Precise nutritional composition for improving cognitive function

Abstract

The invention provides a composition. The composition consists of spirulina, astaxanthin, vitamin C and health food or food acceptable auxiliary materials. The composition has the advantages that the composition has a synergistic effect, and can effectively relieve cognitive impairment of a tested object and improve learning and memory functions, so that the composition can be used for preventing or adjunctively treating the Alzheimer's disease and can also be used for precise nutritional supplement of specific people. In addition, the multi-component compound form of the product can obviously improve the taking compliance of users, and the total use cost is saved.

Description

Technical Field

[0001] The invention relates to a composition containing spirulina, astaxanthin, vitamin C and supplementary materials acceptable to health products or foods and use thereof, belonging to the field of precision nutritional foods. Background Art

[0002] Alzheimer's disease (AD), also known as senile dementia, is a neurodegenerative disease. The specific cause and pathogenesis are still unclear. The clinical symptoms are mainly manifested as memory loss, cognitive dysfunction and decreased learning ability. The symptoms progressively worsen, and severe dementia occurs in the late stage. It is believed that the disease is mainly caused by the aggregation of β-amyloid protein (Aβ) in the brain that destroys nerve cells. It is a disease of whole brain function decline. Although chemical drugs or biological drugs for the treatment of AD have been actively developed both at home and abroad in recent years, the results of clinical trials have been unsatisfactory and have failed to achieve the expected results. In short, there is currently no effective treatment for AD, so early prevention of cognitive decline is of great clinical significance.

[0003] Spirulina is a prokaryotic organism that is spiral or filamentous. It is a photosynthetic multicellular blue-green algae with the characteristics of high protein, low cholesterol and low sugar. It contains 60-70% high-quality protein, essential amino acids, vitamins, essential fatty acids, provitamin A (β-carotene) and other nutrients. It has a wide range of biological activities and health functions and is an ideal pure natural biologically active food. Astaxanthin is a keto-carotenoid with strong antioxidant capacity. It can remove nitrogen dioxide, sulfide, disulfide, etc., and can also effectively inhibit lipid peroxidation caused by free radicals. Vitamin C is a water-soluble vitamin with strong reducing properties. It participates in the complex metabolic process of the body, promotes growth and enhances resistance to disease.

[0004] In our experiment, we explored the combined application of the above substances in various forms and different proportions. The results showed that the combined use of a certain proportion of spirulina, astaxanthin and vitamin C can effectively reduce the cognitive dysfunction of experimental animals, improve the spatial learning and memory function of animals after brain damage, increase the antioxidant capacity of hippocampal tissue, and improve the learning or memory ability of animals. Based on this, the present invention provides a multi-component precision nutrient composition with synergistic effects through optimization, which is used to assist in improving memory and cognitive function. Summary of the invention

[0005] In response to the urgent need for the above AD prevention and treatment medications, the present invention provides a safe and effective precision nutrient composition.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] A composition comprising:

[0008] a) spirulina; b) astaxanthin; c) vitamin C; d) health food or an excipient acceptable to food, wherein the mass ratio of spirulina, astaxanthin and vitamin C is 50-10000:1-20:50-1000.

[0009] In the present invention, as a preferred embodiment, the mass ratio of spirulina, astaxanthin and vitamin C is 50-5000:3-12:100-500.

[0010] In the present invention, the spirulina is 50 to 10,000 parts, the astaxanthin is 1 to 20 parts, and the vitamin C is 50 to 1,000 parts.

[0011] In the present invention, the spirulina is 50 to 5000 parts, the astaxanthin is 3 to 12 parts, and the vitamin C is 100 to 500 parts.

[0012] In the present invention, a portion may be micrograms, milligrams, grams, microliters, milliliters, deciliters, etc.

[0013] In the present invention, the spirulina is selected from one or more of Spirulina platensis, Spirulina maxima and Spirulina salizawa.

[0014] In the present invention, the spirulina includes spirulina powder and effective spirulina extract, wherein the effective spirulina extract is selected from a combination of one or more of spirulina polysaccharide extract, superoxide dismutase extract and phycocyanin extract.

