KR20040098785A - Acetylcholinesterase inhibitor comprising extract of Dipsacus asper and pharmaceutical preparation, food product and feed product containing the same - Google Patents

Abstract

PURPOSE: Provided are an acetylcholinesterase inhibitor comprising the extract of Dipsacus asper and a pharmaceutical preparation, a food product and a feed product containing the same to prevent and treat diseases caused by decrease of acetylcholine concentration effectively as well as to increase one's memory and prevent Alzheimer's disease. CONSTITUTION: The acetylcholinesterase inhibitor comprises the extract of Dipsacus asper which inhibits the activity of acetylcholinesterase. The pharmaceutical preparation for acetylcholine associated diseases contains the extract of Dipsacus asper as an effective ingredient, with pharmaceutically acceptable carrier. The food, feed or food additive for increasing one's memory contains the extract of Dipsacus asper.

Description

Acetylcholinesterase inhibitor comprising extract of Dipsacus asper and pharmaceutical preparation, food product and feed product containing the same}

The present invention relates to an inhibitor of acetylcholinesterase (hereinafter referred to as AChE) containing a fast extract and a pharmaceutical agent comprising the same, more specifically, various diseases caused by a decrease in the concentration of acetylcholine in the body, namely Alzheimer's disease. And pharmaceutical preparations for treating or preventing senile dementia, myasthenia gravis, asthenia of the gastrointestinal tract and bladder smooth muscle, and glaucoma diseases and foods comprising the same.

Acetylcholinesterase (AChE) is an enzyme that hydrolyzes acetylcholine, one of the neurotransmitters that mediate the activity of parasympathetic nerves in the body, to choline and acetate. Its function is most distributed in the cholinergic nerve and its surroundings, especially in the muscle nerve junction, and is an important enzyme found in plasma, liver and other tissues.

In general, the acetylcholine is secreted into a gap called synaptic cleft in the axon-end membrane of nerve cells, and binds to receptors on post-synaptic neuronal cell membranes to transfer action potentials. After delivering excitability, it is known to be degraded into choline and acetate by the enzyme AChE, which is then absorbed into cells and reused.

Active research has shown that many physical and mental disorders are deeply linked to abnormal levels of acetylcholine, which are associated with acetylcholine synthesis and degradation mechanisms.

In Alzheimer's disease, a typical senile dementia related to acetylcholine, the brain of the patient mostly dies of neuronal neurons at the base of the forebrain, and the neuronal dominant synapses and the cerebral cortex are degenerated. The death of these neurons has been reported to significantly reduce the production of acetylcholine, a neurotransmitter that plays an important role in memory.

As part of the treatment of Alzheimer's disease, maintaining high levels of acetylcholine in the brain significantly improves the memory of patients. Currently, in the clinical field, acetylcholine is reversibly inhibited by the degradation of acetylcholine as a treatment for Alzheimer's disease. The use of anti-cholinesterase (anti-AChE) to maintain the concentration of is preferred. Therefore, currently, acetylcholine degrading enzyme inhibitors such as tacrine and aricept are mainly used for the treatment of Alzheimer's disease. However, although some of these drugs are recognized, long-term high-dose administration often requires discontinuation of treatment due to side effects such as muscle pain, nausea due to gastrointestinal disorders, vomiting, diarrhea and loss of appetite, and liver toxicity. Problems such as this have been pointed out.

According to another pathological study of the choline nervous system, gastrointestinal motility is regulated by nerve stimulation, and acetylcholine has been reported to promote this gastrointestinal motility. Therefore, neostigmine, which is a type of anticholinesterase, may be used for the treatment of postoperative bloating due to intestinal obstruction or difficulty urination due to inability of bladder detrusor.

In addition, myasthenia gravis is a neuromuscular disorder caused by the destruction of acetylcholine receptors in the muscle membranes due to autoimmune diseases and the inability of acetylcholine released from the nerve endings to the muscle membranes. As part of the treatment, acetylcholine degradation inhibitors such as mestinone and neostigmine are used.

