KR20190123045A - Composition comprising fractions of ginseng extract for preventing or treating learning, cognition or memory disabilities - Google Patents

Abstract

The present invention relates to a fraction of a ginseng extract, in which, according to a type of ginseng, fractions obtained by changing extraction conditions or fraction conditions have an excellent effect improving memory. Therefore, the fraction of the ginseng extract can be used for a pharmaceutical composition and a health food composition for preventing or treating at least one disease selected from a group consisting of learning disability, cognition disability or memory damage.

Description

Composition comprising fractions of ginseng extract for preventing or treating learning, cognition or memory disabilities}

The present invention relates to a pharmaceutical composition for preventing or treating brain diseases, including fractions of ginseng extract.

The brain has many functions, but the most important ones are memory and cognitive abilities. If human beings do not have cognitive and memory skills, it is difficult for them to carry out their daily activities and they are a problem for their survival.

The stage of memory is divided into the process of registering and encoding information, the process of storing, and the process of accessing and withdrawing the place of memory. Coding is a process in which information coming into the brain through the sense organs is learned and memorized. Although the information is stored once through encoding, it is necessary to go through the process after encoding in order to keep the stored information continuously and to store it with more robust memory. If this process is not performed well, the forgetting of memory occurs quickly and the memory is difficult to maintain.

Withdrawal refers to the process of consciously recalling the contents stored in long-term memory. There are two ways to withdraw: recollection and acknowledgment. Recall is to consciously recall the contents of memory, and jane is to call it with hints. In most cases, recall is harder than recognition. However, even if the recall is difficult, such as patients with frontal lobe damage or subcortical vascular dementia, recognition is good. In this case, the encoding and storage of memory is good, but it means that there is a drawback disorder. In case of a memory storage disorder, the memory of both the recall and the acknowledgment is shown simultaneously.

In addition, short-term memory is also called working memory, and refers to a process that can store the information for a short time and then use it to perform the next task. The information that enters the brain stays temporarily before it hardens into long-term memory. The characteristic of working memory is that after performing a certain task, the working memory is usually erased.

Long-term memory means learning something new and remembering it after a certain time. Most of the things we have experienced and learned in our daily lives come back to memory after a long period of time.

Memory and cognitive impairments are very serious conditions that make life impossible, including aging, Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, Peak disease, Creutzfeldt-Jakob disease, depression, aging, head trauma, stroke, CNS hypoxia, cerebral ischemia, encephalitis, forgetfulness, traumatic brain injury, hypoglycemia, Wernicke Korsakov syndrome, drug addiction, epilepsy, epilepsy, hippocampus, headache, cerebral senile dysfunction, dementia, prefrontal degeneration, tumors, normal hydrocephalus, HIV , Cerebrovascular disease, cerebral neurological disease, cardiovascular disease, memory loss, radiation exposure, metabolic disease, hypothyroidism, mild cognitive impairment, cognitive deficit or attention deficit.

Various efforts have been made to address these memory and cognitive impairments. Among these, research is being conducted to obtain a substance that can improve memory from natural products, because there is a risk of side effects when using a specific compound. Patent Document 1 discloses a technique that can be used to prevent forgetfulness by using the extract of hachocho.

Panax Ginseng contains amino acids, vitamins, organic acids, carbohydrates, minerals, etc., which are effective in preventing and treating various diseases such as tonic action, quenching thirst, strengthening immune function, blood pressure, diabetes and fatigue. Known as The physiological effects on ginseng itself have been reported in many literatures, but the analytical research on whether ginseng-derived extracts have an effect on improving memory has been insufficient.

The present inventors studied whether natural-derived materials can be used to improve learning, cognitive, and memory disorders, and completed the present invention by confirming that the fraction derived from ginseng extract enhances memory, among natural products.

Korean Patent Registration No. 1508395

Summary of the Invention An object of the present invention is to improve a memory-derived material derived from natural products that can be used in place of these compounds in order to solve the risk that side effects occur when using certain compounds to solve memory and cognitive impairments. To provide.

In order to solve the above problems, the present invention provides a pharmaceutical composition for the prevention or treatment of at least one disease selected from the group consisting of learning disorders, cognitive disorders and memory impairment comprising a fraction of ginseng extract.

In addition, the present invention provides a health food composition for improving at least one disease selected from the group consisting of learning disorders, cognitive disorders and memory impairment comprising a fraction of ginseng extract.

When the fraction of the ginseng extract according to the present invention is treated in the animal model of memory loss, the retention time is increased in the manual avoidance test, so the memory improvement effect is excellent.

1 is a schematic diagram showing a process of obtaining a fraction of the ginseng extract of the present invention.
Figure 2 shows the retention time when the ginseng leaf water extract and its fractions were respectively treated: lw; Ginseng Leaf Water Extract, Fr. One; Fraction of Ginseng Leaf Water Extract 1, Fr. 2; Fraction of ginseng leaf water extract 2, Fr. 3; Fraction of Ginseng Leaf Water Extract 3.
Figure 3 shows the retention time when the ginseng leaf ethanol extract and its fractions were respectively treated: le; Ginseng Leaf Ethanol Extract, Fr. One; Fraction of Ethanol Extract of Ginseng Leaf 1, Fr. 2; Fraction of Ginseng Leaf Ethanol Extract 2, Fr. 3; Fraction of Ethanol Extract of Ginseng Leaf 3.
Figure 4 shows the retention time when the ginseng fruit water extract and its fractions were respectively treated: bw; Ginseng Berry Water Extract, Fr. One; Fraction of Ginseng Berry Water Extract 1, Fr. 2; Fraction 2 of Ginseng Berry Water Extract, Fr. 3; Fraction of Ginseng Berry Water Extract 3, Fr. 4; Fraction of Ginseng Berry Water Extract 4, Fr. 5; Fraction of Ginseng Berry Water Extract 5.
FIG. 5 shows the retention time for each case treated with red ginseng water extract and fractions thereof: pg; Red Ginseng Water Extract, Fr. One; Fraction of red ginseng water extract 1, Fr. 2; Fraction of red ginseng water extract 2, Fr. 3; Fraction of red ginseng water extract 3, Fr. 4; Fraction of red ginseng water extract 4, Fr. 5; Fraction of Red Ginseng Water Extract 5.

Hereinafter, the present invention will be described in detail.

1. Of Ginseng Extract Fraction  Produce

Ginseng may be selected from the group consisting of ginseng leaves, ginseng fruit, red ginseng and combinations thereof, preferably ginseng leaf, ginseng fruit and red ginseng alone. When the ginseng includes two or more raw materials, the raw materials may be mixed and extracted, and the extract obtained by extracting each raw material may be mixed, but is not limited thereto.

