Pharmaceutical composition for preventing or treating epileptic seizure and application thereof

Abstract

The invention relates to a pharmaceutical composition for preventing or treating epileptic seizure and application thereof. The invention discloses a traditional Chinese medicine composition for preventing or treating epileptic seizure and application of the traditional Chinese medicine composition in preparation of medicines. The traditional Chinese medicine composition has the characteristics of high efficiency, safety and convenience, can effectively prevent or treat epileptic seizure, and can be further combined with other anti-epileptic medicaments to enhance the anti-epileptic effect and reduce the side effects of the anti-epileptic medicaments. The invention also provides a method for preventing or treating epileptic seizure by using the traditional Chinese medicine composition or the medicinal composition.

Description

Technical Field

[0001] The present invention relates to a traditional Chinese medicine composition for preventing or treating epileptic seizures and its application. The present invention also relates to a pharmaceutical combination comprising the traditional Chinese medicine composition and at least one antiepileptic agent and its application. Background Art

[0002] The description of the background of the invention includes information that helps to understand the present invention. This does not admit that any information provided herein is the background of the invention or is related to the claimed invention, nor does it admit that any publication explicitly or implicitly cited is the background of the invention.

[0003] Epilepsy is a common neurological disorder that affects up to 70 million people worldwide. This disorder is characterized by abnormal electrical discharges of brain nerve cells, resulting in recurrent, spontaneous, and unpredictable seizures, mainly occurring in the cerebral cortex and hippocampal regions. The causes of epilepsy may be related to congenital or acquired brain lesions, such as intracranial trauma, infection, stroke, and tumors. However, approximately 70% of epilepsy patients have no identifiable cause. Although the causes of most epilepsy cases are unknown, it is generally believed that it may be due to an imbalance between the inhibitory nervous system (i.e., the GABA system) and the excitatory nervous system (i.e., the glutamate system) in the brain, leading to overexcitation of nerve cells.

[0004] Currently, the main mechanisms of action of antiepileptic drugs used to control epileptic seizures are to directly inhibit the excitability of nerve cells by blocking sodium channels (e.g., phenytoin, carbamazepine); and to inhibit glutamate (e.g., lamotrigine, felbamate) or enhance GABA (such as benzodiazepines, tiagabine, vigabatrin) to regulate the stability of nerve cells. However, although there are nearly 30 drugs currently used to treat epilepsy, approximately one-third of epilepsy patients are resistant to existing drugs. In addition, the side effects of the drugs also limit the compliance of patients with existing drugs.

[0005] Currently, commonly used anti-epileptic drugs are known to have many side effects. For example, the side effects that may occur as indicated in the package inserts of carbamazepine drugs include drowsiness, stomach discomfort, diarrhea, dizziness, heaviness in the head, unsteady gait (ataxia), leukopenia, aplastic anemia, abnormal liver function, arrhythmia, skin rash, etc. The side effects indicated in the package inserts of phenytoin drugs include nausea, vomiting, heartburn, loss of appetite, diplopia, nystagmus, unsteady gait (ataxia), gingival hyperplasia, hirsutism, coarse face, athetoid movement, lymphadenopathy, teratogenesis, skin rash, etc. After the occurrence of side effects, the usual treatment methods are to change the drug, reduce the dosage or add other drugs to inhibit the side effects. However, reducing the dosage is likely to cause the recurrence of epilepsy, bringing physical and mental pain to epilepsy patients.

[0006] Therefore, it is necessary to search for and develop more effective and safer new drugs for the treatment of epilepsy. Medicinal plants have received attention because they are widely used in traditional and folk medicine for the treatment and prevention of different neurological diseases (including epilepsy). In recent years, many plant-derived bioactive molecules have been proven to have anti-epileptic effects by affecting ion channels, GABA or glutamate. For example, flavonoids, alkaloids, terpenoids and cannabidiol. Therefore, medicinal plants have become the target of anti-epileptic drug research.

[0007] Qingguan No. 1 in Taiwan, China, was developed in 2020 based on the prescription of "Jingfang Baidu Powder" compiled from "She Sheng Zhong Miao Fang" in the Ming Dynasty. It is a traditional Chinese medicine formula used to treat coronavirus disease and has antiviral, immunomodulatory, and anti-inflammatory effects. Qingguan No. 1 in Taiwan, China, is made from ten herbs, including Scutellaria Root (Scutellariabaicalensis), Heartleaf Houttuymia (Houttuynia cordata), Indigowoad Root (Isatis indigotica), Mongolian Snakegourd Fruit (Trichosanthes kirilowii), Mulberry Leaf (Morus alba), Magnolia Bark (Magnolia officinalis), Peppermint Herb (Mentha haplocalyx), Fineleaf Nepeta (Nepeta tenuifolia), Saposhnikovia Root (Saposhnikovia divaricate), and Baked Liquorice Root (Glycyrrhiza glabra). In addition, various bioactive components have also been found in Qingguan No. 1 in Taiwan, China, such as baicalin, epi-goitrin, liquiritin, quercetin 3-galactoside, quercetin 3-rhamnoside, scutellarin, rutin, wogonoside, and caffeoylquinic acid, which may account for the pharmacological properties of Qingguan No. 1 in Taiwan, China. However, no data have explored the anti-epileptic efficacy of Qingguan No. 1 in Taiwan, China, which has the potential as a new option for preventing or treating epileptic seizures or for combining with other anti-epileptic agents to reduce the side effects of the well-known anti-epileptic agents. Summary of the Invention

[0008] The present invention provides an application of a traditional Chinese medicine composition in the preparation of a drug for preventing or treating epileptic seizures, wherein the traditional Chinese medicine composition comprises Scutellaria Root, Heartleaf Houttuymia, Indigowoad Root, Mongolian Snakegourd Fruit, Mulberry Leaf, Magnolia Bark, Peppermint Herb, Fineleaf Nepeta, Saposhnikovia Root, and Baked Liquorice Root.

[0009] In one embodiment, epilepsy is triggered by damage to brain nerve cells. In another embodiment, epilepsy is triggered by the activation of glial cells. In another embodiment, epilepsy is triggered by an inflammatory response in the brain caused by inflammatory molecules. In another embodiment, the inflammatory molecules are selected from the group consisting of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high mobility group Box 1 (HMGB1), interleukin-1 receptor 1 (IL-1R1), and Toll-like receptor-4 (TLR-4).

[0010] In one embodiment, the traditional Chinese medicine composition of the present invention is further combined with at least one anti-epileptic agent for preparing a drug for preventing or treating epileptic seizures. In another embodiment, the at least one anti-epileptic agent is selected from the group consisting of western medicine preparations of phenytoin, carbamazepine, lamotrigine, vigabatrin, benzodiazepines, tiagabine, and gabapentin.

