan can be used to treat wind-phlegm convulsions. Xu Li et al., "Dong's Jinsudan for Preventing and Treating Febrile Seizures in Children," Shanghai Journal of Traditional Chinese Medicine, Vol. 51, No. 2, 2017, discusses the use of Dong's Jinsudan for preventing and treating febrile seizures in children from the perspectives of etiology, pathogenesis, and syndrome differentiation and treatment. The prescription published in the literature is: processed Arisaema cinerea 60g, Tianma herb (fried with ginger juice) 60g, frankincense (degreased), magnetite (calcined and water-ground) 30g, whole scorpion (tail and legs removed, soaked in decoction to remove salt, sun-dried, stir-fried and ground) 30g, musk 6g, white aconite (fried in earth) 30g, borneol 18g, white silkworm (fried) 30g, coated with gold foil. Grind all ingredients into a fine powder and form into pills with water. This prescription for treating convulsions contains numerous medicinal ingredients, including toxic compounds with a narrow safety window. Both Arisaema consanguineum and Rhizoma Aconiti Lateralis Preparata contain calcium oxalate raphes and toxic proteins. Raw use or excessive dosage can cause mucosal irritation and nerve paralysis (Rhizoma Aconiti Lateralis Preparata is even more severe and requires thorough treatment with ginger and alum). Scorpion venom peptides (neuro-cardiotoxic), and hematite (residues after calcination) contain arsenic and lead, posing a risk of cumulative poisoning with long-term use. Musk and borneol: They can open the orifices and dissipate qi, potentially damaging yin. Excessive use can cause convulsions (the daily dose of borneol is ≤ 0.3g, and 18g in this prescription far exceeds the safe dose). The combination is unbalanced: the attack is excessive and the protection is insufficient. The sedative effects of scorpion and hematite in this prescription can easily deplete liver yin and exacerbate "deficient wind."

[0005] Epilepsy is a chronic brain disease characterized by recurrent seizures. Triggered by abnormal electrical discharges in brain neurons, seizures are recurrent and transient. Causes of epilepsy include muscle contractions, cerebral cortical developmental disorders, brain tumors, head trauma, central nervous system infections, and may also be genetic. The primary manifestation of epilepsy is sudden, unprovoked seizures. While symptoms vary, they are similar in each patient. Symptoms may include momentary loss of consciousness and falls, paresthesias in the limbs, hallucinations, repetitive words or single syllables, and body or eye rotations. There is no specific treatment for epilepsy. The primary treatment is medication, which aims to control the condition, reduce seizure frequency, achieve a seizure-free state, eliminate side effects, and restore or near-normal quality of life. During medication, patients should regularly monitor their blood levels to adjust their regimen. Lifestyle adjustments, such as maintaining good sleep, avoiding excessive fatigue and stress, and avoiding excessive alcohol and smoking, are also important preventative measures for epileptic seizures.

[0006] Vertigo is a subjective sensory disturbance in which the patient experiences a sensation of spinning or shaking themselves or their surroundings. It can be categorized as either rotational or non-rotational, and also as spontaneous or induced. Rotational vertigo involves a sensation of spinning or tumbling of the self or surroundings, while non-rotational vertigo involves a sensation of swaying, tilting, drifting, or sliding. Common causes of vertigo include medical conditions (such as peripheral vestibular vertigo and central vestibular vertigo), medications, environmental factors, and lifestyle. Certain groups, such as the elderly and those with disorders of the visual, vestibular, and proprioceptive systems, are more susceptible to vertigo. Clinical symptoms of vertigo include sensations of spinning, shaking, and moving, sometimes accompanied by tinnitus, hearing loss, limb weakness, chest tightness, and headaches. Dysfunctions in the complex visual, vestibular, and proprioceptive systems can cause this symptom, but vertigo itself is not contagious. Treatment for vertigo depends primarily on the cause. Medication, such as vestibular suppressants and glucocorticoids, is a common treatment. If dizziness is caused by a medication adverse reaction, your healthcare provider may recommend reducing, changing, or stopping the medication. Surgery is recommended for physical problems like tumors. Preventive measures for dizziness primarily focus on avoiding triggering factors, such as taking medications that may cause dizziness or avoiding situations that could trigger it. Summary of the Invention

[0007] The technical solution of the present invention is to provide a new traditional Chinese medicine composition for treating and / or preventing convulsions. It is a further optimization of the prescription of Jinsudan. On the one hand, the optimized and streamlined prescription is more conducive to clinical application and development, and on the other hand, the dosage ratio of the raw materials of Jinsudan is optimized to produce better efficacy. Another technical solution of the present invention is to provide a preparation method and use of the traditional Chinese medicine composition.

[0008] The present invention provides a traditional Chinese medicine composition for treating and / or preventing convulsions, which is prepared from the following raw materials in the following weight ratios: 8-12 parts of Bombyx Batryticatus, 8-12 parts of Rhizoma White Rhizoma, 12-20 parts of Rhizoma Gastrodiae, and 8-12 parts of Rhizoma Scorpio.

[0009] Preferably, it is prepared from the following raw materials in the following weight ratio:

[0010] 10 parts of Bombyx Batryticatus, 10 parts of Rhizoma White Rhizoma, 15 parts of Rhizoma Gastrodiae, and 10 parts of Scorpio.

[0011] The raw material medicine also contains one or a combination of two or more of antelope horn powder, borneol and musk.

[0012] Preferably, the weight ratio of the raw materials is: Bombyx batryticatus 10 parts, Rhizoma white aconiti 10 parts, Rhizoma Gastrodiae 15 parts, Scorpio 10 parts, Antelope horn powder 5 parts; or 10 parts of Bombyx Batryticatus, 10 parts of Rhizoma White Rhizoma, 15 parts of Rhizoma Gastrodiae, 10 parts of Scorpio, 3 parts of Borneolum Syntheticum, and 1-3 parts of Musk.

[0013] The raw material medicine further contains Arisaema cinerea, magnetite, frankincense, borneol and musk, and the weight ratio of the raw material medicine is: 10 parts of Bombyx Batryticatus, 10 parts of Rhizoma White Rhizoma, 15 parts of Rhizoma Gastrodiae, 10 parts of Scorpio, 20 parts of Arisaema Cum Bile, 10 parts of Hematite, 15 parts of Frankincense, 3 parts of Borneolum Syntheticum, 2 parts of Musk; or, 10 parts of Bombyx Batryticatus, 10 parts of Rhizoma White Rhizoma, 15 parts of Rhizoma Gastrodiae, 10 parts of Scorpio, 20 parts of Arisaema Cum Bile, 10 parts of Hematite, 15 parts of Frankincense, 3 parts of Borneolum Syntheticum, 1 part of Musk; or, 10 parts of Bombyx Batryticatus, 10 parts of Rhizoma White Rhizoma, 15 parts of Rhizoma Gastrodiae, 10 parts of Scorpio, 20 parts of Arisaema Cum Bile, 10 parts of Hematite, 15 parts of Frankincense, 3 parts of Borneolum Syntheticum, 3 parts of Musk; or, 10 parts of Bombyx Batryticatus, 10 parts of Rhizoma White Rhizoma, 20 parts of Arisaema Cum Bile, 10 parts of Scorpio, 20 parts of Rhizoma Gastrodiae, 10 parts of Hematite, 20 parts of Olibanum, 3 parts of Borneolum Syntheticum, and 2 parts of Musk.

[0014] Wherein, the white aconite root is processed white aconite root, the gastrodia elata is ginger gastrodia elata, the borneol is natural borneol, and the musk is artificial musk or natural musk.

[0015] The Chinese medicine composition of the present invention is prepared from the raw medicine powder, water or organic solvent extract of the raw medicine as active ingredients, and pharmaceutically acceptable excipients or auxiliary ingredients to form a commonly used oral preparation in medicine.

[0016] Wherein, the oral preparation is powder, tablet, capsule, granule, oral liquid, honey pill, water-honey pill, water pill, paste pill, wax pill, concentrated pill, dripping pill or sugar pill.

[0017] The present invention also provides a method for preparing the Chinese medicine composition for treating and / or preventing convulsions, which comprises the following steps: a. Weigh the APIs of various weight ratios; b. Powdering, or extracting with water or organic solvent, and then adding pharmaceutically acceptable excipients or auxiliary ingredients to prepare a commonly used oral preparation in medicine.

