Traditional Chinese medicine composition for promoting neuron regeneration

Abstract

The invention discloses a traditional Chinese medicine composition for promoting neuron regeneration. Relates to the technical field. Comprising ginseng flowers, sanchi flowers, gastrodia elata, earthworms and nervonic acid. The traditional Chinese medicine composition can repair and dredge a nerve fiber network, activate nerve cells, recover the coordination function of the brain, eliminate sequelae such as hemiplegia, numbness of limbs and unclear speech caused by cerebral apoplexy, and realize autonomous behavior ability and life self-care.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and more particularly to a traditional Chinese medicine composition for promoting neuron regeneration. Background Art

[0002] Neurons in the brain do not regenerate easily, so damage is often permanent. Therefore, new ways need to be found to replace lost neurons. One possible strategy is to convert other cells in the brain into neurons.

[0003] Research has found that the innate immune response molecule "Tripartite motif-containing protein 32" (TRIM32) plays an important role in the innate immune response. Researchers from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences and other institutions have shown that the "TRIM32" protein controls the formation of neurons and participates in a variety of biological processes as an E3 ubiquitin ligase, such as cell proliferation, differentiation into neurons, neural development, and apoptosis. Neurons are the structural and functional units of the nervous system of higher animals. Their basic function is to exchange information by receiving, integrating, conducting and outputting information. They are differentiated from neural stem cells.

[0004] During differentiation, neural stem cells usually generate two cells, one of which is a neuron and the other maintains the state of a neural stem cell, and then repeatedly differentiates. The expression of the "TRIM32" protein can promote the generation of neurons from neural stem cells. If the expression of this protein is inhibited, both daughter cells will maintain the state of neural stem cells.

[0005] If neural stem cells are needed to treat a certain disease, more neural stem cells can be cultivated by inhibiting the expression of "TRIM32"; if it is necessary to activate neural stem cells that are still sleeping in the adult brain to form new neurons, methods can also be adopted to promote the expression of this protein.

[0006] Astrocyte DNA contains vascular neuron coding, which can trigger the production of NeuroD1 protein for neuronal conversion, indicating that these DNAs contain instructions for producing NeuroD1. In the prior art, Chen Gong's team revealed the molecular mechanism by which NeuroD1 induces glial cells to transdifferentiate into neurons, where NeuroD1 is a protein that induces neuronal conversion; in addition, there are studies that use lentivirus to implant a DNA fragment into microglia in the injured area. This DNA fragment contains instructions for producing NeuroD1. In the following weeks, the infected microglia began to develop into neurons, and the area of ​​neuronal loss in the brain decreased. By eight weeks, the newly induced neurons had been successfully integrated into the brain circuit. Only three weeks after infection, the mice showed improved motor function in behavioral tests.

[0007] However, lentiviral and retroviral systems have disadvantages:

[0008] Limited vector capacity: The wild-type lentiviral genome size is about 9.2kb. In the lentiviral vector, the necessary elements for viral packaging and transduction are about 2.8kb, and the remaining 6.4kb of space accommodates the target sequence. When the viral vector exceeds the above size limit, the packaging titer of the virus will be greatly reduced. In addition to inserting the sequence of the target gene, the lentiviral vector can also insert vector elements such as promoters and screening markers. If the target gene and these vector elements exceed 6.4kb in length, the virus yield may drop significantly. In addition, the technology is complex. When using lentiviral vectors, live viruses need to be produced in packaging cells and then the virus titer is measured.

[0009] Therefore, lentiviral transfection to induce neuronal regeneration is technically difficult and time-consuming.

[0010] Therefore, whether the above-mentioned technical defects can be overcome by providing a Chinese medicine composition that promotes neuron regeneration is an urgent problem that needs to be solved by those skilled in the art. Summary of the invention

[0011] In view of this, the present invention provides a Chinese medicine composition for promoting neuronal regeneration. It can induce IFN-γll type interferon, and is composed of a micron Chinese medicine complex with neuraminic acid (cis-15-tetradecenoic acid) as the main formula, which can increase the proliferation of astrocytes and induce type II endogenous interferon. Type II endogenous interferon produces TRIM32 protein through natural immune response. TRIM32 protein can activate the "vascular nerve unit" information carried by endogenous astrocytes, open the neuronal regeneration code on the gene system, promote neuronal regeneration, regenerate new nerve axons, dendrites and lateral buds, and proliferate and differentiate in large quantities, and can be directly converted into neurons in situ. It is expected to make cerebral ischemia (CI) and brain damage

[0012] The symptoms of people with neuron loss and damage such as myelopathy (BI), epilepsy (EP), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), and Pick's disease were improved.

[0013] In view of the theoretical basis that natural immune response enhances endogenous astrocytes through lentiviral and retroviral systems at home and abroad, after inducing type II interferon, it can be directly converted into neurons in situ. There are also Chinese herbal medicines that can induce type II interferon in traditional Chinese medicine. Type II interferon, namely gamma interferon, is mainly produced by activated T cells and NK cells. It is a kind of so-called lymphokine (LyTnPhokine) and can induce TRIM32 protein. IFN-γ can exist in the form of extracellular matrix connection, so it controls cell growth in a paracellular manner. It can be distributed on the surface of almost all cells except mature red blood cells. IFN-γ is a water-soluble dimeric cytokine. It is the only member of type II interferon. It is only produced by activated T cells and natural killer cells (NK cells). IFN-γ has antiviral, immunomodulatory and anti-tumor properties. It can bind to the gamma-interferon receptor (IFNGR) and is also a signature cytokine of Th1 cells. When TRIM32 protein increases, endogenous glial cells can differentiate into neurons, astrocytes and oligodendrocytes.

