Nerve repair composition, preparation method therefor, and use thereof

Abstract

The present application provides a nerve repair composition, a preparation method therefor, and a use thereof. The nerve repair composition of the present application comprises the following components in parts by weight: 0.1-10 parts of curcumin or turmeric powder and 4-460 parts of Acer truncatum Bunge seed oil. By means of the synergistic effect of Acer truncatum Bunge seed oil and curcumin, the present application can have good anti-aging and nerve repair effects, the effects are mild, and no irritation is caused to a human body. The composition of the present application has significant effects in the prevention and treatment of neurodegenerative diseases, especially depression, and the improvement of memory.

Description

A nerve repair composition and its preparation method and application

[0001] This application claims priority to the Chinese patent application filed with the Patent Office of China on July 20, 2023, with application number CN202310895575.3 and invention name “A nerve repair composition, its preparation method and application”, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The present application relates to the technical field of medical and health products, and in particular to a nerve repair composition, a preparation method thereof, and an application thereof. Background Art

[0003] The fast pace of modern life, fierce competition, and high stress levels, coupled with various unhealthy lifestyle habits, can leave the brain and nervous system in a state of chronic tension and fatigue. This can easily damage the human nervous system, accelerate matrix aging, and increase the risk of neurodegenerative diseases. Neurodegenerative diseases are a class of conditions characterized by the loss or death of neuronal function, and include Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). These diseases are linked to genetic, environmental, and metabolic factors, and currently lack effective treatments, placing a significant burden and suffering on patients and their families.

[0004] Acer truncatum seed oil is a vegetable oil extracted from the seeds of Acer truncatum. It is rich in active ingredients such as unsaturated fatty acids, vitamin E, and plant sterols, and has antioxidant, anti-inflammatory, and lipid-lowering effects. Curcumin is a polyphenol compound extracted from the rhizome of turmeric, which has antioxidant, anti-inflammatory, and anti-amyloid protein deposition effects. Currently, many antioxidant and anti-aging skin care products and health care products have appeared. However, in order to improve the anti-aging effect, existing anti-aging skin care products usually add a large amount of artificially synthesized antioxidant additives. The addition of these additives will cause certain irritation to the human body and affect the effect of nerve repair. Although people are committed to developing pure natural antioxidant products with better antioxidant properties, the antioxidant and anti-aging properties of existing products still need to be improved.

[0005] Therefore, it is necessary to provide a new health product with better anti-aging and nerve repair effects.

[0006] Summary of the Invention

[0007] The purpose of this application is to overcome the drawbacks of existing anti-aging products (especially those for preventing neurodegenerative diseases) that are highly irritating and require further improvement in anti-aging performance, and to provide a new health product composition with improved anti-aging and nerve repair effects. This application utilizes the synergistic effects of Acer truncatum seed oil, curcumin, and phosphatidylcholine, resulting in a mild, non-irritating anti-aging and nerve repair product.

[0008] Another object of the present application is to provide a method for preparing the nerve repair composition.

[0009] Another object of the present application is to provide a use of the nerve repair composition in the preparation of a health product having the efficacy of preventing and treating neurodegenerative diseases.

[0010] To achieve the above objectives, this application adopts the following technical solutions:

[0011] A nerve repair composition comprising the following components calculated in parts by weight:

[0012] 0.1-10 parts of curcumin or turmeric powder, 4-460 parts of Acer truncatum seed oil.

[0013] Curcumin or turmeric powder (containing curcumin) is a polyphenolic compound extracted from the rhizome of turmeric, which has antioxidant, anti-inflammatory, and amyloid protein deposition inhibitory effects. The curcumin or turmeric powder of the present application can be an existing commercially available product, or can be extracted or prepared from the rhizome of a plant of the ginger family. The curcumin or turmeric powder can be prepared according to a method comprising the following steps:

[0014] The dried turmeric root powder is added to ethanol and ultrasonically extracted to obtain an ethanol extract, that is, the curcumin; the ethanol extract is vacuum concentrated to obtain a concentrated solution; and the concentrated solution is freeze-dried to obtain the turmeric powder.

