CN115317507A - Application of low molecular weight fucoidan in preparation of anti-hyperactivity drugs - Google Patents
Application of low molecular weight fucoidan in preparation of anti-hyperactivity drugs Download PDFInfo
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- CN115317507A CN115317507A CN202211147640.6A CN202211147640A CN115317507A CN 115317507 A CN115317507 A CN 115317507A CN 202211147640 A CN202211147640 A CN 202211147640A CN 115317507 A CN115317507 A CN 115317507A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
The invention belongs to the technical field of biological medicines, and relates to application of low-molecular-weight fucoidan in a medicine or a pharmaceutical composition for treating hyperactivity. The low molecular weight fucoidan can effectively inhibit the motion level of the hyperactivity model animal and improve the spatial memory ability of the animal in the water maze. The low molecular weight fucoidan sulfate provided by the invention can be used for preparing medicines or health products related to hyperactivity, and has good development and utilization values.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to application of low-molecular-weight fucoidan in preparation of a drug for resisting hyperactivity.
Background
Attention Deficit Hyperactivity Disorder (ADHD) is a highly heterogeneous group of neurodevelopmental diseases, with clinical symptoms manifested as Attention Deficit disorders and or Hyperactivity disorders. ADHD is complex in etiology and has individual variability, and the biological mechanism of ADHD pathogenesis is not clarified yet. ADHD is currently considered to be a syndrome of multiple disorders caused by multiple causes, and is associated with a variety of factors including genetics, psychology, and neurobiology. The genetic factors are the main causes of ADHD, the genetic degree of the ADHD reaches 80 percent, and the ADHD has obvious familial aggregation. Neurobiology and neuroimaging research finds that ADHD children have frontal lobe function and cortical junction defects, and cortical development delay causes executive dysfunction, so that problems in response inhibition, attention control and working memory occur. The central symptoms of ADHD are caused by the deregulation of dopamine, norepinephrine, 5-hydroxytryptamine. Therefore, the current clinical treatment of ADHD mainly takes western medicines with the effects of regulating neurotransmitter level and improving inhibition on prefrontal lobe activity as main medicines, including central stimulant methylphenidate, amphetamine and pimoline, and central norepinephrine regulation medicines of tomoxetine and clonidine. NICE evidence-based recommendations suggest methylphenidate and tomoxetine as first-line treatments for ADHD. The Chinese guideline for preventing and treating attention deficit hyperactivity disorder recommends tomoxetine with higher safety as a first-line treatment medicament. Tomoxetine selectively inhibits presynaptic operation of norepinephrine and increases norepinephrine function, thereby improving ADHD symptoms, but adverse reactions of tomoxetine include severe liver injury, causing dizziness, headache, insomnia, lethargy, and gastrointestinal reactions such as nausea, anorexia, dyspepsia, abdominal pain, and the like. Therefore, a novel anti-hyperactivity disorder medicament which is safe, efficient and free of toxic and side effects is clinically needed.
Based on the defects that western medicines are accompanied with various adverse reactions and are narrow in applicable population and the like, researchers transfer the eyesight to safer natural components such as astragalosides and ginsenosides, and study the treatment effect of ADHD by using important compound preparations and single natural product components. Fucoidan is a sulfated polysaccharide containing fucose as main component monosaccharide, and has multiple biological activities of regulating immunity, resisting oxidation, resisting tumor, resisting blood coagulation, resisting bacteria, resisting virus, resisting complement activation, resisting radiation, and treating cardiovascular diseases and kidney diseases. A great deal of research shows that the molecular weight of the polysaccharide has significant influence on the pharmacological activity, the digestion and the absorption and the safety of the polysaccharide. For example, in animal models of collagen-induced arthritis, high molecular weight fucoidan acts in contrast to low molecular weight fucoidan, which enhances The inflammatory process by enhancing The immune activation of macrophages, while low molecular weight fucoidan inhibits The development of arthritis by inhibiting Th-1 mediated immune responses (The differential effect of high and low molecular weight polysaccharides on The basis of The sensitivity of collagen-induced arthritis microorganism Research,2010,24,1384-1391). So far, reports of brown algae polysaccharide sulfate and sea urchin polysaccharide in the aspect of resisting hyperactivity are not seen. The invention discloses that low molecular weight fucoidin has obvious anti-hyperactivity activity for the first time by using the accepted young SHR rat as a hyperactivity model animal to carry out in-vivo animal experiments, and lays a foundation for developing the application of marine polysaccharide anti-hyperactivity drugs and health care products.
Disclosure of Invention
The invention aims to provide application of low-molecular-weight fucoidan sulfate in preparation of a drug for resisting hyperactivity.
