KR20130131797A - A pharmaceutical composition for the improvement of memory and cognition ability, and prevention or treatment of alzheimer's disease comprising the glucoceramide derivatives - Google Patents

Abstract

Glucoceramide of the present invention has the effect of treating dementia by improving memory and the effect of degrading the generation of inflammation enzymes in the hippocampus region. Accordingly, the glucoceramide and glucoceramide derivatives of the present invention can be used in pharmaceutical compositions for improving memory, preventing and treating dementia and functional health supplements for improving memory and cognitive functions, and preventing and treating dementia.

Description

A pharmaceutical composition for the improvement of memory and cognition ability, and prevention or treatment of Alzheimer's disease comprising the Glucoceramide derivatives}

The present invention relates to a memory composition comprising glyceramide and derivatives thereof, a pharmaceutical composition for treating and preventing dementia, and a functional dietary supplement for improving memory, improving cognition, preventing or improving dementia.

Dementia is a syndrome with a wide range of mental disorders. The incidence of dementia is estimated to reach 10% in those aged 65 and older and 20% in those aged 80 and older. It is reported that there are many causes of dementia, and other degenerative diseases of the brain, such as Parkinson's disease, plasma disorders, and low frequency of addictive or metabolic abnormalities are also causes. The establishment of a causal relationship in the onset mechanism of Alzheimer's disease was difficult for the following three reasons. 1) The temporal distance between cause and effect reaches decades. 2) human specific disease. 3) Pathological and biochemical interpretations are possible only in the postmortem brain.

Alzheimer's disease begins with a decrease in memory, progresses through progressive memory cognitive impairment, and eventually leads to high dementia. There are between 10 and 15 million patients worldwide, and the number is estimated to increase from year to year. The pathological characteristics of Alzheimer's disease include changes in senile plaques and neurofibrillary tangles, which require a histochemical examination of histologic specimens of the brain, and biopsy or autopsy is required. Not practical in the field. Therefore, the diagnosis is made based on the presence or absence of symptoms characteristic of Alzheimer's disease (memory, cognitive deterioration, and dementia). Until 1980, the pathologic analysis of Alzheimer's disease was mainly performed. Pathological analysis then identified these material entities, revealing that the former consists of beta-amiroid (Aβ) peptides, the latter consisting of tau protein.

The beta amyloid (Aβ) is made in small quantities in various places in the human body even though it is reported that beta-amiroid plays a role in protecting neurons, but its exact function is not known. In normal people, beta-amiroids are rapidly decomposed and do not accumulate in the human body, but when looking at the brain tissues of Alzheimer's disease, abnormally large amounts of beta-amiroids are excessively accumulated in the hippocampus or cerebral cortex. Accumulated beta-amiroids cause inflammatory reactions in surrounding cells, thus damaging nerve cells and gradually damaging neural networks that maintain normal brain function. Accumulated beta amyloid also activates a signaling system that kills nerve cells, producing excess free radicals.

Alzheimer's disease is an early symptom of memory disorder, and as in the case of Parkinson's disease, patients in early stages with no significant neurodegeneration respond well to drug therapy. In addition, theoretical evidence has been reported that cholinergic drugs can help improve memory disorders (Corina Bejar, Eur J Pharmacol 383, 231-240, 1999). Thus, there have been major attempts to improve memory by using choline contracts in Alzheimer's patients.

In addition, neuropsychological evidence has been reported in Alzheimer's patients that the choline-type disorders of the hippocampus and temporal lobe are particularly prominent, and that these areas are related to memory disorders. It has also been reported that anticholinergic drugs such as scopolamin worsen human memory, whereas administration of cholinergic drugs such as physostigmine has been reported to improve human memory (Davis KL, Science 201, 272-274, 1978, Corina Bejar, Eur J Pharmacol 383, 231-240, 1999).

Currently, acetylcholine esterase inhibitors, such as donepezil, galantamine, and rivastigmine, are used in clinical trials as dementia-improving drugs. There is no situation.