Mestinone, which is most commonly used in the treatment of myasthenia gravis, also intends to increase the concentration of acetylcholine in the body by inhibiting the action of acetylcholinesterase, which breaks down the neurotransmitter acetylcholine, so that acetylcholine stays on muscle receptors for a long time. As a therapeutic agent developed in, there is an advantage that the effect appears within a short time when taking, but often complain of abdominal pain or diarrhea depending on the dose of the drug. In addition, AChE inhibitors used to treat myasthenia gravis, including mestinone, lack the selective discrimination of nicotine and muscarinic acetylcholine receptors, resulting in side effects from the excitation of muscarinic receptors in patients with drugs. However, the absorption rate is very low, and the therapeutic effect may be partially, so the treatment range is narrow.

In addition, it has been reported that AChE inhibitors effectively lower intraocular pressure by promoting waterproof resorption in the case of glaucoma, an eye disease caused by optic nerve damage caused by increased intraocular pressure. However, currently developed AChE inhibitors require special care because they are at risk of developing cataracts when used for 6 months or longer to treat glaucoma.

In order to effectively treat and prevent various diseases caused by the decrease in the level of the neurotransmitter acetylcholine, alternative methods of promoting the synthesis of acetylcholine by administering acetylcholine precursors such as choline have been suggested. Due to the drawback of failing to cross the cerebrovascular barrier and ending in a short time, drug treatments that currently inhibit the hydrolytic action of acetylcholine using an acetylcholinesterase inhibitor such as tacrine, as described above, are mainly used. It is used. However, currently developed and commercially available acetylcholine degrading enzyme inhibitors are reported to have side effects such as liver disorders caused by toxicity, gastrointestinal disorders such as abdominal pain or diarrhea, and muscle pain.

Accordingly, the present inventors have continued the scientific research on a new substance with reduced toxicity or side effects compared to conventional acetylcholinease inhibitors, and found an inhibitory activity of acetylcholinesterase in fast extract and It was completed.

The present invention is to provide a fast-acting extract that can be used as an inhibitor of acetylcholine degrading enzymes to effectively inhibit the activity of acetylcholinesterase to treat and prevent various diseases related to the concentration of acetylcholine in the body without toxicity or side effects. The purpose.

In addition, the present invention is useful for treating and preventing various diseases caused by a decrease in the concentration of acetylcholine in the body, that is, senile dementia including Alzheimer's disease, myasthenia gravis, ataxia of the gastrointestinal tract and bladder smooth muscle, and glaucoma without toxicity or side effects. It is to provide a pharmaceutical formulation comprising a fast extract as a component.

Furthermore, the present invention is to provide a food or feed comprising fast-acting extract that can be ingested for the purpose of preventing the disease, promoting memory, and the like by inhibiting the decomposition of acetylcholine.

1 is a graph showing that the fast extract of the present invention has an effect of concentration-dependently inhibiting the activity of acetylcholine degrading enzyme.

Figure 2 is measured by the Y-maze test to evaluate the memory effect by the fast extract extract, each value is the mean value ± standard error (n = 10). The memory of the control group was 67.2 ± 5.3%, whereas the memory damage-induced group due to scopolamine showed a significantly decreased memory of 45.7 ± 6.2%, which was 53.5 ± 6.9 in the group treated with fast extract and scopolamine. Fast extract was shown to restore the memory reduced by the scopolamine administration in%.

3 is measured by the passive avoidance test method of memory enhancement effect by the rapid extract administration, each value is the mean value ± standard error (n = 10). The avoidance time (hesitation time) of the control group was 467.2 ± 36.7 seconds among the maximum 300 seconds, while the memory damage-induced group due to scopolamine administration showed a significantly decreased memory of 297.5 ± 41.7 seconds. In the group of scopolamine co-administration, fast extracts recovered the memory decreased due to scopolamine administration at 381.5 ± 42.2 seconds.

The present invention relates to acetylcholinesterase (AChE) inhibitors containing Sokcho extract and pharmaceutical preparations comprising the same, more specifically various diseases caused by decreasing concentrations of acetylcholine in the body, namely Alzheimer's disease, including elderly A pharmaceutical agent for treating or preventing dementia, myasthenia gravis, ataxia of the gastrointestinal tract and bladder smooth muscle, and glaucoma disease, and a food and feed comprising the same.