[0011] The present invention also provides a pharmaceutical combination for preventing or treating epileptic seizures, which comprises a traditional Chinese medicine composition, at least one anti-epileptic agent, and a pharmaceutically acceptable carrier and / or stabilizer, wherein the traditional Chinese medicine composition comprises Scutellaria baicalensis, Houttuynia cordata, Isatis tinctoria, Trichosanthes kirilowii, Morus alba, Magnolia officinalis, Mentha haplocalyx, Schizonepeta tenuifolia, Saposhnikovia divaricata, and roasted licorice root, and the dose of the anti-epileptic agent is lower than the dose used when treating epilepsy with the anti-epileptic agent alone. In one embodiment, the at least one anti-epileptic agent is selected from the group consisting of phenytoin, carbamazepine, lamotrigine, vigabatrin, benzodiazepines, tiagabine, and gabapentin. In one embodiment, the traditional Chinese medicine composition and the at least one anti-epileptic agent are administered to a patient simultaneously, sequentially, or intermittently.

[0012] Various objects, features, aspects, and advantages of the present invention will become more apparent from the following detailed description of the preferred embodiments and the accompanying drawings. Description of the Drawings

[0013] As illustrated in the accompanying drawings, further features and advantages of the present case will become apparent from the following and more specific description of the preferred embodiments, and wherein like reference characters generally refer to the same parts or components throughout the text, and wherein:

[0014] Figure 1 It is a chromatogram of the phytochemical characteristics of Qingguan Yifang in Taiwan, China.

[0015] Figure 2Bar graph showing the performance of pretreatment with Qingguan No. 1 from Taiwan, China, in preventing KA-induced epileptic behavior in animals. Data are mean ± SEM (n = 3 - 8 rats / group). Compared with the KA group, *, p < 0.05; **, p < 0.01; ***, p < 0.001.

[0016] Figure 3A and 3B Bar graph showing the performance of pretreatment with Qingguan No. 1 from Taiwan, China, in preventing KA-induced electroencephalogram seizures in animals. Data are mean ± SEM (n = 3 rats / group). ***, p < 0.001 compared with the control group; #, p < 0.05 compared with the KA group. Detailed implementation mode

[0017] The following description includes information that helps to understand the present invention. This does not admit that any information provided herein is the background of the invention or is related to the invention claimed in this case, nor does it admit that any publication explicitly or implicitly cited is the background of the invention.

[0018] It should be understood that the present invention is not limited to the specific exemplary materials, structures, procedures, methods or configurations listed herein. Therefore, although some options are listed herein, those similar or with the same efficacy can be applied to the implementation or embodiments of the present invention, and only the preferred materials and methods are described herein.

[0019] The following detailed description related to the accompanying drawings is considered to be an illustration of the exemplary embodiments of the present invention and is not intended to represent the only exemplary embodiments in which the present invention can be implemented. The term "exemplary" used throughout this specification means "serving as an example, instance or illustration", and should not necessarily be construed as preferred or superior to other exemplary embodiments. The detailed description includes specific details for the purpose of providing a comprehensive understanding of the exemplary embodiments of this specification. It will be apparent to those of ordinary skill in the art to which the present invention pertains that the exemplary embodiments of this specification can be implemented without these specific details.

[0020] Definitions

[0021] As used herein, the following terms have the meanings described in this paragraph. It should also be understood that the terms used in this case are only for the purpose of describing the specific embodiments of the present invention and are not intended to be limiting.

[0022] Unless otherwise defined, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein and laboratory procedures in animal pharmacology, pharmaceutical sciences, separation sciences, and organic chemistry are well known and commonly used in the art. In the methods described herein, actions can be performed in any order, except when a specific time or order of operations is explicitly recited. Additionally, unless the claims explicitly state otherwise, the recited actions can be performed simultaneously. For example, the required actions of performing X and performing Y can be carried out simultaneously in a single operation, and the resulting method will fall within the scope of the claimed method.

[0023] The following non-limiting abbreviations are used herein: KA, kainic acid; IL-1β, interleukin-1β; IL-6, interleukin-6; TNF-α, tumor necrosis factor-α; HMGB1, high mobility group Box 1; IL-1R1, interleukin-1 receptor 1; CBZ, carbamazepine; CABA, gamma-aminobutyric acid; and TLR-4, Toll-like receptor-4; HPLC, high-performance liquid chromatography.

[0024] Unless the context clearly indicates otherwise, as used in this specification and the appended claims, the singular forms "a", "an", and "the" include plural referents. For example, "a component" refers to one component or more than one component.

[0025] As used herein, the term "about" will be understood by those of ordinary skill in the art and will vary to some extent depending on the context in which it is used. As used herein, when referring to measurable values such as amounts, lengths of time, etc., "about" means a variation of ±20%, ±10%, ±5%, ±1% or ±0.1% of the specified value. Since these variations are suitable for carrying out the disclosed methods. Thus, in some embodiments, the numerical parameters set forth in this specification and the appended claims are approximations, which may vary depending on the desired characteristics sought in a particular embodiment. In some embodiments, numerical parameters should be interpreted in accordance with the number of significant digits recited and by applying ordinary rounding techniques. The numerical values presented in some embodiments of the present invention may contain certain errors, which are necessarily caused by the standard deviations present in their respective experimental measurements.

[0026] In one aspect, the term "co-administered" with respect to a subject means administering to the subject the traditional Chinese medicine composition of the present invention together with other agents that can also treat or prevent the diseases contemplated herein. In certain embodiments, the co-administered traditional Chinese medicine composition and other agents are administered separately, or in any kind of combination as part of a single therapeutic regimen.

[0027] As used herein, a "disease" is a state of health of a subject in which the subject is unable to maintain homeostasis, and in which the health of the subject will continue to deteriorate if the disease is not improved.

[0028] As used herein, a "condition" in a subject is a state of health in which the subject is able to maintain homeostasis, but the subject's health is not as good as when there is no condition. Without treatment, the disease does not necessarily cause the subject's health condition to deteriorate further.

[0029] As used herein, the term "pharmaceutically acceptable" refers to a substance, such as a carrier or diluent, that does not eliminate the biological activity or properties of the useful compounds in the present invention, and is relatively non-toxic, i.e., the substance can be administered to a subject without causing unwanted biological effects or interacting in a harmful manner with any of the components contained in the composition.

[0030] As used herein, the "pharmaceutically effective amount", "therapeutically effective amount" or "effective amount" of a compound is the amount of the compound sufficient to provide a beneficial effect to a subject to which the compound is administered.

