CN115381924A

CN115381924A - Composition for nerve repair and preparation method and application thereof

Info

Publication number: CN115381924A
Application number: CN202211030646.5A
Authority: CN
Inventors: 李晴; 银孟卓
Original assignee: Guangzhou First Peoples Hospital
Current assignee: Guangzhou First Peoples Hospital
Priority date: 2022-08-26
Filing date: 2022-08-26
Publication date: 2022-11-25
Anticipated expiration: 2042-08-26
Also published as: CN115381924B

Abstract

The invention provides a composition for nerve repair, which is characterized by comprising the following components in parts by mass of 1-3; the nutritional aid comprises compound vitamins, compound trace elements, compound probiotics and compound protein. The invention improves the stability of the nervous system from multiple aspects, protects the nervous system from damage, promotes the repair of the nervous system damage and has good effect.

Description

Composition for nerve repair and preparation method and application thereof

Technical Field

The invention relates to the technical field of pharmacy, in particular to a composition for nerve repair and a preparation method and application thereof.

Background

The nervous system includes the central nervous system (brain, spinal cord) and the peripheral nervous system. Nervous system injury can be caused by a variety of factors: (1) Physical injury, which directly causes damage to nerve tissue at the injury site, such as brain nerve tissue injury or spinal cord injury caused by trauma; (2) Temporary or permanent ischemia or hypoxia of a portion of the nervous system, such as brain nerve tissue damage caused by stroke or brain embolism; (3) Exposure to a neurotoxin, such as a chemical for the treatment of cancer or dideoxy cytarabine for the treatment of AIDS; (4) Chronic metabolic diseases, such as peripheral nerve injury caused by diabetes or renal dysfunction; (5) Neurodegenerative diseases, including Parkinson's disease, alzheimer's disease, and the like. With the aging of the population accelerating, the social risks due to aging-related diseases are increasing. The aging-related nerve injury diseases are diseases with nerve cell loss and nerve tissue damage caused by various reasons, the common diseases comprise vascular dementia (VaD) and most Neurodegenerative Diseases (ND), such as Alzheimer's Disease (AD), parkinson's Disease (PD) and the like, are frequently encountered diseases of the elderly, are mainly related to age, and most of the aging-related nerve injury diseases have the characteristics of high disability rate and death rate, seriously affect the late life of patients and cause great family burden and social stress, so that the aging-related nerve injury diseases become an emergency task for domestic and foreign researchers.

Many senile nerve injury diseases are closely related to aging, but the pathogenesis is different, and the pathogenesis of one of the main types of Alzheimer's disease is still unclear, so many hypotheses mainly exist about the pathogenesis of the disease at present, namely a cholinergic hypothesis, an A beta protein generation and metabolism disorder hypothesis, an oxidative stress and free radical injury hypothesis, an inflammation hypothesis, a Tau protein abnormal phosphorylation hypothesis, a metal ion metabolism hypothesis and the like, however, no single hypothesis can completely explain various pathological characteristics of the disease, the disease is mainly considered to be a result of the combined action of multiple factors, and the aging is the only determinable factor. At present, there are no definite diagnosis and treatment methods and treatment medicines for prevention, early diagnosis and late treatment of Alzheimer's disease. Therefore, there is a need for a composition for nerve repair that facilitates repair of physical, pharmaceutical, disease or aging-induced nerve damage.

Disclosure of Invention

The invention aims to provide a composition for nerve repair, which can be applied to repair of nerve damage caused by physics, medicines, diseases or aging.

In order to achieve the purpose, the invention provides a composition for nerve repair, which comprises the following components in parts by mass of 1-3;

the nutrition aid comprises compound vitamins, compound trace elements, compound probiotics and compound protein.

Further preferably, the mass ratio of the cerebroprotein hydrolysate to the rehmannia root extract to the sea cucumber extract to the gastrodia elata extract to the schisandra chinensis extract to the liquorice extract to the nutritional supplement is 1.8.

Further preferably, the nutritional aid comprises, by mass, 1.5:0.3:1:1.2 vitamin complex, trace element complex, probiotics complex and protein complex.

Further preferably, the composite probiotics are one or a mixture of more of lactobacillus, lactobacillus reuteri, clostridium butyricum, bacillus subtilis, bacillus coagulans, streptococcus thermophilus and bifidobacterium.

Further preferably, the vitamin complex comprises vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E.

Further preferably, the composite trace elements include a plurality of iron, zinc, chromium, iodine, molybdenum, selenium and copper.

Further preferably, the application is applied to the repair of nerve damage caused by physical, medicine, diseases or aging. Is particularly suitable for repairing degenerative nerve injury.