As used herein, the term "extract" refers to a material extracted by any method from raw materials, and is used to include all extracts, concentrates obtained therefrom, dried products of the concentrates, and powders without limitation.

The extract may be obtained by extracting from a raw material or a dried product thereof, and the raw material of the extract may be used without limitation, such as being grown or commercially available.

When extracting and extracting the extract from the raw material, all conventionally known conventional extraction methods such as solvent extraction, ultrasonic extraction, filtration and reflux extraction can be used as the extraction method, and are preferably prepared by using solvent extraction or reflux extraction. can do. The extraction process may be repeated several times, after which it may be further subjected to steps such as concentration or lyophilization. Specifically, the obtained extract may be concentrated under reduced pressure to obtain a concentrate, and the extract may be lyophilized to prepare a high concentration of extract powder using a grinder.

At least one of water and ethanol may be used as a solvent used when preparing the ginseng extract. The ethanol may be ethanol or an ethanol aqueous solution, the ethanol aqueous solution may be 40% (v / v) or more of less than 100% (v / v) ethanol aqueous solution, preferably 45% (v / v) to 90% (v / v) aqueous solution of ethanol, more preferably 50% (v / v) to 80% (v / v) aqueous solution of ethanol, still more preferably 60% (v / v). v) to 80% (v / v) may be an aqueous ethanol solution, but is not limited thereto. When the concentration of the ethanol solution is less than the lower limit, even after fractionation may reduce the effect of improving the memory of the fraction.

When the ginseng is ginseng leaves, ginseng fruit, the amount of solvent added during the extraction may be 10 to 30 times, preferably 13 to 27 times, more preferably 15 to 25 times compared to 2kg of ginseng weight, but is not limited thereto. Not.

When the ginseng is red ginseng, the amount of solvent added during extraction may be 3 to 15 times, preferably 3 to 13 times, and more preferably 3 to 10 times compared to 1 kg of ginseng weight, but is not limited thereto.

Extraction may be carried out at 60 ° C to 100 ° C, preferably at 65 ° C to 95 ° C, and more preferably at 70 ° C to 90 ° C, but is not limited thereto.

Extraction may be performed for 3 to 20 hours, preferably 3 to 16 hours, more preferably 3 to 12 hours, but is not limited thereto.

Extraction may be performed once to eight times, preferably may be carried out once to six times, more preferably may be carried out once to five times, but is not limited thereto, the extract is obtained in each extraction It may be a single extract or a mixed extract of extracts obtained in each extract, preferably a mixed extract of extracts obtained in each extract.

The method for preparing fractions of ginseng extract is as follows:

A primary fraction obtained by treating the ginseng extract with base, treating butanol, and separating the butanol layer (1) and the non-butanol layer (1), and fractionating only the butanol layer (1) to obtain a first fraction;

The non-butanol layer (1) obtained in the first fractionation step was acid treated, butanol treated and separated into a butanol layer (2) and a non-butanol layer (2), and only the butanol layer (2) was fractionated to obtain a second Secondary fraction to obtain a fraction; And

A third fraction in which the third fraction is obtained by concentrating the non-butanol layer 2 obtained in the second fractionation step.

The base used in the base treatment may be any one selected from the group consisting of calcium hydroxide (Ca (OH) ₂ ), sodium bicarbonate (NaHCO ₃ ), sodium carbonate (Na ₂ CO ₃ ), and sodium hydroxide (NaOH), Preferably sodium hydroxide (NaOH).

The solution used for the base treatment may be 0.1-20% (w / v) NaOH aqueous solution, 1-15% (w / v) NaOH aqueous solution, 1-10% (w / v) NaOH aqueous solution And, 2.5 to 7% (w / v) may be an aqueous NaOH solution, but is not limited thereto. If the aqueous NaOH solution is less than the lower limit, fractionation of ginseng extract may reduce the memory improvement effect of the fraction, and the fractionation time is longer than 24 hours. If the NaOH aqueous solution exceeds the upper limit, the worker preparing the fraction may be dangerous.

The solution used in the acid treatment may be used without limitation as long as the food having acetic acid, citric acid, lactic acid or acidity, preferably may be acetic acid.

The fraction may be selected from the group consisting of the first fraction, the second fraction, the third fraction, and combinations thereof prepared by the fractionation process consisting of the above steps, preferably each fraction alone.

The fractionation process further comprises a fourth fractionation step, the fourth fraction is acid-treated in the butanol layer (1) obtained in the first fraction, and the base treatment to terminate the reaction, butanol layer (3) ) And the non-butanol layer 3, and fractionate only the butanol layer 3 to obtain a fourth fraction.

The fractionation process further comprises a fifth fractionation step, the fifth fraction is acid-treated in the butanol layer (2) obtained from the secondary fraction, and the base is terminated the reaction, the butanol layer (4) ) And the non-butanol layer 4, and fractionate only the butanol layer 4 to obtain a fifth fraction.

The fraction may be selected from the group consisting of the first to fifth fractions and combinations thereof prepared by the fractionation process consisting of the above steps, preferably each fraction alone.

When the ginseng is ginseng leaf, and the extraction solvent is water, the fraction may be at least one of the second fraction and the third fraction, preferably the second fraction.

When the ginseng is ginseng leaves and the extraction solvent is ethanol, the fraction may be a third fraction.

When the ginseng is a ginseng fruit, the extraction solvent may be water, the fraction may be selected from the group consisting of the first fraction, the second fraction, the fourth fraction and the fifth fraction.

When the ginseng is red ginseng, the extraction solvent may be water, and the fraction may be selected from the group consisting of the first fraction, the second fraction, the fourth fraction, and the fifth fraction.

In the embodiment of the present invention, fractions of the ginseng extract obtained by the above method, for example, at least one fraction of the second fraction and the third fraction of the ginseng leaf water extract, the third fraction of the ginseng leaf ethanol extract, ginseng fruit One fraction selected from the group consisting of a first fraction, a second fraction, a fourth fraction and a fifth fraction of the water extract, a first fraction, a second fraction, a fourth fraction and a fifth fraction of the red ginseng water extract One fraction selected from was treated with scopolamine-induced memory decay animal models, respectively, and the passive avoidance test confirmed that the retention time was longer to improve memory.

The fraction may be obtained by further performing a conventional fractionation process in order to enhance the memory improving effect. For example, a fraction obtained by passing the fraction according to the present invention through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity), and the like. In addition, the active fraction obtained through various purification methods carried out additionally is included in the fraction of the present invention. Fractions in which several components are mixed may be separated according to the nature of the active ingredient through concentration gradient column chromatography to prepare a specific active fraction having a higher memory improvement effect.