[0014] Through traditional Chinese medicine, IFN-γll interferon is induced and TRIM32 molecules are enhanced to regulate neuronal regeneration. The research results will provide basic data for the application of micron traditional Chinese medicine and provide a preliminary research basis for natural immune enhancers.

[0015] In order to achieve the above object, the present invention adopts the following technical solution:

[0016] A traditional Chinese medicine composition for promoting neuron regeneration comprises: ginseng flower, notoginseng flower, gastrodia elata, earthworm and neuraminic acid.

[0017] Preferably, the mass ratio of ginseng flower, notoginseng flower, gastrodia elata, earthworm and nervonic acid is 30:30:70:70:2.

[0018] Preferably, auxiliary materials are also included.

[0019] The present invention also provides application of the above traditional Chinese medicine composition in preparing medicines.

[0020] The beneficial technical effects of the above-mentioned formula are:

[0021] King of medicine: Ginseng flower Pharmacological effects

[0022] Ginseng's effects on the central nervous system:

[0023] (1) Ginseng has both excitatory and inhibitory effects on the central nervous system, with the excitatory effect being more pronounced. The effect of ginseng on central nervous system function is related to its ingredients and dosage. Ginsenoside Rg has an excitatory effect, while Rb has an inhibitory effect. Small doses are mainly excitatory, while large doses are inhibitory.

[0024] (2) Ginseng can enhance learning and memory abilities. Its main active ingredients are ginsenosides Rb1 and Rg1. The mechanism of ginseng's intelligence-enhancing effect may be: ① promoting RNA and protein synthesis in the brain; ② improving neurotransmitter transmission function, promoting the synthesis and release of Ach in the central nervous system; ③ enhancing the function of hippocampal neurons; ④ improving blood and oxygen supply to the brain, promoting brain nerve development; ⑤ protecting nerve cells, reducing the mortality rate of nerve cells cultured in vitro, and prolonging their survival time.

[0025] also:

[0026] Protect cardiovascular and cerebrovascular vessels: Ginsenosides in ginseng flowers can increase blood activity, accelerate blood circulation, inhibit platelet aggregation and thrombus formation, and play a role in protecting cardiovascular and cerebrovascular vessels.

[0027] Delaying aging: Ginsenosides in ginseng flowers can reduce the body's oxidative reactions, eliminate free radicals in the body, and have the effect of delaying aging.

[0028] Enhance the body's immunity: The active substances contained in ginseng flowers can enhance the body's immune function, improve the body's resistance, and enhance the body's immunity.

[0029] Eliminate free radicals in the body, anti-oxidation, and delay aging: The ingredients in ginseng flowers can eliminate free radicals in the body, have anti-oxidation effects, and can delay the aging process of cells.

[0030] Anti-tumor: Ginseng flower has anti-tumor effects, can inhibit the growth and spread of tumor cells, and has certain effects on the prevention and treatment of certain tumors.

[0031] Regulate endocrine: Ginseng flower can regulate the function of the human endocrine system, balance the hormone levels in the body, and has a certain effect on some diseases caused by endocrine disorders.

[0032] Tonify Qi and prolong life: Ginseng flower, as the inflorescence of ginseng, has the medicinal value of tonifying Qi and prolonging life, and can be used to treat symptoms such as dizziness, fatigue, chest tightness and shortness of breath.

[0033] Non-toxic.

[0034] Ginsenosides can reduce the activation state of astrocytes by inhibiting the production of inflammatory factors such as TNF-α, IL-6 and IL-1β. Ginsenoside Rb1 is one of the most abundant ginsenosides in ginseng and has a known neuroprotective effect on ischemic brain injury due to its anti-inflammatory, antioxidant and anti-apoptotic effects. Ginsenoside Rb1 reversibly inhibits the activity of mitochondrial complex I, blocks the production of ROS, thereby inhibiting the activation of astrocytes, and promotes the transfer of functional mitochondria from astrocytes to neurons, protecting ischemic neurons.

[0035] Assistant drug: Panax notoginseng flower pharmacological effects

[0036] The flowers and leaves of Panax notoginseng contain more ginsenosides, which are components with central nervous system inhibitory effects. The flowers of Panax notoginseng contain more ginsenosides, which are components with central nervous system inhibitory effects.

[0037] Panax notoginseng total saponins have analgesic effects.

[0038] The hot infusion, water decoction and water-decoction alcohol extract of Panax notoginseng flower have a significant dilating effect on the isolated rabbit ear blood vessels. The total saponins in Panax notoginseng flower have a temporary effect of lowering the arterial blood pressure and peripheral resistance of dogs.

[0039] The total saponins of Panax notoginseng flower have anti-inflammatory effects on ear inflammation induced by croton oil in mice and rats, dye exudative inflammation induced by intraperitoneal injection of glacial acetic acid, and carrageenan, kaolin, 5-hydroxytryptamine, egg white,

[0040] It has an inhibitory effect on ankle joint swelling and foot swelling in mice or rats caused by hyaluronidase.

[0041] Non-toxic.