The invention also provides a preparation method of the composition for nerve repair, which comprises the following steps:

s1, respectively mixing to prepare powdery compound vitamin, compound trace elements, compound probiotics and compound protein;

s2, dissolving the cerebroprotein hydrolysate bulk drug in water, filtering with a nanofiltration membrane, and freeze-drying the filtrate to obtain a cerebroprotein hydrolysate;

s3, mixing and uniformly stirring compound vitamins, compound trace elements, the coated compound probiotics, the brain protein hydrolysate, the powdery rehmannia root extract, the sea cucumber extract, the gastrodia elata extract, the schisandra chinensis extract powder and the liquorice extract powder according to a mass ratio to obtain the composition.

Further preferably, the method also comprises S4. The composition is coated with hydroxypropyl methyl cellulose phthalate for the first time, and then is coated with soluble soybean polysaccharide for the second time at a low temperature of 50 +/-5 ℃ for 3 hours to obtain the coating composition.

The invention has the beneficial effects that: the composition for nerve repair is prepared by synergistically matching brain protein hydrolysate, rehmannia root extract, sea cucumber extract, gastrodia tuber extract, schisandra fruit extract powder, liquorice extract powder and nutrition aids, and is used for inhibiting apoptosis of neurons, eliminating Abeta deposition and resisting PC12 apoptosis and signal mechanism caused by Abeta injury from 1; 2. oxidation, slowing down the aging of nerve cells; 3. increasing the expression of the brain-derived nerve factor and the vascular endothelial growth factor to repair the ischemic brain tissue; 4. modulating neurotransmitter levels in the hippocampus to protect the central nervous system; 5. promoting the survival and differentiation of neurons, improving the stability of the central nervous system and promoting the protection and repair of the nervous system; 6. improving intestinal flora, regulating central gamma-aminobutyric acid receptor by vagus nerve to influence brain neurochemistry (neurotransmitter level, receptor and various neurotrophic factors) and behavior, improving nerve injury or apoptosis, and promoting nerve repair; 7. promoting nutrient absorption, ensuring organism nutrition level, improving organism immunity, promoting organism repair, etc., improving nervous system stability, protecting nervous system from damage, and promoting nervous system damage repair.

The compound vitamins, the compound trace elements, the compound probiotics and the compound protein are cooperated, on one hand, the required nutrition is fully supplemented for the organism respectively; and secondly, the composition can inhibit the growth of harmful bacteria, promote the multiplication of beneficial bacteria, regulate the ecological balance of intestinal tracts, form a biological protection barrier, improve the immunity of organisms, improve the circulation of the intestinal tracts, enhance the functions of the intestinal tracts and improve the conversion rate of substances, thereby promoting the absorption of the organisms on nutrient elements, ensuring the nutrition level of the organisms and improving the immunity of the organisms.

Detailed Description

The embodiments described below are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The invention provides a composition for nerve repair, which comprises the following components in parts by mass of 1-3; the nutrition aid comprises compound vitamins, compound trace elements, compound probiotics and compound protein.

The composition comprises the following components in percentage by mass of 1.8.

The nutrition aid comprises the following components in a mass ratio of 1.5:0.3:1:1.2 vitamin complex, trace element complex, probiotics complex and protein complex.

The compound vitamin comprises vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E.

The compound protein comprises two or more of soybean protein, casein, whey protein and pea protein.

The composite probiotics are one or a mixture of more of lactobacillus, lactobacillus reuteri, clostridium butyricum, bacillus subtilis, bacillus coagulans, streptococcus thermophilus and bifidobacterium. The probiotics can resist the infection of bacteria and viruses, improve immunity, and eliminate the harm of harmful bacteria to human bodies by inhibiting the growth of the harmful bacteria, inhibiting the harmful bacteria from generating toxin and eliminating the toxin generated by the harmful bacteria. The vitamins including pantothenic acid, nicotinic acid, B1, B2, B6, vitamin K and the like are generated, short-chain fatty acid, antioxidant, amino acid and the like can be generated, the important effects on bone growth and heart health are achieved, certain diseases such as intestinal syndrome, gastric ulcer and the like can be prevented and treated, the balance of intestinal flora is regulated, the intestinal function is improved, and the absorption of nutrient substances is promoted. The active compound can be absorbed and utilized by human body after being absorbed by organism and passing through intestinal tract, and can interact with intestinal flora, so as to embody its physiological activity, inhibit or repair nerve injury, and the beneficial intestinal flora can improve intestinal function, promote absorption of active substance, and improve substance effectiveness and availability. Meanwhile, the intestinal flora can influence the brain function through the intestinal nervous system, the endocrine system, the metabolic system and the immune system. Hormones and neurotransmitters produced by intestinal bacteria (e.g., 5-tryptamine, dopamine, gamma-aminobutyric acid, norepinephrine, etc.) pass through the vagus nerve and enter the central nervous system, producing corresponding neuronal inhibitory or excitatory effects. Gamma-aminobutyric acid, in turn, is a major central nervous system inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. The change of central gamma-aminobutyric acid receptor expression relates to the pathogenesis of AD (Alzheimer disease), and lactobacillus reuteri in intestinal tract can regulate the central gamma-aminobutyric acid receptor through vagus nerve to influence the brain neurochemistry (neurotransmitter level, receptor and various neurotrophic factors) and behaviors, thereby playing a role in improving AD.