[0018] The present invention also provides use of the traditional Chinese medicine composition in preparing medicine for treating and / or preventing convulsions.

[0019] Wherein, the medicine is a medicine for treating and / or preventing febrile convulsions in children.

[0020] The medicine is a medicine that prolongs the latent time of febrile convulsion and shortens the duration of febrile convulsion.

[0021] The present invention also provides use of the traditional Chinese medicine composition in preparing medicines for treating and / or preventing epilepsy.

[0022] The present invention also provides use of the traditional Chinese medicine composition in preparing medicine for treating and / or preventing vertigo.

[0023] The vertigo of the present invention mainly refers to central vertigo, which is caused by lesions in the brainstem, cerebellum or brain, accounting for 10%-20% of vertigo cases, but has a higher potential risk (such as stroke).

[0024] Febrile seizures in children are primarily fever-related and typically occur when the body temperature rises suddenly. They are commonly associated with infections such as upper respiratory tract infections and gastroenteritis. Fever increases excitability in the cerebral cortex, causing abnormal electrical activity and leading to muscle rigidity or clonic seizures. Clinically, febrile seizures in children present with generalized or localized muscle rigidity or clonic seizures, often accompanied by loss of consciousness, upward rolling of the eyes, foaming at the mouth, and a cyanotic complexion. Current treatment focuses on reducing fever and providing sedation, with anticonvulsant therapy (such as ibuprofen and acetaminophen) and anticonvulsants (such as diazepam) administered as needed. From the Spring and Autumn Period to the Sui and Tang Dynasties, "infantile convulsions" were collectively referred to as "epilepsy," which were categorized according to their cause as wind-induced epilepsy, convulsion-induced epilepsy, food-induced epilepsy, and heat-induced epilepsy. The book "Youyou Xinshu" records that the names "infantile convulsions," "infantile acute convulsions," "infantile slow convulsions," "infantile slow spleen wind," and "acute and slow convulsions" appeared in the rhymes of pre-Song medical texts such as "Yu Jue" and "Shibi Jing." During the Song, Jin, and Yuan dynasties, "convulsions" and "epilepsy" coexisted, both referring to infantile convulsions. The book "Taiping Shenghui Fang" divided convulsions into acute convulsions and slow convulsions, establishing the distinction between infantile convulsions and epilepsy. Qian Yi's "Xiaoer Yaozheng Zhijue" redefined the concept of slow convulsions. The book "Youyou Xinshu" was the first to comprehensively compile and organize pediatric convulsion literature, preserving a large number of lost texts from ancient medical texts, supplementing and refining Qian Yi's theories on infantile convulsions. Starting in the Ming Dynasty, starting with the "Medical Compendium," "infantile epilepsy" almost exclusively referred to childhood epilepsy, clearly distinguishing between infantile convulsions and epilepsy. In the Treatise on the Origin and Symptoms of Various Diseases, it is mentioned that: "Children's convulsions are caused by disharmony of blood and qi, internal heat, and restlessness of the mind, so they suffer from syncope." "If the high fever does not subside, it will turn into convulsions. In very severe cases, it will also turn into epilepsy." The Taiping Shenghui Fang also says: "Children's sudden convulsions cause breastfeeding disorders, stagnation of internal organs, internal heat accumulation, and damage by wind evil, which enters the heart." Wang Shouchuan [Chen Hui, Wang Shouchuan. Differentiation and treatment of febrile convulsions in children based on "heat, phlegm, convulsion, and wind" [J]. Journal of Nanjing University of Chinese Medicine, 2021, 37(02): 290-293] believes that convulsions in children are located in the heart and liver, and are related to the lungs, spleen, and kidneys. The pathogenesis is the instability of the lung defense, the accumulation of wind and phlegm, and the deficiency of both the heart and spleen. When an attack occurs, the syndrome differentiation is based on "heat, phlegm, convulsion, and wind", and the treatment is to clear heat, resolve phlegm, calm the convulsion, and stop wind. Professor Dong Youqi [Zheng Hongzhou. Professor Dong Youqi's Experience in Treating Febrile Seizures in Children [J]. Journal of Traditional Chinese Medicine Pediatrics, 2015, 11(05):8-10.] believes that recurrent convulsions in children are related to three aspects: first, children have a pure yang constitution, and their liver is often in excess, which is prone to fire, phlegm, and wind; second, children's internal organs are delicate and their defenses are not strong; third, it is related to phlegm and turbidity blocking the meridians and phlegm and turbidity inside the body. Children's spleen is often insufficient, and the spleen is not functioning properly, which is prone to phlegm and dampness. Xuan's Pediatrics [Xuan Xiaobo, Shen Danping, Zhang Huiting, et al. Xuan's Pediatrics Experience in Preventing Recurrence of Febrile Seizures by Stages [J]. Chinese Journal of Traditional Chinese Medicine, 2019, 34(11):5021-5023.] believes that the pathogenesis of recurrent convulsions in children should be "deficiency in the root and excess in the superficial", which is closely related to pathological products such as food, phlegm, and blood stasis, as well as the constitution of children with yin deficiency and fire excess.

[0025] Combining the theories of ancient physicians with the advice of many modern clinical physicians, from an internal perspective, children's purely yang constitutions often result in excess liver function, making them susceptible to external pathogens, which can transform into wind and heat. Excessive heat can generate wind and phlegm, which in turn can cause fright, leading to convulsions. From an external perspective, phlegm and food retention can both trigger convulsions. Children's spleen and stomach functions are delicate, and improper feeding can lead to food accumulation, which can transform into fire and generate phlegm. Phlegm and fire can then block the meridians and cause convulsions.

[0026] Among the raw materials of the pharmaceutical composition of the present invention, the monarch drug: processed white aconite root has a pungent, dispersing, warming and unblocking effect, with a sharp, ascending nature. It is good at dispelling wind and phlegm from the head and face, calming convulsions and relieving spasms, and is the monarch drug. The assistant drugs: ginger and gastrodia elata enter the liver meridian, have a sweet taste and a moist texture, and are mild in nature, and are excellent at calming wind and relieving spasms. Bombyx batryticatus has a pungent and dispersing effect, which can not only calm wind and relieve spasms, but also resolve phlegm and calm convulsions, and also dissipate wind-heat. Scorpion specifically enters the liver meridian, has a wandering nature, and can calm liver wind and clear wind and dredge the meridians. It has excellent wind-calming and relieving spasms, and is a key drug for treating spasms and convulsions. The three drugs work together to calm liver wind, dissipate wind-heat, and calm wind and relieve spasms, and are therefore the assistant drugs. Auxiliary drugs: Arisaema is bitter in taste and cool in nature, and has the functions of clearing away heat and resolving phlegm, calming wind and relieving convulsions, and strengthens the effects of the auxiliary drugs in calming wind and dissipating heat, resolving phlegm and relieving spasms; vinegar and frankincense are pungent and dispersing, and can enter both the blood and the qi, and can relieve qi stagnation in the blood, promote the flow of qi and blood in the internal organs, penetrate the meridians, and promote the flow of blood; forged ochre is heavy and sinking, calms the liver and reduces adverse reactions, and is good at calming the latent liver yang; natural borneol can eliminate filth and turbidity, and has a fragrant aroma to open the orifices. When used together with musk, which is good at aromatic opening the orifices and refreshing the mind, the power of opening the orifices is doubled. The above are all adjuvants.

[0027] The drug of this invention has many years of clinical application experience, dispelling wind and phlegm, unblocking the meridians, and relieving spasms and invigorating the mind. It is characterized by its specificity and treatment of both the symptoms and the root cause. Its formulation, drug selection, and composition are consistent with Traditional Chinese Medicine theory and the etiology and pathogenesis of the indicated disease, thus providing a theoretical basis for this project. The drug formulation of this invention has been reviewed by clinical experts with long-term experience in related research, and preliminary empirical research in humans has confirmed its clear clinical therapeutic effect, the absence of toxic and side effects, and its safety and reliability.