The column chromatography performs column chromatography using a filler selected from the group consisting of silica gel, Sephadex, LH-20, ODS gel, RP-18, polyamide, Toyopearl and XAD resin to separate active fractions. And may be purified, and column chromatography may be performed several times by selecting an appropriate filler as necessary, but is not limited thereto. In using the chromatography, an eluting solvent, an eluting rate, and an eluting time may apply a solvent, a rate, or a time generally used in the art.

2. A pharmaceutical composition for the prophylaxis or treatment of at least one disease selected from the group consisting of learning disorders, cognitive impairments and memory impairment comprising fractions of ginseng extract

The method for preparing a fraction of ginseng extract is the same as mentioned in " 1. Preparation of fraction of ginseng extract ", and thus the description is omitted.

In the present invention, "prevention" refers to any action that inhibits or delays the onset of at least one symptom selected from the group consisting of learning disorders, cognitive impairment and memory impairment by administration of the composition, "treatment" means Any behavior that improves or beneficially changes the symptoms caused by learning disabilities, cognitive impairments, or memory impairments.

In the present invention, "learning disorder" refers to a disease having a general or higher intelligence, but having difficulty in basic learning ability due to certain factors. Students with learning disabilities have difficulty acquiring and using skills such as reading, speaking, writing, or reasoning.

As used herein, "cognitive impairment" refers to a disorder in which cognitive ability is impaired or exhibits behavioral changes, as compared to animals with normal function. Cognitive impairment refers to a disease caused by deterioration of functions such as spatial perception, judgment, executive function, and language ability.

"Memory impairment" in the present invention means short- and long-term memory impairment.

The learning disorder, cognitive impairment or memory impairment may include Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, Peak disease, Creutzfeldt-Jakob disease, depression, aging, head trauma, stroke, CNS hypoxia, brain ischemia, encephalitis, forgetfulness, traumatic Brain damage, hypoglycemia, Wernicke Korsakoff syndrome, drug addiction, epilepsy, epilepsy, hippocampal sclerosis, headache, cerebral senile disease, dementia, frontal lobe degeneration, tumor, normal brain pressure hydrocephalus, HIV, cerebrovascular disease, cerebral neuropathy, cardiovascular system Diseases, memory loss, radiation exposure, metabolic diseases, hypothyroidism, and mild cognitive impairment learning, cognitive impairment or memory impairment, but is not limited thereto.

 The pharmaceutical composition of the present invention, in addition to the fraction of the ginseng extract, within the range that does not impair the desired effect of the present invention, preferably add other ingredients and the like that can give a synergistic effect to the effect of the fraction of the ginseng extract It may contain. For example, conventional adjuvants such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavorings, or carriers.

Routes of administration of the pharmaceutical compositions include oral, intravenous, intramuscular, intraarterial, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, sublingual or rectal, for example topical application by application. Can be applied in a manner. The parenteral includes subcutaneous, intradermal, intravenous, intramuscular, intralesional injection or infusion techniques.

The pharmaceutical composition of the present invention may be administered in a pharmaceutically effective amount.

In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level may be the type of subject and severity, age, sex, type of disease, It can be determined according to the activity of the drug, sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of treatment, factors including the concurrent drug and other factors well known in the medical field. The compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents and may be administered sequentially or simultaneously with conventional therapeutic agents. And single or multiple administrations. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, and can be easily determined by those skilled in the art.

The pharmaceutical composition of the present invention is not particularly limited as long as it is an individual for the purpose of improving learning disorders, cognitive impairment, and memory impairment, and any one can be applied. For example, it can be used for any of non-human animals such as monkeys, dogs, cats, rabbits, morphotes, rats, mice, cattle, sheep, pigs, goats, and the like, humans, birds and fish.

The pharmaceutical composition may further contain at least one active ingredient having the same or similar function in addition to the fraction of the ginseng extract. The composition may be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, oral formulations, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods.

Solid form preparations for oral administration include powders, granules, tablets, capsules, soft capsules, pills and the like. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups. In addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. have. Formulations for parenteral administration include powders, granules, tablets, capsules, sterile aqueous solutions, solutions, non-aqueous solutions, suspensions, emulsions, syrups, suppositories, aerosols, etc. It may be used in the form of a formulation, and preferably, an external skin pharmaceutical composition of cream, gel, patch, spray, ointment, warning agent, lotion agent, linen agent, pasta agent or cataplasma agent may be prepared and used. It is not limited to this. 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. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The composition may further contain preservatives, stabilizers, emulsifiers or emulsifiers, auxiliaries such as salts and / or buffers for the control of osmotic pressure, and other therapeutically valuable substances and may be mixed, granulated or It may be formulated according to the coating method.

The dosage of the pharmaceutical composition can vary depending on several factors, including the age, body weight, general health, sex, time of administration, route of administration, rate of release, drug combination and severity of the particular disease of the individual. In addition, the pharmaceutical compositions of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers. In addition, the pharmaceutical composition may be administered at a dosage within the range of 0.001 to 200 mg / kg on an adult basis, when the pharmaceutical composition is an external preparation once to 5 times a day in an amount of 1.0 to 3.0 ml on an adult basis Although it is preferable to continue application | coating for 1 month or more, the said dosage does not limit the scope of the present invention.

When the pharmaceutical composition is formulated in unit dose form, the active ingredient fraction of the ginseng extract of the present invention is preferably contained in a unit dose of about (0.01 to 1,500) mg, the dosage required for the treatment of an adult is administered Depending on the frequency and intensity of the range of about (1 to 500) mg per day is moderate, but not limited to, a higher daily dosage may be desirable for some patients.

The pharmaceutical composition composition may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers.

3. Health food composition for improving at least one disease selected from the group consisting of learning disorders, cognitive impairment and memory impairment comprising a fraction of ginseng extract

The method for preparing a fraction of ginseng extract is the same as mentioned in " 1. Preparation of fraction of ginseng extract ", and thus the description is omitted.

The fraction of the ginseng extract is preferably contained in an amount of 0.005 to 20.0% by weight based on the total weight of the health functional food, more preferably in an amount of 0.01 to 10.0% by weight, but is not limited thereto. When the effective content of the fraction of the ginseng extract is less than 0.005% by weight, symptoms such as learning disabilities, cognitive impairment and memory impairment cannot be alleviated. When the content of the fraction of the ginseng extract exceeds 20% by weight, the effect of increasing the content decreases markedly. It is uneconomical.