In order to achieve the purpose, the invention adopts the technical scheme that:
the application of low molecular weight fucoidan polysaccharide sulfate in preparing anti-hyperactivity drugs, pharmaceutical compositions or health products. The low molecular weight fucoidan has a molecular weight of 2-12 kDa, preferably 6-8 kDa.
Male SHR rats of 3-4 weeks old are selected as model animals, and WKY is selected as a control animal. Tomoxetine hydrochloride (ATO) is used as a positive drug, and the gavage dose is 5mg/Kg according to the effective dose of a rat and the body surface conversion coefficient of the rat and a human. The fucoidan (DFPS) and sea urchin (HT) with low molecular weight are dissolved in normal saline, and the stomach-administration dosage is 100mg/Kg. The administration is carried out according to the weight of the rat per 100g and the amount of the liquid medicine is 1ml, the administration is carried out for 1 time every day, and the administration is carried out continuously for 21 days. The BLK model group and the WKY control group were gavaged with the same volume of saline.
The preparation process of the low molecular weight fucoidan polysaccharide sulfate comprises the following steps: dried undaria pinnatifida is mixed with 1-2:20-25 of hydrochloric acid, filtering to obtain an extracting solution, repeatedly extracting algae residue, adjusting the filtrate with alkali, filtering with diatomite, ultrafiltering and desalting with an ultrafiltration membrane with the molecular weight cutoff of 5000 daltons, concentrating under reduced pressure, adding 4-6 times of volume of absolute ethyl alcohol for precipitation, washing the precipitate with absolute ethyl alcohol, and drying in vacuum to obtain the fucoidan. Dissolving the fucoidan sulfate in deionized water, adding vitamin C and hydrogen peroxide, stirring for degradation, filtering with diatomite, ultrafiltering with ultrafiltration membrane with cut-off molecular weight of 3000 Dalton for desalination, concentrating the ultrafiltration cut-off solution under reduced pressure, adding anhydrous ethanol with 4-6 times volume of the concentrated solution for precipitation, washing the precipitate with anhydrous ethanol, and vacuum drying to obtain low molecular weight fucoidan sulfate.
The low molecular weight fucoidan and echinus polysaccharide have no adverse effect on the growth speed and ingestion willingness of animals, and have high safety and no toxic or side effect.
The low molecular weight brown alga polysaccharide sulfate is taken as an active ingredient, and is mixed with pharmaceutically or food acceptable auxiliary materials or auxiliary additive ingredients, and then the mixture can be used for preparing a medicament or a medicinal composition or a health-care product with the effect of resisting the hyperactivity according to a conventional preparation method.
The invention has the advantages that:
the invention provides the application of the low molecular weight fucoidan polysaccharide sulfate in preparing the anti-hyperactivity drug, the drug composition or the health care product for the first time. The low molecular weight fucoidan sulfate can effectively reduce the total distance of the animal moving in the open field, the total number of passing grids and the times of entering the central area, and reduce the latency of the animal finding the platform in the water maze and the times of passing through the area where the platform is located, thereby showing that the low molecular weight fucoidan sulfate can effectively regulate the inhibition of the hyperactivity and anxiety behaviors of the animal, improve the spatial working memory capacity and have certain development and utilization values.
Drawings
FIG. 1 is a graph showing the effect of intragastric administration of fucoidan and echinacon on the weight gain of WKY and SHR rats;
FIG. 2 is a graph showing the effect of intragastric administration of fucoidan and echinacon on the intake of WKY and SHR rats;
FIG. 3A is a graph showing the effect of intragastric administration of fucoidan and sea urchin polysaccharides on the total movement distance of WKY and SHR rats in an open field experiment, according to the embodiment of the present invention;
FIG. 3B is a graph showing the effect of intragastric administration of fucoidan and echinacon on the total number of crossing lattices in open field experiments in WKY and SHR rats, according to the embodiment of the present invention;
FIG. 3C is a graph showing the effect of intragastric administration of fucoidan and sea urchin polysaccharides on the percentage of times WKY and SHR rats enter the central region in the open field experiment;
FIG. 3D is a graph showing the effect of intragastric administration of fucoidan and echinacon on the number of times that rats WKY and SHR stand upright in open field experiments, according to the embodiment of the present invention;
FIG. 4 is a graph showing the effect of intragastric administration of fucoidan and echinacon on the movement trajectory of WKY and SHR rats in an open field experiment, according to the embodiment of the present invention;
a set of shr models; WKY control group; ATO group; dfps group; HT group;
FIG. 5 is a graph showing the effect of intragastric administration of low molecular weight fucoidan and echinus polysaccharide on the latency of the platform found in the Morris water maze directional navigation experiment in WKY and SHR rats;
FIG. 6A is a graph showing the effect of intragastric administration of fucoidan and echinacon on the distance traveled by the WKY and SHR rats in the Morris water maze space exploration experiment;
FIG. 6B is a graph showing the effect of intragastric administration of fucoidan and echinacon on the number of times WKY and SHR rats enter the platform region in the Morris water maze space exploration experiment, according to the embodiment of the present invention;
FIG. 7 is a graph showing the effect of intragastric administration of low molecular weight fucoidan and echinus polysaccharide on the trajectory of movement in the Morris water maze space exploration experiment in WKY and SHR rats;
a set of shr models; WKY control group; ATO group; dfps group; ht group.