Memory tests to assess memory improvement in drug studies exist as follows. The so-called radiation maze or Morris water maze test, which evaluates so-called spatial cognitive memory to find or recognize directions or places, is known as a very sensitive test for cognitive deficits associated with cholinergic dysfunction. There is a bar.

Conventionally, it has been disclosed that C2-ceramide has an effect of protecting the rat hippocampal neurons by preventing cell death induced by glutamate, FeSO ₄ and Aβ, that is, having antioxidant activity (Journal of Neurochemistry, Vol. 66, 869). -872, 1996). It has also been reported that intravenous ceramides induce resistance to ischemia and that cell permeable exogenous ceramides reduce infarct size in spontaneous hypertensive rats (Journal of Cerebral Blood Flow Metabolism, Vol. 21, 226-232, 2001). ).

On the other hand, when ceramidase acts on ceramide that induces apoptosis, fatty acid is released from ceramide and sphingosine is produced, and sphingosine is phosphorylated by spingosine kinase. It is known to turn over to sphingosine-1-phosphate (S1P), which is a type of high lipid, and S1P is known to act to inhibit apoptosis by acting opposite to ceramide. In addition, when ceramide kinase acts on intracellular ceramide, it is converted to ceramide-1-phosphate to inhibit apoptosis induced by ceramide and exhibit cell survival and proliferation. . Phosphorylated sphingolipids are produced by phosphorylation of sphingosine and ceramides by activation of sphingosine kinase and ceramide kinase. It is known to exhibit various physiological activities. In addition, the production of ceramide and sphingosine is known to cause apoptosis. Therefore, intracellular balance between these lipid components is an important factor in determining the life and death of cells.

However, in the above conventional studies, the cell-permeable synthetic ceramide is used, which is different from the glyceramide in the present invention. Thus, there are no examples of glyceramides that can be used to improve memory and to treat or prevent dementia.

Therefore, the present inventors are studying to improve the memory and the possibility of glyceramide as a therapeutic agent for dementia. As a novel glyceramide derivative, iNOS and COX, which are inflammation-related enzymes in the hippocampus, which improve memory memory and manage memory, are improved. Confirmed that -2 is reduced to show the anti-dementia effect and completed the present invention.

The present invention is to provide a pharmaceutical composition comprising a novel glyceramide derivative improves memory, improve cognition, prevent dementia or therapeutic effect. In addition, the present invention is to provide a functional dietary supplement for improving memory, cognition, dementia prevention or improvement comprising a novel sugar ceramide derivative.

In order to solve the above problems, the present invention provides a pharmaceutical composition comprising a compound represented by the following formula (1), or a pharmaceutically acceptable salt thereof, showing memory improvement, cognitive improvement, dementia prevention or therapeutic effect .

[Formula 1]

Wherein, R ₁ is hydrogen, C _{1 -30} alkyl, phenyl, glucose, arabinose, rhamnose or mannose group,

R ₂ is hydrogen, C _{1 -30} alkyl, phenyl, glucose, arabinose, rhamnose or mannose group.

In a preferred embodiment of the invention, R ₁ And R ₂ is preferably hydrogen.

Glyceramide, which is a compound represented by Chemical Formula 1, may be used by purchasing or preparing a commercially available or commercialized product through microbial fermentation or soybean fermentation by a known method.

The term "dementia" used in the present invention is caused by irreversible destruction of the cranial nerve due to atrophy of the brain and the reduction of nerve cells and the appearance of senile plaque, such as memory, speech and behavioral disorders. Refers to a syndrome accompanied by various acquired cognitive impairment symptoms. Dementia is also classified as Alzheimer's disease, degenerative diseases caused by vascular dementia and Parkinson's disease, metabolic diseases caused by hypothyroidism, brain tumors or infectious diseases, and the like.