Sokdan extract is a solution extracted from the roots of the perennial herbaceous Dipsacus asper belonging to the genus Bunnyaceae, using hot or cold water or various organic solvents such as methanol, ethanol and acetone, or Materials processed therefrom are currently Guizhou Highyin Biological Product Co. (Guiyang, China), Zhejang Zhongke Plant Technical Co. Ltd. (Zeyang, China) It is commercially available in the form of a powder or a solution from the manufacturer, such as).

Sokdan is a type of food and herbal medicine that has been used by people since ancient times. Recently, as the usefulness of fastening ingredient for growth hormone secretion and growth promotion is revealed, the demand is gradually expanding and the safety and efficacy studies are conducted. Is an active trend.

Currently known pharmacological actions of fasting are reported anti-diabetic effect, muscle joint pain relief effect, anti-complement effect, seawater asthma and diarrhea treatment due to physical weakness, and continued research on new efficacy of fast-acting extract in various fields Is in progress.

The inventors of the present invention have also completed the present invention, confirming that the substance exhibits the action of inhibiting the activity of acetylcholinesterase in the body during extensive research on the efficacy of the fast extract.

Acetylcholinesterase is an enzyme that hydrolyzes acetylcholine, one of the neurotransmitters in the body, to choline and acetate, and is closely related to the increase and decrease of acetylcholine in the body. Therefore, in order to treat and prevent various diseases caused by abnormal concentration of acetylcholine, namely Alzheimer's disease, senile dementia, myasthenia gravis, weakness of gastrointestinal tract and bladder smooth muscle, and glaucoma, a substance which inhibits the action of acetylcholinesterase as a therapeutic agent I use it.

Acetylcholinesterase inhibitory activity against the fast-acting extract of the present invention was determined using acetylcholinesterase extracted from cultured PC12 cell line, as described in Chung YK, HeoHJ, Kim EK, Kim HK, Huh TL, Lim Y, Kim SK, Shin DH. Mol Cells 2001; 11: 137].

Homogenation was carried out with a sufficient amount of 10 mM Tris-HCl (pH 7.2) containing 1M NaCl, 50mM MgCl ₂ and 1% Triton X-100 in a culture PC12 cell line, followed by centrifugation to remove acetylcholinestera from the cell line. The extract was used as an enzyme, and 0.5mM acetylthiocholine and 1 mM 5,5'-dithio-bis (2-nitrobenzoic acid) were used as substrates. Each enzymatic reaction was carried out on the tacrine sample being used.

After incubating the reaction solution in which the substrate solution was added to the enzyme for 30 minutes, the absorbance was measured at a wavelength of 405 nm, and the enzyme activity inhibition was determined from the following equation (1):

% Enzyme activity inhibition = {1-[(SR-SC) / (ER-EC)]} x 100

Where

SR is the absorbance value measured in the sample reaction with enzyme inhibitor,

SC is the absorbance value using a buffer instead of enzyme as a control of the sample reaction,

ER is the absorbance value measured in the enzyme reaction without adding a sample,

EC shows absorbance values using buffer instead of enzyme as a control of the enzyme reaction.

As a result of the test, it was possible to obtain a graph of the enzyme activity inhibition for the fast extract as shown in FIG. According to this graph, the IC ₅₀ value of the fast extract was found to be 2.1 µg / ml, and the concentration of 10 µg / ml was found to inhibit the activity of the enzyme by 100%.

In addition, as an acute toxicity test for the fast-acting extract of the present invention, seven Sprague-Dawley-based white rats were administered daily by 500 mg per kg per day, but 7 days at the completion of the test There were no cases of death until. Mice were also administered daily to 100 mg / kg daily for the memory test roll, but there was no case of death until 7 days of the completion of the test.

As can be seen from the test results described above, the acetylcholinesterase inhibitory activity against the fast-acting extract of the present invention shows a lower value than that of tacrine, which is currently mainly used as an anticholinesterase substance, but As the extract is known to be a natural physiologically active substance, unlike conventional acetylcholinesterase inhibitors such as tacrine and aricept, it is a relatively safe ingredient in terms of side effects or acute toxicity when administered to humans or animals. Therefore, it can be said to be an excellent material that can be safely used without substantial problems even in large doses.