Detailed Description
The invention is further explained below with reference to the figures and examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Furthermore, it should be understood that various changes or modifications can be made by those skilled in the art after reading the disclosure of the present invention, and such equivalents also fall within the scope of the invention.
Example 1
Preparation of low molecular weight fucoidan polysaccharide sulfate
Crushing 5kg of dried undaria pinnatifida, adding 100L 0.1M hydrochloric acid, stirring and extracting at room temperature for 3 hours, filtering an extracting solution, repeatedly extracting algae residues for 1 time by using 100L 0.1M hydrochloric acid, filtering, combining extracting filtrates, adjusting the pH of the filtrate to 5-7 by using alkali, filtering by using diatomite, ultrafiltering and desalting the filtrate by using an ultrafiltration membrane with the molecular weight cutoff of 5000 daltons, concentrating ultrafiltration cutoff liquid under reduced pressure, adding 4 times of volume of absolute ethyl alcohol of concentrated liquid for precipitation, washing the precipitate by using absolute ethyl alcohol, and drying in vacuum to obtain 1512g of fucoidan sulfate. Dissolving the obtained fucoidan sulfate in deionized water to prepare a solution with the concentration of 1%, respectively adding vitamin C and hydrogen peroxide until the final concentration is 30mmol/L, stirring and degrading at 50 ℃ for 2 hours, filtering the degradation solution by diatomite, ultrafiltering and desalting the filtrate by adopting an ultrafiltration membrane with the cut-off molecular weight of 3000 daltons, concentrating the ultrafiltration cut-off solution under reduced pressure, adding absolute ethyl alcohol with the volume of 4 times of that of the concentrated solution for precipitation, washing the precipitate by absolute ethyl alcohol, and drying in vacuum to obtain 1065g of the low-molecular-weight fucoidan sulfate.
The result of analyzing the low molecular weight fucoidan sulfate shows that the low molecular weight fucoidan sulfate has a molecular weight of 6500Da.
Example 2
Preparation of sea urchin polysaccharide
Purchasing 9.5kg of echinus grandis, dissecting to obtain the wet weight of gonad of the echinus grandis, adding the gonad homogenate of the echinus into equal volume of absolute ethyl alcohol, repeatedly treating for 3 times, soaking with equal volume of petroleum ether, repeatedly treating for 3 times, air-drying to obtain 169.2g of echinus gonad degreasing powder, and drying and storing for later use. Dissolving the defatted powder of gonad of sea urchin with 10 times volume of pure water, extracting in 90 deg.C water bath under stirring for 4 hr, recovering to room temperature after extraction, centrifuging (4000rpm, 15min), collecting supernatant, adding the precipitate into pure water again, and repeating the above steps for three times. And finally, concentrating the supernatant to a proper volume, adding anhydrous ethanol with three times of volume by adopting an ethanol precipitation method, and standing for 24 hours at 4 ℃. Centrifuging, collecting precipitate, re-dissolving the precipitate with pure water, centrifuging again, removing insoluble substances, dialyzing the supernatant with dialysis bag with molecular weight cut-off (MWCO) of 3.5kDa, concentrating, and lyophilizing to obtain crude polysaccharide extracted from gonad of sea urchin, with yield of 11.1%. Adding 10 times of 0.2 mol/L NaOH solution into residue obtained after hot water extraction of sea urchin gonad, stirring and extracting at 70 ℃ for 2 hours, neutralizing the extracting solution after the extraction is finished, centrifuging to remove the residue, collecting supernatant, concentrating to a proper volume, adding three times of volume of absolute ethyl alcohol for alcohol precipitation, and standing at 4 ℃ for 24 hours. Centrifuging, collecting precipitate, re-dissolving the precipitate, centrifuging again, collecting supernatant, dialyzing (MWCO: 3.5 kDa), concentrating, and lyophilizing to obtain crude polysaccharide extracted from gonadal gland of sea urchin with yield of 6.2%. Carrying out enzymolysis on sea urchin gonadal polysaccharide by using alkaline protease and papain to remove protein. Inactivating enzyme of the crude polysaccharide after enzymolysis at 100 ℃, centrifuging the enzymolysis solution, filtering with a 0.22 mu m filter membrane, performing step gradient elution by adopting DEAE Fast Flow weak anion exchange column chromatography, and purifying the polysaccharide to obtain the HT-1 component. Separating and purifying sea urchin polysaccharide with Sephadex G75 chromatographic column according to molecular weight difference to obtain HT-1B component.