[0042] Notoginseng total saponins, the main active ingredient of Panax notoginseng flower, can protect against ischemia-induced AS damage. Adding notoginseng total saponins to hypoxia-reoxygenation injury can increase the expression of Bcl-2 protein, effectively prevent the decrease of AS mitochondrial membrane potential caused by ischemia, and inhibit the expression of Bax and Caspase-3 proteins, indicating that its protective mechanism may be achieved by regulating the expression of Bcl-2 and Bax proteins on the mitochondrial membrane and mitochondrial membrane potential.

[0043] Minister drug: Gastrodia elata

[0044] Gastrodia elata belongs to the genus Gastrodia of the orchid family. Its dried tubers can be used as medicine. Gastrodia elata tastes sweet and is slightly warm in nature. It has the functions of calming the liver and extinguishing wind, calming spasms, and dredge meridians to relieve pain. Gastrodin is the main chemical component of the drug Gastrodia elata. Modern pharmacological studies have shown that gastrodin has the effects of sedation, hypnosis, vasodilation, improvement of microcirculation, protection of brain cells, reduction of ischemia-reperfusion injury, and inhibition of apoptosis. Gastrodin has a significant effect in the treatment of ischemic stroke. In addition, gastrodin can treat spinal cord injury, and its mechanism may also be related to its antioxidant and anti-inflammatory properties. Gastrodin has significant therapeutic effects in the treatment of various neurological diseases such as stroke, dementia, and epilepsy, and has a variety of different pharmacological effects.

[0045] Gastrodin can regulate the damage of free radicals, Bax / Bcl-2mRNA, caspase-3 and PARP to nerves in SH-SY5Y cells stimulated by MPP. This regulation is dose-dependent and can also improve bradykinesia and dyskinesia in the subchronic MPTP mouse PD model, and effectively prevent neuronal apoptosis. Gastrodia extract can activate A2A, protect the apoptosis of rat pheochromocytoma (PC12) cells induced by serum deprivation, and prevent the aggregation of Hunston's (HTT), so it can be used as a treatment for Hunston's neurological injury.

[0046] Gastrodia extract can significantly reduce the infarct area of ​​the cortex and striatum of brain tissue, inhibit transient cerebral ischemia caused by neuronal damage, and affect the expression of antioxidant protein genes in reperfusion cerebral ischemia, which can be used in clinical applications. Other studies have found that gastrodin can reduce the expression levels of inflammatory factors IL-1β and TNF-α in glial cells of Alzheimer's disease mice, thereby reducing neuronal apoptosis caused by inflammation.

[0047] Adjuvant: earthworm

[0048] Earthworms are commonly known as Qushen, and are called earthworms in traditional Chinese medicine. Earthworms are cold and salty in nature. Functions: clearing away heat, calming the liver, stopping asthma, and unblocking meridians. They are mainly used to treat high fever, convulsions, wind-heat headaches, red eyes, hemiplegia, etc.

[0049] Earthworms are rich in proteins and polypeptides, such as lipoproteins, calmodulin binding proteins, antimicrobial proteins, antimicrobial peptides, etc. For example, lumbrokinase (LK).

[0050] LK can reduce blood viscosity, improve microcirculation, prolong the time of in vitro thrombosis, anticoagulate but not affect hemostasis, help prevent and treat thrombosis, and is very suitable for the prevention and treatment of cerebrovascular disease, recovery of stroke sequelae, treatment of cerebral infarction and ischemic stroke, etc. In the early stage of ischemic cerebrovascular disease, the expression of P-selectin and E-selectin is enhanced, and P-selectin and E-selectin are very important for the recognition and adhesion between leukocytes and vascular endothelial cells in focal cerebral ischemia. LK may significantly reduce the expression of P-selectin and E-selectin in brain injury, thereby playing an anti-cerebral ischemia role. LK can play an anti-platelet aggregation role by upregulating cAMP levels and reducing the release of calcium ions from calcium stores, and has an anti-thrombotic effect by inhibiting the expression of ICAM-1. It can activate the AK1 / STAT1 pathway by upregulating the expression of JAK1 protein and mRNA in brain tissue and downregulating the expression of STAT1 protein and mRNA, thereby playing an anti-apoptosis and protecting cerebral ischemia damage.

[0051] Earthworms contain 18 kinds of amino acids, such as leucine, glutamic acid, aspartic acid, valine, lysine, arginine, alanine, glycine, serine, threonine, methionine, phenylalanine, proline, histidine and tyrosine, including 8 kinds of free amino acids necessary for the human body. Among them, leucine and glutamic acid have the highest content. Glutamic acid, glycine, etc. are precursors of neurotransmitters or neurotransmitters. Valine and leucine can regulate the metabolism of neurotransmitters through the blood-cerebrospinal fluid barrier and protect brain tissue from hypoxia.

[0052] Earthworms contain a variety of enzymes, such as plasmin, cholinesterase, peroxidase, catalase, superoxide dismutase, alkaline phosphatase, β-D-glucuronidase, porphyrin synthase, esterase, etc.

[0053] There are many fatty acids in the total lipids of earthworms, which are divided into saturated fatty acids and unsaturated fatty acids. Among them, the content of palmitic acid and linoleic acid is relatively high.

[0054] Earthworms contain nucleotides necessary for human metabolism, such as adenine, hypoxanthine, guanine, etc.

[0055] Earthworms contain trace elements such as potassium, strontium, zinc, selenium, calcium, iron, and cadmium.