In the present invention, the term "memory improvement" means all the behaviors in which the decline of memory, which is one of the symptoms of dementia, is improved or beneficially improved by administration of the pharmaceutical composition according to the present invention. In addition, in the present invention, the term "improving cognitive ability" refers to all behaviors in which the cognitive decline of one of the symptoms of dementia is improved or advantageously changed by administration of the pharmaceutical composition according to the present invention. In addition, in the present invention, "prophylaxis" means any action that inhibits or delays the onset of dementia by the administration of the pharmaceutical composition according to the present invention, "treatment" means by dementia by the administration of the pharmaceutical composition Any action that improves or beneficially changes the condition.

In the present invention, the pharmaceutical composition may improve memory by enhancing the acetylcholine-based function of the brain. According to one embodiment of the present invention, it was confirmed by the Y-shaped maze test (FIG. 1) and the maze test (FIGS. 2 and 3) that the memory loss is suppressed in the elderly mice treated with glyceramide of the present invention. In addition, it was confirmed that iNOS and COX-2, which are inflammation-related enzymes, were decreased in the hippocampus, which is a memory region related to glyceramide treatment (FIG. 4).

Y-shaped labyrinth test and Sumi labyrinth test according to an embodiment of the present invention is a test method that is very sensitive to cognitive deficits related to cholinergic nervous system dysfunction. As the system function is improved, the effect of improving memory in the aged mouse can be confirmed.

In addition, when examining the brain tissue of Alzheimer's disease patients, abnormally high levels of beta-amiroids are produced in the hippocampus or cerebral cortex, and these accumulated beta-amiroids cause inflammatory reactions in the surrounding cells and thus damages nerve cells. Increasingly, the neural network that maintains the normal functioning of the brain is compromised. Therefore, it is possible to confirm the prophylactic or therapeutic effect of Alzheimer's disease through the effect of lowering the inflammation-related enzymes iNOS and COX-2 in the hippocampus according to an embodiment of the present invention.

The term "pharmaceutically acceptable salts" of the present invention means all salts that retain the desired biological and / or physiological activity of the compound and exhibit undesired toxicological effects to a minimum. For example, the compounds may include inorganic acids (e.g. hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, etc.), organic carboxylic acids (e.g., acetic acid, halo acetic acid such as trifluoroacetic acid, propionic acid, maleic acid, succinic acid). , Malic acid, citric acid, tartaric acid, salicylic acid), and acidic sugars (e.g. glucuronic acid, galacturonic acid, gluconic acid, ascorbic acid), acidic polysaccharides (e.g. hyaluronic acid, chondroitin sulfate, arginine acid), chondroitin sulphate It may be a salt formed by adding sulfonic acid such as pate, organic sulfonic acid including sugar esters (eg, methane sulfonic acid, p-toluene sulfonic acid), and the like, but is not particularly limited thereto.

The pharmaceutical composition of the present invention may be formulated into a suitable formulation with a pharmaceutically acceptable carrier and administered by various routes. The term "pharmaceutically acceptable" in the present invention means to exhibit properties that are not toxic to cells or humans exposed to the composition. The carrier can be used without limitation so long as it is known in the art such as buffers, preservatives, analgesics, solubilizers, isotonic agents, stabilizers, bases, excipients, lubricants. Carriers, excipients and diluents which may be included in the pharmaceutical compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicates, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Typically available surfactants that facilitate migration across the membrane are those derived from steroids, but N- [1- (2,3-dioleoyl) propyl-N, N, N-trimethylammonium chloride] (DOTMA Cationic lipids, or cholesterol hemisuccinate.

In the present invention, the term "individual" means all animals including humans having or may have a dementia disease, and can effectively prevent or treat the dementia disease by administering the pharmaceutical composition of the present invention to an individual. The pharmaceutical composition of the present invention may be administered in parallel with existing therapeutic agents for dementia.