[0015] Preferably, the volume fraction of ethanol is 70-95%; the ultrasonic extraction time is 30-60 minutes; the ultrasonic extraction temperature is 40-60°C; the vacuum concentration pressure is 0.05-0.1 MPa; the vacuum concentration temperature is 40-60°C; and the freeze-drying temperature is -40 to -20°C.

[0016] The curcumin or turmeric powder contains 2-5 wt% of curcuminoids, wherein the content of C1 curcumin is 50-60 wt%; the content of C2 demethoxycurcumin is 15-17 wt%; and the content of C3 bisdemethoxycurcumin is 0.5-1.5 wt%.

[0017] Acer truncatum seed oil is a vegetable oil extracted from the seeds of Acer truncatum. It is rich in active ingredients such as unsaturated fatty acids, vitamin E and plant sterols. It is a dual-effect magical substance recognized by scientists around the world that can repair and clear damaged nerve fibers in the brain's nerve pathways and promote the regeneration of nerve cells. Its lack will cause brain diseases such as sequelae of cerebral stroke, Alzheimer's disease, cerebral palsy, brain atrophy, memory loss, insomnia and forgetfulness. It has antioxidant, anti-inflammatory and lipid-lowering effects.

[0018] The Acer truncatum seed oil of the present application can be an existing commercially available product, or can be extracted or prepared from Acer truncatum seed kernels. The Acer truncatum seed oil has a relative mass content of linoleic acid greater than 30%, a relative mass content of arachidonic acid greater than 12%, and a relative mass content of nervonic acid greater than 4%.

[0019] Preferably, the Acer truncatum seed oil contains 40-50 wt % of linoleic acid, 15-20 wt % of arachidonic acid, and 5-8 wt % of nervonic acid.

[0020] Preferably, the nerve repair composition comprises the following components calculated in percentage by weight:

[0021] 1-5 parts of curcumin or turmeric powder, 45-250 parts of Acer truncatum seed oil.

[0022] Within the above preferred range, the obtained nerve repair composition has better anti-aging and nerve repair effects.

[0023] The inventors of the present application have discovered through extensive research that curcumin and Acer truncatum seed oil can work together to significantly enhance the antioxidant properties of curcumin and Acer truncatum seed oil, improve the repair of the body's nerves, and effectively prevent and improve neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and ALS.

[0024] The phosphatidylcholine acid is preferably flavin adenine dinucleotide (FAD). Flavin adenine dinucleotide is a cofactor of a flavin coenzyme, formed by the conversion of vitamin B2, and participates in a variety of redox reactions in the human body, mainly in the oxidative dehydrogenation of organic matter, such as fatty acids. Phosphatidylcholine acid can participate in a variety of redox reactions in the human body, and the fatty acids produced by the reaction with the body can regulate the body's metabolism, improve the absorption of vitamins, improve the body's immune level, and improve antioxidant and nerve repair effects. In addition, the inventors of this application have also creatively discovered that the combined action of phosphatidylcholine acid with curcumin and Acer truncatum seed oil also has a significant improvement in patients with depression and memory recovery.

[0025] Therefore, in order to further enhance the antioxidant and nerve repair effects, 0.01-2 parts of vitamins may be added to the nerve repair composition, including 0.01-1 parts of vitamin E and 0.01-1 parts of vitamin B6. The vitamin E is natural or synthetic α-tocopherol or its derivatives.

[0026] Preferably, the other excipients are pharmaceutically acceptable excipients, including but not limited to at least one of a diluent, a preservative, and a suspending agent. The diluent may be one or a combination of polyethylene glycol, propylene glycol, polysorbate, glycerin, peanut oil, corn oil, and soybean oil; the preservative may be one or a combination of benzoic acid, sorbic acid, chlorobutanol, benzyl alcohol, and methyl paraben; and the suspending agent may be one or a combination of beeswax, hydrogenated vegetable oil, hydrogenated castor oil, gum arabic, soy lecithin, cocoa butter, propylene glycol caprylate, glyceryl caprylate, carboxymethyl cellulose, hydroxypropyl cellulose, and hydroxyethyl methyl cellulose.