[0031] As used herein, the terms "subject", "individual" and "patient" are used interchangeably and refer to human or non-human mammals. Non-human mammals include, for example, livestock and pets such as sheep, pigs, canines, felines and murine mammals. In certain embodiments, the subject is human.

[0032] As used herein, the term "traditional Chinese medicine composition" refers to a combination comprising at least two or more traditional Chinese medicinal materials having therapeutic effects, and each of the traditional Chinese medicinal materials can be directly mixed after being ground, or each of the traditional Chinese medicinal materials can be mixed before or after being subjected to well-known processing, refining, concentration and / or other preparation methods.

[0033] As used herein, the term "pharmaceutical combination" or "pharmaceutical composition" refers to a combination comprising at least two or more drugs, and the drugs can be traditional Chinese medicines and / or Western medicines.

[0034] As used herein, the term "prevent" or "prevent from" means to avoid or delay the occurrence of symptoms related to a disease or disorder in a subject who has not yet developed such symptoms at the start of administration of an agent or compound.

[0035] As used herein, the term "treat" means to reduce the frequency or severity of symptoms of a disease or disorder experienced by a subject by administering an agent or compound to the subject.

[0036] As used herein, "treatment effectiveness" refers to a favorable treatment response, such as alleviation, improvement of one or more symptoms of a disease; reduction in the degree of the disease; delay or slowdown of disease progression; improvement, alleviation or stabilization of the disease state; or other beneficial outcomes.

[0037] Range: Throughout this disclosure, various aspects of the present invention may be presented in the form of a range. It should be understood that the description in range form is only for convenience and brevity and should not be construed as a limitation on the scope of the present invention. Therefore, the description of a range should be considered as specifically disclosing all possible sub-ranges and individual values within the range. For example, the description of a range from 1 to 6 should be considered as having specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and individual and fractional numbers within the range, such as 1, 2, 2.7, 3, 4, 5, 5.3 and 6. This applies regardless of the width of the range.

[0038] Traditional Chinese medicine composition

[0039] The traditional Chinese medicine composition in this case is based on Qingguan No. 1 and contains ten traditional Chinese medicinal materials, namely Scutellaria baicalensis, Houttuynia cordata, Isatis indigotica, Trichosanthes kirilowii, Morus alba, Magnolia officinalis, Mentha haplocalyx, Nepeta tenuifolia, Saposhnikovia divaricate, and Glycyrrhiza glabra prepared with honey.

[0040] In one embodiment, the traditional Chinese medicine composition in this case contains 3.75 - 1.25 parts by weight of Scutellaria baicalensis, 3.75 - 1.25 parts by weight of Houttuynia cordata, 3.75 - 1.25 parts by weight of Isatis indigotica, 3.75 - 1.25 parts by weight of Trichosanthes kirilowii, 2.25 - 0.75 parts by weight of Morus alba, 2.25 - 0.75 parts by weight of Magnolia officinalis, 2.25 - 0.75 parts by weight of Mentha haplocalyx, 2.25 - 0.75 parts by weight of Nepeta tenuifolia, 1.5 - 0.5 parts by weight of Saposhnikovia divaricate, and 1.5 - 0.5 parts by weight of Glycyrrhiza glabra prepared with honey. In another embodiment, the traditional Chinese medicine composition in this case preferably contains 2.75 - 2.25 parts by weight of Scutellaria baicalensis, 2.75 - 2.25 parts by weight of Houttuynia cordata, 2.75 - 2.25 parts by weight of Isatis indigotica, 2.75 - 2.25 parts by weight of Trichosanthes kirilowii, 1.65 - 1.35 parts by weight of Morus alba, 1.65 - 1.35 parts by weight of Magnolia officinalis, 1.65 - 1.35 parts by weight of Mentha haplocalyx, 1.65 - 1.35 parts by weight of Nepeta tenuifolia, 1.1 - 0.9 parts by weight of Saposhnikovia divaricate, and 1.1 - 0.9 parts by weight of Glycyrrhiza glabra prepared with honey. In another embodiment, the traditional Chinese medicine composition in this case more preferably contains 2.5 parts by weight of Scutellaria baicalensis, 2.5 parts by weight of Houttuynia cordata, 2.5 parts by weight of Isatis indigotica, 2.5 parts by weight of Trichosanthes kirilowii, 1.5 parts by weight of Morus alba, 1.5 parts by weight of Magnolia officinalis, 1.5 parts by weight of Mentha haplocalyx, 1.5 parts by weight of Nepeta tenuifolia, 1 part by weight of Saposhnikovia divaricate, and 1 part by weight of Glycyrrhiza glabra prepared with honey.

[0041] The traditional Chinese medicinal materials contained in the traditional Chinese medicine composition in this case can be made into liquid preparations through steps such as washing, drying, grinding, and processing. In one embodiment, the liquid preparation can be further made into solid preparations through steps such as extraction, concentration, and adding excipients for spray granulation. The above preparation steps can be increased or decreased according to the well-known traditional Chinese medicine pharmaceutical technology according to the dosage form to be prepared.

[0042] Combination therapy

[0043] In one aspect, the traditional Chinese medicine composition of the present disclosure can be used in combination with one or more agents for preventing or treating seizures, or formulated into a pharmaceutical composition. These agents may include compounds known to be used for treating, preventing or alleviating seizure symptoms (e.g., commercially available compounds).

[0044] In one embodiment, the present invention provides a method for treating or preventing epilepsy in a subject, the method comprising administering to the subject in need a therapeutically effective amount of the traditional Chinese medicine composition of the present invention. In one embodiment, the subject is further co-administered at least one agent that is helpful for treating or preventing epilepsy. In another embodiment, the at least one agent is, for example, phenytoin, carbamazepine, lamotrigine, vigabatrin, benzodiazepines, tiagabine, gabapentin, etc., wherein the dosage of the western medicine preparation can be adjusted by a physician according to the recommended dosage of each agent.

[0045] In one embodiment, the subject suffering from epilepsy may be a subject newly diagnosed with epilepsy or a subject who is taking at least one anti-epileptic agent. In one embodiment, a combination of the traditional Chinese medicine composition of the present invention and at least one anti-epileptic agent can be provided to a subject newly diagnosed with epilepsy, wherein the dosage of the at least one anti-epileptic agent when administered in combination is lower than the dosage when the anti-epileptic agent is used alone to prevent or treat epilepsy. In another embodiment, the traditional Chinese medicine composition of the present invention can be further provided to a subject who is taking at least one anti-epileptic agent, and the dosage of the at least one anti-epileptic agent can be further reduced.

[0046] Administration / Dosage

[0047] The treatment regimen can affect the composition of the effective amount. The therapeutic formulation can be administered to the patient before or after the onset of the disease or disorder. In addition, several separate doses and staggered doses can be administered daily, or the doses can be administered continuously. In addition, the dosage of the therapeutic formulation can be increased or decreased proportionally depending on the urgency of the treatment or prevention situation.