[0056] Effects on neurons

[0057] For focal cerebral ischemia-reperfusion injury, earthworm water extract can improve the damage to the cerebral cortex (such as edema, congestion, etc.), stabilize the morphological structure of neurons, inhibit the expression of caspase-3 protein after cerebral cortex damage, and reduce neuronal apoptosis.

[0058] Pheretima can promote neuronal regeneration and promote the proliferation and survival of Schwanncell by upregulating the expression of IGF-1 and activating the PI3K / Akt signaling pathway.

[0059] Pheretima may alter the expression of proteins that control the cell cycle and upregulate anti-apoptotic proteins, thereby inducing G1 phase cell cycle progression.

[0060] Earthworms can stimulate Schwann cell migration and upregulate the expression of Pas and MMP2 / 9 mediated by the MAPK pathway, ERK1 / 2 and p38. The MAPKs (ERK1 / 2, p38), Pas (uPA, tPA), and MMP (MMP2, MMP9) signaling pathways play a very important role in Schwanncell cell migration and regeneration.

[0061] Earthworms can promote the regeneration of nerve cells, restore nerve function after injury, and have a good repair effect on peripheral nerve damage.

[0062] Effects on cerebral ischemia

[0063] The water extract of earthworm has the effect of resisting cerebral ischemia damage.

[0064] Protect against cerebral ischemia-reperfusion injury.

[0065] Pheretima extract can effectively reduce the infarct area of ​​brain tissue after focal cerebral ischemia-reperfusion injury in rats and improve the degree of neurological damage.

[0066] Syndecan-1 can regulate vascular permeability, prevent the migration and infiltration of inflammatory cells, downregulate the expression of monocyte-macrophage colony stimulating factor (GM-CSF), reduce the proliferation and differentiation of monocytes and macrophages, and the synthesis and expression of iNOS, and can play an anti-inflammatory and anti-apoptotic role. The changes in syndecan-1 are closely related to the pathophysiological changes of ischemia-reperfusion injury in acute cerebral infarction. Upregulating the expression of syndecan-1 can enhance the anti-inflammatory and anti-brain cell edema effects. In existing studies, the extract of leech earthworm can upregulate the expression of syndecan-1, and by enhancing the expression of syndecan-1, it plays an anti-inflammatory and anti-apoptotic role, thereby reducing cerebral ischemia-reperfusion injury.

[0067] It has been found in long-term clinical practice that Hengqing Decoction (earthworm, Gastrodia elata, Uncaria rhynchophylla, Ligusticum chuanxiong, Salvia miltiorrhiza, Pueraria root) has a satisfactory therapeutic effect on vertebral basilar artery insufficiency vertigo, and earthworm is the main ingredient of Hengqing Decoction.

[0068] Effects on cerebral infarction

[0069] Earthworm can reduce neuronal death, glial proliferation, and S100B protein in the cortical penumbra and cortical ischemic core, but there is no change in brain-derived neurotrophic factor protein.

[0070] Earthworm extract can reduce the damaged area of ​​cerebral infarction, reduce platelet adhesion, prolong thrombosis, and has a good thrombolytic effect.

[0071] Effects on epilepsy

[0072] Epilepsy is a neurological syndrome characterized by sudden onset and recurrent seizures. Its clinical manifestations include various disorders of movement, sensation, consciousness, autonomic nerves, and spirit. It is mainly due to abnormal discharges of brain neurons, which in turn cause transient brain dysfunction.

[0073] Epileptic seizures may be mainly related to the imbalance between excitatory and inhibitory amino acids in the central nervous system, to which glutamate (Glu) and γ-aminobutyric acid (GABA) belong.

[0074] Earthworms can not only reduce the content of Glu, but also increase the level of GABA at the same time, improving the imbalance of excitatory and inhibitory amino acid neurotransmitters, thereby significantly prolonging the latency time of epileptic seizures and shortening the duration of seizures. Its effect is similar to that of sodium valproate, but as its dosage increases, its effect tends to be better than the latter.

[0075] Earthworm can not only reduce the content of Glu, but also increase the level of GABA, improve the imbalance of excitatory and inhibitory amino acid neurotransmitters, thus significantly prolonging the latency of epileptic seizures and shortening the duration of seizures. Its effect is similar to that of sodium valproate, but with the increase of its dose, its effect also tends to be better than the latter. Its anti-epileptic mechanism is very complex and may be related to multiple factors such as the related receptors, enzymes, and gene expression of amino acid neurotransmitters.

[0076] Effects on vascular dementia

[0077] Vascular dementia (VaD) is a major type of senile dementia associated with cerebrovascular disease.

[0078] Among senile dementia, Alzheimer's disease is considered to be the leading cause, and VaD is the second leading cause. In Asian countries, VaD is the leading cause of senile dementia.

[0079] LK plus nimodipine can significantly improve the cognitive function and daily self-care ability of VaD patients, and its effect is significantly better than that of patients taking nimodipine alone, and the difference is statistically significant. It can improve the abnormal hemorheological indicators of VaD patients, prolong PT and APTT, and reduce fibrinogen, but there is no obvious bleeding tendency. This shows that LK has a mild effect on coagulation function and has good tolerance.

[0080] Effects on transient ischemic attack

[0081] Transient ischemic attack (TIA) is a transient neurological dysfunction caused by focal ischemia of the brain, spinal cord, or retina without acute cerebral infarction. It is a common acute ischemic cerebrovascular disease. TIA is the most important independent risk factor for ischemic stroke and the most valuable warning sign before stroke. TIA can cause severe neurological deficits and should be intervened early.