[0028] Numerous animal studies have revealed that various Chinese patent medicines (TCMs) have a certain inhibitory effect on the pathogenesis of epilepsy. For example, Chaibei Zhixian Decoction, Fufang Shichangpu Preparation, and Bunao Zhixian Powder primarily inhibit epileptic seizures in rats induced by PTZ by interfering with GABA and Glu levels, achieving a balance between excitation and inhibition. Therefore, exploring the efficacy of more TCMs will open new prospects for epilepsy treatment. The drug of the present invention has the effects of dispelling wind and phlegm, unblocking the meridians, and relieving spasms and invigorating the orifices. This aligns with Traditional Chinese Medicine (TCM) theories of epilepsy treatment and long-term prevention, providing a viable clinical solution for the treatment and / or prevention of epileptic seizures. In an epileptic mouse model, the drug of the present invention has been observed to reduce the frequency of epileptic seizures in mice, alleviate clinical manifestations of epileptic seizures (such as limb rigidity, foaming or bloody at the mouth, urinary incontinence, lethargy, headache, and limb numbness), and shorten the duration of convulsions, providing strong evidence. The mice did not show any noticeable discomfort after administration, but drug dosage and toxicity studies in humans remain to be explored. Next, we will use this invention to support investigator-initiated clinical trials (IITs) to further verify the clinical efficacy of this invention in treating and / or preventing epileptic seizures in epilepsy patients.

[0029] The drug of this invention may have clinical efficacy in the acute treatment of vertigo, particularly central vertigo (such as stroke). It possesses the effects of dispelling wind and phlegm, unblocking the meridians, and relieving spasms and invigorating the orifices. This aligns with Traditional Chinese Medicine (TCM) theories for the treatment of vertigo (and stroke), providing a viable clinical solution for the treatment of central vertigo. In a mouse model of vertigo, strong evidence suggests that the drug of this invention alleviates the clinical manifestations of vertigo (such as incontinence, stress reactions, piloerection, and tremors) and shortens the duration of vertigo. Patients with the following manifestations may benefit: 1) vertigo combined with diplopia / slurred speech / facial paralysis; 2) vertigo combined with impaired consciousness / severe headache; and 3) vertigo combined with bilateral limb weakness, without experiencing significant discomfort after administration.

[0030] The beneficial effects of the present invention are: 1. The Chinese medicine composition of the present invention is used to treat and / or prevent convulsions, has clear efficacy, can significantly prolong the latent time of convulsions and shorten the duration of convulsions, can also strengthen the spleen and stomach function, and effectively improve the ability to withstand high temperatures without convulsions. The effect can still be maintained after discontinuation of the drug, and the drug combination can exert a synergistic effect.

[0031] 2. The core prescription of the Chinese medicine composition of the present invention, "Bombyx Batryticatus, Rhizoma White Rhizoma, Gastrodiae Rhizoma, and Scorpio", can play a synergistic role in treating convulsions under a specific ratio. The optimized core prescription has less medicinal taste, obvious efficacy, and is safer and more effective to use.

[0032] 3. In addition to treating and / or preventing febrile convulsions in children, the Chinese medicine composition of the present invention can also be used to treat and / or prevent epilepsy and vertigo, thereby increasing the clinical application scope of the drug. DETAILED DESCRIPTION

[0033] Example 1 Preparation of the Chinese medicine composition of the present invention Take 10g of Bombyx Batryticatus, 10g of Rhizoma Baiji, 15g of Rhizoma Gastrodiae, and 10g of Scorpio, grind them into powder directly to prepare a powder.

[0034] Example 2 Preparation of the Chinese medicine composition of the present invention Bombyx batryticatus 10g, Rhizoma white aconiti 10g, Rhizoma Gastrodiae 15g, Scorpio 10g, and Antelope horn powder 5g were prepared according to the method of Example 1.

[0035] Example 3 Preparation of the Chinese medicine composition of the present invention Prepare a powder with 10g of Bombyx Batryticatus, 10g of Rhizoma White Rhizoma, 15g of Rhizoma Gastrodiae, 10g of Scorpio, 3g of Borneol, and 3g of Musk.

[0036] Example 4 Preparation of the Chinese medicine composition of the present invention Bombyx batryticatus 10g, Rhizoma Aconiti Lateralis Preparata 10g, Gastrodia elata 15g, Scorpio 10g, Arisaema cinerea 20g, Hematite 10g, Frankincense 15g, Borneol 3g, Musk 2g; Crush and pass through a 100-mesh sieve, sterilize the fine powder, add appropriate amount of water as a binder, mix evenly, refine the medicine, make pills, dry, polish, coat, and encapsulate.

[0037] Example 5 Preparation of the Chinese medicine composition of the present invention Bombyx batryticatus 10g, Rhizoma whitensii 10g, Gastrodia elata 15g, Scorpio 10g, Arisaema cinerea 20g, Hematite 10g, Frankincense 15g, Borneol 3g, Musk 1g were prepared according to the method of Example 4.

[0038] Example 6 Preparation of the Chinese medicine composition of the present invention Bombyx batryticatus 10g, Rhizoma whitensii 10g, Gastrodia elata 15g, Scorpio 10g, Arisaema cinerea 20g, Hematite 10g, Frankincense 15g, Borneol 3g, Musk 3g were prepared according to the method of Example 4.

[0039] Example 7 Preparation of the Chinese medicine composition of the present invention Bombyx batryticatus 10g, Rhizoma white aconiti 10g, Arisaema cinerea 20g, Scorpio 10g, Gastrodia elata 20g, Hematite 10g, Frankincense 20g, Borneol 3g, Musk 2g were prepared according to the method of Example 4.

[0040] The beneficial effects of the present invention are demonstrated by the following pharmacodynamic tests.

[0041] The following raw medicinal materials were weighed, ground into powders, and mixed to prepare 13 formula medicines.

[0042] Formula 1: Gastrodia elata 45g; Formula 2: Bombyx batryticatus 18g, Gastrodia elata 27g; Formula 3: Bombyx batryticatus 12.8g, Gastrodia elata 19.4g, Scorpio 12.8g; Formula 4: Bombyx batryticatus 10g, Rhizoma white aconiti 10g, Gastrodia elata 15g, Scorpio 10g; Formula 5: Bombyx batryticatus 11.25g, Rhizoma white aconiti 11.25g, Gastrodia elata 16.875g, Scorpio 5.625g; Formula 6: Bombyx batryticatus 10g, Rhizoma white aconiti 10g, Rhizoma Gastrodiae 15g, Scorpio 10g, Antelope horn powder 5g; Formula 7: Bombyx batryticatus 10g, Rhizoma Aconiti Lateralis Preparata 10g, Gastrodia elata 15g, Scorpio 10g, Borneol 3g, Musk 2g; Formula 8: Bombyx batryticatus 10g, Rhizoma Aconiti Lateralis Preparata 10g, Gastrodia elata 15g, Scorpio 10g, Borneol 1.5g, Musk 1g; Formula 9: Ministry-issued standard Z6-90WS3-B-1158-92; prescription: Bombyx batryticatus 10g, Rhizoma Aconiti Lateralis Preparata 10g, Arisaema cinerea 20g, Scorpio 10g, Gastrodia elata 20g, Hematite 10g, Frankincense 20g, Borneol 0.3g, Musk 0.2g; Formula 10: Bombyx batryticatus 10g, Rhizoma Aconiti Lateralis Preparata 10g, Gastrodia elata 15g, Scorpio 10g, Arisaema cinerea 20g, Hematite 10g, Frankincense 15g, Borneol 3g, Musk 2g; Formula 11: Bombyx batryticatus 10g, Rhizoma Aconiti Lateralis Preparata 10g, Gastrodia elata 15g, Scorpio 10g, Arisaema cinerea 20g, Hematite 10g, Frankincense 15g, Borneol 3g, Musk 1g; Formula 12: Bombyx batryticatus 10g, Rhizoma Aconiti Lateralis Preparata 10g, Gastrodia elata 15g, Scorpio 10g, Arisaema cinerea 20g, Hematite 10g, Frankincense 15g, Borneol 3g, Musk 3g; Prescription 13: Bombyx batryticatus 10g, Rhizoma Aconitum 10g, Arisaema cinerea 20g, Scorpio 10g, Gastrodia elata 20g, Hematite 10g, Frankincense 20g, Borneol 3g, Musk 2g.

[0043] The above 13 formulas were tested to verify their efficacy in resisting febrile convulsions by analyzing their performance in convulsion latency and convulsion duration in young mice, as well as the difference in body weight during medication.