[0048] The traditional Chinese medicine composition of the present invention can be administered to a patient using known procedures, dosages and time periods to effectively treat or prevent epilepsy. The effective amount of the traditional Chinese medicine composition necessary to achieve the therapeutic and / or prophylactic effect of epilepsy can vary depending on many factors, such as the activity of the specific traditional Chinese medicine composition used; the time of administration; the excretion rate of the extract; the duration of treatment; other drugs, compounds or substances used in combination with the extract; the state, age, sex, weight, symptoms, general health status and previous medical history of the disease or disorder of the patient being treated; and similar factors well known in the medical field. The dosage regimen can be adjusted to provide an optimized therapeutic response. For example, several separate doses can be administered daily, or the dosage can be reduced proportionally depending on, for example, the urgency of the treatment situation.

[0049] While the description of the traditional Chinese medicine composition of the present invention mainly relates to being suitable for administration to humans in a medically ethical manner, those skilled in the art will understand that the traditional Chinese medicine composition is generally suitable for administration to various animals. To be suitable for administration to various animals, it is well known to modify the traditional Chinese medicine composition of the present invention, and generally a veterinary pharmacologist skilled in the art only needs to design and implement such modifications through general tests (if necessary). The subjects to which the traditional Chinese medicine composition of the present invention can be administered include, but are not limited to, humans and other primates, mammals, including commercially relevant mammals such as cattle, pigs, horses, sheep, cats, and dogs.

[0050] In certain embodiments, the traditional Chinese medicine composition of the present invention is administered to a patient in a dosage range of 1 to 5 times or more per day. In other embodiments, the traditional Chinese medicine composition of the present invention can include, but is not limited to, being administered to a patient in a dosage range of once a day, twice a day, three times a day, four times a day, once every two days, once every three days to one week, or once every two weeks. Those skilled in the art will readily understand that the dosing frequency of the various combinations of the composition of the present invention will vary with the subject, depending on many factors, including but not limited to age, the disease or disorder to be treated, gender, overall health status, and other factors. Therefore, the present invention should not be construed as being limited to any specific dosage regimen, and the precise dosage and composition to be administered to any patient should be determined by the attending physician considering all other factors regarding the patient.

[0051] In one embodiment, when administering the pharmaceutical combination of the traditional Chinese medicine composition of the present invention and the at least one antiepileptic agent, the traditional Chinese medicine composition and the at least one antiepileptic agent can be administered to the subject simultaneously. In another embodiment, the traditional Chinese medicine composition and the at least one antiepileptic agent can be administered to the subject sequentially, successively, or at intervals.

[0052] Route of administration

[0053] Oral administration

[0054] The dosage form of the traditional Chinese medicine composition of the present invention for oral administration can be in solid or liquid form. Suitable solid dosage forms include, for example, powders, granules, pellets, pills, lozenges, capsules, buccal tablets, etc. Suitable liquid preparations can be solutions, syrup preparations, suspensions, dispersions, concentrates, etc. The dosage form can be prepared by optionally adding pharmaceutically acceptable additives by well-known pharmaceutical methods.

[0055] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific procedures, embodiments, claims, and examples described herein. Such equivalents are considered to be within the scope of this invention and are covered by the claims herein. For example, it should be understood that modifications of reaction conditions including, but not limited to, reaction time, reaction size / volume, and experimental reagents (such as solvents, catalysts), pressure, gas pressure conditions, and reducing / oxidizing agents, as well as alternatives recognized in the art and using no more than routine experimentation, are within the scope of this application.

[0056] It should be understood that whenever numerical values and ranges are provided herein, the description in range form is merely for convenience and brevity and should not be construed as limiting the scope of the invention. Accordingly, all numerical values and ranges subsumed by these values and ranges are included within the scope of the invention. In addition, all numerical values falling within these ranges, as well as the upper and lower limits of the numerical ranges, are contemplated by this application. The description of a range should be considered to specifically disclose all possible sub-ranges and individual numerical values within the range. Where appropriate, fractional integers of the numerical values are also included within the range. For example, the description of a range from 1 to 6 should be considered to specifically disclose sub-ranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., and individual numbers within the range such as 1, 2, 2.7, 3, 4, 5, 5.3, and 6, regardless of the width of the range.

[0057] The following examples further illustrate aspects of the invention. However, they are not intended as a limitation on the teachings or disclosure of the invention described herein.

[0058] Examples

[0059] The present invention is now described with reference to the following examples, which are for illustrative purposes only and the invention is not limited by these examples, but rather encompasses all variations apparent from the teachings provided herein.

[0060] Materials and Methods

[0061] The following procedures can be used to prepare and / or test exemplary traditional Chinese medicine compositions of the present invention.

[0062] Traditional Chinese Medicine Composition

[0063] The traditional Chinese medicine composition used in the following examples was provided as a commercially available formula (Shun Tian Tang, Qing Guan Yi Hao in Taiwan, China). One formula contains 2.5 parts by weight of Scutellaria baicalensis, 2.5 parts by weight of Houttuynia cordata, 2.5 parts by weight of Isatis tinctoria, 2.5 parts by weight of Trichosanthes kirilowii, 1.5 parts by weight of Morus alba, 1.5 parts by weight of Magnolia officinalis, 1.5 parts by weight of Mentha haplocalyx, 1.5 parts by weight of Schizonepeta tenuifolia, 1 part by weight of Saposhnikovia divaricata, and 1 part by weight of roasted Glycyrrhiza uralensis.

[0064] Experimental Animals

[0065] Male Sprague-Dawley rats (SD, 150-200 g) were purchased from LESCO Company and housed in the Experimental Animal Center of Fu Jen Catholic University. All animal experiments were approved by the Animal Care and Use Committee of Fu Jen Catholic University. According to the 3R principle, all experiments were conducted to minimize animal suffering and use the minimum number of animals required to produce reliable results.

[0066] Example 1 - Component Analysis of Qingguan Yifang in Taiwan, China

[0067] Regarding the phytochemical characteristics of Qingguan Yifang in Taiwan, China, some standard compounds were selected in a literature review, and some active compounds were identified from the methanol extract. The structures of these compounds were confirmed by 3D fingerprint analysis.

[0068] For high-performance liquid chromatography (HPLC) analysis, 0.5 g of Qingguan Yifang in Taiwan, China was extracted with 20 mL of 70% methanol by ultrasonic oscillation at 25 °C for 20 minutes. Then the Qingguan Yifang sample was filtered through a 0.45 μm syringe filter.