[0082] LK plays an important role in the degradation of fibrinogen and in reducing platelet aggregation rate, and has a certain therapeutic effect on TIA.

[0083] Effects on Alzheimer's disease

[0084] Earthworm can alleviate the corresponding symptoms caused by central nervous system deterioration, help improve memory loss, improve patients' cognitive function, and have a certain effect on the treatment of Alzheimer's disease. Its mechanism of action may be related to its unsaturated fatty acids that can inhibit the binding of copper ions.

[0085] other

[0086] Earthworms have the effects of clearing away heat, extinguishing wind and calming the nerves. They can be used clinically to treat intractable insomnia and schizophrenia.

[0087] The main active parts of earthworms that have sedative, hypnotic and anticonvulsant effects are the parts extracted from ethyl acetate, chloroform and water.

[0088] Except for the n-butanol extraction part, earthworms have certain effects on inhibiting the autonomous activities of mice, promoting the hypnosis of pentobarbital, and reducing the convulsion and death of mice caused by pentylenetetrazol, especially the ethyl acetate part. The active parts of earthworms for sedation, hypnosis and anticonvulsant are the ethyl acetate part, chloroform part and water extraction part.

[0089] Adjuvant: Nervonic acid (cis-15-tetracosenoic acid)

[0090] Cis-15-tetradecenoic acid is a long-chain unsaturated fatty acid and a monounsaturated analog of lignoceric acid. It is also called nervonic acid and chelic acid. It is composed of choline, phosphoric acid, sphingosine and fatty acids. It is found as an extension product of oleic acid, and its direct precursor is erucic acid. It is particularly abundant in the white matter of the animal brain and peripheral nerve tissue, where nervulinoids are dotted in the myelin sheath of nerve fibers. It is an important member of the cerebroside fatty acids, which are important components of muscles, the central nervous system and the periphery.

[0091] Neuroacid (cis-15-tetradecenoic acid) is a basic component of nerve cells and brain nerve fibers. Neuroacid (cis-15-tetradecenoic acid) deficiency can lead to a series of brain diseases such as Alzheimer's disease, stroke, brain atrophy, cerebral palsy, insomnia, memory loss, forgetfulness, etc. It is not endogenous and can be obtained through dietary supplements and natural food supplements.

[0092] Prevention of brain atrophy and dementia in Alzheimer's disease is a worldwide topic. Neuroacid (cis-15-tetradecenoic acid) can help solve the problem. Neuroacid (cis-15-tetradecenoic acid) can completely cross the blood-brain barrier and directly enter the damaged parts of nerve fibers or nerve cells, regenerate the protective sheath of damaged parts of nerve fibers, effectively dissolve the channels of necrotic tissue, and repair twisted or broken nerve fibers at the same time, promote the nutrient supply of nerve fibers, help the elderly enhance their memory, and prevent and treat Alzheimer's disease.

[0093] Cholesterol LevelNeuronic acid (cis-15-tetradecenoic acid) can effectively regulate blood lipids, increase beneficial cholesterol and reduce harmful cholesterol. It helps reduce the incidence of heart disease and cardiovascular disease. It has anti-fatigue, anti-aging, and immunity-enhancing effects.

[0094] Stroke: repair and clear the nerve fiber network, activate nerve cells, restore the brain's coordination function, eliminate the sequelae of hemiplegia, numbness of limbs, slurred speech, etc. caused by cerebral stroke, and realize the ability of independent behavior and self-care.

[0095] Alzheimer's disease (senile dementia) is a progressive neurodegenerative disease with an insidious onset. The patient's cerebral cortex is extensively atrophied, the white matter is sparse, and there is diffuse atrophy of the cortex and enlargement of the lateral and third ventricles. These changes cause widespread neurofibrillary tangles and loss of neurons, axons and dendrites in the cerebral cortex and other parts, leading to blockage of the pathways for central nervous fibers to transmit information, causing cell degeneration and necrosis, and blocking the pathways for the brain to form memory, cognition, and action, and the effective transmission of information fails, resulting in obstacles to understanding. Supplementing neuraminic acid can repair damaged and activate dormant nerve cells, enhance brain cell energy, promote cell proliferation and differentiation, establish a new synaptic network system, prevent brain nerve cell aging and damage, and restore the brain's clear cognition, discrimination, learning, thinking and memory abilities.

[0096] Trauma repair: Neuroacid can repair damage to nerve fibers and cells caused by surgical operations or accidental trauma, restore memory, limb motor functions, etc., repair the traumatic injury site, gradually eliminate the numbness of the wound, and restore various tissues such as tendons, bones, skin and flesh to their original appearance as much as possible.

[0097] Cerebral palsy: Neuroacid can completely pass through the blood-brain barrier, directly act on nerve fibers to repair and clear them, regenerate damaged and detached "protective sheaths", dissolve necrotic tissues that block the channels, induce self-growth and division of nerve fibers, activate dormant nerve cells, reshape neural networks, and restore language, memory, sensation, limbs and other functions. It helps children with cerebral palsy to achieve independence and learning ability.

[0098] Parkinson's disease: repairs nerve pathways, ensures accurate information transmission, stabilizes the nervous system, eliminates involuntary tremors in the limbs, restores the body's flexibility, agility and balance function, and enables stable and powerful autonomous actions.