[0027] The present application also provides a method for preparing the above-mentioned nerve repair composition, comprising the following steps:

[0028] According to the components and amounts, the raw materials of each component are mixed evenly to obtain the nerve repair composition.

[0029] The use of the anti-aging composition in the preparation of health products for preventing and treating neurodegenerative diseases also falls within the scope of protection of this application. The neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, ALS, depression, memory impairment, etc.

[0030] Compared with the prior art, the present invention has the following advantages:

[0031] 1) Prolong the survival of ALS (amyotrophic lateral sclerosis, also known as Lou Gehrig's disease) patients and prevent and delay neurodegenerative diseases. ALS is a fatal neuromuscular disease that causes the gradual degeneration and death of motor neurons, and there is currently no effective treatment. The composition of the present application can protect motor neurons from damage caused by oxidative stress and inflammation by providing neuraminic acid and curcumin, delay the decline of neuronal function, and improve the quality of life of ALS patients.

[0032] 2) Reduce the aggregation of Aβ protein (β-amyloid protein) in AD (Alzheimer's disease) patients and alleviate cognitive impairment. AD is a common senile dementia, mainly manifested by memory loss, loss of language ability, impaired judgment, etc. The main pathological feature of AD is the appearance of senile plaques with Aβ protein deposition in the brain, leading to neuronal death and loss of synaptic function. The composition of the present application can inhibit the generation and aggregation of Aβ protein, reduce the formation of senile plaques, protect the structure and function of neurons and synapses, and improve the cognitive ability of AD patients by providing neuraminic acid and curcumin.

[0033] 3) Alleviate depression and anxiety symptoms and improve emotional state. Depression and anxiety are two common mental disorders, mainly manifested as low mood, anxiety, loss of interest, self-denial, etc. Depression and anxiety are related to the imbalance of neurotransmitters in the brain, inflammatory response and oxidative stress. The composition of the present application can regulate the levels of neurotransmitters such as serotonin, dopamine and norepinephrine in the brain by providing nervonic acid, curcumin and phosphatidylcholine, inhibit the release of inflammatory cytokines, scavenge free radicals, improve the neurochemical environment of the brain, and alleviate the symptoms of depression and anxiety. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] FIG1 is a graph showing the immobility time in a forced swimming test of mice after being treated with the compositions of Example 1 and various comparative examples in an experiment on improving depression.

[0035] FIG2 is a test result of oxidative stress level of mice after being treated with the compositions of Example 1 and various comparative examples in an experiment on improving depression using the compositions.

[0036] FIG3 is a test result of oxidative stress level in the hippocampus after being treated with the compositions of Example 1 and various comparative examples in an experiment on improving depression.

[0037] FIG4 shows the test results of the number of errors in jumping off the platform of mice after being treated with the compositions of Example 1 and various comparative examples in the memory improvement experiment.

[0038] FIG5 shows the results of the ratio of time spent by mice exploring new objects after being treated with the compositions of Example 1 and various comparative examples in the memory improvement experiment.

[0039] Figure 6 shows the test results of the number of circles induced in rats with 6-OHDA-induced Parkinson's disease after treatment with the compositions of Example 1 (represented as 6-OHDA / ACP in the figure) and some comparative examples (in the figure, 6-OHDA / A represents treatment with the composition of Comparative Example 5, 6-OHDA / Cu represents treatment with the composition of Comparative Example 4, and 6-OHDA represents treatment with the normal saline control group) in the Parkinson's disease treatment experiment. DETAILED DESCRIPTION

[0040] To better illustrate the purpose, technical solutions and advantages of the present application, the present application will be further described below in conjunction with specific examples and accompanying drawings, but the examples do not limit the present application in any form. Unless otherwise specified, the reagents, methods and equipment used in this application are conventional reagents, methods and equipment in the art. Unless otherwise specified, the reagents and materials used in this application are commercially available.

[0041] Example 1

[0042] This embodiment provides a nerve repair composition, which is prepared according to the following formula (parts by weight) and a method comprising the following steps:

[0043] The nerve repair composition is obtained by mixing 1 part of turmeric powder, 45.5 parts of Acer truncatum seed oil, 1 part of flavin adenine dinucleotide, 0.5 parts of α-tocopherol, and 0.5 parts of vitamin B6 and stirring evenly.