[0015] In the present invention, the effective extract of Spirulina can be formulated into the form of liquid and powder.

[0016] In the present invention, the mass ratio of the effective spirulina extract, astaxanthin and vitamin C is 50-1000:1-20:50-1000.

[0017] In the present invention, astaxanthin is extracted from food, preferably from Haematococcus pluvialis extract or Haematococcus pluvialis product.

[0018] In the present invention, astaxanthin can exist in various forms such as astaxanthin oil and astaxanthin microcapsule powder.

[0019] In the present invention, the vitamin C is selected from one or more of L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, and ascorbyl palmitate.

[0020] In the present invention, the health food or food-acceptable auxiliary materials include one or more of food sugars or functional sweeteners, fillers, wetting agents, adhesives and lubricants.

[0021] In the present invention, the dosage form of the composition is a health food or a food acceptable dosage form, including but not limited to ordinary tablets, double-layer tablets, multi-layer tablets, granules, capsules, pills, oral liquids, compressed candies, solid beverages, syrups, liquid preparations, powders and the like.

[0022] In the present invention, the composition can be further made into fluid dairy products, dairy products, fermented beverages, milk powder, soy milk, juice, sports drinks, desserts, jelly, candy, milk, soft drinks, yogurt, cheese, bread, biscuits, soda crackers, energy bars, pizza crust, formulated milk powder, liquid food, food for specific diets, food for patients, nutritional food, frozen food, processed food, other commercially available foods and the like, baby food, health food, animal feed, Chinese herbal medicine composition or dietary supplement.

[0023] In the present invention, the composition can be used in combination with a traditionally known pharmaceutical product or food having the effect of preventing and treating Alzheimer's disease.

[0024] In the present invention, the composition is in an administrable form selected from nutritional formulations, tube feeding formulations, dietary supplements, functional foods and beverage products.

[0025] In the present invention, the composition is used in preparing a product for improving memory and cognitive function decline.

[0026] In the present invention, the composition is used in preparing a product for preventing or treating Alzheimer's disease.

[0027] In the present invention, the memory and cognitive function decline includes improving cognitive dysfunction after brain surgery, cognitive impairment caused by alcohol or drugs, AIDS dementia syndrome, attention deficit disorder, Parkinson's disease, multi-infarct dementia, age-related cognitive impairment, agnosia, amnesia, forgetfulness, learning disabilities, learning impairment, memory impairment, memory loss, mental retardation, mild cognitive impairment, and post-traumatic stress disorder.

[0028] In the present invention, the composition can be in the form of health food, functional food or food for special medical purposes.

[0029] The beneficial effects of the present invention are as follows: the present invention provides a composition for improving cognitive function, which creatively adds astaxanthin and vitamin C on the basis of selecting a specific type and amount of spirulina, and the combination thereof produces an unexpected synergistic effect, has the effects of alleviating cognitive dysfunction, improving learning ability, and improving memory, so it can be used clinically to prevent Alzheimer's disease, and can also be used for auxiliary treatment of patients with existing Alzheimer's disease to promote improvement of the disease and physical recovery. The raw materials of the product of the present invention are all medicinal and edible or general food-grade raw materials, and can be used as a daily safe and healthy nutritional supplement. DETAILED DESCRIPTION

[0030] The present invention is further described below in conjunction with specific implementation modes, which is not intended to limit the present invention. Any equivalent replacements in the art made according to the contents of the present invention shall fall within the protection scope of the present invention.