[0099] Brain atrophy: Supplementing with neuraminic acid, in addition to repairing damaged nerve tissue, has a very important function. Neuroacid can activate and awaken nerve cells stored in a dormant state in the brain, allowing them to urgently participate in central nervous system activities. It also soothes the smooth muscle cells of cerebral capillaries, increases blood supply to the brain, promotes recovery from brain damage, prevents softening, collapse and atrophy of brain tissue, and enables recovery and self-care.

[0100] Delaying brain aging: Supplementing enough neuraminic acid for 30 days can improve memory, cognition, and action overall, fully activate dormant brain cells, and replenish brain white matter in time, improve brain cell vitality, and help enhance human vitality, thereby delaying brain cell aging. Neuroacid can reduce malondialdehyde in the blood, significantly enhance the activity of superoxide dismutase (SOD), reduce the accumulation of lipofuscin in brain cells, remove the toxic effects of superoxide anion free radicals on cells in the body, provide essential nutrients for nerve cells in capillaries, improve brain blood circulation, ensure sufficient blood oxygen supply to brain cells, and activate nerve cells.

[0101] Neuroacid can directly act on damaged nerve fibers, dissolve necrotic tissues that block nerve fibers, restore the smoothness of nerve information transmission channels, increase the transmission speed and ensure the accuracy and integrity of information transmission. Activate nerve cell adhesion molecules (NCAM), improve the operation function of damaged nerve cells, increase the entry of nutrients, reverse, prevent and restore degeneration, death and damaged nerve cells. Enable nerve cells to receive information stimulation, transmit impulses and improve the ability to integrate and remember information. Damage to nerve fibers will cause gene fragments to temporarily or permanently lose their functions, and the regeneration code cannot be opened. Neuroacid can repair nerve fibers and activate nerve cells. It can accurately identify and start the AT and CG gene expression systems on the DNA chain that control the promotion of nerve regeneration, so that it can open the nerve regeneration code on the gene system, promote nerve regeneration, regenerate new axons, dendrites and lateral buds, and proliferate and differentiate in large quantities, and the number continues to increase, so that the neural network can rebuild and improve its function. Neuroacid can activate and awaken nerve cells stored in the brain in a dormant state, so that they can immediately replace dead brain cells and urgently participate in the activities of the central nervous system, ensuring the normal operation of the brain and nervous system functions.

[0102] Neuroacid has the effect of restoring brain nerves. Cis-15-tetradecenoic acid, as a special fatty acid that can pass through the blood-brain barrier, plays a vital role in restoring brain nerves. Neuroacid (cis-15-tetradecenoic acid) can promote the regeneration and repair of neurons, thereby improving brain function and cognitive ability. It can also increase the flow of cerebral blood vessels, improve blood circulation, and provide more nutrients and oxygen to the brain. All of these help alleviate brain aging and prevent cognitive impairment.

[0103] Neuroacid also has anti-inflammatory, antioxidant and anti-aging effects. These properties make it a very valuable nutritional supplement. As a special fatty acid, it plays an important role in restoring brain nerves, improving brain function and cognitive ability:

[0104] Improve memory and increase memory quotient (IQ);

[0105] Improve understanding, association, judgment, and mood;

[0106] It is beneficial to the nutritional health care and vision protection of the retina and optic nerve;

[0107] Regulate blood lipids, blood pressure, and blood sugar, significantly reduce blood lipids, reduce blood viscosity, and inhibit platelet cohesion and inflammatory factors;

[0108] Improve peripheral nervous system diseases (peripheral facial paralysis, sciatica, multiple sclerosis, trigeminal nerve, etc.).

[0109] It can be seen from the above technical solutions that, compared with the prior art, the present invention discloses a Chinese medicine composition for promoting neuron regeneration, and the technical effects achieved are:

[0110] The present invention screens the Chinese medicine compound ginseng flower, Panax notoginseng flower, Gastrodia elata, earthworm, and neuraminic acid (cis-15-tetracosenoic acid) that can induce IFN-γll interferon for prescription. Endogenous astrocytes in the brain can be enhanced, TRIM32 protein can be produced through natural immune response, TRIM32 protein can induce IFN-γll interferon, TRIM32 protein interacts with type ll endogenous interferon, and can activate the "vascular nerve unit" information carried by endogenous astrocytes. Endogenous astrocytes in the brain proliferate and differentiate in large quantities, and can be directly converted into neurons in situ. Plant stem cells, exosomes, and fatty acids in Chinese medicine preparations can promote the synthesis and release of neurotrophic and nerve growth factors, thereby promoting nerve regeneration. Ginseng (extract) is rich in ginsenosides, which can promote the regeneration of neurons and synapse formation. Chinese medicine has the effect of promoting cell proliferation and activation on astrocytes. Panax notoginseng (extract) can promote the proliferation of astrocytes and activate their functions. These activated astrocytes can release growth factors to promote neuronal regeneration and repair. In addition, the ingredients in the formula can also promote the proliferation of astrocytes by regulating the cell cycle and proliferation-related factors of astrocytes.