The compound vitamin comprises vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E. Vitamin B1 can promote appetite, enhance gastrointestinal resistance, regulate metabolism, and maintain normal nervous activity. Vitamin C helps to maintain skin and mucous membrane health, bone and gum health, promote iron absorption, has antioxidant effect, and can improve organism immunity and promote substance absorption. The main physiological function of vitamin D is to regulate the metabolism of calcium and phosphorus, in particular to promote the absorption of calcium and phosphorus by the small intestine; regulate the excretion of calcium and phosphorus by the kidney; controlling the storage of calcium and phosphorus in bones and the concentration of calcium and phosphorus in blood, etc. When vitamin D is insufficient, even if calcium and phosphorus are sufficient, the vitamin D cannot be well utilized by the human body. Vitamin B12 can promote protein biosynthesis, has the functions of protecting folic acid from transferring and storing in cells, can enhance the immunity of the organism and protect nerves, can improve the physique of the organism and promote nerve repair, and when vitamin B12 is deficient, researches on animal pernicious anemia can show that people with lower vitamin B12 concentration in blood usually have the condition of accelerated bone loss because vitamin B12 can eliminate homocysteine in the blood, can prevent osteoporosis and even hip fracture caused by excessive homocysteine, and has the effect of protecting bones. Vitamin B12 can promote the development and maturation of erythrocyte, keep the hematopoietic function of organism in normal state, and maintain the health of nervous system, and vitamin B12 contains mineral copper, and can promote the absorption of iron in gastrointestinal tract. The main active component of vitamin E in human body is alpha-tocopherol, which is an important fat-soluble antioxidant nutrient in the human body, and the deficiency of vitamin E can cause the damage of neuron axon membranes, the mutagenicity of peripheral nerves, spinal ganglia, spinal cord posterior roots and posterior axis, so that the patients gradually appear weakened or disappeared tendon reflex, cerebellar ataxia, skin sensory disturbance, abnormal posture and vibration sensation, night blindness and the like.

The compound trace elements comprise multiple of iron, zinc, chromium, iodine, molybdenum, selenium and copper. Although the trace elements are not contained in a large amount in a human body, the trace elements are closely related to the survival and health of people and play a vital role in the life of the people. Excessive, insufficient, unbalanced or deficient intake of them can cause physiological abnormalities or diseases in the human body to various degrees. Zinc can promote the synthesis of protein and nucleic acid in brain, promote brain development, improve activity of various zinc-containing enzymes in brain, and regulate the synthesis of hormone and neurotransmitter, thereby affecting nerve signal conduction, maintaining the function of hippocampus in brain, regulating synaptic transmission, and affecting learning and memory. Iodine can influence the neural development by influencing the synthesis of thyroxine, and iodine deficiency can cause the total weight of brain tissues to be reduced and influence the development of hippocampus and motor regions. Selenium element has effects of scavenging free radicals, protecting cell membrane, regulating organism immunity, relieving brain nerve cell injury caused by free radicals, and promoting repair of brain nerve injury. And the deficiency of copper element can cause the transmission obstacle of neurotransmitter, resulting in the nerve dysfunction.

The main disease of nervous system injury, especially nervous system degenerative disease is the elderly, which usually suffer from gastrointestinal tract degeneration, intestinal mucosa atrophy, influence on nutrient absorption, and are prone to malnutrition, especially the decrease of protein intake in food, and further aggravate brain function injury and disease condition.

The composition can be applied to nerve injury repair caused by physics, medicines, diseases or aging, and is particularly suitable for application to degenerative nerve injury repair.

The preparation method of the composition for nerve repair comprises the following steps:

s3, mixing and uniformly stirring the compound vitamins, the compound trace elements, the coated compound probiotics, the brain protein hydrolysate, the powdery rehmannia extract, the sea cucumber extract, the gastrodia elata extract, the schisandra chinensis extract powder and the liquorice extract powder according to the mass ratio to obtain the composition.