The health functional food, in addition to the fraction of the ginseng extract of the present invention within the range that does not impair the effect of the present invention, preferably add other ingredients and the like that can give a synergistic effect to the effect of the fraction of the ginseng extract It may contain. For example, conventional adjuvants such as stabilizers, solubilizers, vitamins, pigments and flavorings, or carriers.

It may also include ingredients conventionally added in the manufacture of foods, including, for example, proteins, carbohydrates, fats, nutrients, seasonings and flavoring agents. Examples of such carbohydrates are monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol. As the flavoring agent, natural flavoring agent taumartin, stevia extract and synthetic flavoring agent may be used. For example, when the health functional food of the present invention is prepared with a drink, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, natural extracts and the like may be further included in addition to the fraction of the ginseng extract of the present invention.

There is no particular limitation on the type of dietary supplement. Examples of the food to which the fraction of the ginseng extract of the present invention can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice products including ice cream, various soups, drinks , Teas, drinks, alcoholic beverages and vitamin complexes and the like, and include all dietary supplements in the conventional sense.

Hereinafter, the present invention will be described in detail by production examples and examples.

However, the following Preparation Examples, Experimental Examples, and Examples are only for illustrating the present invention, and the content of the present invention is not limited to the following Preparation Examples and Examples.

Preparation Example 1 Preparation of Ginseng Leaf Extract

<1-1> Preparation of Ginseng Leaf Water Extract

20 g of distilled water was added to 2,000 g of dried ginseng leaves (P. ginseng C.A. Meyer, Yeoju, Gyeonggi-do), and the extract was first extracted at 85 ° C. for 6 hours, and the extract was filtered and cooled to 10 ° C. For the residue, 20 times of distilled water was added, and the second extraction was further performed for 6 hours, and the extracts were all filtered and then cooled to 10 ° C. The cooled extract was centrifuged at 6,000 rpm for 15 minutes at 4 ° C (Hanil Simed Co., Ltd., Supra 22K) to remove precipitates, and 60 ° C at 55 ° C using a rotary pressure reducer (BUCHI, R-220). Concentrated to Brix. Finally, sterilized distilled water was added to the concentrate, diluted to 15 ° Brix, and then lyophilized (OPERON, FDT-12012) to obtain 680 g of a concentrate powder of ginseng leaf water extract.

<1-2> Preparation of Ginseng Leaf Ethanol Extract

610 g of a concentrate powder of ginseng leaf ethanol extract was obtained in the same manner as in Production Example 1-1, except that 70% (v / v) ethanol aqueous solution was used as the extraction solvent.

Summary of Production Examples 1-1 and 1-2

The ginseng leaf water extract of Preparation Example 1-1 and the ginseng leaf ethanol extract of Preparation Example 1-2 were prepared by using ginseng leaf as an extraction solvent and water and ethanol aqueous solution. Shown in

Raw materials Water extract Ethanol extract Production amount (g) Manufacture yield (%) Production amount (g) Manufacture yield (%) Ginseng leaf 680 34.0 610 30.5

Preparation Example 2 Preparation of Ginseng Fruit Water Extract

1020 g (yield: 51.0%) of ginseng fruit concentrate was prepared in the same manner as in Preparation Example 1-1, except that dried ginseng fruit ( P. ginseng CA Meyer, Yeoju , Gyeonggi-do) was used as a raw material.

Preparation Example 3 Preparation of Red Ginseng Water Extract

1,000 g of six-year-old red ginseng ( P. ginseng CA Meyer, 75%, 35% US) was dried and then sliced at 110 ° C for 17 minutes using a far-infrared dryer (HKD-LAB). Six times distilled water was added to the dried red ginseng, and the extract was first extracted at 85 ° C. for 12 hours, and the extract was filtered and cooled to 10 ° C. For the residue, 6 times distilled water was added, extraction was carried out for 1 to 4 times for 12 hours, and the extracts were filtered and combined and cooled to 10 ° C. The cooled extract was centrifuged at 5,000 to 8,000 rpm for 10 to 20 minutes at 4 ° C (Hanil Cymed Co., Ltd., Supra 22K) to remove sediment, and using a rotary pressure reducer (BUCHI, R-220). Concentrated at 71 ° C. to Brix. Finally, sterilized distilled water was added to the concentrate, diluted to 15 ° Brix, and lyophilized (OPERON, FDT-12012) to prepare 460 g of red ginseng concentrate powder.

Preparation Example 4 Fraction of Ginseng Leaf Extract

The ginseng leaf water extract, ginseng leaf ethanol extract, ginseng fruit water extract, and red ginseng water extract obtained in Preparation Example 1, Preparation Example 2, and Preparation Example 3 were respectively fractionated. The fractions were carried out five times, and the fractions obtained from each fraction were named fraction 1, fraction 2, fraction 3, fraction 4, and fraction 5, respectively.

Fraction 1 was fractionated and the remaining layer was used for fraction 2 preparation, fraction 2 was fractionated and the remaining layer was used for fraction 3 preparation. Fraction 4 is an acid treated fraction 1 and fractionated with butanol, and fraction 5 is an acid treated fraction 2 and fractionated with butanol. Sample names of each extract or fraction are shown in Table 2 below.

For the fraction, base solution (5% NaOH), butanol, and acid solution (99.7% acetic acid) were used. The approximate process of each fraction is shown below (see FIG. 1):

First fraction: The extract was treated with a base solution, butanol was added, and the layers were separated to obtain only butanol layer.

Second fraction: After neutralization by treating the acid solution to the base solution-treated layer except the butanol layer in the first fraction, adding butanol, and then separating the layers to obtain only butanol layer to prepare fraction 2.

Third Fraction: A fraction 3 was obtained by obtaining only a water layer except a butanol layer in a second fraction.

Fourth Fraction: After the acid treatment of fraction 1, the reaction was terminated by base treatment, butanol treatment, and only butanol layer was obtained to prepare fraction 4.

Fifth Fraction: After the acid treatment of fraction 2, the reaction was terminated by base treatment, butanol treatment, and only butanol layer was obtained to prepare fraction 5.