The term "administration" of the present invention means introducing a predetermined substance into a patient in an appropriate manner, and the route of administration of the composition may be administered via any general route as long as it can reach the target tissue. Intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, nasal administration, pulmonary administration, rectal administration, but is not limited thereto. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may include at least one excipient such as starch, calcium carbonate, sucrose, or lactose, Prepare by mixing gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, and syrups.In addition to the commonly used simple diluents, water and liquid paraffin, various excipients such as wetting agents, flavoring agents, preservatives, etc. Can be. However, upon oral administration, since the peptides are easy to digest, it is desirable to formulate oral compositions to coat the active agent or protect it from degradation in the stomach. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. The suppository base includes Uittepsol, Macrogol, and Twin 61. Cacao butter, laurin butter, glycerogelatin and the like can be used. Carbohydrates such as glucose, sucrose, dextran, antioxidants such as ascorbic acid, glutathione, chelating substances, small molecule proteins or other stabilizers may be used to increase the stability or absorption of the peptide.

In addition, the pharmaceutical compositions of the present invention may be administered by any device in which the active substance may migrate to target cells. Preferred modes of administration and preparations are intravenous, subcutaneous, intradermal, intramuscular, injectable and the like. Injections include non-aqueous solvents such as aqueous solvents such as physiological saline solution and ring gel solution, vegetable oils, higher fatty acid esters (e.g., oleic acid, etc.), and alcohols (e.g., ethanol, benzyl alcohol, propylene glycol, glycerin, etc.). Stabilizers (e.g. ascorbic acid, sodium bisulfite, sodium pyrosulfite, BHA, tocopherol, EDTA, etc.), emulsifiers, buffers for pH control, to prevent microbial growth Preservatives (eg, mercury nitrate, chimerosal, benzalkonium chloride, phenol, cresol, benzyl alcohol, etc.) may be included.

On the other hand, the pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and not causing side effects, and the effective dose level is determined by the patient's sex, Including, but not limited to, medicaments and other medical fields that are used in combination, or in combination with, or in combination with, a pharmaceutically acceptable carrier, excipient, Can be readily determined by those skilled in the art according to known factors. Generally, the active substance can be administered at a dose of about 0.01 mg / kg / day to 1000 mg / kg / day. In the case of oral administration, a range of 50 to 500 mg / kg may be suitable and may be administered at least once a day.

In another aspect, the present invention provides a method for preventing or treating dementia, comprising administering the pharmaceutical composition for improving memory, improving cognition, preventing or treating dementia, to an individual in whom dementia is expressed or probable. To provide.

The present invention also provides a functional dietary supplement for improving memory, improving cognition, preventing or improving dementia, including a compound represented by Formula 1 below, or a pharmaceutically acceptable salt thereof. That is, the compound of formula 1 or a pharmaceutically acceptable salt thereof may be added to the food for the purpose of preventing or improving dementia.

[Formula 1]

Wherein, R ₁ is hydrogen, C _{1 -30} alkyl, phenyl, glucose, arabinose, rhamnose or mannose group,

R ₂ is hydrogen, C _{1 -30} alkyl, phenyl, glucose, arabinose, rhamnose or mannose group.

In a preferred embodiment of the invention, R ₁ And R ₂ is preferably hydrogen.

Glyceramide, which is a compound represented by Chemical Formula 1, may be used by purchasing or preparing a commercially available or commercialized product through microbial fermentation or soybean fermentation by a known method.

Dementia that can be prevented or improved through the dietary supplement of the present invention is the same as described in the pharmaceutical composition for the prevention or treatment of dementia.

In addition, the health supplement in the present invention can improve the memory by enhancing the acetylcholine-based function of the brain.

In the present invention, "prevention" means all the actions to suppress the symptoms or delay the onset of dementia by the intake of functional dietary supplements, "improved" means that symptoms caused by dementia by the intake of dietary supplements Means any action that improves or changes beneficial;

The dietary supplement of the present invention corresponds to all forms of health functional foods, nutritional supplements, nutritional supplements, pharmafood, health food, nutraceutical, designer food, food additives and the like.

When the compound of Formula 1 or a pharmaceutically acceptable salt thereof is used as an additive of the dietary supplement, the compound or a pharmaceutically acceptable salt thereof may be added as it is, or may be used together with other food or food ingredients. It may be appropriately used depending on the method. The mixed amount of the active ingredient can be suitably determined according to the purpose of use (preventive or improved treatment).