[0044] Test Example 1: Febrile Seizure Screening Experiment for Formulations 1 to 4 1. Animal Preparation Twenty-five 7-day-old C57BL / 6 mice of random sex, weighing between 2.9 and 5.6 g, were selected and fed adaptively before the experiment.

[0045] 2. Preparation Accurately weigh 75 mg of each of the formulated crude drugs for Formulations 1, 2, 3, and 4 and add 0.9% sodium chloride injection to a final volume of 1 mL of the test preparation. Use 0.9% sodium chloride injection as the negative control. Transport the prepared preparations and negative control to the animal room at room temperature for administration. After administration, dispose of any remaining preparations as medical waste.

[0046] 3. Experimental methods 3.1 Animal grouping Twenty-five 7-day-old C57BL / 6 mice of random sex were divided into formula group 1, formula group 2, formula group 3, formula group 4, and a model control group, with 5 mice in each group.

[0047] 3.2 Animal modeling The water bath temperature for the model control group and groups 1, 2, 3, and 4 was set at 45°C. A timer was started after the rats were placed in the water bath and stopped when their hind legs began to twitch. This period was the convulsion latency. The timer was started after the rats were removed from the water bath and continued until the convulsions stopped. Convulsion duration = convulsion cessation time minus convulsion onset time. All rats in the experimental groups were modeled on days 8 and 9. After modeling, the convulsion latency and duration were recorded, and body weight was measured.

[0048] 3.3 Animal Dosing The young mice in Group 1, Group 2, Group 3, and Group 4 were given oral administration of 0.75 g / kg every day for the first 8 days, and 0.75 g / kg 30 minutes before induction of convulsions on the 9th day of the experiment. The model control group was given an equal volume of 0.9% sodium chloride injection.

[0049] 3.4 Observation indicators After modeling, the convulsion latency and convulsion duration of the young mice were recorded, and their body weights were measured.

[0050] 3.5 Statistical methods The data were processed using Excel, and the measurement data were expressed as mean ± standard deviation ( ) were used for comparison; P < 0.05 indicated statistically significant differences.

[0051] 4. The experimental results are shown in Table 1 and Table 2: Table 1 Seizure latency and duration of startle in rats of each group (D8) Group Quantity (pieces) Test drug Dosage (mg / kg) Latency (seconds) Duration (seconds) Model control group 5 0.9% sodium chloride injection 750 27.00±4.30 94.40±5.13 Formula 1 5 Formulation 1 preparation 750 40.00±4.00 74.00±3.39 Formula 2 5 Formulation 2 preparation 750 52.40±4.56 72.00±5.96 Formula 3 groups 5 Formulation 3 preparation 750 67.80±4.55 65.60±4.04 4 groups of prescriptions 5 Formula 4 preparation 750 70.80±2.77 50.60±7.02 On Day 8, the comparison of the convulsion latency of mice in each group showed that the model control group (27.00±4.30 seconds) was significantly different from group 1 (40.00±4.00 seconds) (P=0.0138), and the model control group was extremely significantly different from group 2 (52.40±4.56 seconds), group 3 (67.80±4.55 seconds), and group 4 (70.80±2.77 seconds) (P<0.0001). There was a significant difference between group 1 and group 2 (P=0.0214), and there was an extremely significant difference between group 1 and group 3 and group 4 (P<0.0001). There was an extremely significant difference between group 2 and group 3 (P=0.0020) and group 4 (P=0.0001). There was no significant difference among the other groups.

[0052] On Day 8, the duration of convulsions in mice in each group was compared as follows: the model control group (94.40±5.13 seconds) was significantly different from group 1 (74.00±3.39 seconds), group 2 (72.00±5.96 seconds), group 3 (65.60±4.04 seconds), and group 4 (50.60±7.02 seconds) (P<0.0001); group 1 was significantly different from group 4 (P<0.0001); group 2 was significantly different from group 4 (P<0.0001); group 3 was significantly different from group 4 (P=0.0010), and there was no significant difference in the other groups.

[0053] Table 2 Seizure latency and duration of startle in rats of each group (D9) Group Quantity (pieces) Test drug Dosage (mg / kg) Latency (seconds) Duration (seconds) Model control group 5 0.9% sodium chloride injection 750 27.60±6.84 88.00±6.82 Formula 1 5 Formulation 1 preparation 750 42.20±3.83 72.40±3.65 Formula 2 5 Formulation 2 preparation 750 52.60±3.65 65.20±5.07 Formula 3 groups 5 Formulation 3 preparation 750 62.40±3.05 59.40±2.70 4 groups of prescriptions 5 Formula 4 preparation 750 68.80±2.39 50.80±2.77 On Day 9, the comparison of the convulsion latency time of mice in each group showed that there were extremely significant differences between the model control group (27.60±6.84 seconds) and group 1 (42.20±3.83 seconds) (P=0.0039), group 2 (52.60±3.65 seconds) (P<0.0001), group 3 (62.40±3.05 seconds) (P<0.0001), and group 4 (68.80±2.39 seconds) (P<0.0001). There were also extremely significant differences between group 1 and group 3 and group 4 (P<0.0001), and between group 2 and group 4 (P=0.0010). There were no significant differences among the other groups.

[0054] On Day 9, the duration of convulsions in mice in each group was compared as follows: there were extremely significant differences between the model control group (88.00±6.82 seconds) and group 1 (72.40±3.65 seconds) (P=0.0005), group 2 (65.20±5.07 seconds), group 3 (59.40±2.70 seconds), and group 4 (50.80±2.77 seconds) (P<0.0001); there were extremely significant differences between group 1 and group 3 (P=0.0061) and group 4 (P<0.0001); there was extremely significant difference between group 2 and group 4 (P=0.0017), and there was no significant difference among the other groups.

[0055] This study used a hot water bath to induce febrile seizures in 7-day-old mice, both single and repeated. The results showed that hot water stimulation promoted seizures in young mice. A core formula for treating febrile seizures was identified through studies of formulas 1-4. The results showed that formula 4 (10g of Bombyx Batryticatus, 10g of Rhizoma Aconiti Lateralis Preparata, 15g of Gastrodia elata, and 10g of Scorpio scorpio) at a dose of 750mg / kg significantly outperformed the other groups in both the latency and duration of febrile seizures on days 8 and 9. These results demonstrate that the core formula of this traditional Chinese medicine composition (Bombyx Batryticatus, Rhizoma Aconiti Lateralis Preparata, Gastrodia elata, and Scorpio scorpio) can, when combined in a specific ratio, exert a synergistic effect in treating seizures.

[0056] Test Example 2: Febrile Seizure Screening Experiment of Formulations 4 to 7 1. Animal Preparation Twenty-five 7-day-old C57BL / 6 mice of random sex, weighing 2.2-4.5 g, were selected and fed adaptively before the experiment.

[0057] 2. Preparation Accurately weigh 75 mg of each of the crude drugs in Formulas 4, 5, 6, and 7 and add 0.9% sodium chloride injection to a final volume of 1 mL of the test preparation. Use 0.9% sodium chloride injection as the negative control. Transport the prepared preparations and negative control to the animal room at room temperature for administration. After administration, dispose of any remaining preparations as medical waste.

[0058] 3. Experimental methods 3.1 Animal grouping Twenty-five 7-day-old C57BL / 6 mice of random sex were divided into four groups: group 4, group 5, group 6, group 7, and a model control group, with 5 mice in each group.

[0059] 3.2 Animal modeling The water bath temperature was set at 45°C for the model control group and groups 4, 5, 6, and 7. A timer was started after the rats were placed in the water bath and stopped when their hind legs began to twitch. This period was the convulsion latency. The timer was started after the rats were removed from the water bath and continued until the convulsions stopped. Convulsion duration = convulsion cessation time minus convulsion onset time. All rats in the experimental groups were modeled on days 6 and 8. After modeling, the convulsion latency and duration were recorded, and body weight was measured.

[0060] 3.3 Animal Dosing The young mice in groups 4, 5, 6, and 7 were given 0.75 g / kg of the drug by gavage daily for 8 consecutive days. Convulsions were induced once on the 6th and 8th days of the experiment, and the model control group was given an equal volume of 0.9% sodium chloride injection.

[0061] 3.4 Observation indicators After modeling, the convulsion latency and convulsion duration of the young mice were recorded, and their body weights were measured.

[0062] 3.5 Statistical methods The data were processed using Excel, and the measurement data were expressed as mean ± standard deviation ( ) were used for comparison; P < 0.05 indicated statistically significant differences.