Fraction type Name of sample obtained by fraction Ginseng Leaf Water Extract Ginseng Leaf Water Extract First Fraction Fraction 1-1 Ginseng Leaf Water Extract Secondary Fraction Fraction 2-1 Ginseng Leaf Water Extract Third Fraction Fraction 3-1 Ginseng Leaf Ethanol Extract First Fraction of Ethanol Extract of Ginseng Leaf Fraction 1-2 Ginseng Leaf Ethanol Extract Secondary Fraction Fraction 2-2 Ginseng Leaf Ethanol Extract Third Fraction Fraction 3-2 Ginseng Berry Water Extract Ginseng Berry Water Extract First Fraction Fraction 1-3 Ginseng Berry Water Extract Secondary Fraction Fraction 2-3 Ginseng Berry Water Extract Third Fraction Fraction 3-3 Ginseng Berry Water Extract 4th Fraction Fraction 4-3 Ginseng Berry Water Extract 5th Fraction Fraction 5-3 Red ginseng water extract Red ginseng water extract primary fraction Fraction 1-4 Red Ginseng Water Extract Second Fraction Fraction 2-4 Red Ginseng Water Extract Third Fraction Fraction 3-4 4th fraction of red ginseng water extract Fraction 4-4 5th fraction of red ginseng water extract Fraction 5-4

<3-1> Fraction  1, manufacture

The ginseng leaf water extract, ginseng leaf ethanol extract, ginseng fruit water extract and red ginseng water extract obtained in Preparation Example 1, Preparation Example 2 and Preparation Example 3 were used as raw materials, and 200 g of 5% aqueous solution of 5% NaOH (99%, Merck) was used. After dissolving in 5 n of n-BuOH (99.0%, gold), the mixture was stirred at 200 rpm for 3 hours and then left for 1 hour. The layers were separated and the BuOH fraction was concentrated using a rotary pressure reducer (BUCHI, R-220), and then freeze-dried with FDT-12012 (Operon) to prepare a concentrate powder of fraction 1. Table 3 shows the amount and yield of fraction 1 prepared.

Leaf (water)
(Fraction 1-1) Leaf (70% spirit)
(Fragment 1-2) Fruit (water)
(Fraction 1-3) Red ginseng (water)
(Fraction 1-4) Production amount (g) 22.1 41.2 14.1 2.0 Manufacture yield (%) 11.1 20.6 7.1 1.0

<3-2> Preparation of Fraction 2

To prepare fraction 1, 350 ml of acetic acid (99.7%, Daejeon gold) was neutralized by adding 5% NaOH fraction separated (butanol fraction after butanol addition in Preparation Example 3-1) to neutralize BuOH 5L. Stirred at 200 rpm for 1 hour. When the layers were separated, the BuOH layer was concentrated using a rotary pressure reducer (BUCHI, R-220), and then freeze-dried with FDT-12012 (Operon) to prepare a concentrate powder of fraction 2. Table 4 shows the production amount and production yield of fraction 2.

Leaf (water)
(Fraction 2-1) Leaf (70% spirit)
(Fraction 2-2) Fruit (water)
(Fraction 2-3) Red ginseng (water)
(Fraction 2-4) Production amount (g) 22.3 33.8 26.0 3.2 Manufacture yield (%) 11.2 16.9 13.0 1.6

<3-3> Preparation of Fraction 3

When preparing the fraction 2, the water-separated layer (the remaining part of the butanol fraction obtained after the addition of butanol in Preparation Example 3-2) was concentrated using a rotary pressure reducer (BUCHI, R-220), followed by FDT-12012 (Operon). It was freeze-dried to prepare a concentrate powder of fraction 3. Table 5 shows the production amount and production yield of fraction 3.

Leaf (water)
(Fraction 3-1) Leaf (70% spirit)
(Fraction 3-2) Fruit (water)
(Fraction 3-3) Red ginseng (water)
(Fraction 3-4) Production amount (g) 79.6 71.4 125.0 154.0 Manufacture yield (%) 39.8 35.7 62.5 77.0

<3-4> Preparation of Fraction 4

10 g of fractions 1-3 (fraction 1 of ginseng fruit water extract) or 10 g of fractions 1-4 (fraction 1 of red ginseng water extract) were used as raw materials. Each raw material was dissolved in 200 ml 1% acetic acid aqueous solution (99.7%, large purified gold) and then hydrolyzed by reflux for 5 hours. After 5 hours, 1 ml of saturated aqueous NaOH solution (99%, Merck) was added to terminate the reaction, and 200 ml of BuOH was added thereto, followed by stirring and layer separation. The BuOH layer was concentrated and freeze-dried to prepare a concentrate powder of fraction 4. Table 6 shows the preparation amount and the production yield of fraction 4.

Fruit (water)
(Fraction 4-3) Red ginseng (water)
(Fraction 4-4) Production amount (g) 9.1 9.3 Manufacture yield (%) 91 93

<3-5> Preparation of Fraction 5

Except for using 10g of fraction 2-3 (fraction 2 of ginseng fruit water extract), or 10g of fraction 2-4 (fraction 2 of red ginseng water extract) as raw materials, A concentrate powder of fraction 5 was prepared. Table 7 shows the preparation amount and the production yield of fraction 5.

Fruit (water)
(Fraction 5-3) Red ginseng (water)
(Fraction 5-4) Production amount (g) 9.1 9.2 Manufacture yield (%) 91 92

<Example 1> Check the effect of improving the memory of the ginseng-derived extract or fraction

<1-1> Composition of Experimental Group

Male C57BL / 6N mice weighing 20-23 g at 6 weeks of age were supplied from Orient Bio Co., Ltd. (Seoul, Korea) and used for 7 days. The water and feed were freely consumed, and the temperature (23 ± 2 ℃) and humidity ( 55 ± 10%) and contrast period (12 hours) were automatically adjusted. Mice used for the test were separated from each of the six groups used for the experiment.

First, the normal group, the negative control group was dissolved in distilled water, the experimental group was dissolved in distilled water at a dose of 5mg / kg or 10mg / kg in ginseng-derived extracts or fractions for 7 days orally. In the negative / positive control group and the experimental group, except for the normal group, scopolamine (Scopolamine hydrobromide, S0929, Sigma. USA) was administered intraperitoneally on the day of the study trial by dissolving 1 mg / kg in physiological saline. In the positive control group, acetylcholinesterase inhibitor Aricept (Donepezil hydrochloride monohydrate, D6821, Sigma. USA) was dissolved in distilled water at a dose of 5 mg / kg and administered once orally on the same day.

<1-2> scopolamine memory improvement experiment

For each extract or fraction prepared in Preparation Example 1, the scopolamine-induced memory loss animal model showed the effects of improvement in learning disability, cognitive impairment, memory improvement through passive avoidance test. In order to confirm, the method described in the existing literature was applied and experimented as follows (Park SJ et al., Eur J Pharmacol., 2012, 676, 64-70).