There is no particular limitation on the type of food, for example, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, drinks, tea, Drinks, alcoholic beverages and vitamin complexes and the like, and include all dietary supplements in the conventional sense.

In addition, the dietary supplement may further include food additives, and the suitability as a "food additive" is related to such items in accordance with the General Regulations and General Test Act of the Food Additives Code approved by the Food and Drug Administration unless otherwise specified. Judging by the standards and standards.

Examples of the products listed in the above-mentioned "food additives" include natural products such as ketones, chemical products such as glycine, potassium citrate, nicotinic acid and cinnamic acid, coloring matter, licorice extract, crystalline cellulosic, high- , A sodium L-glutamate preparation, a noodle-added alkaline agent, a preservative preparation, a tar coloring agent, and the like.

In this case, the compound of Formula 1 according to the present invention or a pharmaceutically acceptable salt thereof according to the present invention added to a food including a beverage in the process of preparing the health supplement food may be appropriately added or decreased as necessary, preferably It is preferred to add 1 to 15% by weight to 100% by weight of food.

In addition, the health supplement of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage.

In the present invention, the glyceramide derivative exhibits an effect of treating dementia by improving memory by administering it to an aged mouse. It also has an effect of decreasing the production of inflammatory enzymes in the hippocampus. Therefore, the sugar ceramide of the present invention and derivatives thereof may be usefully used as a functional composition for improving memory, treating and preventing dementia, and improving functional memory, improving cognition, preventing or improving dementia.

Figure 1 shows the effect of enhancing the memory of aging mice in the Y-shaped maze test by administration of glyceramide according to an embodiment of the present invention.
Figure 2 shows the effect of memory training by training aging mice for 4 days in the Sumiro test with the administration of glyceramide according to an embodiment of the present invention.
Figure 3 shows the effect of improving memory through a probe test of aging mice trained in Sumiro test with the administration of glyceramide according to an embodiment of the present invention.
Figure 4 shows the results of immunochemical measurement that the increase in iNOS and COX-2 is inhibited in the hippocampus after the administration of glyceramide according to an embodiment of the present invention to the aging mouse.

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided to further understand the present invention, and the present invention is not limited by the examples.

Example  1: Formula 1 of the present invention R _One And R ₂ Is hydrogen Of sugar ceramide  Physicochemical Analysis

Mp: 195-196 ° C .; IR (neat, NaCl) 3353 (OH), 2920 (CH), 2851, 1726 (C = O), 1620 (C = C), 1530, 1466, 1406, 1378, 1264, 1182, 1168, 1040 (CO) , 721 cm ^-1 ; ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.60-5.52 (m, 2H), 5.42-5.28 (m, 2H), 5.01-4.87 (m, 1H), 4.55-4.48 (m, 1H), 4.13-4.09 ( m, 1H), 4.04-3.99 (m, 1H), 3.85-3.78 (m, 2H), 3.54-3.28 (m, 6H), 2.50 (brs, 6H), 2.05-1.90 (m, 6H), 1.54- 1.45 (m, 2 H), 1.33-1.19 (m, 38 H), 0.88-0.81 (m, 6 H); ¹³ CNMR (100 MHz, CDCl ₃ ) δ 173.75, 132.31, 130.23, 129.73, 127.76, 76.89, 76.53, 73.11, 71.59, 70.01, 33.91, 33.22, 32.54, 31.99, 31.29, 30.89, 29.03, 28.71, 28.58, 26.59, 25.21 , 24.43, 22.09, 21.96, 14.11; HRMS calcd. for C ₄₀ H ₇₆ NO ₉ : 714.5520 [M + H] ⁺ , found: 714.5531.

