KR100838253B1 - Composition for enhancing learning or memory comprising loganin or its salt - Google Patents

Abstract

A pharmaceutical composition or a food composition comprising loganin(7-hydroxy-6-desoxyverbenalin) or a salt thereof is provided to prevent or treat learning disorder or memory and enhance learning or memory. A pharmaceutical composition for preventing and treating difficulty of learning or memory disorder, or enhancing the memory comprises loganin or a salt thereof and a pharmaceutically acceptable carrier. The loganin or the salt thereof is used as a food composition for enhancing the learning or the memory.

Description

Composition for enhancing learning or memory comprising loganin or its salt}

1 shows the inhibitory effect of loganan on scopolamine-induced forgetfulness in mice.

Figure 2 shows the effect of improving the learning and memory by Loganin in the mouse.

The present invention relates to a pharmaceutical composition for preventing or treating learning disorders or memory disorders or a pharmaceutical composition for improving learning or memory, comprising logannin or a salt thereof and a pharmaceutically acceptable carrier. The present invention also relates to a food composition for preventing or treating learning disorders or memory disorders or a food composition for improving learning or memory, comprising logannin or a salt thereof as an active ingredient.

Memory refers to the process of acquiring new information, learned experiences, and knowledge from the environment, encoding it in specific parts of the brain, storing it, and recalling it (William F Ganong; Ganong's Physiology, Seoul, Hanwoori, p289, p291-). 292, 1999). The process of memory is divided into several stages: acquisition, encoding, reinforcement, maintenance, and recall.

Modern society is a complex and specialized trend, and accordingly, a large amount of information and learning amount is required, and therefore effective brain activity is required. In addition, many people suffer from memory loss due to aging and disease, and high mental activity is required as the life span of human beings is extended. In order to cope with this situation, various efforts have been made to clear the brain, improve memory, and require mental activities, and the development of medicines, functional foods, etc. that can effectively promote these functions is required in the art. It is becoming.

Korean Patent Publication No. 10-2007-0015372 discloses 6-amino-5-cyano-pyrimidin-4-one derivatives useful for the prevention and / or treatment of impairment of cognition, concentration, learning and / or memory. I've done it.

The present inventors conducted various searches for compounds derived from natural products that have secured safety that can enhance learning ability and / or memory. As a result, it was found that the glycan, a glycoside known to be contained in Cornus, Homica and the like, has an excellent learning ability and / or memory enhancement effect.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating learning disorders or memory disorders or a pharmaceutical composition for improving learning or memory, comprising logannin or a salt thereof and a pharmaceutically acceptable carrier.

In addition, an object of the present invention is to provide a food composition for preventing or treating learning disorders or memory disorders or a food composition for learning or memory enhancement, comprising a lignin or a salt thereof as an active ingredient.

According to one aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating learning disorders or memory disorders, comprising logannin or a salt thereof and a pharmaceutically acceptable carrier.

According to another aspect of the present invention, there is provided a pharmaceutical composition for improving learning or memory, comprising logannin or a salt thereof and a pharmaceutically acceptable carrier.

According to still another aspect of the present invention, there is provided a food composition for preventing or treating learning disorders or memory disorders, which comprises logannin or a salt thereof as an active ingredient.

According to another aspect of the present invention, there is provided a food composition for learning or memory enhancement, comprising logannin or a salt thereof and a pharmaceutically acceptable carrier.

Hereinafter, the present invention will be described in detail.

As used herein, "learning" refers to an ability or behavior that can perceive and change one's own behavior, and includes spatial perception, cognition, concentration, and the like.

"Learning disorder or learning disability" refers to "learning disorder or learning disability" due to a variety of causes, regardless of IQ, for example, depression, anxiety, obsessive compulsive disorder, social and environmental factors (failure, poverty, missing family, stress, etc.). "Ability is lowered than normal, and it includes a decrease in spatial perception, a decrease in cognition, a concentration, and a decrease in academic achievement of children.

The term "memory" or "memory" refers to the ability to acquire new information, learned experience, and knowledge from the environment, encode it in a specific area of the brain, store it, and recall it.

"Memory disorder" or "memory deficiency" refers to a condition in which the "memory" is lowered than a normal person due to various causes such as trauma, attention deficit, aging, disease, etc., amnesia, concentration disorder, space Loss of perception, slowing learning, loss of cognition.