[0069] The Waters HPLC system (Milford, Massachusetts, USA) consists of a Waters 600 pump system, a Waters 2996 photodiode array detector, a Waters 717 plus autosampler, and a Sugai U-620 column oven (Wakayama, Japan). A Cosmosil 5C18-MS-II reversed-phase chromatography column (5 μm, 4.6 mm × 250 mm, Nacalai tesque, Japan) equipped with a Lichrospher RP-18 end-capped guard column (5 μm, 4.0 mm × 10 mm, Merck, Germany) was used as the stationary phase. The gradient elution consisted of eluents A, B, and C (A: H2O / KH2PO4 / 10% H3PO4 = 1000 mL / 2.72 g / 1 mL; B: acetonitrile; C: H2O) according to the following curve: 0 - 30 minutes, 90% - 75% A and 10% - 25% B; 30 - 40 minutes, 75% - 65% A and 25% - 35% B; 40 - 55 minutes, 65% - 0% A, 35% - 75% B, and 0% - 25% C; 55 - 60 minutes, 75% - 10% B and 25% - 90% C; 60 - 65 minutes, 0% - 90% A, 10% - 10% B, and 90% - 0% C. The gradient elution was used for 3D fingerprint analysis and for liquiritin (25.94 minutes, 280 nm), rosmarinic acid (29.44 minutes, 320 nm), baicalin (34.61 minutes, 280 nm), oroxylin A-7-O-glucuronide (40.39 minutes, 280 nm), wogonin-7-O-glucuronide (42.53 minutes, 280 nm), glycyrrhizic acid (51.37 minutes, 250 nm), magnolol (61.79 minutes, 290 nm). The flow rate was 1 mL / min and the column temperature was maintained at 35°C.

[0070] Figure 1 The chromatogram of Qingguan Yihao from Taiwan, China, is shown. The contents of baicalin, oroxylin A-7-O-glucuronide, wogonin-7-O-glucuronide, glycyrrhizic acid, liquiritin, magnolol, and rosmarinic acid in the freeze-dried extract of Qingguan Yihao from Taiwan, China, were 18.34, 1.33, 2.67, 2.42, 1.70, 1.07, and 0.91 mg / g, respectively.

[0071] Example 2 - KA-induced epileptic animal model

[0072] The kainic acid (KA)-induced animal epilepsy model was used to evaluate the antiepileptic effect of the traditional Chinese medicine composition of the present invention. KA is an analogue of glutamate. Injecting KA into rats can cause increased glutamate release and overactivation of glutamate receptors, leading to progressive limbic seizures in rats. This phenomenon can cause an increase in intracellular calcium ions, oxidative stress, and mitochondrial dysfunction in nerve cells, and further cause nerve cell death in many regions of the brain, especially in the cerebral cortex and hippocampal regions. In addition, KA-induced nerve cell death is related to the inflammatory response caused by the activation of glial cells and inflammatory molecules [e.g., interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-mobility group protein 1 (HMGB1), interleukin-1 receptor 1 (IL-1R1), and toll-like receptor 4 (TLR-4)]. Since these pathological changes induced by KA are similar to the behaviors and pathologies of human epilepsy, the KA-induced animal epilepsy model is widely used to screen new compounds with antiepileptic activity.

[0073] The epileptic behavioral manifestations were analyzed within 4 hours after intraperitoneal injection of KA in rats. The seizure severity was evaluated according to the Racine scale (1972), as shown in the following table.

[0074]

[0075] Example 3 - Evaluation of the Effect of the Traditional Chinese Medicine Composition on KA-Induced Animal Epileptic Behaviors

[0076] To evaluate the effect of the traditional Chinese medicine composition on KA-induced animal epileptic behaviors, physiological saline, the traditional Chinese medicine composition, and CBZ were fed to rats at a fixed time every day through a feeding tube. After seven days, KA (15 mg / kg) was intraperitoneally injected. The epileptic behavioral manifestations were analyzed within 4 hours after intraperitoneal injection of KA in rats, and the epileptic behavioral manifestations were evaluated according to the above-mentioned Racine scale (1972).

[0077] Sprague-Dawley rats were divided into the following groups according to the different test substances given:

[0078] 1. Negative control group: physiological saline

[0079] 2. KA group: no test substance was given before injecting kainic acid (KA)

[0080] 3. Low-dose traditional Chinese medicine composition group: 100 mg / kg of the traditional Chinese medicine composition

[0081] 4. Medium-dose traditional Chinese medicine composition group: 200 mg / kg of the traditional Chinese medicine composition

[0082] 5. High-dose group of traditional Chinese medicine composition: 300 mg / kg of traditional Chinese medicine composition

[0083] 6. Anti-epileptic drug group: 100 mg / kg carbamazepine (CBZ)

[0084] 7. Anti-epileptic medicine composition group: containing 100 mg / kg of traditional Chinese medicine composition and 50 mg / kg of carbamazepine (CBZ)

[0085] The test substances were fed to the rats in each group at a fixed time every day by gavage. Among them, the control group was fed with physiological saline, the traditional Chinese medicine composition group was fed with the traditional Chinese medicine composition, the anti-epileptic drug group was fed with carbamazepine, and the anti-epileptic medicine composition group was fed with the traditional Chinese medicine composition and carbamazepine. The traditional Chinese medicine composition and carbamazepine were mixed with physiological saline in powder form and then given to the rats. After seven days, except for the negative control group, each group of rats was intraperitoneally injected with KA (15 mg / kg / i.p. / single dose), and the dose of KA injection was based on previous studies. The epileptic behavior of the rats was analyzed within 3 hours after the intraperitoneal injection of KA. The results are as Figure 2 shown.

[0086] As Figure 2 shown, compared with the KA group, the high-dose group of the traditional Chinese medicine composition of the present invention (300 mg / kg) has a significant effect (p < 0.001). In addition, the number of animals without seizures under the treatment of the high-dose group of the traditional Chinese medicine composition is the highest (77%, p < 0.001), followed by the medium-dose group of the traditional Chinese medicine composition (200 mg / kg) (33%, p > 0.05) or the low-dose group of the traditional Chinese medicine composition (100 mg / kg) (40%, p > 0.05). At the same time, the effect of the high-dose group of the traditional Chinese medicine composition on the seizure time and seizure score is similar to that of 100 mg / kg CBZ (p > 0.05). This result proves that the traditional Chinese medicine composition of the present invention has the effect of preventing KA-induced epilepsy. In other words, the traditional Chinese medicine composition of the present invention can be used to replace anti-epileptic drugs.