[0044] The preparation method of turmeric powder comprises the following steps: adding dried turmeric root powder to 95% ethanol by volume, performing ultrasonic extraction for 60 minutes to obtain an ethanol extract, vacuum concentrating the ethanol extract at 50° C. and 0.1 MPa to obtain a concentrated solution; freeze-drying the concentrated solution at -40° C. to obtain the turmeric powder;

[0045] The prepared turmeric powder contains 5wt% of curcuminoids, wherein the content of C1 curcumin (Curcumin) in the curcuminoids is 60wt%; the content of C2 demethoxycurcumin (Demethoxycurcumin) is 17wt%; the content of C3 bisdemethoxycurcumin (Bisdemethoxycurcumin) is 1.5wt%, and the balance is other types of curcuminoids.

[0046] Example 2

[0047] This embodiment provides a nerve repair composition, which is prepared according to the following formula (parts by weight) and a method comprising the following steps:

[0048] 5 parts of turmeric powder, 228.75 parts of Acer truncatum seed oil, 3 parts of flavin adenine dinucleotide, 0.5 parts of α-tocopherol, and 0.5 parts of vitamin B6 were mixed and stirred to obtain the nerve repair composition. The preparation method of turmeric powder is the same as that of Example 1.

[0049] Example 3

[0050] This embodiment provides a nerve repair composition, which is prepared according to the following formula (parts by weight) and a method comprising the following steps:

[0051] The nerve repair composition is obtained by mixing 10 parts of turmeric powder, 459.5 parts of Acer truncatum seed oil, 5 parts of flavin adenine dinucleotide, 0.5 parts of α-tocopherol, and 0.5 parts of vitamin B6 to obtain the nerve repair composition. The preparation method of turmeric powder is the same as that of Example 1.

[0052] Example 4

[0053] This embodiment provides a nerve repair composition, which is prepared according to the following formula (parts by weight) and a method comprising the following steps:

[0054] The nerve repair composition is obtained by mixing 0.1 parts of turmeric powder, 4.525 parts of Acer truncatum seed oil, 0.1 parts of flavin adenine dinucleotide, 0.5 parts of α-tocopherol, and 0.5 parts of vitamin B6. The preparation method of turmeric powder is the same as that of Example 1.

[0055] Example 5

[0056] This embodiment provides a nerve repair composition, which is prepared according to the method of Example 1. The difference from Example 1 is that α-tocopherol and vitamin B6 are not added.

[0057] Comparative Example 1

[0058] This comparative example provides a nerve repair composition, which is prepared by adding only turmeric powder according to the following steps:

[0059] The nerve repair composition is obtained by mixing 1 part of turmeric powder, 0.5 parts of α-tocopherol, and 0.5 parts of vitamin B6 and stirring them evenly. The preparation method of turmeric powder is the same as that of Example 1.

[0060] Comparative Example 2

[0061] This comparative example provides a nerve repair composition, which is prepared by adding only Acer truncatum seed oil according to a method comprising the following steps:

[0062] The nerve repair composition is obtained by mixing and stirring 45.5 parts of Acer truncatum seed oil, 0.5 parts of α-tocopherol, and 0.5 parts of vitamin B6.

[0063] Comparative Example 3

[0064] This comparative example provides a nerve repair composition, which only contains flavin adenine dinucleotide and is prepared according to the following steps:

[0065] The nerve repair composition is obtained by mixing and evenly stirring 0.1 parts of flavin adenine dinucleotide, 0.5 parts of α-tocopherol, and 0.5 parts of vitamin B6.

[0066] Comparative Example 4

[0067] This comparative example provides a nerve repair composition, which is a combination of flavin adenine dinucleotide and turmeric powder, compared with Example 1, and is prepared according to a method comprising the following steps:

[0068] The nerve repair composition is obtained by mixing and stirring 1 part of turmeric powder, 1 part of flavin adenine dinucleotide, 0.5 parts of α-tocopherol, and 0.5 parts of vitamin B6 evenly.