With the present invention, it has been newly discovered that logannin or salts thereof can prevent or treat learning or memory disorders, and also enhance learning or memory. The administration of loganan showed significantly increased learning and / or memory for scopolamine-induced forgetfulness, and the mice treated with loganan showed significantly better learning or It showed a memory enhancing effect.

The present invention includes a pharmaceutical composition for the prevention or treatment of learning or memory disorders, comprising logannin or a salt thereof and a pharmaceutically acceptable carrier. In addition, the present invention includes a pharmaceutical composition for improving learning or memory, comprising logannin or a salt thereof and a pharmaceutically acceptable carrier.

Loganin has the chemical name of 7-hydroxy-6-desoxyverbenalin (7-Hydroxy-6-desoxyverbenalin), and has the structure of Formula 1 below.

The loganine can be isolated from Strychni Semen (Dunstan, Short, Pharm. J. 14, 1025, 1883), and various methods of synthesis are known. The salts of loganin include conventional non-toxic salts, for example hydrochloride, sulfate, maleate, sodium salt, carbonate, tartrate, bitartrate, nitrate ), Benzoate, lysine, citrate, bromide, hydrobromide, and the like.

The composition according to the invention may be formulated into a pharmaceutical composition comprising a pharmaceutically acceptable carrier, oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc. according to conventional methods, It may be formulated in the form of external preparations, suppositories, and sterile injectable solutions.

The pharmaceutically acceptable carrier is lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like. Also included are diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, and the like. Oral solid preparations include tablets, pills, powders, granules, capsules and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, sucrose or lactose. ), Gelatin, and the like, and may include a lubricant such as magnesium stearate, talc, and the like. Oral liquid preparations include suspensions, solvents, emulsions, syrups, and the like, and may include water, diluents such as liquid paraffin, wetting agents, sweeteners, fragrances, preservatives, and the like. Parenteral preparations include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, and non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and ethyl. Injectable esters such as oleate and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The dosage of loganan or a salt thereof contained in the pharmaceutical composition of the present invention depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. For example, the loganine or salt thereof may be administered at a dose of 0.01 to 500 mg / kg, preferably 10 to 100 mg / kg, and the administration may be administered once or several times a day. It may be. In addition, the pharmaceutical composition of the present invention may comprise 0.001 to 50% by weight of the lignin or salt thereof relative to the total weight of the composition.

The present invention includes a food composition for the prevention or treatment of learning disorders or memory disorders, including lignin or a salt thereof as an active ingredient. In addition, the present invention includes a food composition for learning or memory enhancement, comprising logannin or a salt thereof as an active ingredient.

The food composition of the present invention can be used as a dietary supplement. The term "health functional food" means a food manufactured and processed using raw materials or ingredients having functional properties useful for the human body according to Act No. 6767 of the Health Functional Food Act, and "functionality" refers to the structure of the human body. And ingestion for the purpose of obtaining nutrients for function or for obtaining useful effects in health uses such as physiological actions.

The food composition of the present invention may include a conventional food additives, and the suitability as the "food additives", unless otherwise specified, corresponding items according to the General Regulations and General Test Methods of the Food Additives approved by the Food and Drug Administration It is determined by the standard and the standard.

Examples of the items listed in the "Food Additive Revolution" include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamon acid, natural additives such as color pigments, licorice extracts, crystalline cellulose, high color pigments, guar gum, Mixed preparations, such as a sodium L- glutamate preparation, an addition of an alkali, a preservative preparation, and a tar pigment preparation, are mentioned.

The food composition of the present invention is 0.01 to 95%, preferably 1 to 80% of lignin or a salt thereof, based on the total weight of the composition, for the purpose of preventing or treating learning disorders or memory disorders or for the purpose of improving learning or memory. It can be included as a percentage by weight. In addition, it may be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills and the like for the purpose of preventing or treating learning disorders or memory disorders or for the purpose of improving learning or memory.

For example, the health functional food in the form of tablets may be formed by granulating a mixture of rogannine or its salts, excipients, binders, disintegrants, and other additives in a conventional manner, and then compression molding with a lubricant or the like. The mixture may be directly compression molded. In addition, the health functional food in the form of tablets may contain a mating agent and the like, if necessary, may be coated with a suitable coating agent.

Hard capsules of the health functional food in the form of capsules may be prepared by filling a conventional hard capsule with a mixture of additives such as roganine or its salts and excipients, or granules or avoided granules thereof. It can be prepared by filling a capsule base such as gelatin with a mixture of additives such as ganine or salts thereof and excipients. The soft capsule agent may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, as necessary.