[0087] In addition, in the anti-epileptic medicine composition group (100 mg / kg of traditional Chinese medicine composition + 50 mg / kg of CBZ), the seizure time and severity of the animals were significantly improved compared with the KA (15 mg / kg) group (p < 0.05). In other words, the anti-epileptic medicine composition can greatly improve the disadvantage that low-dose anti-epileptic drugs cannot effectively inhibit epileptic symptoms. Since the anti-epileptic medicine composition group can produce a similar effect of preventing KA-induced epilepsy as the anti-epileptic drug group, this result shows that the combination of low-dose (100 mg / kg) of the traditional Chinese medicine composition and low-dose (50 mg / kg) of CBZ can be used to prevent the manifestation of KA-induced epileptic behavior in animals, and this low-dose CBZ can further reduce the side effects caused by anti-epileptic drugs.

[0088] In rat experiments, it was confirmed that the method provided by the present invention can be used to prevent epileptic seizures, especially for epileptic symptoms that are difficult to control, and has a significant preventive effect. When the traditional Chinese medicine composition of the present invention is used alone, an anti-epileptic effect equivalent to that of anti-epileptic drugs (such as CBZ) can be obtained. In other words, the traditional Chinese medicine composition can be used to replace anti-epileptic drugs. In addition, when the traditional Chinese medicine composition of the present invention and anti-epileptic drugs are used in combination, the dose of anti-epileptic drugs (such as CBZ) can be further reduced while achieving the anti-epileptic effect. Therefore, whether the traditional Chinese medicine composition of the present invention is used alone or in combination with anti-epileptic drugs, the side effects of anti-epileptic drugs can be reduced. The method provided by the present invention has low toxicity and side effects, making it a safe and effective method for preventing epilepsy.

[0089] Example 4 - Electroencephalogram recording to evaluate the effect of the traditional Chinese medicine composition on KA-induced epileptic behavior in animals

[0090] The rats were grouped as in Example 3 above. Every day at a fixed time, the control group was fed physiological saline through a feeding tube, the traditional Chinese medicine composition group was fed the traditional Chinese medicine composition, the anti-epileptic drug group was fed carbamazepine, and the anti-epileptic medicine composition group was fed the traditional Chinese medicine composition and carbamazepine. After seven days, except for the negative control group, each group of rats was intraperitoneally injected with KA (15 mg / kg / i.p. / single dose), and the dose of KA injection was based on previous studies. Electroencephalogram recording of epileptic seizures was analyzed within 3 hours after intraperitoneal injection of KA.

[0091] Electroencephalogram (EEG) recordings were performed using a three-channel EEG system (Pinnacle Technology Inc., Lawrence, Kansas, USA) according to the previously described method (references). After anesthesia with 3% isoflurane, the rats were fixed in a stereotaxic frame (RWD, Life.Science, Dover, USA), and four electrodes were surgically implanted. Two electrodes were placed on both sides of the frontal cortex relative to the bregma (anteroposterior (AP), +3.9; medial (M), ±2.0), and two electrodes were placed on the parietal cortex (AP - 6.4, ML ±4.0). The surgery was performed under isoflurane anesthesia. One week after surgery, the rats were connected to an EEG recording amplifier (model #8213-SE3), and EEG signals were recorded for 3 hours using a data acquisition system (Pinnacle Technology Inc., Lawrence, Kansas, USA). The electrical signals from the brain were pre-amplified through an eight-channel probe (HS-8-CNR-MDR50, Neuralynx). Subsequently, the signals were digitized at 1.6 kHz and band-pass filtered online between 0.1 and 100 Hz using Cheetah 6.2.0 recording software. The criteria for determining a recorded event as a seizure were high-amplitude, rhythmic discharges, including repetitive spikes, spike-wave discharges, and slow waves, with a duration of at least 10 seconds. The number and duration of EEG seizures were analyzed using PAL-8200EEG software (Pinnacl Technologies).

[0092] The seizure spikes in the rat brain were evaluated by EEG recording. As Figure 3A and 3B shown, compared with the control group, KA treatment significantly increased the number and duration of seizure spikes. However, compared with the KA group, the number and duration of seizures in the Taiwan Qingguan No. 1 300 mg / kg + KA group (high-dose traditional Chinese medicine composition group) and the Taiwan Qingguan No. 1 100 mg / kg + CBZ 50 mg / kg + KA group (anti-epileptic medicine composition group) were reduced, and this effect was similar to that of the 100 mg / kg CBZ + KA group (anti-epileptic drug group) (p > 0.05). These results demonstrate that the traditional Chinese medicine composition of the present invention and the pharmaceutical combination of the traditional Chinese medicine composition and anti-epileptic drugs both have the effect of preventing KA-induced epilepsy, and when the traditional Chinese medicine composition of the present invention and anti-epileptic drugs are used in combination, the dose of anti-epileptic drugs (such as CBZ) can be further reduced while achieving the anti-epileptic effect.

[0093] The above animal experiment results confirm that the traditional Chinese medicine composition of the present invention can significantly prolong the inhibition time of KA-induced epileptic seizures and reduce the severity of KA-induced epilepsy, which can prove that the traditional Chinese medicine composition has the effect of preventing epilepsy. Therefore, the traditional Chinese medicine composition of the present invention has the prospect of being used to develop anti-epileptic drugs and / or related products.

[0094] Enumerated embodiments:

[0095] The following exemplary embodiments are provided, and their numbers should not be construed as designating the degree of importance.

[0096] Embodiment 1 provides an application of a traditional Chinese medicine composition in the preparation of a drug for preventing or treating epileptic seizures, wherein the traditional Chinese medicine composition comprises Scutellaria baicalensis, Houttuynia cordata, Isatis tinctoria, Trichosanthes kirilowii Maxim., Morus alba L., Magnolia officinalis, Mentha haplocalyx Briq., Schizonepeta tenuifolia Briq., Saposhnikovia divaricata (Turcz.) Schischk. and Radix Glycyrrhizae Preparata.

[0097] Embodiment 2 provides the application of Embodiment 1, wherein the traditional Chinese medicine composition comprises 3.75 - 1.25 parts by weight of Scutellaria baicalensis, 3.75 - 1.25 parts by weight of Houttuynia cordata, 3.75 - 1.25 parts by weight of Isatis tinctoria, 3.75 - 1.25 parts by weight of Trichosanthes kirilowii Maxim., 2.25 - 0.75 parts by weight of Morus alba L., 2.25 - 0.75 parts by weight of Magnolia officinalis, 2.25 - 0.75 parts by weight of Mentha haplocalyx Briq., 2.25 - 0.75 parts by weight of Schizonepeta tenuifolia Briq., 1.5 - 0.5 parts by weight of Saposhnikovia divaricata (Turcz.) Schischk. and 1.5 - 0.5 parts by weight of Radix Glycyrrhizae Preparata.