Further preferably, the method also comprises S4. The composition is coated with hydroxypropyl methyl cellulose phthalate for the first time, and then coated with soluble soybean polysaccharide for the second time at a low temperature of 50 plus or minus 5 ℃ for 3 hours to obtain the coating composition.

Example 1

The embodiment provides a composition for nerve repair, which comprises the following components in a mass ratio of 1; the nutrition aid comprises the following components in a mass ratio of 1.5:0.3:1:1.2 vitamin complex, compound trace elements, compound probiotics and compound protein.

The compound vitamin comprises vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E with equal mass. The composite protein comprises equal mass of soybean protein and casein. The composite probiotics comprise lactobacillus, lactobacillus reuteri, clostridium butyricum and bacillus subtilis with equal mass.

s1, respectively mixing vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E in formula amounts to prepare compound vitamin; mixing iron fumarate, biological protein zinc, chromium picolinate, iodized salt, ammonium molybdate, selenium malt and copper sulfate to obtain composite trace elements; mixing lactobacillus, lactobacillus reuteri, clostridium butyricum and bacillus subtilis freeze-dried powder to prepare composite probiotics; mixing soybean protein and casein powder to obtain composite protein;

Example 2

The embodiment provides a composition for nerve repair, which comprises a brain protein hydrolysate, a rehmannia glutinosa extract, a sea cucumber extract, a gastrodia elata extract, schisandra chinensis extract powder, liquorice extract powder and a nutrition aid in a mass ratio of 1.4; the nutrition aid comprises the following components in a mass ratio of 1.5:0.3:1:1.2 vitamin complex, compound trace elements, compound probiotics and compound protein.

The compound vitamin comprises vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E with equal mass. The compound protein comprises soybean protein, whey protein and pea protein with equal mass. The composite probiotics comprise lactobacillus, lactobacillus reuteri, bacillus subtilis and bacillus coagulans with equal mass.

s1, respectively mixing vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E in formula amounts to prepare compound vitamin; mixing iron fumarate, biological protein zinc, chromium picolinate, iodized salt, ammonium molybdate, selenium malt and copper sulfate to obtain composite trace elements; mixing lactobacillus, lactobacillus reuteri, bacillus subtilis and bacillus coagulans freeze-dried powder to prepare composite probiotics; mixing soybean protein, whey protein and pea protein powder to obtain composite protein;

Example 3

The embodiment provides a composition for nerve repair, which comprises a brain protein hydrolysate, a rehmannia glutinosa extract, a sea cucumber extract, a gastrodia elata extract, a schisandra chinensis extract powder, a liquorice extract powder and a nutrition aid in a mass ratio of 1.8; the nutrition aid comprises the following components in a mass ratio of 1.5:0.3:1:1.2 vitamin complex, compound trace elements, compound probiotics and compound protein.

The compound vitamin comprises vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E with equal mass. The compound protein comprises whey protein and pea protein with equal mass. The composite probiotics comprise lactobacillus, lactobacillus reuteri, clostridium butyricum, bacillus subtilis and bifidobacterium with equal mass.

s1, respectively mixing vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E in a formula amount to prepare compound vitamin; mixing iron fumarate, biological protein zinc, chromium picolinate, iodized salt, ammonium molybdate, selenium malt and copper sulfate to obtain composite trace elements; mixing lactobacillus, lactobacillus reuteri, clostridium butyricum, bacillus subtilis and Bacillus bifidus lyophilized powder to obtain composite probiotic; mixing whey protein and pea protein powder to obtain composite protein;

Example 4

The embodiment provides a composition for nerve repair, which comprises a brain protein hydrolysate, a rehmannia glutinosa extract, a sea cucumber extract, a gastrodia elata extract, a schisandra chinensis extract powder, a liquorice extract powder and a nutrition aid in a mass ratio of 2.2; the nutrition aid comprises the following components in a mass ratio of 1.5:0.3:1:1.2 vitamin complex, trace element complex, probiotics complex and protein complex.