The dietary supplement in cyclic form can be prepared by molding a mixture of logannin or its salts, excipients, binders, disintegrants, etc. in a suitable manner. Or they may be greeted with a suitable substance.

The health functional food in the form of granules may be prepared into granules by a suitable method, such as a mixture of lignin or a salt thereof, an excipient, a binder, a disintegrating agent, and may contain a flavoring agent, a copper, and the like as necessary.

The term definitions of the excipients, binders, disintegrants, glidants, copulation agents, flavoring agents, etc. of the present invention are described in documents known in the art and include those having the same or similar functions. Sacrament, Korean College of Pharmacy, 5 revised edition, p33-48, 1989).

Hereinafter, the present invention will be described in more detail through Examples and Test Examples. However, these Examples and Test Examples are for illustrating the present invention, and the scope of the present invention is not limited to these Examples and Test Examples.

Example .

Six-week-old male ICR mice (22-27 g) were supplied by MJ LTD (Seoul, South Korea) and used in the animal breeding room of Sungkyunkwan University Pharmacy for more than a week. Temperature (23 ± 2 ° C), humidity (55 ± 10%) and contrast cycle (12 hours) were automatically adjusted. Loganin was purchased from Extrasynthese (France).

Example  One. Loganine Scopolamine  Induced forgetfulness

Mice were divided into 5 groups, 10 of each group. The first group (control) was a saline-administered group, the second group was a saline and scopolamine-administered group, and the third to fifth groups were 10, 20, 40 mg / kg and scopolamine-administered groups, respectively.

Loganin was dissolved in physiological saline and orally administered to mice at doses of 10, 20, 40 mg / kg, and after 30 minutes, scopolamine 0.25 mg / kg was injected subcutaneously. After 30 minutes the mice were placed in a step-through device into a dark box and trained by applying an electric shock of 0.4 mA (2 seconds). After 24 hours, the mice were placed in bright boxes again to measure the length of time until they entered the black boxes, which were used as indicators of learning and memory about scopolamine-induced forgetfulness. At this time, the cut-off time of the mouse was set to 300 seconds and compared with the control group. The test results are shown in FIG. 1.

The physiological saline control group showed memory retention of 207 seconds, while the control group of scopolamine showed 64 seconds of stay time on the test day, leading to forgetfulness (p <0.05). In addition, the stay time was increased by 75 seconds, and the 20 mg / kg administration group showed 196 seconds, which increased the stay time of mice by 132 seconds (p <0.05). Therefore, administration of loganin significantly increased dose-dependently the learning and memory of degraded mice.

Example  2. Loganine  Learning and memory improvement

Mice were divided into 3 groups, 10 of each group. The first group was a saline-administered group, the second group and the third group were 10 and 40 mg / kg administration group, respectively.

Loganine was dissolved in physiological saline and orally administered to mice at doses of 10 and 40 mg / kg, and after 30 minutes the mouse was placed in a step-through device into a dark box at 0.15 mA (2 seconds). Trained by applying an electric shock. After 24 hours, the mice were placed in bright boxes again, and the stay time until entering the black boxes was measured as an index of learning and memory. At this time, the cut-off time of the mouse was set to 300 seconds and compared with the control group. The test results are shown in FIG. 2.

The mice in the control group had a stay time of 38 seconds on the test day, and the loganin 10 mg / kg group showed 177 seconds, increasing the stay time by 139 seconds (p <0.01), and the 40 mg / kg group received 203 seconds. Increasing the stay time of the mice by 165 seconds (p <0.01) significantly increased the learning and memory of the mice in a dose-dependent manner.

The pharmaceutical composition and / or food composition according to the present invention comprising logannin or salts thereof can prevent or treat learning disorders or memory disorders, and also enhance learning or memory.

Claims (4)

A pharmaceutical composition for the prophylaxis or treatment of learning or memory disorders, comprising loganan or a salt thereof and a pharmaceutically acceptable carrier. A memory composition for enhancing memory, comprising a lignin or a salt thereof and a pharmaceutically acceptable carrier. Food composition for improving or alleviating symptoms of learning or memory impairment, comprising logannin or salts thereof as an active ingredient. A food composition for learning or memory enhancement comprising a lignin or a salt thereof and a pharmaceutically acceptable carrier.

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