[0031] In order to verify the scientific nature of the pharmaceutical composition provided by the present invention, and to illustrate that the three components of the pharmaceutical composition are reasonably matched and can play a synergistic role in combination, rather than simply superimposing pharmacological effects, the Jin Zhengjun Q value method is introduced for analysis. The Jin Zhengjun Q value method is also known as the probability addition method. According to the pharmacological effects of the combination of two drugs and the pharmacological effects of the two drugs alone in the dose-effect curve area, the following calculation formula is used to calculate: Q = E A+B / (E A +E B -E A *E B ), where the numerator represents the "measured combined effect" and the denominator represents the "expected combined effect". (In order to analyze the pharmacological effects of components and combinations, their pharmacological effects are converted into effects that can intuitively reflect the strength of the pharmacological effects. The calculation formula is: E i =1-P i / P 模型组 , P i is the pharmacological index of each component, P 模型组 is the pharmacological index of the model group), Q is the ratio of the two: when Q is less than 0.85, the combination of the two drugs is considered to be antagonistic; when it is less than 1.15 and greater than 0.85, it is considered to be additive; when it is greater than or equal to 1.15, it is considered to be synergistic.

[0032] Example 1: Improvement of the composition of the present invention on scopolamine-induced cognitive dysfunction in rats

[0033] 1. Methods

[0034] Experimental animals and groups: SPF grade SD rats, half male and half female, weighing 150±20g, were purchased from Guangdong Medical Experimental Animal Center. They were raised in an environment with a room temperature of 18-28℃ and a relative humidity of 40%-70%, with free access to water. After 1 week of adaptive feeding with ordinary feed, they were randomly divided into the groups shown in Table 1 below, with 10 rats in each group.

[0035] Modeling: Except for the blank control group injected with normal saline, the other groups were intraperitoneally injected with scopolamine 1.8 mg / kg to establish the rat cognitive dysfunction model. At the same time as the modeling, the corresponding test samples were given according to Table 1 below. The blank control group and the model control group were given an equal volume of normal saline once a day for 14 consecutive days. The extraction rate of the Spirulina extract involved in the group was about 10%.

[0036] Y-type maze experiment: A Y-type maze instrument was used to measure the learning and memory functions of rats. The experiment was conducted in a quiet dark room. The rats were placed in the maze to familiarize themselves with the environment for 5 minutes before the test. During the test, the stimulation voltage was adjusted to ensure that the rats escaped within 10 seconds. The correct response was that the rat ran directly to the safe area after receiving the electric shock, otherwise it was an incorrect response. Each time the rat ran to the safe area, the light continued for 15 seconds, and then the light was turned off for 45 seconds before the next test. The standard was met when the rat had 9 correct responses in 10 consecutive tests. The time to meet the standard was recorded. After the rat rested for 15 minutes, it was put back into the maze and the test was repeated 10 times. The total number of correct responses and the time to meet the standard on the 14th day were recorded.

[0037] 2. Results

[0038] As shown in Table 1, compared with the blank control group, the correct response times of the rats in the model control group in the Y-type maze test were significantly reduced after the 14th day (P < 0.01), and the time to reach the standard was significantly prolonged (P < 0.01), indicating that the rat model of cognitive dysfunction was successfully established. Compared with the model control group, the correct response times of the rats in the Spirulina extract group and the astaxanthin group increased, and the time to reach the standard was shortened, but there was no significant difference (P > 0.05); the correct response times of the rats in the Spirulina extract + astaxanthin group increased significantly, and the time to reach the standard was significantly shortened (P < 0.05); the correct response times of the rats in the Spirulina extract + astaxanthin + VC group increased extremely significantly, and the time to reach the standard was extremely significantly shortened (P < 0.01), thus indicating that the above-mentioned group composition has a significant effect on reducing the number of errors in training and shortening the time to reach the standard in rats with cognitive dysfunction.

[0039] At the same time, the effect of Spirulina extract + astaxanthin group in increasing the number of correct responses and shortening the time to reach the target was 1.04 and 1.08 respectively compared with the group given Spirulina extract and astaxanthin alone, which was a simple additive effect. The Q values ​​of Spirulina extract + astaxanthin + VC group and the group given VC alone were 1.26 and 1.88 respectively (Q values ​​> 1.15), indicating that the triple combination has a synergistic effect compared with the dual combination and VC group in reducing cognitive dysfunction caused by scopolamine and improving spatial learning and memory function after brain injury.