The physical and chemical property analysis of sea urchin polysaccharide shows that the molecular weight of sea urchin polysaccharide HT-1B is 4000Da.
Example 3
Pharmacodynamics of low molecular weight fucoidan for improving hyperactivity
The fucoidan sulfate of low molecular weight of example 1 and the echinus polysaccharide of example 2 were accurately weighed, dissolved in normal saline, and the solvent was prepared in an amount of 100mg/Kg for intragastric administration. The gavage is carried out according to the weight of the rat per 100g and the liquid medicine amount of 1ml, the gavage is carried out for 1 time every day, and the gavage is continuously carried out for 21 days. 10 WKY rats as normal control group were subjected to intragastric administration of physiological saline; 40 SHR rats were divided into 4 groups according to body weight, and divided into BLK group (gavage physiological saline), ATO group (gavage 5mg/Kg tomoxetine), DFPS group (gavage 100mg/Kg low molecular weight fucoidan-obtained in example 1), and HT group (gavage 100mg/Kg echinacon-obtained in example 2).
(1) Body weight and food intake
Animals were monitored for weight change every 3 days. The level of food intake of the animals was measured at the initial stage of administration and one week after administration. According to the number of animals per cage, 50 g/feed is given, the balance is weighed every 3 days and made up to the initial level, and the average food intake per day of the animals is calculated according to the difference.
The results are shown in fig. 1-2, and fig. 1 shows that the body weights of animals in various groups of SHR at the initial administration stage are not obviously different, the body weights of animals in ATO group are obviously fluctuated in the middle and later stages, which indicates that tomoxetine may influence the growth and development of animals and the desire to eat, and the body weights of animals in DFPS group and HT group are uniformly increased, which indicates that DFPS and HT have no toxic or side effect on animal bodies. The body weight levels of the animals in each group were substantially maintained as DFPS > HT > BLK > ATO > WKY. FIG. 2 shows that there is no significant difference in average intake amount between SHR groups and WKY groups at the initial administration stage, and after one week of administration, the intake amount of BLK animals is significantly higher than those of ATO group and DFPS group, and significantly higher than that of WKY group (p < 0.05), which indicates that the drug may reduce the intake amount by reducing the activity level of animals.
(2) Effect of drugs on animal motion levels in open field
The open field experiment divide into 3 stages, and the animal is tempered in the earlier stage of dosing, divides into groups the animal through the first open field experiment, and the later stage of dosing carries out the second open field experiment, and the motion level of inspection animal, anxiety, exploration level.
1. An exercise period:
after the adaptive feeding period, the animals were subjected to open field exercise. 3h before the start of the experiment, the animals were transferred to a behavioural laboratory to exclude increased activity of the animals due to stress or a novel environment. The open field experimental box is a wooden box with the height of 40cm and the bottom of 50cm multiplied by 50 cm. Animals were placed in the central area of the experimental box and allowed to move freely for 3min.
2. The first field-opening experiment:
after the animals are subjected to the open field exercise, the first open field experiment is carried out. The animals are placed in the central area of the test box and allowed to freely move for 5min, and weak light illumination is adopted in the experimental process to keep the environment stable and the light and noise consistent. After the experiment started, the experimenter separated from the animals immediately, and after the experiment was finished, the tested animals were taken out, and the test area was cleaned with 75% alcohol to avoid the smell from interfering with the next animal. The movement of the animals in the open field was recorded and analyzed using smartv3.0.0.6.
3. Second field opening experiment:
14 days after dosing, a second open field experiment was performed. The experimental operation is the same as the first field-opening experiment. And evaluating the influence of the medicament on the movement level of the animal according to the indexes of the total movement distance of the animal, the movement distance (%) in the central grid, the total number of grids passing through, the number of times of entering the central grid, the rest time, the erection time and the like.