The compound vitamin comprises vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E with equal mass. The composite protein comprises soybean protein, casein, whey protein and pea protein with equal mass. The composite probiotics comprise lactobacillus, lactobacillus reuteri, clostridium butyricum, bacillus subtilis, bacillus coagulans, streptococcus thermophilus and bifidobacterium in equal mass.

s1, respectively mixing vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E in formula amounts to prepare compound vitamin; mixing iron fumarate, biological protein zinc, chromium picolinate, iodized salt, ammonium molybdate, selenium malt and copper sulfate to obtain composite trace elements; mixing freeze-dried powder of lactobacillus, lactobacillus reuteri, clostridium butyricum, bacillus subtilis, bacillus coagulans, streptococcus thermophilus and bifidobacterium to prepare composite probiotics; mixing soybean protein, casein, whey protein and pea protein powder to obtain composite protein;

Example 5

The embodiment provides a composition for nerve repair, which comprises a brain protein hydrolysate, a rehmannia glutinosa extract, a sea cucumber extract, a gastrodia elata extract, schisandra chinensis extract powder, liquorice extract powder and a nutrition aid in a mass ratio of (2.6); the nutritional aid comprises the following components in a mass ratio of 1.5:0.3:1:1.2 vitamin complex, compound trace elements, compound probiotics and compound protein.

The compound vitamin comprises vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E with equal mass. The composite protein comprises soybean protein, casein and whey protein with equal mass. The composite probiotics comprise clostridium butyricum, bacillus subtilis, bacillus coagulans, streptococcus thermophilus and bifidobacterium with equal mass.

s1, respectively mixing vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E in formula amounts to prepare compound vitamin; mixing iron fumarate, biological protein zinc, chromium picolinate, iodized salt, ammonium molybdate, selenium malt and copper sulfate to obtain composite trace elements; mixing clostridium butyricum, bacillus subtilis, bacillus coagulans, streptococcus thermophilus and bifidobacterium freeze-dried powder to prepare composite probiotics; mixing soybean protein, casein and whey protein powder to obtain composite protein;

Example 6

The embodiment provides a composition for nerve repair, which comprises the following components in parts by mass; the nutrition aid comprises the following components in a mass ratio of 1.5:0.3:1:1.2 vitamin complex, compound trace elements, compound probiotics and compound protein.

The compound vitamin comprises vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E with equal mass. The composite protein comprises soybean protein and casein with equal mass. The composite probiotics comprise lactobacillus and lactobacillus reuteri with equal mass.

s1, respectively mixing vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E in formula amounts to prepare compound vitamin; mixing iron fumarate, biological protein zinc, chromium picolinate, iodized salt, ammonium molybdate, selenium malt and copper sulfate to obtain composite trace elements; mixing the lactobacillus and the lactobacillus reuteri freeze-dried powder to prepare composite probiotics; mixing soybean protein and casein powder to obtain composite protein;

Comparative example 1

The difference from example 3 is that the comparative example provides composition 1 ingredient that does not contain brain protein hydrolysate and the corresponding manufacturing process does not contain the above step S3.

Comparative example 2

Unlike example 3, this comparative example provides composition 2 ingredients that do not contain nutritional aids. The preparation method of the composition 2 comprises the following steps:

s1, dissolving a cerebroprotein hydrolysate raw material medicament in water, filtering by using a nanofiltration membrane, and freeze-drying filtrate to obtain a cerebroprotein hydrolysate;

s2, mixing and uniformly stirring the composite vitamins, the composite trace elements, the coated composite probiotics and the cerebroprotein hydrolysate according to the mass ratio to obtain the composition 2.

Comparative example 3

The difference from example 3 is that the composition 3 provided in this comparative example does not contain rehmannia glutinosa extract, stichopus japonicus extract, gastrodia elata extract, schisandra chinensis extract powder, and Glycyrrhiza uralensis extract powder. The preparation method of the composition 3 comprises the following steps:

s1, respectively mixing vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E in a formula amount to prepare compound vitamin; mixing iron fumarate, biological protein zinc, chromium picolinate, iodized salt, ammonium molybdate, selenium malt and copper sulfate to obtain composite trace elements; mixing the lactobacillus and the lactobacillus reuteri freeze-dried powder to prepare composite probiotics; mixing soybean protein and casein powder to obtain composite protein;

s3, mixing and uniformly stirring the composite vitamins, the composite trace elements, the coated composite probiotics and the cerebroprotein hydrolysate according to the mass ratio to obtain the composition 3.

1. The therapeutic effects of the compositions prepared in examples 1 to 6 on mice model of Alzheimer's disease were investigated

And (3) establishing an AD model, namely injecting a half D lactose solution into the abdominal cavity of a mouse according to the dose of 120mg/kg/D, filling a gastric trichloride solution according to the dose of 10mg/kg/D, continuously feeding the gastric trichloride solution for 60D, measuring the learning and memory capacity of the mouse by using a water maze, screening the AD mouse, and injecting physiological saline with the same amount as that of the AD mouse and distilled water with the same amount as that of the gastric lavage into a normal group.