[0040] Table 1 Effects of the composition on the number of correct responses and target time in the Y-maze test of rats with cognitive impairment ( n=9~10)

[0041]

[0042] Note: Compared with the blank control group, aa P<0.01; compared with the model control group, b P<0.05, bbP<0.01.

[0043] Example 2: Protective effect of the composition of the present invention on Aβ-induced damage in Alzheimer's disease rats

[0044] 1. Methods

[0045] Experimental animals and groups: SPF SD rats, half male and half female, weighing 270±20g, were purchased from Guangdong Medical Experimental Animal Center. They were raised in an environment with a room temperature of 18-28℃ and a relative humidity of 40%-70%, with free access to water. They were adaptively fed with ordinary feed for 1 week.

[0046] Modeling: 10 rats were injected with 5 μL PBS into the lateral ventricle to establish a sham operation group, and the remaining rats were injected with 5 μL Aβ into the lateral ventricle 25-35 Carry out modeling.

[0047] Drug administration: Starting from the 8th day after modeling, oral administration was performed according to Table 2 below, and continued for 4 weeks. Each rat in the sham operation group and the model control group was given an equal volume of normal saline. The extraction rate of the Spirulina extract involved in the group was about 10%.

[0048] Behavioral observation: After 4 weeks of continuous administration, the learning and memory abilities of rats were tested according to the Morris water maze test method. All rats were first trained for 4 days of orientation navigation, and then tested for spatial exploration on the 5th day. In the orientation navigation training experiment, the time taken by the rats to escape latency was dynamically observed, and those with shorter escape latency had stronger memory; in the spatial exploration experiment, the greater the ratio of the target quadrant residence time to the total time in the water maze and the more times the platform was crossed, the better the spatial learning and memory ability of the rats.

[0049] Index determination: ELISA method was used to detect oxidative stress indexes and p-Tau content in hippocampal tissue. According to the instructions of the SOD assay kit, the absorbance value was measured at a wavelength of 450nm using an enzyme reader to calculate the SOD activity. According to the instructions of the p-Tau protein assay kit, the absorbance value was measured at a wavelength of 405nm to calculate the p-Tau protein content.

[0050] Indicator description: 1. Superoxide dismutase (SOD) is an important enzyme in the body that performs anti-oxidative damage and can effectively remove free radicals and superoxide. The oxidative stress response theory believes that the increase in the level of highly active molecular oxygen free radicals leads to AD neuronal damage and causes cognitive and learning dysfunction in AD patients. 2. There is a close correlation between the anatomical location of NFT in AD and the brain area with the most severe neuronal loss, so it is believed that phosphorylated Tau protein plays a core role in AD disease.

[0051] 2. Results

[0052] As shown in Tables 2 and 3, compared with the sham operation group, the rats in the model control group had difficulty finding the platform after training, and the average escape latency and p-Tau protein content in the hippocampus were significantly increased (P < 0.01), and the percentage of residence time in the target quadrant, the number of platform crossings and SOD activity in the hippocampus were significantly reduced (P < 0.01), indicating that oxidative damage occurred in the rat brain tissue and showed peroxidation, Tau protein showed abnormal excessive phosphorylation, and learning and memory abilities declined, indicating that the Alzheimer's disease model was successfully constructed.

[0053] Compared with the model control group, the percentage of target quadrant residence time, the number of platform crossings and SOD in hippocampal tissue of rats in the high-dose spirulina extract + astaxanthin group, the low-dose spirulina extract + astaxanthin + VC group and the high-dose spirulina extract + astaxanthin + VC group were significantly increased after training (P < 0.05 or P < 0.01), and the average escape latency and p-Tau protein content in hippocampal tissue were significantly decreased (P < 0.05 or P < 0.01), indicating that the above-mentioned combination has the effects of significantly shortening the escape latency time of the positioning navigation training experiment, increasing the number of platform crossings in the space exploration experiment, increasing the SOD content in hippocampal tissue, alleviating oxidative stress, and reducing the level of phosphorylated Tau protein in rats with Alzheimer's disease.