[0063] 4. The experimental results are shown in Table 3, Table 4, and Table 5: Table 3 Seizure latency and duration of startle in rats of each group (D6) Group Quantity (pieces) Test drug Dosage (mg / kg) Latency (seconds) Duration (seconds) Model control group 5 0.9% sodium chloride injection 750 38.40±13.20 50.80±15.50 4 groups of prescriptions 5 Formula 4 preparation 750 45.40±9.45 32.20±7.33 5 groups of prescriptions 5 Formula 5 preparation 750 66.20±12.26 29.00±6.08 6 groups of prescriptions 5 Formula 6 preparation 750 67.80±18.54 33.40±17.40 7 groups of prescriptions 5 Formula 7 preparation 750 92.20±24.54 28.20±29.28 On Day 6, the comparison of the convulsion latency of mice in each group showed that the model control group (38.40±13.20 seconds) was significantly different from group 5 (66.20±12.26 seconds) (P=0.0161); the differences between group 6 (67.80±18.54 seconds) (P=0.0093) and group 7 (92.20±24.54 seconds) (P<0.0001) were extremely significant. There was an extremely significant difference between group 4 and group 7 (P<0.0001), an extremely significant difference between group 5 and group 7 (P=0.0288), and a significant difference between group 6 and group 7 (P=0.047). There were no significant differences in the other groups.

[0064] On Day 6, the duration of convulsions in mice of each group showed no significant difference.

[0065] Table 4 Convulsion latency and duration of startle in rats of each group (D8) Group Quantity (pieces) Test drug Dosage (mg / kg) Latency (seconds) Duration (seconds) Model control group 5 0.9% sodium chloride injection 750 41.40±10.06 48.00±13.55 4 groups of prescriptions 5 Formula 4 preparation 750 47.00±10.20 30.20±7.53 5 groups of prescriptions 5 Formula 5 preparation 750 70.40±4.72 26.40±12.68 6 groups of prescriptions 5 Formula 6 preparation 750 72.60±13.15 27.40±7.70 7 groups of prescriptions 5 Formula 7 preparation 750 96.60±24.48 10.40±7.09 On Day 8, the comparison of the convulsion latency of mice in each group showed that the model control group (41.40±10.06 seconds) was significantly different from group 5 (70.40±4.72 seconds) (P=0.0107) and group 6 (72.60±13.15 seconds) (P=0.0049); the model control group was significantly different from group 7 (96.60±24.48 seconds) (P<0.0001), and group 4 was significantly different from group 6 (P=0.0327); the model control group was significantly different from group 7 (P<0.0001), and group 5 was significantly different from group 7 (P=0.0271). There were no significant differences in the other groups.

[0066] On Day 8, the duration of convulsions in mice in each group was compared: there was a significant difference between the model control group (48.00±13.55 seconds) and formula 7 (10.40±7.09 seconds) (P=0.0058), while there was no significant difference in the other groups.

[0067] Table 5 Comparison of body weight of young mice in each group on day 6 Group Quantity (pieces) Test drug Dosage (mg / kg) D6 weight (g) Model control group 5 0.9% sodium chloride injection 750 4.68±0.31 4 groups of prescriptions 5 Formula 4 preparation 750 5.00±0.34 5 groups of prescriptions 5 Formula 5 preparation 750 4.50±0.22 6 groups of prescriptions 5 Formula 6 preparation 750 4.34±0.42 7 groups of prescriptions 5 Formula 7 preparation 750 5.32±0.47 On Day 6, the body weights of mice in each group were compared: there was a significant difference between group 5 (4.50±0.22 g) and group 7 (5.32±0.47 g) (P=0.0173), and there was an extremely significant difference between group 6 (4.34±0.42 g) and group 7 (P=0.0023). There were no significant differences in the other groups.

[0068] Among the prescriptions in this experiment, prescription 5 adjusted the dosage ratio of the raw materials in prescription 4, and prescriptions 6 and 7 added one or more of antelope horn, borneol, and musk on the basis of prescription 4. The results showed that the prescription 7 (10g of Bombyx batryticatus, 10g of Rhizoma Baiji, 15g of Gastrodia elata, 10g of Scorpio, 3g of borneol, and 2g of musk) group, with a dosage of 750mg / kg, was superior to the other groups in the latent time and duration of febrile convulsions on D6 and D8, and the differences were significant.

[0069] Test Example 3: Febrile Seizure Screening Test of Formula 4-5-6-8 1. Animal Preparation Twenty-five 7-day-old C57BL / 6 mice of random sex, weighing 3.2-4.9 g, were selected and fed adaptively before the experiment.

[0070] 2. Preparation Accurately weigh 150 mg of each of the crude drugs in Formulas 4, 5, 6, and 8 and add 0.9% sodium chloride injection to a final volume of 1 mL of the test preparation. Use 0.9% sodium chloride injection as the negative control. Transport the prepared preparations and negative control to the animal room at room temperature for administration. After administration, dispose of any remaining preparations as medical waste.

[0071] 3. Experimental methods 3.1 Animal grouping Twenty-five 7-day-old C57BL / 6 mice of random sex were divided into four groups: group 4, group 5, group 6, group 8, and a model control group, with 5 mice in each group.

[0072] 3.2 Animal modeling The water bath temperature was set at 45°C for the model control group and groups 4, 5, 6, and 8. A timer was started after the rats were placed in the water bath and stopped when their hind legs began to twitch. This period was the convulsion latency. The timer was started after the rats were removed from the water bath and continued until the convulsions stopped. Convulsion duration = convulsion cessation time minus convulsion onset time. All rats in the experimental groups were modeled on days 6 and 8. After modeling, the convulsion latency and duration were recorded, and body weight was measured.

[0073] 3.3 Animal Dosing The young mice in groups 4, 5, 6, and 8 were given 1.5 g / kg of the drug by gavage daily for 8 days. Convulsions were induced once on days 6 and 8 of the experiment, and the model control group was given an equal volume of 0.9% sodium chloride injection.

[0074] 3.4 Observation indicators After modeling, the convulsion latency and convulsion duration of the young mice were recorded, and their body weights were measured.

[0075] 3.5 Statistical methods The data were processed using Excel, and the measurement data were expressed as mean ± standard deviation ( ) were used for comparison; P < 0.05 indicated statistically significant differences.

[0076] 4. The experimental results are shown in Table 6 and Table 7: Table 6 Convulsion latency and duration of startle in rats of each group (D6) Group Quantity (pieces) Test drug Dosage (mg / kg) Latency (seconds) Duration (seconds) Model control group 5 0.9% sodium chloride injection 1500 28.80±2.49 96.40±5.37 4 groups of prescriptions 5 Formula 4 preparation 1500 29.80±8.26 49.00±19.39 5 groups of prescriptions 5 Formula 5 preparation 1500 61.60±4.83 75.60±12.12 6 groups of prescriptions 5 Formula 6 preparation 1500 53.80±5.89 16.20±14.64 8 groups of prescriptions 5 Formula 8 preparation 1500 45.60±4.51 14.60±10.36 On Day 6, the comparison of the convulsion latency of mice in each group showed that the model control group (28.80±2.49 seconds) was significantly different from group 5 (61.60±4.83 seconds), group 6 (53.80±5.89 seconds), and group 8 (45.60±4.51 seconds) (P<0.0001); group 4 (29.80±8.26 seconds) was significantly different from group 5, group 6, and group 8 (P<0.0001); group 5 was significantly different from group 8 (P<0.0001); there was no significant difference among the other groups.

[0077] On Day 6, the duration of convulsions in mice in each group was compared as follows: there were extremely significant differences between the model control group (96.40±4.66 seconds), group 4 (49.00±19.39 seconds), group 6 (16.20±14.64 seconds), and group 8 (14.60±10.36 seconds) (P<0.0001); there were significant differences between group 4 and group 5 (75.60±12.12 seconds) (P=0.0161); there were extremely significant differences between group 4 and group 5 (P=0.0005), group 6 (P<0.0001), and group 8 (P<0.0001); there were extremely significant differences between group 5 and group 6 and group 8 (P<0.0001); there were no significant differences among the other groups.