The AD model mouse is divided into a blank group, an experimental group 1-6 and a control group 1-3 according to a random method in an animal grouping method, one group is 10 mice, the administration is carried out according to the following groups and dosage, and the blank group and a normal group are injected with distilled water with the same amount as that of intragastric administration; experimental groups 1 to 6 respectively dissolve the compositions prepared in the embodiments 1 to 6 in warm water of 35 to 40 ℃ and then irrigate the stomach, the dosage of the compositions is 0.05g/kg/d, and comparison groups 1 to 3 respectively dissolve the compositions prepared in the embodiments 1 to 6 in warm water of 35 to 40 ℃ and irrigate the stomach, the dosage of the compositions is 0.5g/kg/d, wherein the administration time is 30d, and the modeling agents are continuously administered to all groups while administration is carried out, so that natural recovery is avoided.

1. Open box experiment

The experimental mice are subjected to box opening experiment tests after being grouped, and the experimental device for the box opening experiment comprises two parts, a box opening device and a recording device. The height of the used open box is 30cm, the length and the width of the used open box are both 50cm, the open box is hollow, the peripheral wall of the open box is painted black, the upper part of the open box is connected with a camera, and the camera is connected with a computer so as to record the experimental result. The bottom of the open box is divided into 25 blocks with equal area by computer software, 16 blocks at the periphery of the open box are used as the peripheral area, and 9 blocks at the center are used as the central area. Each animal was assayed 1 time, 5min each time. The experimental period was memorized in an open box for 5 days, and the total course of each mouse in the open box and the time of stay of the mouse in the peripheral area and the central area were recorded on the 6 th day of the experiment, and the peripheral time ratio was calculated. After each cleaning of the open box, the next mouse was tested.

2. Barnes maze experiment

Barnes maze testing was performed after the open box experiment, and the procedure of the Barnes maze experiment was referenced to the method of Barnes [9], with minor adjustments. The Barnes maze consists of a circular platform with 20 wells and a small, lightless chamber called the "target box" at the bottom of one of the wells, the prototype platform 92cm in diameter and the small well 5cm in diameter. A camera is arranged above the maze and is connected with a computer. The mouse is placed in the center of the maze at the beginning of each training, the mouse freely enters the small hole on the platform, the training time is 4min each time, and the time (escape latency) taken by the mouse to enter the target box within 4min is recorded. If the mouse does not enter the target box within 4min, the escape latency is recorded as 240s for 6 days, the first 5 days are labyrinth memory experiment periods, and the data of the escape latency and the error times are recorded on the 6 th day. After each mouse finishes doing, the maze is wiped by alcohol, and the Barnes maze is rotated without changing the relative spatial position of the target box, so that the mouse is prevented from finding the position of the target box through information such as smell.

The results of experiments 1 and 2 are shown in table 1.

TABLE 1

2. The therapeutic effects of the compositions prepared in examples 1 to 6 on Alzheimer's disease were investigated

Comprises coating the compositions of examples 1, 3 and 6 with hydroxypropyl methylcellulose phthalate for one time, and coating with soluble soybean polysaccharide at 50 + -5 deg.C for 3 hr to obtain coated compositions 1, 3 and 6 with specification of 15 mg/tablet.

The patients with Alzheimer's disease 100 are aged 50-70 years, wherein 58 men and 42 women have disease course of 1-5 years, and have symptoms of behavior disorder, aphasia, hypomnesia, slow action, agnosia, character change, etc., and are clinically diagnosed as Alzheimer's disease. :

randomly dividing 100 patients with Alzheimer's disease into 5 groups, wherein the 1 st group is placebo control group, and the 2 nd group is orally administered with commercial oral liquid of cerebroprotein hydrolysate 50-100mg once and 3 times a day; the 3 rd to 5 th groups respectively take the coating compositions 1, 3 and 6 orally, 2 tablets at a time, 3 times a day.

Group 5 patients were treated according to this method for 3 months.

The curative effect standard is as follows:

the effect is shown: the mind is clear, the relatives are known, the orientation is healthy, the actions are normal, the answer questions are basically correct, the life is self-care, and the general social activities can be performed;

effective in normal action, correct answer to questions, self-care in life, slow response, and partial intelligence and personality.

The main clinical symptoms are not improved, the life cannot be self-managed, the questions are answered incorrectly, and the mind is dull.

Therapeutic results

The cure rate of each group of patients is shown in table 2, and the effective rate = (effective number + significant number)/total number.