[0111] Secondly, the ingredients of the formula have anti-inflammatory effects on astrocytes. Many Chinese medicines, such as Gastrodia elata, have been found to inhibit the production of inflammatory factors in astrocytes and reduce the inflammatory response of the nervous system. The anti-inflammatory effect is exerted by inhibiting the activation of inflammatory pathways and regulating the expression of inflammation-related signaling molecules. Inflammatory response is a common feature of many neurological diseases. By regulating the inflammatory response of astrocytes, the ingredients of the formula may be able to reduce inflammatory damage and promote the repair of the nervous system.

[0112] The present invention repairs and dredges the nerve fiber network, activates nerve cells, restores the coordination function of the brain, eliminates sequelae such as hemiplegia, numbness of limbs, slurred speech, etc. caused by cerebral apoplexy, and realizes the ability of autonomous behavior and self-care. BRIEF DESCRIPTION OF THE DRAWINGS

[0113] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.

[0114] Figure 1 The accompanying drawing is a process route diagram provided by the present invention. DETAILED DESCRIPTION

[0115] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0116] The embodiment of the present invention discloses a traditional Chinese medicine composition (customized as new neuron protein generating granules) for promoting neuron regeneration.

[0117] The process route diagram of the present invention is as follows Figure 1 , by screening the traditional Chinese medicines ginseng flower, Panax notoginseng flower, Gastrodia elata, earthworm, and neuraminic acid (cis-15-tetracosenoic acid) that can induce IFN-γⅡ interferon → processing them into a traditional Chinese medicine composition (granules) including plant stem cells, exosomes, and unsaturated fatty acids → oral administration → observing the number of TRIM32 protein, astrocytes, and neurons → explaining the mechanism and material basis of the efficacy of the traditional Chinese medicine composition in multiple dimensions.

[0118] The raw materials or related reagents not mentioned in the examples are commercially available, for example, the human triple domain containing protein 32 (TRIM32) enzyme-linked immunosorbent assay (ELISA) kit was purchased from Shanghai Bohu Biotechnology Co., Ltd.;

[0119] Experimental principle of the kit:

[0120] This kit uses the double antibody sandwich method to determine the level of human three-domain-containing protein 32 (TRIM32) in the sample. The microplate is coated with purified human three-domain-containing protein 32 (TRIM32) antibody to prepare a solid-phase antibody, and three-domain-containing protein 32 (TRIM32) is added to the microwells coated with the monoclonal antibody in sequence, and then combined with the HRP-labeled three-domain-containing protein 32 (TRIM32) antibody to form an antibody-antigen-enzyme-labeled antibody complex. After thorough washing, the substrate TMB is added for color development. TMB is converted into blue under the catalysis of HRP enzyme, and converted into the final yellow under the action of acid. The depth of color is positively correlated with the three-domain-containing protein 32 (TRIM32) in the sample. The absorbance (OD value) is measured at a wavelength of 450nm using an enzyme reader, and the concentration of human three-domain-containing protein 32 (TRIM32) in the sample is calculated using a standard curve.

[0121] Other general materials and equipment:

[0122] This experiment mainly uses reagents produced by Applied Biosystems for experiments related to miRNA of spinal cord-derived neural stem cells and neurons, such as TaqMan geneexpression master mix, Transcription Kit, etc. Secondly, the experimental instruments commonly used in this experiment, such as UV spectrophotometer, 7300 fluorescence quantitative PCR system, etc. In addition, this experiment also needs to prepare a certain amount of RNase-free water, its main purpose is to extract RNA or reverse transcription. In the process of preparing RNase-free water, you need to use RNase-free glass bottles, and then add DEPC to the ultrapure water to a final concentration of 0.01% (v / v).

[0123] The operation steps or experimental steps not mentioned are all routine operations, such as the use of fluorescent quantitative PCR technology to analyze the relative expression changes of the TRIM32 gene, as well as the number of astrocytes (such as Cai Huazhu, Ji Lijin, the effect of Qiangpi Yizhi capsule on the proliferation of astrocytes in the hippocampus of rats with Alzheimer's disease [J]. Journal of Fujian University of Traditional Chinese Medicine. 2009, 19(6): 57-63), the expression of the number of neurons (such as Yan Limei, Wu Jianyong, Yu Xiaohua, et al. The effect of intron-derived microRNA on the expression of endothelial nitric oxide synthase and the proliferation of vascular endothelial cells [J]. Progress in Biochemistry and Biophysics, 2010, 37(7): 747-753).

[0124] Example 1

[0125] A traditional Chinese medicine composition for promoting neuron regeneration comprises: 3g of ginseng flower, 3g of notoginseng flower, 7g of gastrodia elata, 7g of earthworm, and 0.2g of neuranthic acid.

[0126] Preparation process: conventional preparation process is adopted, that is, vacuum spray drying method is used to suspend the above Chinese medicine raw materials in a suitable solution, and prepare them into micron-level particles by spray drying under vacuum conditions, which is not specifically limited.

[0127] Technical effect verification 1:

[0128] Experimental principle introduction:

[0129] Cerebellar Purkinje neuron protein (CEPU-1) is a member of the immunoglobulin superfamily with a relative molecular mass of 51000. CEPU-1 is strongly expressed in the cell bodies, axons, and dendrites of developing cerebellar Purkinje neurons and is considered to be a specific recognition protein for developing Purkinje neurons.

[0130] Almost all macromolecules in neurons are synthesized in the cell body from mRNA originating from the nucleus. Because the cell body is only one of four key regions of a neuron, and because the axon and the terminal are usually far from the cell body, transport mechanisms are critical to neuronal function. Protein synthesis usually occurs only in the cell body and dendrites, with axonal proteins being turned over primarily in the cell body and proximal dendrites. However, some protein turnover can indeed occur in dendrites, through active transport of ribosomes and mRNA to dendrites, especially dendritic spines.