[0069] Comparative Example 5

[0070] This comparative example provides a nerve repair composition, which is a combination of flavin adenine dinucleotide and Acer truncatum seed oil, compared with Example 1, and is prepared according to a method comprising the following steps:

[0071] The nerve repair composition is obtained by mixing and stirring 45.5 parts of Acer truncatum seed oil, 0.1 parts of flavin adenine dinucleotide, 0.5 parts of α-tocopherol, and 0.5 parts of vitamin B6.

[0072] Application Example 1 - Improvement of Depression by the Composition

[0073] The improvement of depression by the composition was determined by forced mouse swimming test and testing of oxidative stress level in the mouse cerebral cortex. The specific operation is as follows:

[0074] 8-9 week old mice were selected as test subjects (10 mice were selected for each composition for difference analysis and multiple comparisons. In the difference analysis, * indicates p < 0.05, ** indicates p < 0.01, and *** indicates p < 0.001). The nerve repair composition prepared in the above examples and comparative examples was used to gavage the mice, and an LPS-treated dominant control group and a saline-treated blank control group were added. Specifically, on days 1 to 5, the mice were gavaged at a dose of 0.02 mL (based on **) / 10 g at the same time every day. On days 3, 4, and 5, while the above composition was used for gavage treatment, lipopolysaccharide (LPS, abbreviated as LPS, at a dose of 1 mg / kg) was also administered intraperitoneally. The difference between the dominant control group and the above composition treatment was that LPS (at a dose of 1 mg / kg) was administered on days 3, 4, and 5, while the blank group was only administered saline on days 1 to 5. On the 6th day, the mice were subjected to behavioral testing (detection of the immobility time of the mice in the forced swim test, in seconds) and tissue sampling to test the oxidative stress level (active oxygen absorption level, expressed as absorbance). The test results are detailed in Figures 1-2 and Tables 1-2.

[0075] In addition, in this application, the oxidative stress level test was conducted using the hippocampus as the test subject according to the above-mentioned treatment method for mice. The specific test results are shown in Figure 3.

[0076] Table 1 Immobility time in mice forced swimming test Note: In the table, ACP represents the nerve repair composition of the present application, and the effective ingredients are "curcumin + Acer truncatum seed oil + phosphatidylcholine"; LPS+A represents "Acer truncatum seed oil + phosphatidylcholine"; LPS+Cu represents "curcumin + phosphatidylcholine"; WT represents the blank control group treated with normal saline.

[0077] Table 2 Test results of oxidative stress levels in mice Note: In the table, ACP represents the nerve repair composition of the present application, and the effective ingredients are "curcumin + Acer truncatum seed oil + phosphatidylcholine"; LPS+A represents "Acer truncatum seed oil + phosphatidylcholine"; LPS+Cu represents "curcumin + phosphatidylcholine"; WT represents the blank control group treated with normal saline.

[0078] Application Example 2: Impact on Memory Improvement

[0079] Experiment 1: Six-month-old mice were treated with the compositions obtained in the above examples and comparative examples and normal saline (as a blank control group), and treated with 0.01 mL / g / d of the Acer truncatum seed oil in the composition for three months. The number of errors in jumping off the platform was detected by an electric jumping platform. Ten mice were selected for each composition-treated group for differential analysis. The test results are shown in Table 3 and Figure 4.

[0080] Table 3 Number of errors in mice jumping off the platform

[0081] Experiment 2: Ratio of time mice spent exploring novel objects

[0082] Six-month-old mice were divided into 10 / group on average. The mice in different groups were treated with the compositions obtained in the above embodiments and comparative examples, and normal saline (as a blank control group) according to the dosage of 0.01 mL / g / d of Acer truncatum seed oil in the composition for 3 months. The new object recognition was determined. The new object recognition refers to: in the training phase, the mice were exposed to two identical objects (A+A) in the room for 5 minutes to familiarize themselves with them. In the test phase, one of the familiar objects was replaced with another new object (A+B). The mice were put back in the room to explore these objects for 5 minutes, while recording the video and tracking the mice in real time. Detection is defined as the mouse pointing its nose towards the object, sniffing or touching it with its nose, and recording the distance from the nose to the object ≤ 2 cm. The discrimination index (DI) is used to explore each object, and the calculation method is: (time to explore the new object - time to explore the old object) / (time to explore the new object + time to explore the old object) * 100. The test results are shown in Table 4 and Figure 5.