Manual evasion tests on scopolamine-induced memory loss models were performed using the Modular shuttle box (MED associates inc., USA) as follows. Seven days after receiving the mouse of Example 1-1, each extract or fraction prepared in Preparation Example 1 was administered 7 times at a concentration of 5 mg / kg or 10 mg / kg once a day for 7 days each. On the seventh day of administration, scopolamine was administered to conduct a learning experiment and a passive avoidance test.

<1-2-1> Aquisition trial

30 minutes after oral administration of distilled water, positive control, extract or fraction, scopolamine at a dose of 1 mg / kg, 30 minutes after scopolamine administration The guillotin door then opened to allow access to the dark compartment. Mice that did not enter the dark side within 20 seconds after the guillotine door were opened were excluded from the experiment. After the guillotine door was opened, the time until the mouse entered the dark side was measured. When the mouse enters the dark side, the guillotine door closes and a 0.5 mA electric shock flows through the bottom of the grid for 5 seconds, and the mouse remembers this electrical stimulus.

<1-2-2> Retention trial

The experiment was conducted 24 hours after the study test. After 30 seconds of search time, the time required for the guillotine door to open and all four feet to enter the dark side (latency time) was measured up to 300 seconds. The longer the retention time, the better the learning ability and memory of passive avoidance (mean ± S.E.M.). Differences in retention time in the learning test and retention time in the passive avoidance test are shown in FIGS.

Experimental Example 1 Memory Improvement Effect of Ginseng Leaf-derived Extract and Its Fractions

In Example 1, the ginseng leaf water extract or the fraction fractionated therefrom was used as an experimental group to confirm the memory improving effect. Figure 2 shows the retention time when the ginseng leaf water extract of Preparation Example 1-1 and fraction 1-1, fraction 2-1, and fraction 3-1 obtained therefrom, respectively. Figure 3 shows the retention time when the ginseng leaf ethanol extract of Preparation Example 1-2 and fractions 1-2, fractions 2-2, and fractions 3-2 respectively treated therefrom. In Table 8, when the retention time of the ginseng leaf water extract and the ginseng leaf ethanol extract were treated as 100%, the retention time of the fractions obtained from each extract was expressed as a ratio. The percentage of retention time shows the degree of increase in efficacy of the fraction compared to the extract.

division Oral Dose (mg / kg) Retention time (s) Latency Rate (%) Water extraction Ginseng Leaf Water Extract 10 79.9 ± 11.9 (p <0.01) 100 Fraction 1
(Fraction 1-1) 10 45.2 ± 9.6 56.5 Fraction 2
(Fraction 2-1) 10 109.7 ± 19.1 (p <0.001) 137.2 Fraction 3
(Fraction 3-1) 10 92.4 ± 12.0 (p <0.05) 115.6 Ethanol Extract Ginseng Leaf Ethanol Extract 10 97.7 ± 22.2 (p <0.01) 100 Fraction 1
(Fragment 1-2) 10 83.3 ± 28.6 (p <0.05) 85.3 Fraction 2
(Fraction 2-2) 10 79.8 ± 23.0 (p <0.05) 81.6 Fraction 3
(Fraction 3-2) 10 129.5 ± 38.6 (p <0.001) 132.6

As can be seen from Table 8, fraction 2-1 and fraction 3-1 derived from the ginseng leaf water extract exceeded 100% on the basis of the extract, and in particular, fraction 2-1 had the longest retention time to improve memory. The effect was found to be excellent. On the other hand, when ginseng leaf ethanol extract is used as a raw material, fraction 3-2 derived from ginseng leaf ethanol extract has a long retention time of more than 100% based on the ginseng leaf ethanol extract, and thus has an excellent memory improvement effect. .

Ginseng leaf water extracts and fractions showed a short retention time of 20 seconds in all groups in the learning test, and as shown in FIG. 2, in the passive avoidance test, memory decay was induced with scopolamine and only the negative control group administered with distilled water. All groups were found to have a longer retention time. Among the fractions 1-1, 2-1, and 3-1 obtained from the ginseng leaf water extract of Preparation Example 1-1, fraction 2-1 had the longest retention time compared to the other fractions. .

Ginseng leaf ethanol extract and fractions showed a short retention time of 20 seconds in all groups in the learning test, and as shown in Figure 3, the passive avoidance test induced memory loss with scopolamine and the mice in the negative control group administered only distilled water. All groups were found to have a longer retention time. Among fractions 1-2, 2-2, and 3-2 obtained from the ginseng leaf ethanol extract of Preparation Example 1-2, fraction 3-2 had the longest retention time compared to the other fractions, indicating an excellent memory improvement effect. .

From the above results, even if ginseng leaves as a raw material, it can be seen that the memory improvement effect is remarkably different according to the fractionation method, and the fractions having better memory improvement effect than the extract can be obtained by changing the fractional conditions during fractionation. For example, among the fractions of the ginseng leaf water extract, the fractionation condition is a base treatment and a butanol treatment sequentially to the ginseng leaf water extract (primary fraction), and then the acid treatment to the base-treated extract except the butanol layer (1). The butanol layer 2 (fraction 2) and the non-butanol layer 2 (fraction 3) obtained by (second fraction) were excellent in memory improvement effect, and the butanol layer (2) had the highest effect.

In addition, according to the extraction conditions, it was found that the fractions having a high memory improvement effect can be obtained by changing the fraction conditions. For example, in the case of ginseng leaf ethanol extract, unlike the ginseng leaf water extract, the non-butanol layer 2 (fraction 3) had a better memory effect than the butanol layer 2 (fraction 2).

Experimental Example 2 Memory Improvement Effect of Ginseng Berry Water Extract and Its Fractions

As an experimental group in Example 1, the effect of improving memory was confirmed by using ginseng fruit water extract or fractions fractionated therefrom. Figure 4 shows the ginseng fruit water extract of Preparation Example 2 and the retention time when the fractions 1-3, fraction 2-3, fraction 3-3, fraction 4-3, fraction 5-3, respectively, which are fractionated therefrom. . Table 9 shows the retention times of the fractions obtained from each extract based on the retention time when the ginseng fruit water extract was treated as 100%.

division Oral Dose (mg / kg) Retention time (s) Latency Rate (%) Ginseng Berry (water) 5 73.8 ± 20.0 (p <0.05) 100 Fraction 1
(Fraction 1-3) 5 89.8 ± 36.3 (p <0.05) 121.6 Fraction 2
(Fraction 2-3) 5 114.2 ± 32.7 (p <0.05) 154.7 Fraction 3
(Fraction 3-3) 5 42.8 ± 11.1 (p <0.05) 57.9 Fraction 4
(Fraction 4-3) 5 82.4 ± 34.0 (p <0.05) 111.7 Fraction 5
(Fraction 5-3) 5 100.7 ± 19.1 (p <0.001) 136.5

As can be seen from Table 9, fraction 1-3, fraction 2-3, fraction 4-3 and fraction 5-3 of the ginseng fruit water extract exceeded 100% of the retention time based on the extract, especially fraction 2-3. In the case of, the retention time was the longest and the memory improvement effect was excellent.