[0078] Table 7 Convulsion latency and duration of startle in rats of each group (D8) Group Quantity (pieces) Test drug Dosage (mg / kg) Latency (seconds) Duration (seconds) Model control group 5 0.9% sodium chloride injection 1500 27.20±3.63 94.80±4.66 5 groups of prescriptions 5 Formula 5 preparation 1500 60.80±3.11 71.80±5.89 6 groups of prescriptions 5 Formula 6 preparation 1500 43.60±4.72 33.20±3.42 8 groups of prescriptions 5 Formula 8 preparation 1500 44.20±5.17 13.40±7.27 On Day 8, the comparison of the convulsion latency of mice in each group showed that the model control group (27.20±3.63 seconds) was significantly different from group 5 (60.80±3.11 seconds), group 6 (43.60±4.72 seconds), and group 8 (44.20±5.17 seconds) (P<0.0001). The group 5 was significantly different from group 6 and group 8 (P<0.0001). There was no significant difference in the other groups.

[0079] On Day 8, the duration of convulsions in mice in each group was compared: there were extremely significant differences between the model control group (94.80±4.66 seconds) and group 5 (71.80±5.89 seconds) (P=0.0047), group 6 (33.20±3.42 seconds) (P<0.0001), and group 8 (13.40±7.27 seconds) (P<0.0001). There were extremely significant differences between group 5 and group 6 and group 8 (P<0.0001), and there was a significant difference between group 6 and group 8 (P=0.0269). There were no significant differences in the other groups.

[0080] Among the prescriptions in this experiment, prescription 5 adjusted the dosage ratio of the raw materials in prescription 4. Prescriptions 6 and 8 added one or more of antelope horn, borneol, and musk on the basis of prescription 4, with a dosage of 1500 mg / kg. The results showed that prescription 8 (10g of Bombyx batryticatus, 10g of Aconitum white root, 15g of Gastrodia elata, 10g of Scorpion, 1.5g of borneol, and 1g of musk) was significantly better than prescriptions 5 and 6.

[0081] Combining Experiment 2 and Experiment 3, the results showed that at a lower dosage, Formulation 7 achieved the best latent time and duration, and was further studied as the preferred formulation.

[0082] Test Example 4: Febrile Seizure Screening Experiment of Formula 9-10-11-12-13 1. Animal Preparation Thirty 7-day-old C57BL / 6 mice of random sex, weighing 2.7-4.1 g, were selected and fed adaptively before the experiment.

[0083] 2. Preparation Accurately weigh 150 mg of each of the crude drugs in Formulas 9, 10, 11, 12, and 13 and add 0.9% sodium chloride injection to a final volume of 1 mL of the test preparation. Use 0.9% sodium chloride injection as the negative control. Transport the prepared preparations and negative control to the animal room at room temperature for administration. After administration, dispose of any remaining preparations as medical waste.

[0084] 3. Experimental methods 3.1 Animal grouping Thirty 7-day-old C57BL / 6 mice of random sex were divided into group 9, group 10, group 11, group 12, group 13, and a model control group, with 5 mice in each group.

[0085] 3.2 Animal modeling The water bath temperature for the model control group and groups 9, 10, 11, 12, and 13 was set at 45°C. A timer was started after the rats were placed in the water bath and stopped when their hind legs began to twitch. This period was the convulsion latency. The timer was started after the rats were removed from the water bath and continued until the convulsions stopped. Convulsion duration = convulsion cessation time minus convulsion onset time. All rats in the experimental groups underwent modeling on days 1 and 8. After modeling, the convulsion latency and duration were recorded, and body weight was measured.

[0086] 3.3 Animal Dosing The young mice in groups 9, 10, 11, 12, and 13 were given 1.5 g / kg by oral gavage daily for 8 consecutive days. On days 1 and 8 of the experiment, 1.5 g / kg was given by oral gavage 30 minutes before inducing convulsions. The model control group was given an equal volume of 0.9% sodium chloride injection.

[0087] 3.4 Observation indicators After modeling, the convulsion latency and convulsion duration of the young mice were recorded, and their body weights were measured.

[0088] 3.5 Statistical methods The data were processed using Excel, and the measurement data were expressed as mean ± standard deviation ( ) were used for comparison; P < 0.05 indicated statistically significant differences.

[0089] 4. The experimental results are shown in Table 8 and Table 9: Table 8 Convulsion latency and duration of startle in rats of each group (D1) Group Quantity (pieces) Test drug Dosage (mg / kg) Latency (seconds) Duration (seconds) Model control group 5 0.9% sodium chloride injection 1500 25.2±5.3 97.4±17.8 9 groups of prescriptions 5 Formula 9 preparation 1500 34.6±6.7 72.2±35.0 10 groups of prescriptions 5 Formula 10 preparations 1500 43.4±12.8 46.2±14.2 11 groups of prescriptions 5 Formula 11 preparation 1500 39.2±8.6 57.8±7.2 12 groups of prescriptions 5 Formula 12 preparations 1500 43.0±9.8 55.2±15.6 13 groups of prescriptions 5 Formula 13 preparation 1500 50.0±5.3 34.0±15.2 On Day 1, the comparison of the convulsion latency time of mice in each group showed that there were significant differences between the model control group (25.2±5.3 seconds) and group 10 (43.4±12.8 seconds) (P=0.0053), group 12 (43.0±9.8 seconds) (P=0.0068), group 13 (50.0±5.3 seconds) had an extremely significant difference (P<0.0001), group 9 (34.6±6.7 seconds) had a significant difference with group 13 (P=0.0271), and there were no significant differences in the other groups.

[0090] On Day 1, the duration of convulsions in mice in each group showed extremely significant differences between the model control group (97.4±17.8 seconds) and group 10 (46.2±14.2 seconds) (P=0.0002) and group 13 (34.0±15.2 seconds) (P<0.0001). There were also significant differences between the model control group and group 11 (57.8±7.2 seconds) (P=0.0053) and group 12 (55.2±15.6 seconds) (P=0.0025). There was a significant difference between group 9 (72.2±35.0 seconds) and group 13 (P=0.0078). There were no significant differences in the other groups.

[0091] Table 9 Convulsion latency and duration of startle in each group of mice (D8) Group Quantity (pieces) Test drug Dosage (mg / kg) Latency (seconds) Duration (seconds) Model control group 5 0.9% sodium chloride injection 1500 25.6±4.7 79.8±26.4 9 groups of prescriptions 5 Formula 9 preparation 1500 33.6±8.0 46.8±4.3 10 groups of prescriptions 5 Formula 10 preparations 1500 51.4±6.2 30.0±3.3 11 groups of prescriptions 5 Formula 11 preparation 1500 48.6±3.2 49.0±13.6 12 groups of prescriptions 5 Formula 12 preparations 1500 50.2±6.1 39.4±5.7 13 groups of prescriptions 5 Formula 13 preparation 1500 49.2±9.3 33.0±7.5 On Day 8, the comparison of the convulsion latency of mice in each group showed that there were extremely significant differences between the model control group (25.6±4.7 seconds) and group 10 (51.4±6.2 seconds) (P<0.0001), group 11 (48.6±3.2 seconds) (P=0.0002), group 12 (50.2±6.1 seconds) (P<0.0001), and group 13 (49.2±9.3 seconds) (P=0.0001). There were significant differences between group 9 (33.6±8.0 seconds) and group 10 (P=0.0068), group 11 (P=0.0337), group 12 (P=0.0138), and group 13 (P=0.0243). There were no significant differences in the other groups.

[0092] On Day 8, the duration of convulsions in mice in each group showed significant differences between the model control group (79.8±26.4 seconds) and group 9 (46.8±4.3 seconds) (P=0.0307) and group 11 (49.0±13.6 seconds). There were extremely significant differences between the model control group and group 10 (30.0±3.3 seconds) (P=0.0002), group 12 (39.4±5.7 seconds) (P=0.0042), and group 13 (33.0±7.5 seconds) (P=0.0006). There were no significant differences in the other groups.