[0131] All protein synthesis begins in the cytosol, where mRNA molecules bind to free ribosomes, which are often linked by mRNA into small clusters called polysomes. The final destination of the protein is encoded in the amino acid sequence. The majority of newly synthesized proteins remain in the solute. Cytosolic proteins include the two most widespread groups of proteins in neurons: cellulose, which makes up the skeleton; enzymes, which catalyze reactions.

[0132] Experimental Procedure

[0133] Inclusion criteria (taking stroke as an example):

[0134] a. Meet the diagnostic criteria for stroke and be confirmed by head CT or MRI;

[0135] b. First onset of illness, with stable vital signs, normal cognitive ability, and normal communication ability;

[0136] C. Disease duration 3-6 months (50%), 3-12 months (100%), in recovery period, age 18-80 years;

[0138] d. Unilateral limb dysfunction;

[0139] e. Lower limbs: Have the ability of static balance in standing position, the strength of the main muscle groups of the lower limbs is level 3 or above, and the lower limbs

[0140] Brunnstrom stage III and above.

[0141] f: Upper limbs: modified Ashworth <3, Brunnstrom stage ll and above.

[0142] Exclusion criteria: severe spastic imaging movements, severe dysphagia, and severe complications.

[0143] A total of 100 patients in outpatient and inpatient stroke rehabilitation in Handan Traditional Chinese Medicine Hospital were screened and randomly assigned to set up an observation group and a control group, including 50 people in the observation group and 50 people in the control group. The observation group was treated with the Chinese medicine composition prepared in Example 1 on the basis of the basic treatment related to the stroke guidelines such as glucocorticoids, antibiotics, and anticoagulants; the control group was treated with the basic treatment related to the stroke guidelines such as glucocorticoids, antibiotics, and anticoagulants.

[0144] The molecular weight of TIRM32 of the two groups of patients was detected, and the efficacy of the micron "Chinese herbal composition" on stroke rehabilitation was compared and observed, and it was confirmed that the TIRM32 level was closely correlated with the regeneration of stroke neurons.

[0145] Based on the research theories of the Institute of Molecular Biotechnology of the Austrian Academy of Sciences and other institutions mentioned in the background technology, experiments have confirmed that when TRIM32 protein increases, neuronal protein increases at the same time, and stroke patients recover. The results show that: TRIM32 increases, neuronal protein increases. Cerebellar Purkinje neuronal protein is strongly expressed in the cell bodies, axons, and dendrites of developing cerebellar Purkinje neurons.

[0146] This experiment uses a Chinese medicine composition that can induce IFN-γll type interferon to increase the amount of endogenous astrocytes, enhance the body's natural immune TIRM32 molecules, and treat various diseases caused by neuron loss. It is clear that the increase in TIRM32 is positively correlated with neuron regeneration and has statistical significance. Chinese medicine new neuron regeneration granules can induce type II interferon, proliferate the number of astrocytes, and induce TRIM32 protein. TRIM32 protein stimulates, activates, induces, and responds to neuronal proteins carried in astrocytes, and activates the "vascular nerve unit" information carried by endogenous astrocytes, so that it opens the neuron regeneration code on the gene system, promotes neuron regeneration, regenerates new nerve axons, dendrites and lateral buds, and proliferates and differentiates in large quantities, which can be directly converted into neurons in situ.

[0147] Technical effect verification 2:

[0148] Clinical efficacy of rehabilitation treatment with "Chinese medicine combination" for elderly patients with sequelae of cerebral infarction.

[0149] Methods: 32 elderly patients with cerebral infarction who were admitted to the Department of Neurology of Handan Traditional Chinese Medicine Hospital from November 2022 to December 2023 were selected. According to different treatment methods, all patients were randomly divided into a control group and a study group with 16 cases in each group. The control group was treated with intravenous drip of Danshen or Naofukang; the study group was given the Chinese medicine composition prepared in Example 1 for rehabilitation treatment and limb function training on the basis of the medication of the control group.

[0150] Results: After the treatment, the limb function of both groups of patients improved significantly, and the total clinical effective rate of the patients in the study group was as high as 93.75% through the treatment of "Chinese medicine combination" and the exercise of limb function, which was significantly better than 75.00% in the control group. The difference was statistically significant (p<0.05). After treatment, the qol score of the patients in the study group was significantly different from that in the control group, which was statistically significant (p<0.05). Through early and scientific rehabilitation treatment and limb function exercise, the patients' joint, muscle strength, and tension functions were improved, and the quality of life was significantly improved. The total clinical effective rate was higher than that of other drug treatments alone, which has clinical promotion value.

[0151] The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other.

[0152] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A Chinese medicine composition for promoting neuron regeneration, characterized in that: include: Ginseng flower, Panax notoginseng flower, Gastrodia elata, earthworm, and neuraminic acid.

2. The Chinese medicine composition according to claim 1, characterized in that The mass ratio of the ginseng flower, notoginseng flower, gastrodia elata, earthworm and nervonic acid is 30:30:70:70:

2.

3. The Chinese medicine composition according to claim 2, characterized in that: Also includes auxiliary materials.

4. Use of the Chinese medicine composition according to claims 1 to 3 in the preparation of medicines.

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