Accordingly, the present invention provides an acetylcholinesterase inhibitor containing fast extract.

In addition, the present invention, in the treatment of various diseases caused by abnormal concentration of acetylcholine, namely Alzheimer's disease, senile dementia, myasthenia gravis, asthma of the gastrointestinal tract and bladder smooth muscle, and glaucoma, with a pharmaceutically acceptable carrier, the active ingredient It provides a pharmaceutical formulation comprising a fast extract as.

In addition, the present invention provides a food or food supplement comprising a fast extract to effectively inhibit the decomposition of acetylcholine in the body, thereby preventing the disease and promoting memory.

When prepared in the form of a pharmaceutical preparation according to the invention, the fast extract may be combined with a pharmaceutically acceptable conventional carrier, depending on the purpose of administration, tablets, hard or soft capsules, chewing tablets, powders, solutions or suspensions. It may be formulated in the form of preparations for oral administration such as preparations or preparations for parenteral administration such as injectable solutions or suspensions.

In the case of formulating the active compounds of the present invention into tablets, capsules, chewing tablets, powders, solutions, suspensions and the like for the purpose of oral administration, binders such as gum arabic, corn starch, microcrystalline cellulose or gelatin , Excipients such as dicalcium phosphate or lactose, disintegrants such as alginic acid, corn starch or potato starch, lubricants such as magnesium stearate, sweeteners such as sucrose or saccharin and flavors such as peppermint, methyl salicylate or fruit flavor In the case where the dosage unit form is a capsule, a liquid carrier such as polyethylene glycol or fatty oil may be included in addition to the above components.

In addition, injections in the form of solutions or suspensions for parenteral administration can be administered parenterally, eg, subcutaneously, intravenously, intramuscularly, or intraperitoneally. Generally, an injectable solution or suspension is an effective amount in a pharmaceutically acceptable liquid carrier such as water, saline, aqueous dextrose and related sugar solutions, nonvolatile oils, glycols such as ethanol, glycerin, polyethylene glycol, propylene glycol, and the like. It can be prepared by homogeneously mixing the active compounds of. In addition, if necessary, auxiliary agents such as antibacterial agents, chelating agents, buffers, and preservatives may be included.

As the above-mentioned pharmaceutically acceptable carrier, any adjuvant can be used which is pharmaceutically pure, substantially non-toxic, and which does not inhibit the action of the active ingredient.

The acetylcholinesterase inhibitory effective amount referred to herein is a dose necessary to sufficiently achieve the effect of inhibiting the activity of the enzyme acetylcholinesterase, and the type of disease and the severity of the disease that the patient suffers from Depending on the sex, age, weight and health of the patient, mode of administration, frequency and time of administration, the use of concomitant medications and other relevant circumstances, an appropriate range may be determined at the discretion of the patient's physician.

Pharmaceutical preparations containing the fast-acting extract of the present invention as an active ingredient, in the case of oral administration, 1 to 500 mg, preferably 50 to 100 mg per 1 kg body weight once to several times a day, preferably 1 to 3 times. In the case of injection administration, 0.5 to 250 mg, preferably 10 to 100 mg per kg of body weight can be administered once to several times a day, preferably once to three times in the case of injection administration. .

In addition to the pharmaceutical preparations described above, the fast extract of the present invention may be formulated in a suitable amount in conventional beverage products, such as soft drinks, mineral water, alcoholic beverages, chewing gum or caramel products, candy, ice cream, confectionary, or the like, including vitamins and minerals. It can also be prepared in the form of food or food supplements by inclusion in supplements, food additives and the like.

In the case of the food including the fast extract, it is possible to obtain the effect of improving the memory when ingested continuously for a long time and preventing the disease such as dementia prevention.

Hereinafter, the acetylcholinesterase inhibitory activity test and specific formulation examples for the fast extract of the present invention will be described in more detail based on the following examples.

However, these examples are provided to illustrate and specifically describe the present invention, and the scope of the present invention should not be understood as being limited thereto.

Example 1 Preparation of Rapid Extract

1 kg of dried fasteners were selected, 2 liters of ethanol aqueous solution was added, and divided into a predetermined amount and ultrasonically pulverized for 15 minutes or more to extract the active ingredient from the fasteners.