[0098] Embodiment 3 provides the application of Embodiment 1, wherein the traditional Chinese medicine composition comprises 2.75 - 2.25 parts by weight of Scutellaria baicalensis, 2.75 - 2.25 parts by weight of Houttuynia cordata, 2.75 - 2.25 parts by weight of Isatis tinctoria, 2.75 - 2.25 parts by weight of Trichosanthes kirilowii Maxim., 1.65 - 1.35 parts by weight of Morus alba L., 1.65 - 1.35 parts by weight of Magnolia officinalis, 1.65 - 1.35 parts by weight of Mentha haplocalyx Briq., 1.65 - 1.35 parts by weight of Schizonepeta tenuifolia Briq., 1.1 - 0.9 parts by weight of Saposhnikovia divaricata (Turcz.) Schischk. and 1.1 - 0.9 parts by weight of Radix Glycyrrhizae Preparata.

[0099] Embodiment 4 provides the application of Embodiment 1, wherein the traditional Chinese medicine composition comprises 2.5 g of Scutellaria baicalensis, 2.5 g of Houttuynia cordata, 2.5 g of Isatis tinctoria, 2.5 g of Trichosanthes kirilowii Maxim., 1.5 g of Morus alba L., 1.5 g of Magnolia officinalis, 1.5 g of Mentha haplocalyx Briq., 1.5 g of Schizonepeta tenuifolia Briq., 1 g of Saposhnikovia divaricata (Turcz.) Schischk. and 1 g of Radix Glycyrrhizae Preparata.

[0100] Embodiment 5 provides the application of Embodiment 1, wherein the epileptic seizure is caused by damage to brain nerve cells.

[0101] Embodiment 6 provides the application of Embodiment 1, wherein the epileptic seizure is caused by activation of glial cells.

[0102] Embodiment 7 provides an application of Embodiment 1, wherein the seizure is caused by a brain inflammatory response induced by inflammatory molecules.

[0103] Embodiment 8 provides an application of Embodiment 5, wherein the inflammatory molecules are selected from the group consisting of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-mobility group protein 1 (HMGB1), interleukin-1 receptor 1 (IL-1R1), and toll-like receptor 4 (TLR-4).

[0104] Embodiment 9 provides an application of Embodiment 1, which further comprises at least one antiepileptic agent combined with the traditional Chinese medicine composition for preparing the drug for preventing or treating seizures.

[0105] Embodiment 10 provides an application of Embodiment 9, wherein the at least one antiepileptic agent is selected from the group consisting of phenytoin, carbamazepine, lamotrigine, felbamate, benzodiazepines, tiagabine, and vigabatrin.

[0106] Embodiment 11 provides an application of Embodiment 10, wherein the at least one antiepileptic agent is carbamazepine.

[0107] Embodiment 12 provides an application of Embodiment 1, wherein the drug is used for treating or preventing epilepsy in humans.

[0108] Embodiment 13 provides an application of Embodiment 1, wherein the drug is used for treating or preventing epilepsy in non-human mammals.

[0109] Embodiment 14 provides a pharmaceutical combination for preventing or treating seizures, which comprises a traditional Chinese medicine composition and at least one antiepileptic agent, wherein the traditional Chinese medicine composition comprises Scutellaria baicalensis, Houttuynia cordata, Isatis tinctoria, Trichosanthes kirilowii Maxim., Morus alba L., Magnolia officinalis Rehd. et Wils., Mentha haplocalyx Briq., Schizonepeta tenuifolia Briq., Saposhnikovia divaricata (Turcz.) Schischk., and prepared licorice root.

[0110] Embodiment 15 provides the pharmaceutical combination of Embodiment 14, wherein the traditional Chinese medicine composition comprises 3.75 - 1.25 parts by weight of Scutellaria baicalensis, 3.75 - 1.25 parts by weight of Houttuynia cordata, 3.75 - 1.25 parts by weight of Isatis tinctoria, 3.75 - 1.25 parts by weight of Trichosanthes kirilowii Maxim., 2.25 - 0.75 parts by weight of Morus alba L., 2.25 - 0.75 parts by weight of Magnolia officinalis Rehd. et Wils., 2.25 - 0.75 parts by weight of Mentha haplocalyx Briq., 2.25 - 0.75 parts by weight of Schizonepeta tenuifolia Briq., 1.5 - 0.5 parts by weight of Saposhnikovia divaricata (Turcz.) Schischk., and 1.5 - 0.5 parts by weight of prepared licorice root.

[0111] Embodiment 16 provides the pharmaceutical combination of Embodiment 14, wherein the traditional Chinese medicine composition comprises 2.75 - 2.25 parts by weight of Scutellaria baicalensis, 2.75 - 2.25 parts by weight of Houttuynia cordata, 2.75 - 2.25 parts by weight of Isatis tinctoria, 2.75 - 2.25 parts by weight of Trichosanthes kirilowii Maxim., 1.65 - 1.35 parts by weight of Morus alba L., 1.65 - 1.35 parts by weight of Magnolia officinalis Rehd. et Wils., 1.65 - 1.35 parts by weight of Mentha haplocalyx Briq., 1.65 - 1.35 parts by weight of Schizonepeta tenuifolia Briq., 1.1 - 0.9 parts by weight of Saposhnikovia divaricata (Turcz.) Schischk. and 1.1 - 0.9 parts by weight of prepared Glycyrrhiza uralensis Fisch..

[0112] Embodiment 17 provides the pharmaceutical combination of Embodiment 14, wherein the traditional Chinese medicine composition comprises 2.5 g of Scutellaria baicalensis, 2.5 g of Houttuynia cordata, 2.5 g of Isatis tinctoria, 2.5 g of Trichosanthes kirilowii Maxim., 1.5 g of Morus alba L., 1.5 g of Magnolia officinalis Rehd. et Wils., 1.5 g of Mentha haplocalyx Briq., 1.5 g of Schizonepeta tenuifolia Briq., 1 g of Saposhnikovia divaricata (Turcz.) Schischk. and 1 g of prepared Glycyrrhiza uralensis Fisch..

[0113] Embodiment 18 provides the pharmaceutical combination of Embodiment 14, wherein the dose of the antiepileptic agent is lower than the dose used when the antiepileptic agent is used alone to prevent or treat epileptic seizures.

[0114] Embodiment 19 provides the pharmaceutical combination of Embodiment 14, wherein the at least one antiepileptic agent is selected from the group consisting of phenytoin, carbamazepine, lamotrigine, vigabatrin, benzodiazepines, tiagabine, and gabapentin.

[0115] Embodiment 20 provides the pharmaceutical combination of Embodiment 14, wherein the at least one antiepileptic agent is carbamazepine.

[0116] Embodiment 21 provides the pharmaceutical combination of Embodiment 14, wherein the traditional Chinese medicine composition and the at least one antiepileptic agent are administered to the patient simultaneously, sequentially, or at intervals.