[0054] The Q values ​​of the effects of the low-dose Spirulina extract + astaxanthin + VC group and the high-dose Spirulina extract + astaxanthin + VC group on increasing the percentage of time spent in the target quadrant, the number of platform crossings and SOD in the hippocampal tissue, and reducing the average escape latency and p-Tau protein content in the hippocampal tissue were all greater than 1.15, indicating that the spirulina, astaxanthin and vitamin C composition, combined with VC, played a significant synergistic role in improving the antioxidant capacity of the hippocampal tissue and improving the impairment of learning and memory functions on the basis of the Spirulina + astaxanthin group, suggesting that the Spirulina + astaxanthin + VC composition can be used to prevent or assist in the treatment of Alzheimer's disease.

[0055] Combined with the experimental data, the low-dose Spirulina extract + astaxanthin + VC group had comparable effects to the high-dose group in terms of increasing the percentage of time spent in the target quadrant, the number of platform crossings and hippocampal SOD, and reducing the average escape latency and p-Tau protein content in the hippocampal tissue. In addition, the low-dose combination had a stronger synergistic effect among the components (larger Q value), making it a better dosage combination.

[0056] Table 2 Effect of the composition of the present invention on spatial learning and memory ability of AD rats induced by Aβ ( n=8~10)

[0057]

[0058]

[0059] Note: Compared with the sham operation group, a P<0.05, aa P<0.01; compared with the model control group, b P<0.05, bb P<0.01.

[0060] Table 3 Effects of the composition of the present invention on oxidative stress and p-Tau protein in hippocampal tissue of AD rats ( n=8~10)

[0061]

[0062] Note: Compared with the sham operation group, a P<0.05, aa P<0.01; compared with the model control group, b P<0.05, bb P<0.01.

Claims

1. A composition comprising: a) Spirulina; b) Astaxanthin; c) Vitamin C; d) A health food or an excipient acceptable to food, wherein the mass ratio of spirulina: astaxanthin: vitamin C is 50-10000: 1-20: 50-1000.

2. The composition according to claim 1, characterized in that The spirulina is in an amount of 50 to 10,000 parts, the astaxanthin is in an amount of 1 to 20 parts, and the vitamin C is in an amount of 50 to 1,000 parts.

3. The composition according to claim 2, characterized in that The spirulina is in an amount of 50 to 5000 parts, the astaxanthin is in an amount of 3 to 12 parts, and the vitamin C is in an amount of 100 to 500 parts.

4. The composition according to claim 1, characterized in that The spirulina is selected from one or more of Spirulina platensis, Spirulina maxima and Spirulina salizawa.

5. The composition according to claim 1, characterized in that The spirulina comprises spirulina powder and effective spirulina extract, wherein the effective spirulina extract is selected from a combination of one or more of spirulina polysaccharide, superoxide dismutase extract and phycocyanin extract, and the mass ratio of the effective spirulina extract: astaxanthin: vitamin C is 50-1000:1-20:50-1000.

6. The composition according to claim 1, characterized in that The astaxanthin is selected from Haematococcus pluvialis products.

7. The composition according to claim 1, characterized in that The vitamin C is selected from one or more of L-ascorbic acid, L-sodium ascorbate, L-calcium ascorbate and ascorbyl palmitate.

8. Use of the composition according to any one of claims 1 to 7 in the preparation of a product for improving memory and cognitive decline in the elderly.

9. The use according to claim 8, characterized in that The memory and cognitive function decline includes alcohol- or drug-induced cognitive impairment, AIDS dementia syndrome, attention deficit disorder, Parkinson's disease, multi-infarct dementia, age-related cognitive impairment, agnosia, amnesia, forgetfulness, learning disabilities, learning impairment, memory impairment, memory loss and mental retardation.

10. Use of the composition according to any one of claims 1 to 7 in the preparation of a product for preventing and / or assisting in the treatment of Alzheimer's disease.

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