After ultrasonic extraction, each was combined and filtered, and then the organic solvent was distilled off and concentrated under reduced pressure. The resulting concentrate was lyophilized to give a fast extract in a yield of at least 5%, which was used as the sample and active ingredient of Example 2-8 below.

Example 2 Acetycholinesterase Inhibitory Activity of Sokpan Extract

In this example, the following experiment was conducted to demonstrate the inhibitory activity of acetylcholinesterase of the Sokpan extract.

Acetylcholinesterase experiments to determine the inhibitory activity against acetylcholine degradation of enzymes are described in Chung YK, Heo HJ, Kim EK, Kim HK, Huh TL, Lim Y, Kim SK, Shin DH. Mol. Cells 2001; 11: 137].

Acetylcholinesterase enzyme was extracted from PC12 cell (obtained from the Korean Cell Line Bank) culture and used as a fastener extract obtained in Example 1 as an enzyme inhibitor sample. Tacrine, the most commonly used anticholinesterase substance in the clinical field, was purchased from Sigma Co., USA.

First, a 10 mM Tris-HCl (pH 7.2) solution containing 1 M NaCl, 50 mM MgCl ₂ and 1% Triton X-100 was added to a culture in which PC12 cell line was incubated in Dulbecco's Modified Eagle Medium (DMEM) medium for 7 days. Enzymes were prepared by adding 5 times the amount of PC12 cells, homogenizing homogeneously, centrifuging at 10,000 g for 30 minutes and separating the supernatant.

Sokcho extract 25, 12.5, 6.3, 3.1, 1.6. It was dissolved in distilled water to a concentration of 0.8, 0.4, 0.2, and 0.1 mg / ml, and tacrine used as a comparative substance was dissolved in distilled water at a concentration of 1, 10, 100, 1,000, 10,000 nM.

To each well of a 96 well plate, 30 μl of 50 mM phosphate buffer (pH 8.0), 10 μl of the rapid extract solution of this concentration and 10 μl of enzyme AChE as a sample were added, followed by 0.5 mM acetylthiocholine as a substrate solution for the enzyme. 50 μl of 50 mM phosphate buffer (pH 8.0) containing (acetylthiocholine) and 1 mM 5,5'-dithio-bis (2-nitrobenzoic acid) [5,5'-dithio-bis (2-nitrobenzoic acid)] A total of 100 µl of the reaction solution was prepared for each sample concentration, and the reaction solution was incubated for 30 minutes in an incubator at 37 ° C.

After incubation, the absorbance was measured at an wavelength of 405 nm with an Eliza reader to obtain an SR value, that is, the absorbance value measured after the reaction of the sample to which the enzyme inhibitor was added.

As a control for the sample reaction, after incubating the buffer instead of the enzyme, the absorbance was measured in the same manner to obtain an SC value.

Subsequently, in order to determine the enzyme reactivity when no enzyme inhibitor was added, a buffer solution was added instead of the sample to obtain the absorbance ER value. As a control, a buffer solution was added instead of the sample and the enzyme, and then the absorbance EC value was obtained.

As a result of the enzyme activity inhibition calculated by the above formula (1) from the absorbance values SR, SC, ER and EC values measured above, a graph as shown in FIG. 1 was obtained.

According to this, the IC ₅₀ value of the Sokcho extract was found to be 2.1 µg / ml, and it was found to inhibit the activity of the enzyme 100% at a concentration of 10 µg / ml.

As for the comparative substance of the enzyme inhibitory activity, tacrine was also subjected to the enzyme activity inhibition experiment in the same manner and in the same manner as the experiments performed on the fast extract. As a result, the IC ₅₀ value of tacrine was about 130nM.

Acetylcholinesterase inhibitory activity against the fast-acting extract of the present invention shows a lower value than the case of tacrine, but fast-acting extract is a bioactive material with excellent biosafety and almost no toxicity as it is known. Considering the serious side effects of conventional AChE inhibitors such as tacrine liver disorders, gastrointestinal disorders such as abdominal pain or diarrhea, myalgia and the like, acetylcholinesterase inhibitory activity of the fast-acting extract of the present invention is very meaningful. It can be seen.