[0117] Embodiment 22 provides a method for preventing or treating epileptic seizures, comprising administering to a patient suffering from epilepsy a traditional Chinese medicine composition, the traditional Chinese medicine composition comprising Scutellaria baicalensis, Houttuynia cordata, Isatis tinctoria, Trichosanthes kirilowii Maxim., Morus alba L., Magnolia officinalis Rehd. et Wils., Mentha haplocalyx Briq., Schizonepeta tenuifolia Briq., Saposhnikovia divaricata (Turcz.) Schischk. and prepared Glycyrrhiza uralensis Fisch..

[0118] Embodiment 23 provides the method of Embodiment 22, wherein the traditional Chinese medicine composition comprises 3.75 - 1.25 parts by weight of Scutellaria baicalensis, 3.75 - 1.25 parts by weight of Houttuynia cordata, 3.75 - 1.25 parts by weight of Isatis tinctoria, 3.75 - 1.25 parts by weight of Trichosanthes kirilowii Maxim., 2.25 - 0.75 parts by weight of Morus alba L., 2.25 - 0.75 parts by weight of Magnolia officinalis Rehd. et Wils., 2.25 - 0.75 parts by weight of Mentha haplocalyx Briq., 2.25 - 0.75 parts by weight of Schizonepeta tenuifolia Briq., 1.5 - 0.5 parts by weight of Saposhnikovia divaricata (Turcz.) Schischk. and 1.5 - 0.5 parts by weight of prepared Glycyrrhiza uralensis Fisch..

[0119] Embodiment 24 provides the method of Embodiment 22, wherein the traditional Chinese medicine composition comprises 2.75 - 2.25 parts by weight of Scutellaria baicalensis Georgi, 2.75 - 2.25 parts by weight of Houttuynia cordata Thunb., 2.75 - 2.25 parts by weight of Isatis tinctoria L., 2.75 - 2.25 parts by weight of Trichosanthes kirilowii Maxim., 1.65 - 1.35 parts by weight of Morus alba L., 1.65 - 1.35 parts by weight of Magnolia officinalis Rehd. et Wils., 1.65 - 1.35 parts by weight of Mentha haplocalyx Briq., 1.65 - 1.35 parts by weight of Schizonepeta tenuifolia Briq., 1.1 - 0.9 parts by weight of Saposhnikovia divaricata (Turcz.) Schischk. and 1.1 - 0.9 parts by weight of Radix Glycyrrhizae Preparata.

[0120] Embodiment 25 provides the method of Embodiment 22, wherein the traditional Chinese medicine composition comprises 2.5 g of Scutellaria baicalensis Georgi, 2.5 g of Houttuynia cordata Thunb., 2.5 g of Isatis tinctoria L., 2.5 g of Trichosanthes kirilowii Maxim., 1.5 g of Morus alba L., 1.5 g of Magnolia officinalis Rehd. et Wils., 1.5 g of Mentha haplocalyx Briq., 1.5 g of Schizonepeta tenuifolia Briq., 1 g of Saposhnikovia divaricata (Turcz.) Schischk. and 1 g of Radix Glycyrrhizae Preparata.

[0121] Embodiment 26 provides the method of Embodiment 22, which comprises further administering at least one antiepileptic agent.

[0122] Embodiment 27 provides the method of Embodiment 26, wherein the at least one antiepileptic agent is selected from the group consisting of phenytoin, carbamazepine, lamotrigine, felbamate, benzodiazepines, tiagabine, vigabatrin.

[0123] Embodiment 28 provides the method of Embodiment 26, wherein the at least one antiepileptic agent is carbamazepine.

[0124] Embodiment 29 provides the method of Embodiment 26, wherein the traditional Chinese medicine composition and the at least one antiepileptic agent are administered to the patient simultaneously, sequentially or intermittently.

[0125] Embodiment 30 provides the method of Embodiment 22 or 26, wherein the patient is a mammal.

[0126] Embodiment 31 provides the method of Embodiment 30, wherein the patient is a human.

[0127] Although the present invention has been disclosed with reference to specific embodiments, it is obvious to those of ordinary skill in the art to which the present invention pertains that other embodiments and variations can be designed without departing from the true spirit and scope of the present invention. The appended claims are intended to be construed to include all such embodiments and equivalent variations.

Claims

1. Use of a traditional Chinese medicine composition in the preparation of a drug for preventing or treating epileptic seizures, wherein the traditional Chinese medicine composition comprises Scutellaria baicalensis, Houttuynia cordata, Isatis indigotica, Trichosanthes kirilowii, Morus alba, Magnolia officinalis, Mentha haplocalyx, Nepeta tenuifolia, Saposhnikovia divaricate, and Glycyrrhiza glabra prepared with honey.

2. The use according to claim 1, wherein the epilepsy is triggered by damage to brain nerve cells.

3. The use according to claim 1, wherein the epilepsy is triggered by activation of glial cells.

4. The use according to claim 1, wherein the epilepsy is triggered by an inflammatory reaction in the brain caused by inflammatory molecules.

5. The use according to claim 1, wherein the inflammatory molecules are selected from the group consisting of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high mobility group box 1 (HMGB1), interleukin-1 receptor 1 (IL-1R1), and Toll-like receptor-4 (TLR-4).

6. The use according to claim 1, further comprising at least one antiepileptic agent for use in combination with the traditional Chinese medicine composition for the preparation of the drug for preventing or treating epileptic seizures.

7. The use according to claim 1, wherein the at least one antiepileptic agent is selected from the group consisting of phenytoin, carbamazepine, lamotrigine, felbamate, benzodiazepines, tiagabine, and vigabatrin.

8. A pharmaceutical combination for preventing or treating epileptic seizures, comprising a traditional Chinese medicine composition and at least one antiepileptic agent, wherein the traditional Chinese medicine composition comprises Scutellaria baicalensis, Houttuynia cordata, Isatis indigotica, Trichosanthes kirilowii, Morus alba, Magnolia officinalis, Mentha haplocalyx, Nepeta tenuifolia, Saposhnikovia divaricate, and Glycyrrhiza glabra prepared with honey, and wherein the dose of the antiepileptic agent is lower than the dose used when the antiepileptic agent is used alone to prevent or treat epileptic seizures.

9. The pharmaceutical combination according to claim 8, wherein the at least one antiepileptic agent is selected from the group consisting of phenytoin, carbamazepine, lamotrigine, felbamate, benzodiazepines, tiagabine, and vigabatrin.

10. The pharmaceutical combination according to claim 8, wherein the traditional Chinese medicine composition and the at least one antiepileptic agent are administered to a patient simultaneously, sequentially, or intermittently.

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