[0083] Table 4 Test results of the time ratio of mice exploring new objects

[0084] Application Example 3 - Application in the Treatment of Parkinson's Disease

[0085] After three weeks of 6-OHDA injection, rats with Parkinson's disease were treated with the compositions of the above examples and comparative examples (with saline as a control group), using 0.01 mL / g / day of Acer truncatum seed oil. After two weeks of treatment, the rats were induced to rotate, and their behavioral changes were observed in a quiet, spacious environment. Specific test results are shown in Figure 6.

[0086] From the above results we can see that:

[0087] The nerve repair composition prepared in the above examples of the present application has significant effects in improving memory and treating depression and Parkinson's disease.

[0088] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application and are not intended to limit the scope of protection of the present application. Although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application may be modified or replaced by equivalents without departing from the essence and scope of the technical solutions of the present application.

Claims

1. A nerve repair composition, characterized in that: The composition includes the following components calculated by weight: 0.1-10 parts of curcumin or turmeric powder, 4-460 parts of Acer truncatum seed oil.

2. The nerve repair composition according to claim 1, characterized in that The composition includes the following components calculated by weight: 1-5 parts of curcumin or turmeric powder, 45-250 parts of Acer truncatum seed oil.

3. The nerve repair composition according to claim 1, characterized in that The nerve repair composition further comprises 0.1-5 parts of phosphatidylinositol and / or 0.01-2 parts of other auxiliary materials, wherein the phosphatidylinositol is flavin adenine dinucleotide.

4. The nerve repair composition according to claim 1, characterized in that The curcumin contains 2-5wt% of curcuminoids, wherein the content of C1 curcumin in the curcuminoids is 50-60wt%; the content of C2 demethoxycurcumin is 15-17wt%; C3 bisdemethoxycurcumin content of 0.5-1.5wt%; The Acer truncatum seed oil contains 40-50wt% of linoleic acid, 15-20wt% of arachidonic acid and 5-8wt% of nervonic acid.

5. The nerve repair composition according to claim 1, characterized in that: The turmeric powder contains 5 wt% of curcuminoids, wherein the content of C1 curcumin in the curcuminoids is 60 wt%; the content of C2 demethoxycurcumin is 17 wt%; and the content of C3 bisdemethoxycurcumin is 1.5 wt%.

6. The nerve repair composition according to any one of claims 1 to 5, characterized in that: Also includes 0.01-2 servings of vitamins.

7. The nerve repair composition according to claim 6, characterized in that: The vitamins include 0.01-1 part of vitamin E and 0.01-1 part of vitamin B6; the vitamin E is natural or synthetic α-tocopherol or its derivatives.

8. The nerve repair composition according to claim 3, characterized in that: The other auxiliary materials include one or a combination of diluents, preservatives or suspending agents.

9. The nerve repair composition according to claim 7, characterized in that: The invention comprises the following components calculated in parts by weight: 1 part of turmeric powder, 45.5 parts of Acer truncatum seed oil, 1 part of flavin adenine dinucleotide, 0.5 part of alpha-tocopherol and 0.5 parts of vitamin B6.

10. The nerve repair composition according to claim 7, characterized in that: The invention comprises the following components calculated in parts by weight: 5 parts of turmeric powder, 228.75 parts of Acer truncatum seed oil, 3 parts of flavin adenine dinucleotide, 0.5 parts of alpha-tocopherol and 0.5 parts of vitamin B6.

11. The method for preparing the nerve repair composition according to any one of claims 1 to 10, characterized in that: The steps include: According to the components and dosages, the raw materials of each component are mixed evenly to obtain the nerve repair composition.

12. Use of the nerve repair composition according to any one of claims 1 to 10 in the preparation of a health product having the efficacy of preventing and treating neurodegenerative diseases.

13. The use according to claim 12, characterized in that: The neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, depression or memory impairment.

Images