Example 3 Measurement of In Vivo Memory Enhancement Effect by Sokcho Extract

In order to investigate the effect of Sokdan extract in vivo, the Y-maze test and manual avoidance of the memory-promoting effect after oral administration of Sokdan extract using animal model that induced memory loss Measured through a test (passive avoidance test).

1) Measurement of Memory Enhancement Effect of Sokcho Extract Using Y-Maze Test

Mamiya and Ukai et al. [Br. J. Pharmacol. 134 (8): 1597-9 (2001)]. In other words, mice of the control group, the scopolamine-administered group, and the scopolamine-fast extract extract group were placed in the center of the Y-shaped maze measuring device and visited to each arm. In this experiment, physiological saline or fast extract (100 mg / kg) was orally administered 7 days before the experiment, followed by intraperitoneal injection of scopolamine (1 mg / kg), and after 30 minutes, a maze test. Placed in the center of the measuring device, the number of total arms entered in 10 minutes and the number of visits in order was measured, and the percentage of the number of visits in order divided by the total number of times minus 2 was measured as memory (%). Higher memory levels mean better learning and memory in places. The results showed that the memory of the control group was 67.2 ± 5.3%, whereas the memory damage-induced group due to scopolamine administration was significantly decreased to 45.7 ± 6.2%, and 53.5 in the fast-acting extract and scopolamine group. Sokcho extract showed an effect of restoring memory decreased by scopolamine administration at ± 6.9%.

2) Measurement of Memory Enhancement Effect of Sokcho Extract Using Passive Evasion Test

To measure the effect of memory enhancement using the passive avoidance test, a shuttle box with a middle partition and divided into bright and dark rooms left and right was used. Experiments were performed using mice in the control group and the scopolamine administered group and the scopolamine and fast extract treatment group. In this experiment, physiological saline or fast extract (100 mg / kg) was orally administered 7 days before the experiment, followed by intraperitoneal injection of scopolamine (1 mg / kg), and after 30 minutes, the electric grit was attached to the floor. Into the cubicle room (A) of the shuttle box with electric grid floor (19L × 9W × 10.875H, Columbus Instruments, Model PACS-30, USA) and turn on the lighting of 1500Lux while connecting the guillotine door: 3H × 2.625 W) opened.

At this time, the mouse looks around the room and moves to the illuminated partition room (B), and at the same time the partition door is automatically closed. When the mice were moved to the compartment room (B), the mice were subjected to footshock by passing a current of 1 mA for 5 seconds while the lights were turned off. Then, the mouse remembers the relationship between the dark room and the foot shock, and after 24 hours, he puts it in the partition room (A) and hesitates to move to the partition room (B) even if it lights up. At this time, the latency of the control group not administered scopolamine and the group administered scopolamine (1 mg / kg), and the fast extract (50 mg / kg) and scopolamine (1 mg / kg) Were compared with each group, and measured in terms of memory enhancement effect (sec) is shown in FIG. In summary, the avoidance time (hesitation time) of the control group was 467.2 ± 36.7 seconds out of the maximum 300 seconds, whereas the memory damage-induced group due to scopolamine administration significantly decreased to 297.5 ± 41.7 seconds. In the group administered with fast extract and scopolamine, fast extract extract recovered the memory decreased by scopolamine administration to 381.5 ± 42.2 seconds.

2 and 3 of the drawings, it can be seen that the memory enhancing effect of the fast extract significantly increased. Therefore, it was confirmed that the fast extract can be used as an effective memory hyperthermia and dementia treatment with a pharmaceutically acceptable carrier.

Example 4 Preparation of Tablets Containing Sok Extract

Component content

Fast extract 100mg

Corn Starch 68mg

Lactose 90mg

Microcrystalline Cellulose 40mg

Magnesium Stearate 2mg

According to the conventional method of preparing tablets, the above ingredients were added to the indicated contents, mixed uniformly, stirred and granulated. After drying, using a tableting machine, a desired tablet containing 100 mg of fast-acting extract, an active ingredient, was prepared per tablet.