The results are shown in FIGS. 3 to 4. The distance of movement of the animal in the open field, the number of grid crossings, the number of entries into the central zone, the number of erections, indicate the level of hyperactivity, anxiety and curiosity sought by the animal. FIG. 3A shows that the total kinesthetic distance in the open field was significantly lower for the WKY group animals than for the BLK group (p < 0.05), with the ATO and DFPS groups being significantly lower than for the BLK group; FIG. 3B shows that the number of crossing lattices of animals in the WKY, ATO and DFPS groups is significantly lower than that in the BLK group (p < 0.05); FIG. 3C shows that the number of entries into the central region was significantly lower in the WKY and DFPS groups than in the BLK group (p < 0.05); FIG. 3D shows that the animals in the WKY, ATO, and DFPS groups were significantly less erect than the BLK group (p < 0.05). Fig. 4 is a trace of the animal's locomotion during the open field, illustrating that DFPS effectively inhibits the level of hyperactivity and anxiety in the animal. HT animals have no obvious improvement effect in all aspects of the open field experiment.
(3) Morris Water maze test for animal behaviourology
The Morris water maze experiment is divided into 2 stages, including a 5-day oriented navigation experiment and a 1-sky exploration experiment, so as to explore the space learning and working memory capacity of animals.
Experimental method
1. Exercise period
After 15 days of administration, water maze exercise was performed. The water maze consists of a prototype reservoir with the diameter of 180cm and the height of 50cm and a black iron platform, wherein the water depth in the reservoir is 25cm, the water temperature is controlled to be 25 +/-1 ℃, ink is added into the water, and the platform cannot be seen when the reservoir is opaque. The pool is divided into four quadrants of 1, 2, 3 and 4 artificially and evenly, a platform is placed in the 3 rd quadrant, and the area of the top plane of the platform is 8cm multiplied by 8cm. And the peripheral pure-color curtain is used for sticking patterns with different colors and shapes above four quadrants of the curtain to be used as the directional marker of the animal. In a directional navigation experiment, a platform is arranged to be exposed out of the water surface on the 1 st day, animals are placed in the center of the first quadrant in a manner of facing the pool wall, the exploration time is given for 60s, if the animals do not find the platform, the animals are guided to ascend the platform, each animal is guaranteed to stay on the platform for 20s for observation and memory, and the animals are fished out, wiped dry and placed back into a cage.
2. Experiment of directional navigation
And on days 2-5, arranging the platform 2cm below the water surface, putting the animals facing the pool wall from the centers of quadrants 1, 2, 3 and 4 respectively, evacuating the experimenters immediately to avoid forming wrong reference for the animals, ensuring no shadow on the water surface and avoiding software recognition errors, guiding the mice to travel to the platform and enabling the mice to stay for 20s if the mice 60s cannot reach the platform by self, and allowing all the mice to stay for 20s after reaching the platform to form space memory. Latency for animals to find the platform was recorded and analyzed using smartv3.0.0.6.
3. Experiment of space exploration
And (4) withdrawing from the platform on the 6 th day, carrying out a space exploration experiment, putting the animal into the platform from the first quadrant, analyzing the latency of the animal entering the area where the original platform is located, the number of times of shuttling the platform area, and the distance and time in the platform area by utilizing Smartv3.0.0.6.
The results are shown in fig. 5-7, fig. 5 shows that in the directional sailing experiment, the latency of the animals for finding the platform is shortened along with the increase of sailing times, the latency of the animals for finding the platform is shorter in the DFPS group and the HT group than in the model group, and DFPS < HT < ATO < BLK < WKY; fig. 6A shows that the percentage of the moving distance of the animal in the original platform area is higher than that of the DFPS group, fig. 6B shows that the number of times of the animal entering the original platform area is higher than that of the BLK group, and fig. 7 shows that the moving trajectory of the animal in the water maze is biased, the moving trajectory of the animal in the BLK group is disordered, and the animals in the DFPS group and the HT group are biased to search in the platform area, which shows that the DFPS effectively improves the spatial memory ability of the animal, and the HT has no obvious effect on the spatial memory ability of the animal.
Claims (3)
1. The application of the low molecular weight fucoidan polysaccharide sulfate is characterized in that: the application of low molecular weight fucoidan polysaccharide sulfate in preparing anti-hyperactivity drugs, pharmaceutical compositions or functional foods.
2. Use according to claim 1, characterized in that: the low molecular weight fucoidan has a molecular weight of 2-12 kDa, preferably 6-8 kDa.
3. Use according to claim 1, characterized in that: the brown algae polysaccharide sulfate with low molecular weight is taken as an active component, and is mixed with pharmaceutically or food acceptable auxiliary materials or auxiliary additive components to prepare a medicament or a medicament composition with the function of resisting hyperactivity, or functional food.
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