[0093] In this experiment, the formulas of each group were supplemented with three herbs: Arisaema cinerea, Daizheshi and Frankincense on the basis of formula 7. The results showed that the formula 10 (10 parts of Bombyx batryticatus, 10 parts of Rhizoma whitebirica, 15 parts of Rhizoma gastrodiae, 10 parts of Scorpio scorpion, 20 parts of Arisaema cinerea, 10 parts of Daizheshi, 15 parts of Frankincense, 3 parts of Borneolum, 2 parts of Musk) and the formula 13 (10 parts of Bombyx batryticatus, 10 parts of Rhizoma whitebirica, 20 parts of Arisaema cinerea, 10 parts of Scorpio scorpion, 20 parts of Rhizoma gastrodiae, 10 parts of Daizheshi) were significantly better than those of the formula 14 (10 parts of Bombyx batryticatus, 10 parts of Rhizoma whitebirica, 20 parts of Arisaema cinerea, 10 parts of Scorpio scorpion, 20 parts of Gastrodia elata, 10 parts of Daizheshi). The latent time and duration of febrile convulsions on D1 and D8 in the group of formula 9 (i.e., the ministerial standard Z6-90WS3-B-1158-92: 10 parts of bombyx batryticatus, 10 parts of white aconite root, 20 parts of biliary arisaema, 10 parts of scorpion, 20 parts of gastrodia elata, 10 parts of magnetite, 20 parts of frankincense, 0.3 parts of borneol, 0.2 parts of musk) were significantly better than those in the model control group and the group of formula 9, and the differences were significantly different.

[0094] In addition, compared with Formula 9 in this experiment, Formula 4 in Experimental Example 1 has a longer latent time and a shorter duration at half the dose of Formula 9, which proves that the optimized Formula 4 uses less medicinal ingredients and has better efficacy.

[0095] Test Example 5: Epilepsy screening experiment of formula 9-10-11-12-13 1. Animal Preparation Thirty C57BL / 6 mice of random sex aged 4-6 weeks were selected and fed adaptively before the experiment.

[0096] 2. Preparation Accurately weigh 150 mg of each of the crude drugs in Formulas 9, 10, 11, 12, and 13 and add 0.9% sodium chloride injection to a final volume of 1 mL of the test preparation. Use 0.9% sodium chloride injection as the negative control. Transport the prepared preparations and negative control to the animal room at room temperature for administration. After administration, dispose of any remaining preparations as medical waste.

[0097] 3. Experimental methods 3.1 Animal grouping Single-dose experiment: 30 C57BL / 6 mice aged 4-6 weeks were randomly divided into model control group, 9# formulation group, 10# formulation group, 11# formulation group, 12# formulation group, and 13# formulation group, with 5 mice in each group.

[0098] Multiple-dose experiment: 30 C57BL / 6 mice aged 4-6 weeks were randomly divided into model control group, 9# formulation group, 10# formulation group, 11# formulation group, 12# formulation group, and 13# formulation group, with 5 mice in each group.

[0099] 3.2 Animal modeling Single-dose experiment: The drug was administered once. 30 minutes after administration, the mouse epilepsy model was established using the PTZ ignition method, and 65 mg / kg of pentylenetetrazol was injected intraperitoneally.

[0100] Multiple-dose experiment: The drug administration lasted for 7 days. 30 minutes after the drug administration on the 7th day, the mouse epilepsy model was established using the PTZ ignition method, and 65 mg / kg of pentylenetetrazol was injected intraperitoneally.

[0101] 3.3 Animal Dosing Single-dose experiment: Each group of mice was dosed once. The 9#, 10#, 11#, 12#, and 13# groups were gavaged with 1500 mg / kg of 9#, 10#, 11#, 12#, and 13# formulations, respectively. The model control group was given an equal volume of 0.9% sodium chloride injection.

[0102] Multiple-dose experiment: Each group of mice was dosed seven times daily for seven days. The 9#, 10#, 11#, 12#, and 13# groups were gavaged with 1500 mg / kg of each of the following formulations: 9#, 10#, 11#, 12#, and 13#, respectively. The model control group was given an equal volume of 0.9% sodium chloride injection.

[0103] 3.4 Observation indicators 3.4.1 Racine Score After the model was constructed, the Racine score was calculated according to the degree of epilepsy, as shown in Table 10.

[0104] Table 10 Racine seizure classification Level 0 No behavioral changes Class I Animals appear to be moving and chewing Level II The animal experiences head and facial convulsions Level III Rhythmic twitching or clonus of the animal's forelimbs or hindlimbs Level IV Rhythmic twitching of the limbs V-level Whole-body tonic convulsions with tail-flicking or rolling 3.4.2 Determination of the time from V-level classification to recovery The timer starts when the mouse reaches Grade V and stops when the mouse resumes free exploration. This is counted as the mouse's recovery time. If the mouse does not reach Grade V, the time count is zero.

[0105] 3.5 Statistical methods The data were processed using Excel, and the measurement data were expressed as mean ± standard deviation ( ) were used for comparison; P < 0.05 indicated statistically significant differences.

[0106] 4. Experimental results Racine score The convulsion latency of each group is shown in Table 11 for the single-dose experiment.

[0107] Table 11. Racine score record for mouse epilepsy Group Quantity (pieces) Test drug Dosage (mg / kg) Racine score after multiple (D7) administration Model control group 5 0.9% sodium chloride injection 1500 5.0±0.0 9 groups of prescriptions 5 Formula 9 preparation 1500 4.8±0.4 10 groups of prescriptions 5 Formula 10 preparations 1500 2.4±1.1 11 groups of prescriptions 5 Formula 11 preparation 1500 3.2±1.3 12 groups of prescriptions 5 Formula 12 preparations 1500 3.6±1.1 13 groups of prescriptions 5 Formula 13 preparation 1500 2.6±1.5 After single administration on Day 1, there was no significant difference in the Racine scores of mice in each group.

[0108] Comparison of Racine scores of mice in each group on Day 7 after multiple administration: Model control group (5.0±0.0 There were significant differences between the two groups (P = 0.0057) and group 10 (3.8 ± 1.6 points) (P = 0.0086), group 13 (3.4 ± 1.8 points) (P = 0.0173), group 9 (4.6 ± 0.9) and group 10 (P = 0.0173), group 13 (P = 0.0341), and there were no significant differences in the other groups.

[0109] The present invention uses PTZ to ignite the amygdala in the brain of 4-6 week-old mice, inducing abnormal neural discharges and thus causing epilepsy. The results showed that the Racine scores of Group 10 and Group 13 on Day 7 were significantly better than those of the model control group and Group 9, and the differences were extremely significant.

[0110] Test Example 6: Dizziness screening experiment of formula 9-10-11-12-13 1. Animal Preparation Thirty C57BL / 6 mice of random sex aged 4-6 weeks were selected and fed adaptively before the experiment.

[0111] 2. Preparation Accurately weigh 150 mg of each of the crude drugs in Formulas 9, 10, 11, 12, and 13 and add 0.9% sodium chloride injection to a final volume of 1 mL of the test preparation. Use 0.9% sodium chloride injection as the negative control. Transport the prepared preparations and negative control to the animal room at room temperature for administration. After administration, dispose of any remaining preparations as medical waste.

[0112] 3. Experimental methods 3.1 Animal grouping Thirty C57BL / 6 mice aged 4-6 weeks were randomly divided into model control group, 9# prescription group, 10# prescription group, 11# prescription group, 12# prescription group, and 13# prescription group, with 5 mice in each group.

[0113] 3.2 Animal modeling Thirty minutes after drug administration, mice were placed in a vertigo device modified from a hand-cranked centrifuge to induce vertigo. The centrifuge speed was controlled at 120-180 rpm (angular velocity ≈12.6-18.8 rad / s). The rotation duration was: a single rotation of 2 minutes, followed by a 1-minute interval, for one cycle, repeated three times.

[0114] 3.3 Animal Dosing Each group of mice was administered once. The 9#, 10#, 11#, 12#, and 13# groups were gavaged with 1500 mg / kg of 9#, 10#, 11#, 12#, and 13# formulations, respectively. The model control group was given an equal volume of 0.9% sodium chloride injection.

[0115] 3.4 Observation indicators 3.4.1 Vertigo severity score After the model was constructed, it was scored according to the vertigo severity scoring table, see Table 12.

[0116] Table 12 Dizziness Index Assessment Standards Symptom classification Scoring Criteria fecal pellets None: 0 points; 1 point for each fecal pellet urination None: 0 points; 1.2 points for urination (regardless of frequency) Piloerectile reaction None: 0 points; mild piloerection (localized hair standing up): 0.6 points; severe piloerection (all body hair standing up): 1.2 points Tremor No: 0 points; 1.2 points for tremor (shaking of limbs or whole body) 3.4.2 Determination of vertigo duration The timer starts when the mouse model is completed and the mouse is immediately placed on the table to observe its state. The timer stops when the mouse begins to explore. The time from the completion of the mouse model to the resumption of exploration is the duration of dizziness.