Example 5 Preparation of Capsules Containing Sokcho Extract

Component content

Fast extract 100mg

Corn Starch 68mg

Lactose 90mg

Microcrystalline Cellulose 40mg

Magnesium Stearate 2mg

According to the conventional method for preparing the capsules, the above-mentioned ingredients were added in a given amount to be uniformly mixed, and then the desired capsules were prepared by filling into gelatin capsules of appropriate size to contain 100 mg of fast-acting extract per capsule.

Example 6 Preparation of Chewing Tablets with Sokcho Extract

Component content

Fast extract 100mg

240mg granulated sugar

Fragrance (Pepamine or Lemon) 2mg

Corn Starch 60mg

Mannitol 100mg

Magnesium Stearate 20mg

Purified water

According to a conventional method of preparing chewing tablets, the above ingredients were mixed in an appropriate amount of water, dissolved while heating, cooled and placed in a molding machine to prepare chewing tablets of a desired shape, such that 100 mg of fast-acting extracts were contained per piece. .

Example 7 Preparation of Injectables Including Rapid Extract

Component content

Fast extract 100mg

Sodium Metabisulfite 3.0mg

Methyl Paraben 0.8mg

Propyl Paraben 0.1mg

Appropriate amount of purified water for injection

According to a conventional method for preparing an injection, the above components are dissolved in boiling water with a given content, stirred, and then cooled and filled into a 2 ml sterile vial, and supplemented with an appropriate amount of purified water for injection to 2 ml. A desired injection was prepared comprising 100 mg of fast-acting extract per piece.

Example 8 Preparation of Candy Containing Sok Extract

Component content

Fast extract 100mg

Granule Syrup 640mg

Fragrance (Pepamine or Lemon) 2mg

Starch syrup 230mg

50% tartaric acid 20mg

Purified water

The granulated sugar syrup was heated to 110 ° C. while completely dissolving in a small amount of water, and then the remaining water and starch syrup was dissolved, and the temperature was raised to 145 ° C. The fire was turned off, the fragrance and tartaric acid were added, mixed, cooled to 75 to 80 ° C, and molded with a forming roller to prepare a fast-containing extract-containing candy.

Example 9 Preparation of Drinks Containing Sok Extract

Component content

Fast extract 100mg

2 g of concentrated juice

Sucrose 12g

100 mg sodium citrate

Fragrance 70mg

Water

According to a conventional method for preparing a beverage, the above ingredients are mixed with an appropriate amount of water in a given amount, heated to dissolve, cooled and filled into a container, and a beverage containing 100 mg of fast-acting extract per bottle of 200 ml of beverage. Was prepared.

Sokcho extract according to the present invention is an effective acetylcholine degrading enzyme inhibitor that can inhibit the activity of acetylcholinesterase, in the form of a pharmaceutical preparation containing it as an active ingredient, senile dementia including Alzheimer's disease, myasthenia gravis It can be effectively used for the treatment and prevention of various diseases caused by the decrease in the concentration of acetylcholine in the body, such as asthenia of the gastrointestinal tract and bladder smooth muscle and glaucoma.

In particular, since Sokdan extract is a natural active substance extracted from Sokdan, it has excellent biosafety. Therefore, it is toxic compared to conventional acetylcholinesterase inhibitors. There is an advantage that can be administered to patients with confidence.

In addition, the fast extract of the present invention can be added to various foods and feeds, or used as a food supplement, it is possible to obtain the effect of promoting memory or mental concentration, dementia prevention according to the improvement of the function of the neurotransmitter system.

Claims (7)

An acetylcholinesterase inhibitor, comprising a fast extract. A pharmaceutical preparation for the treatment or prevention of acetylcholine-related diseases, comprising a pharmaceutically acceptable carrier together with a fast extract as an active ingredient. The method of claim 2, The acetylcholine-related disease is senile dementia or Alzheimer's disease. The method of claim 2, Pharmaceutical formulation, characterized in that the acetylcholine-related disease is myasthenia gravis. The method of claim 2, The pharmaceutical preparation, characterized in that the acetylcholine-related disease is a disability of the gastrointestinal tract and bladder smooth muscle. The method of claim 2, Pharmaceutical formulation, characterized in that the acetylcholine-related disease is glaucoma. Food and feed or food additives and feed additives for promoting memory, characterized in that it comprises a fast extract.