TABLE 2

	Show effect	Is effective	Invalidation	High efficiency
					Placebo	0	1	19	5％
Oral liquid	5	9	6	70％
					Coating composition 1	12	5	3	85％
Coating Complex 3	14	6	0	100％
					Coating complex 6	12	7	1	95％

Analysis and conclusion:

as can be seen from table 1, the total distance traveled by the experimental groups 1 to 6 is equivalent to the total distance traveled by the normal group, the percentage of the peripheral time is equivalent to the total distance traveled by the normal group, and there is no significant difference in the physical performance of the mice in each group, and the percentage of the peripheral time is also equivalent to the total percentage of the peripheral time, which indicates that there is no significant difference in the mental status of the mice in the experimental groups 1 to 6 from the normal group. In addition, the ratio of the total walking distance and the peripheral time of the experimental groups 1-6 is slightly lower than that of the control groups 1-3, which shows that the mental state of the experimental groups 1-6 mice is slightly better than that of the control groups 1-3, the organism recovery of the compositions of the examples 1-6 to AD model mice is higher than that of the compositions of the comparative examples 1-3, and the brain protein hydrolysate, the rehmannia root extract, the sea cucumber extract, the gastrodia tuber extract, the schisandra fruit extract powder, the liquorice extract powder and the nutrition aid have synergistic effect. And the total walking path and the peripheral ratio of the experimental groups 1-6 and the control groups 1-3 are far smaller than those of the blank group, which shows that the blank group of mice is far inferior to the experimental groups 1-6 and the control groups 1-3 in mental state, and the compositions of the examples 1-6 and the comparative examples 1-3 have promotion effect on mental state, memory and organism repair of AD model mice. The incubation period and the error times of the mice of the experimental groups 1-6 and the control groups 1-3 are far lower than those of the blank group, which shows that the learning memory capability and the cognitive function of the mice of the experimental groups 1-6 and the control groups 1-3 are far better than those of the blank group, the cognitive function of the mice of the blank group is seriously damaged, and the data of the experimental groups 1-6 have no obvious difference with the data of the normal group, namely the learning memory capability and the cognitive function of the mice of the experimental groups 1-6 are not poor with those of the normal group, which shows that the composition of the examples 1-6 can effectively improve the cognitive disorder and the behavioral disorder of the AD model mice and improve the cognitive function. The data of the control groups 1 to 3 are superior to those of the blank group, but the latency and the number of errors are higher than those of the experimental groups 1 to 6, indicating that the cognitive function of the mice of the control groups 1 to 3 is weaker than that of the experimental groups 1 to 6, and the composition of the comparative examples 1 to 3 has a lower effect of improving cognitive disorders than the composition of the examples 1 to 6. As shown by comparison of the data in table 1, the data of the mice in the experimental group 3 are relatively excellent, and it can be concluded that the composition of example 3 has an excellent effect of improving cognitive function.

As can be seen from the table 2, the composition for nerve repair provided by the invention has an auxiliary treatment effect on Alzheimer's disease, and the effect is obviously superior to that of the commercially available cerebroprotein hydrolysate oral liquid.

The composition for nerve repair provided by the invention is prepared by the synergistic combination of brain protein hydrolysate, rehmannia extract, sea cucumber extract, gastrodia elata extract, schisandra extract powder, liquorice extract powder and nutrition aids, wherein the brain protein hydrolysate is a special peptide neurotrophic medicament for the brain, can act on central nerves, regulates and improves the metabolism of neurons, promotes the formation of synapses, induces the differentiation of the neurons, and further protects nerve cells from being damaged by various ischemia and neurotoxins. Catalpol in the rehmannia root extract can reduce the content of lipid peroxide, increase the activity of a peroxide scavenger glutathione peroxidase, scavenge free radicals, resist PC12 cell apoptosis and signal mechanism caused by Abeta injury, reduce the apoptosis of nerve cells, promote the expression of hippocampal neurotrophic factor BDNF and signal molecules PKC, enhance hippocampal neural plasticity and promote nerve repair. The sea cucumber cephalin in the sea cucumber extract has a protective effect on nerve cells, can improve the activities of T-AOC and SOD, increase the antioxidant capacity of the cells, down-regulate apoptosis-promoting genes Bax, caspase-9 and Caspase-3, promote the expression of an anti-apoptosis gene Bcl-2, inhibit the apoptosis of the nerve cells, promote the growth of the nerve cells, and protect the nerve cells from oxidative damage through the antioxidant activity and the anti-apoptosis activity of the sea cucumber cephalin the sea cucumber extract. The active ingredients such as vanillin, gastrodine and gastrodine polysaccharide in the rhizoma gastrodiae extract can slow down apoptosis, show good anti-aging effect, clear away free radicals of organisms, regulate immune system and repair ischemic brain tissues by increasing the expression of brain-derived nerve factors and vascular endothelial growth factors. The fructus Schisandrae polysaccharide in fructus Schisandrae can regulate neurotransmitter level in hippocampus to protect central nervous system, improve stability of central nervous system, and promote nervous system protection and repair. Licochalcone A in Glycyrrhrizae radix has effects of promoting neurite growth activity, promoting neuron survival and differentiation, maintaining nervous system stability and promoting injured nerve repair. There is also a connection between diseases related to the central nervous system and the intestinal flora, metabolites, bacteriocins and neurotransmitters produced by microorganisms in the intestinal tract can influence the excitability of neurons in the central nervous system through the vagus nerve so as to influence brain tissues, the addition of the composite probiotics can improve the intestinal flora of the organism, the flora can regulate central gamma-aminobutyric acid receptors through the vagus nerve so as to influence the brain neurochemistry (neurotransmitter level, receptors and various neurotrophic factors) and behaviors, improve nerve injury or apoptosis and promote nerve repair. And nerve damage and repair are also influenced by nutrition level, and most nerve damage diseases, such as Alzheimer disease and Parkinson patients, usually the old, are mostly accompanied with intestinal mucosa atrophy, influence nutrition absorption, are easy to cause malnutrition, especially reduce protein intake in food, and further aggravate brain function damage and disease conditions. The addition of the compound probiotics, compound vitamins, compound trace elements and compound protein not only increases the nutrient source, but also improves the intestinal absorption function, ensures the nutrient level of the organism, improves the immunity of the organism and promotes the organism to repair.