Ginseng fruit water extracts and fractions showed a short retention time of 20 seconds in all groups in the learning test, and as shown in FIG. 4, in the passive avoidance test, memory decay was induced with scopolamine and only the negative control group administered with distilled water. All groups were found to have a longer retention time. Among the fractions 1-3, 2-3, 3-3, 4-3, 5-3 obtained using the ginseng fruit water extract of Preparation Example 3, the fractions 1-3, 2-3, 4-3, 5-3 Compared with these other fractions, the retention time was the longest and the memory improvement effect was excellent (FIG. 4).

From the above results, even if it is derived from the same ginseng, it can be seen that the fractions having a high memory improvement effect can be obtained by different fractionation method for each site. In Experimental Example 1, when preparing a fraction from the ginseng leaf water extract, after the base treatment and butanol treatment were sequentially performed on the ginseng leaf water extract (first fraction), the non-butanol layer except for the butanol layer (1) (1) The butanol layer (2) and the non-butanol layer (2) (fraction 3) obtained by acid treatment (second fraction) were excellent in memory improvement effect, butanol layer (2) (fraction 2) had the highest effect. However, in the case of the ginseng fruit water extract obtained by using ginseng fruit as a raw material, the butanol layer (1) and butanol layer (2) were excellent in memory improvement effect, and the butanol layer was different from when ginseng leaves were used as a raw material. (1) (Fragment 1) and butanol layer 2 (fraction 2) were each treated with an acid, followed by base treatment to terminate the reaction, butanol layer 3 (fraction 4) obtained by butanol treatment, and butanol layer 4 (fractions) 5) This memory improvement effect was excellent. Therefore, in order to prepare a fraction having a high memory improvement effect using the raw material derived from ginseng, it was found that the appropriate fraction conditions for each raw material should be applied.

Experimental Example 3 Memory Improvement Effect of Red Ginseng Water Extract and Its Fractions

In Example 1, the red ginseng water extract or the fractions fractionated therefrom as the experimental group was used to confirm the memory improving effect. Figure 5 shows the red ginseng water extract of Preparation Example 3 and the retention time when the fractions 1-4, fractions 2-4, fractions 3-4, fractions 4-4, and fractions 5-4, respectively, fractionated therefrom. Table 10 shows the retention time of the fractions obtained from each extract based on the retention time when the red ginseng water extract was treated as 100%.

division Oral Dose (mg / kg) Retention time (s) Latency Rate (%) Red ginseng (water) 10 51.3 ± 18.4 100 Fraction 1
(Fraction 1-4) 10 69.6 ± 23.3 (p <0.01) 135.56 Fraction 2
(Fraction 2-4) 10 79.9 ± 8.3 (p <0.05) 155.81 Fraction 3
(Fraction 3-4) 10 46.7 ± 15.7 (p <0.01) 90.98 Fraction 4
(Fraction 4-4) 10 106.7 ± 14.6 (p <0.001) 208.02 Fraction 5
(Fraction 5-4) 10 115.4 ± 21.9 (p <0.01) 224.92

As can be seen from Table 10, fraction 1-4, fraction 2-4, fraction 4-4, and fraction 5-4 derived from red ginseng water extracts had a retention time of more than 100%, and the retention time was the longest. The improvement effect was found to be excellent. Red ginseng water extracts and fractions showed a short retention time of 20 seconds in all groups in the study test, and in all groups except the negative control group induced memory loss with scopolamine and manual distilled water in the manual avoidance test. The residence time was confirmed to be longer.

From the above results, even if it is derived from the same ginseng, it can be seen that the fractions having a high memory improvement effect can be obtained by different fractionation method for each site. In Experimental Example 1, when preparing a fraction from the ginseng leaf water extract, after the base treatment and butanol treatment were sequentially performed on the ginseng leaf water extract (first fraction), the non-butanol layer except for the butanol layer (1) (1) The butanol layer (2) (fraction 2) obtained by acid treatment (second fraction) and the non-butanol layer (2) (fraction 3) had an excellent memory effect, and the butanol layer (2) (fraction 2) was the most effective. The effect was high. However, in the case of the red ginseng water extract obtained using red ginseng as a raw material, the butanol layer (1) (fraction 1) and the butanol layer (2) (fraction 2) have a memory improvement effect differently from the case where the ginseng leaf is used as a raw material. Butanol layer (3) (fraction 4) and butanol layer (4) (fraction 5) obtained by treating the butanol layer (1) and the butanol layer (2) with acid treatment, followed by base treatment to terminate the reaction, and butanol treatment, respectively. This memory improvement effect was excellent. Therefore, in order to prepare a fraction having a high memory improvement effect using the raw material derived from ginseng, it was found that the appropriate fraction conditions for each raw material should be applied.

Preparation Example 5 Preparation of Pharmaceutical Formulation

<5-1> Preparation of powder

Fraction of ginseng extract of the present invention 2 g

1 g lactose

The above ingredients were mixed and filled in airtight cloth to prepare a powder.

<5-2> Preparation of Tablet

100 mg fraction of ginseng extract of the present invention

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.

<5-3> Preparation of Capsule

100 mg fraction of ginseng extract of the present invention

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.

<5-4> Preparation of the ring

Fraction of ginseng extract of the present invention 1 g

Lactose 1.5 g

1 g of glycerin

Xylitol 0.5 g

After mixing the above components, it was prepared to be 4g per ring in a conventional manner.

<5-5> Preparation of Granules

150 mg fraction of ginseng extract of the present invention

Soy extract 50 mg

Glucose 200 mg

Starch 600 mg

After mixing the above components, 100 mg of 30% ethanol was added and dried at 60 ° C. to form granules, which were then filled into fabrics.

Preparation Example 6 Preparation of Health Food

<6-1> Preparation of Flour Food

0.5 to 5.0 parts by weight of a fraction of the ginseng extract of the present invention was added to the flour, and bread, cake, cookies, crackers and noodles were prepared using this mixture.