[0117] 3.5 Statistical methods The data were processed using Excel, and the measurement data were expressed as mean ± standard deviation ( ) were used for comparison; P < 0.05 indicated statistically significant differences.

[0118] 4. Experimental results 4.1 Assessment of Dizziness Severity Index and Dizziness Recovery Time The dizziness index of each group is shown in Table 13: Table 13. Mouse dizziness index score record Group Quantity (pieces) Test drug Dosage (mg / kg) Dizziness Index Model control group 5 0.9% sodium chloride injection 1500 7.4±1.1 9 groups of prescriptions 5 Formula 9 preparation 1500 2.4±0.8 10 groups of prescriptions 5 Formula 10 preparations 1500 4.1±0.9 11 groups of prescriptions 5 Formula 11 preparation 1500 3.2±1.6 12 groups of prescriptions 5 Formula 12 preparations 1500 2.0±0.8 13 groups of prescriptions 5 Formula 13 preparation 1500 1.6±0.5 After the dizziness model was established, the dizziness index of mice in each group was compared as follows: there were extremely significant differences between the model control group (7.4±1.1 points) and group 9 (2.4±0.8 points) (P<0.0001), group 10 (4.1±0.9 points) (P=0.0004), group 11 (3.2±1.6) (P<0.0001), group 12 (2.0±0.8 points) (P<0.0001), and group 13 (1.6±0.5) (P<0.0001). There were significant differences between group 10 and group 12 (P=0.0378) and group 13 (P=0.0091). There were no significant differences among the other groups.

[0119] 4.2 Assessment of dizziness duration The dizziness recovery time of each group is shown in Table 14: Table 14. Record of dizziness recovery time in mice Group Quantity (pieces) Test drug Dosage (mg / kg) Stun duration Model control group 5 0.9% sodium chloride injection 1500 513.0±166.1 9 groups of prescriptions 5 Formula 9 preparation 1500 261.2±68.6 10 groups of prescriptions 5 Formula 10 preparations 1500 272.8±64.8 11 groups of prescriptions 5 Formula 11 preparation 1500 272.6±112.5 12 groups of prescriptions 5 Formula 12 preparations 1500 370.4±156.9 13 groups of prescriptions 5 Formula 13 preparation 1500 270.2±82.2 After the dizziness model was established, the dizziness recovery time of mice in each group was compared: there were significant differences between the model control group (513.0±166.1 seconds) and group 9 (261.2±68.6 seconds) (P=0.0233), group 10 (272.8±64.8 seconds) (P=0.0332), group 11 (272.6±112.5 seconds) (P=0.0330), and group 13 (270.2±82.2 seconds) (P=0.0307), while there were no significant differences in the other groups.

[0120] This study used a vertigo device modified from a hand-cranked centrifuge to create a vertigo model in 4-6 week-old mice. Six formulas were screened for optimal vertigo treatment. The results showed that formulas 10, 11, 12, and 13 all significantly outperformed the model control group in vertigo severity scores, with the differences being extremely significant. In terms of recovery time, formulas 10, 11, and 13 all outperformed the model control group, with statistically significant differences.

Claims

1. A Chinese medicine composition for treating and / or preventing convulsions, characterized in that: It is prepared from the following raw materials in the following weight ratio: 8-12 parts of Bombyx Batryticatus, 8-12 parts of Rhizoma White Rhizoma, 12-20 parts of Rhizoma Gastrodiae, and 8-12 parts of Rhizoma Scorpio.

2. The Chinese medicine composition for treating and / or preventing convulsions according to claim 1, characterized in that: It is prepared from the following raw materials in the following weight ratio: 10 parts of Bombyx Batryticatus, 10 parts of Rhizoma White Rhizoma, 15 parts of Rhizoma Gastrodiae, and 10 parts of Scorpio.

3. The Chinese medicine composition for treating and / or preventing convulsions according to claim 1 or 2, characterized in that: The raw material medicine further contains one or a combination of two or more of antelope horn powder, borneol and musk.

4. The Chinese medicine composition for treating and / or preventing convulsions according to claim 3, characterized in that: The weight ratio of the raw materials is: 10 parts of Bombyx Batryticatus, 10 parts of Rhizoma White Rhizoma, 15 parts of Rhizoma Gastrodiae, 10 parts of Scorpio, 5 parts of Antelope Horn Powder; or 10 parts of Bombyx Batryticatus, 10 parts of Rhizoma White Rhizoma, 15 parts of Rhizoma Gastrodiae, 10 parts of Scorpio, 3 parts of Borneolum Syntheticum, and 1-3 parts of Musk.

5. The Chinese medicinal composition for treating and / or preventing convulsions according to claim 4, characterized in that: The raw material medicine also contains Arisaema cinerea, magnetite, frankincense, borneol and musk, and the weight ratio of the raw material medicine is: 10 parts of Bombyx Batryticatus, 10 parts of Rhizoma White Rhizoma, 15 parts of Rhizoma Gastrodiae, 10 parts of Scorpio, 20 parts of Arisaema Cum Bile, 10 parts of Hematite, 15 parts of Frankincense, 3 parts of Borneolum Syntheticum, 2 parts of Musk; or, 10 parts of Bombyx Batryticatus, 10 parts of Rhizoma White Rhizoma, 15 parts of Rhizoma Gastrodiae, 10 parts of Scorpio, 20 parts of Arisaema Cum Bile, 10 parts of Hematite, 15 parts of Frankincense, 3 parts of Borneolum Syntheticum, 1 part of Musk; or, 10 parts of Bombyx Batryticatus, 10 parts of Rhizoma White Rhizoma, 15 parts of Rhizoma Gastrodiae, 10 parts of Scorpio, 20 parts of Arisaema Cum Bile, 10 parts of Hematite, 15 parts of Frankincense, 3 parts of Borneolum Syntheticum, 3 parts of Musk; or, 10 parts of Bombyx Batryticatus, 10 parts of Rhizoma White Rhizoma, 20 parts of Arisaema Cum Bile, 10 parts of Scorpio, 20 parts of Rhizoma Gastrodiae, 10 parts of Hematite, 20 parts of Olibanum, 3 parts of Borneolum Syntheticum, and 2 parts of Musk.

6. The Chinese medicine composition for treating and / or preventing convulsions according to any one of claims 3 to 5, characterized in that: The white aconite root is processed white aconite root, the gastrodia elata is ginger gastrodia elata, the borneol is natural borneol, and the musk is artificial musk or natural musk.

7. The Chinese medicinal composition for treating and / or preventing convulsions according to any one of claims 1 to 5, characterized in that: The invention is prepared from the raw drug powder, water or organic solvent extract of the raw drug as active ingredients, and pharmaceutically acceptable excipients or auxiliary ingredients to prepare a commonly used oral preparation in medicine.

8. The Chinese medicinal composition for treating and / or preventing convulsions according to claim 7, characterized in that: The oral preparation is powder, tablet, capsule, granule, oral liquid, honey pill, water-honey pill, water pill, paste pill, wax pill, concentrated pill, dripping pill or sugar pill.

9. A method for preparing the Chinese medicine composition for treating and / or preventing convulsions according to any one of claims 1 to 8, characterized in that: It includes the following steps: a. Weigh the APIs of various weight ratios; b. Powdering, or extracting with water or organic solvent, and then adding pharmaceutically acceptable excipients or auxiliary ingredients to prepare a commonly used oral preparation in medicine.

10. Use of the traditional Chinese medicine composition according to any one of claims 1 to 8 in the preparation of a medicament for treating and / or preventing convulsions.

11. The use according to claim 10, characterized in that: The medicine is a medicine for treating and / or preventing febrile convulsions in children.

12. The use according to claim 11, characterized in that: The medicine is a medicine that prolongs the latent time of febrile convulsion and shortens the duration of febrile convulsion.

13. Use of the traditional Chinese medicine composition according to any one of claims 5 to 8 in the preparation of a medicament for treating and / or preventing epilepsy.

14. Use of the traditional Chinese medicine composition according to any one of claims 5 to 8 in the preparation of a medicament for treating and / or preventing vertigo.