Therefore, the composition for nerve repair disclosed by the invention is prepared by synergistically matching the brain protein hydrolysate, the rehmannia root extract, the sea cucumber extract, the gastrodia elata extract, the schisandra chinensis extract powder, the liquorice extract powder and the nutrition aid, and is used for inhibiting the apoptosis of neurons, eliminating the A beta deposition and resisting the PC12 apoptosis and signal mechanism caused by A beta damage in a 1 mode; 2. oxidation, slowing down the aging of nerve cells; 3. increasing the expression of the brain-derived nerve factor and the vascular endothelial growth factor to repair the ischemic brain tissue; 4. modulating neurotransmitter levels in the hippocampus to protect the central nervous system; 5. promoting the survival and differentiation of neurons, improving the stability of the central nervous system and promoting the protection and repair of the nervous system; 6. improving intestinal flora, regulating central gamma-aminobutyric acid receptor by vagus nerve to influence brain neurochemistry (neurotransmitter level, receptor and various neurotrophic factors) and behavior, improving nerve injury or apoptosis, and promoting nerve repair; 7. promoting nutrient absorption, ensuring organism nutrition level, improving organism immunity, promoting organism repair, etc., improving nervous system stability, protecting nervous system from damage, and promoting nervous system damage repair.

While the invention has been described with reference to a certain preferred embodiment, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention.

Claims

1. The composition for nerve repair is characterized by comprising the following components in parts by mass of 1-3;

the nutritional aid comprises compound vitamins, compound trace elements, compound probiotics and compound protein.

2. The composition for nerve repair of claim 1, wherein the mass ratio of the brain protein hydrolysate, the rehmannia root extract, the sea cucumber extract, the gastrodia tuber extract, the schisandra fruit extract powder, the licorice root extract powder and the nutritional aids is 1.8.

3. The composition for nerve repair of claim 1, wherein the nutritional aid comprises, by mass, 1.5:0.3:1:1.2 vitamin complex, trace element complex, probiotics complex and protein complex.

4. The composition for nerve repair of claim 1, wherein the complex probiotic bacteria is a mixture of one or more of lactic acid bacteria, lactobacillus reuteri, clostridium butyricum, bacillus subtilis, bacillus coagulans, streptococcus thermophilus, and bifidobacterium.

5. The composition for nerve repair of claim 1, wherein the multivitamins consist of vitamin B1, vitamin B12, vitamin C, vitamin D and vitamin E.

6. The composition for nerve repair of claim 1, wherein the complex trace element comprises a plurality of iron, zinc, chromium, iodine, molybdenum, selenium, copper.

7. Use of the composition for nerve repair according to claims 1 to 5, characterized in that it is applied to repair of nerve damage caused by physical, pharmaceutical, disease or aging.

8. Use of a composition for nerve repair according to claim 6 for degenerative nerve injury repair.

9. A method of preparing a composition for nerve repair comprising the steps of:

10. The method for preparing a composition for nerve repair according to claim 9, further comprising s4. Primary coating the composition with hydroxypropylmethylcellulose phthalate, and secondary coating with soluble soybean polysaccharide at a coating temperature of 50 ± 5 ℃ for 3 hours to obtain a coated composition.