Example  2: Y-maze test (Y- maze test )

The Y-shaped labyrinth measuring device extends three arms to form an alphabet Y-shape at an angle of 120 ° and each branch is 25 cm long, 14 cm high and 5 cm wide, and is positioned at the same angle. The experimental setup consisted of black polyvinyl plastic. Each branch was set to A, B, C, and then the mouse was carefully placed on one branch and allowed to move freely for 8 minutes, and then the order in which the mice entered (eg, ABCAB) was recorded. Record the movement of the animal and pass it through the passage to the hind paw of the animal. The movement of an animal is represented by an alteration number, which is defined as one crossing when the animal passes through three passages in succession (eg, ABC, CAB, or BCA). The voluntary crossover behavior (%) is the percentage of actual crossovers and the maximum possible crossovers (ie, the total crossovers minus two). The number of entry and exit of each branch may be used as an index of spontaneous movement. The results of the Y maze test after oral administration of the glyceramide of the present invention to 50 mg / kg for 3 months in aged mice over 24 months are shown in FIG. 1. As shown in FIG. 1, the result showed a working memory enhancement effect (FIG. A). In addition, spontaneous movement was also shown to increase (Fig. B).

Example  3: By the sum  exam ( Morris water maze teat )

The circular water tank was filled with water at a temperature of 23 ° C. until the platform was submerged. The platform placed the entire water tank in the center of one of the quarters with the top half below the water surface. The device was installed in a laboratory with markings to identify the location. To make the platform invisible, water was added to the food coloring to make it cloudy. Training trials were conducted three times a day for five consecutive days. Once the animal had found the platform, the next attempt was made 5 minutes after it was left on the platform for about 10 seconds to return to the original cage. If the mouse did not find a platform within 120 seconds, it was placed on the platform for 10 seconds to adapt the platform's position to allow the animal to remember the platform's position. Memory change was measured daily for 4 days of training (FIG. 2). Probe tests were performed on animals after training 24 hours after the last training attempt. At this time, the platform was removed and the time for which the animal stayed in the quadrant where it was placed on the platform for 90 seconds was measured and expressed as a percentage (FIG. 3).

50 mg / kg of glyceramide of the present invention was orally administered to aged mice over 24 months for 3 months, and then memory change was measured during 4 days of training. On the fourth day of training, glyceramide showed an inhibitory effect on memory memory (FIG. 2). After 4 days of training, the probe was removed and the memory change was measured. As a result, the memory was improved (FIG. 3). As a result of the experiment, it was found that spatial memory was enhanced by glyceramide.

Example  4: in the hippocampus of the brain iNOS  And COX Immunological measurement of -2 expression

50 mg / kg of glyceramide was administered orally to aged mice aged over 24 months for 3 months, followed by pulverization of memory-related hippocampal sites, and antibodies to inflammation-related iNOS and COX-2 antibodies. As measured by Western blot using the two enzymes significantly increased in aging mice was significantly reduced by glyceramide treatment (Fig. 4).

Claims (6)

A pharmaceutical composition comprising a compound represented by the following Chemical Formula 1, or a pharmaceutically acceptable salt thereof, which exhibits memory improvement, cognitive improvement, dementia prevention, or therapeutic effect:
[Chemical Formula 1]

Wherein, R ₁ is hydrogen, C _{1 -30} alkyl, phenyl, glucose, arabinose, rhamnose or mannose group,
R ₂ is hydrogen, C _{1 -30} alkyl, phenyl, glucose, arabinose, rhamnose or mannose group.
The compound of claim 1, wherein R ₁ And R ₂ is hydrogen.
The pharmaceutical composition according to claim 1 or 2, wherein the composition improves memory by promoting acetylcholine-based functions of the brain.
A functional dietary supplement for improving memory, improving cognition, preventing or improving dementia, including a compound represented by Formula 1, or a pharmaceutically acceptable salt thereof:
[Chemical Formula 1]

Wherein, R ₁ is hydrogen, C _{1 -30} alkyl, phenyl, glucose, arabinose, rhamnose or mannose group,
R ₂ is hydrogen, C _{1 -30} alkyl, phenyl, glucose, arabinose, rhamnose or mannose group.
The compound of claim 4, wherein R ₁ And R ₂ is a functional health supplement, characterized in that hydrogen.
According to claim 4 or 5, wherein the dietary supplement is a functional dietary supplement, characterized in that to improve memory by promoting the acetylcholine function of the brain.

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