<6-2> Preparation of Soups and Gravys

0.1 to 5.0 parts by weight of the fraction of the ginseng extract of the present invention was added to soups and gravy to prepare meat products for health promotion, soups and noodles of noodles.

<6-3> Preparation of Ground Beef

10 parts by weight of the fraction of the ginseng extract of the present invention was added to the ground beef to prepare a ground beef for health promotion.

<6-4> Production of Dairy Products

5 to 10 parts by weight of a fraction of the ginseng extract of the present invention was added to milk, and various milk products such as butter and ice cream were prepared using the milk.

<6-5> Preparation of Wire

Brown rice, barley, glutinous rice, and yulmu were alphad by a known method, and then dried and roasted to prepare a powder having a particle size of 60 mesh.

Black beans, black sesame seeds, and perilla were also steamed and dried in a known manner, and then roasted to prepare a powder having a particle size of 60 mesh.

Fractions of the ginseng extract of the present invention was concentrated under reduced pressure in a vacuum concentrator, dried by spraying, drying with a hot air dryer, and ground to a particle size of 60 mesh using a grinder to obtain a dry powder.

The grains, seeds, and fractions of the ginseng extract of the present invention prepared above were formulated in the following ratio.

Cereals (30 parts by weight brown rice, 15 parts by weight of barley, 20 parts by weight of barley), seeds (7 parts by weight perilla, 8 parts by weight of black soybeans, 7 parts by weight of black sesame), fractions of the ginseng extract of the present invention (3 parts by weight) , Ganoderma lucidum (0.5 parts by weight), Sulfur (0.5 parts by weight)

Preparation Example 7 Preparation of Drinks

<7-1> Preparation of health drink

Instant sterilization by homogeneously mixing 5 g of the ginseng extract of the present invention with subsidiary materials such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%) and water (75%). After it was prepared by packaging in a small packaging container such as glass bottles, plastic bottles.

<7-2> Preparation of vegetable juice

5 g of a fraction of the ginseng extract of the present invention was added to 1,000 ml of tomato or carrot juice to prepare vegetable juice.

<7-3> Preparation of Fruit Juice

1 g of a fraction of the ginseng extract of the present invention was added to 1,000 ml of apple or grape juice to prepare a fruit juice.

Claims (12)

A pharmaceutical composition for preventing or treating at least one disease selected from the group consisting of a learning disorder, a cognitive disorder and a memory impairment, comprising a fraction of a ginseng extract,
The solvent used to prepare the ginseng extract is at least one of water and ethanol,
The fraction is selected from the group consisting of a first fraction, a second fraction, a third fraction and combinations thereof prepared by a fractionation process consisting of the following steps:
A primary fraction obtained by treating the ginseng extract with base, treating butanol, and separating the butanol layer (1) and the non-butanol layer (1), and fractionating only the butanol layer (1) to obtain a first fraction;
The non-butanol layer (1) obtained in the first fractionation step was acid treated, butanol treated and separated into a butanol layer (2) and a non-butanol layer (2), and only the butanol layer (2) was fractionated to obtain a second treatment. Secondary fraction to obtain a fraction; And
A third fraction in which the third fraction is obtained by concentrating the non-butanol layer 2 obtained in the second fractionation step.
The method according to claim 1,
The fractionation process further comprises a fourth fractionation step,
The fourth fraction is acid-treated in the butanol layer (1) obtained from the first fraction, and the base is terminated by the acid treatment. After the butanol treatment, the fourth fraction is separated into a butanol layer (3) and a non-butanol layer (3). Fraction only layer (3) to obtain a fourth fraction.
The method according to claim 1,
The fractionation process further comprises a fifth fractionation step,
The fifth fraction is acid-treated in the butanol layer (2) obtained from the second fraction, and the base is terminated by the acid treatment. After the butanol treatment, the fifth fraction is separated into a butanol layer (4) and a non-butanol layer (4). Fraction only layer (4) to obtain a fifth fraction.
The method according to claim 1,
The ginseng is selected from the group consisting of ginseng leaves, ginseng fruit, red ginseng and combinations thereof.
The method according to claim 1,
When the ginseng is ginseng leaf and the extraction solvent is water, the fraction is at least one of the second fraction and the third fraction.
The method according to claim 1,
When the ginseng is ginseng leaf, and the extraction solvent is ethanol, the fraction is a third fraction.
The method according to any one of claims 1 to 3,
When the ginseng is a ginseng fruit, the fraction is selected from the group consisting of the first fraction, the second fraction, the fourth fraction, the fifth fraction and combinations thereof.
The method according to any one of claims 1 to 3,
When the ginseng is red ginseng fraction is selected from the group consisting of the first fraction, the second fraction, the fourth fraction, the fifth fraction and combinations thereof.
The method according to claim 1,
The ethanol is a composition of ethanol or an aqueous solution of ethanol of less than 40% (v / v) ~ 100% (v / v).
The method according to claim 1,
The solution used in the base treatment is 0.1-20% (v / v) NaOH aqueous solution composition.
The method according to claim 1,
The diseases include Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, Peak disease, Creutzfeldt-Jakob disease, depression, aging, head trauma, stroke, CNS hypoxia, cerebral ischemia, encephalitis, forgetfulness, traumatic brain injury, hypoglycemia, Wernicke Korsakoff syndrome, drug addiction, epilepsy, epilepsy, hippocampus, headache, cerebral senile disease, dementia, frontal lobe degeneration, tumor, normal brain pressure hydrocephalus, HIV, cerebrovascular disease, cerebral nerve disease, cardiovascular disease, memory loss, radiation exposure At least one pharmaceutical composition selected from the group consisting of metabolic disorders, hypothyroidism, and learning disorders due to mild cognitive impairment, cognitive impairment and memory impairment.
As a health food composition for improving at least one disease selected from the group consisting of learning disorders, cognitive impairment and memory impairment comprising a fraction of ginseng extract,
The solvent used to prepare the ginseng extract is at least one of water and ethanol,
The fraction is selected from the group consisting of a first fraction, a second fraction, a third fraction and combinations thereof prepared by a fractionation process consisting of the following steps:
A primary fraction obtained by treating the ginseng extract with base, treating butanol, and separating the butanol layer (1) and the non-butanol layer (1), and fractionating only the butanol layer (1) to obtain a first fraction;
The non-butanol layer (1) obtained in the first fractionation step was acid treated, butanol treated and separated into a butanol layer (2) and a non-butanol layer (2), and only the butanol layer (2) was fractionated to obtain a second treatment. Secondary fraction to obtain a fraction; And
A third fraction in which the third fraction is obtained by concentrating the non-butanol layer 2 obtained in the second fractionation step.

Images