KR20180082262A - Composition comprising Galsu for prevention and treatment of memory and cognitive impairments involved disorders - Google Patents

Abstract

The present invention relates to a composition for the treatment of forgetfulness containing Galsu (tea using medical herbs, fruits, honey, etc.) as an active ingredient. The Galsu of the present invention has an excellent effect of treating forgetfulness in a scopolamine induced forgetfulness model, and thereby can be useful as a treatment agent for disorders related to the same.

Description

[0001] The present invention relates to compositions for treating, preventing and ameliorating forgetfulness,

The present invention relates to a composition for treating, preventing and ameliorating forgetfulness, which comprises as an active ingredient ganoderma prepared by using Cinnamomum cassia, Syzygium aromaticum, Amomum cadamomum, Amomum villosum, and dermis (Citrus unshiu) .

Dementia is a chronic progressive degenerative brain disease that is defined as a symptom complex that affects both mental cognitive ability and social dysfunction, resulting in normal disability in daily life. The proportion of dementia increases with the progress of aging in recent years And it is emerging as a serious medical, socioeconomic, and economic health problem for the elderly. Alzheimer's disease, cognitive dysfunction, vascular dementia due to cerebrovascular disease such as repeated cerebral infarction, and dementia due to other diseases are categorized as dementia, 50-60% of all dementia patients are known to be caused by Alzheimer's disease. In general, patients with Alzheimer 's disease exhibit clinically significant impairment in intellectual ability, emotional and behavioral changes, and then show signs of serious cerebral cortical dysfunction such as loss of directional sensation, memory impairment, and aphasia.

Cerebral vascular dementia is a major cause of atherosclerotic infarction and can be improved by treatment with thrombolytic agents. However, Alzheimer's disease rarely develops symptoms before the age of 50, but the tendency of the prevalence increases with age. , Which is a typical degenerative brain disease that worsens as brain cells are gradually destroyed. The final diagnosis of this disease is only possible by pathologic examination through post-mortem examination. It is characterized by general atrophy of cerebrum and nerve cell death at autopsy Although there are many researchers actively studying, the cause of the onset has not yet been clarified yet.

However, studies to date have shown that Alzheimer's disease is pathologically characterized by cerebral atrophy of the cerebral cortex or hippocampus and deposition of senile plaques or neurofibrillary tangles in the brain, Observing the process shows that an abnormal protein called beta-amyloid (Aβ) accumulates in the brain and then tau protein in the neuron aggregates, resulting in damage to the synapse, and ultimately, And death of brain cells, it was revealed that dementia and neuronal fibrous enrichment accumulate at the same time. The nervous system is the structure of the cerebral cortex and the horny specks seen in the hippocampus. It has amyloid fibers at its center and surrounds the denatured nerve cell processes. In other words, beta-amyloid is a major component of the elderly that accumulate in the brain of Alzheimer's patients, and the toxicity of this substance to neurons is thought to be a major cause of Alzheimer's disease.

Thus, the mechanism of overexpressing beta-amyloid causing toxicity may vary, but the following two theories explain the progression of the disease. The first theory is that when an amyloid plaque occurs, inflammation of the glia results in a series of inflammatory reactions, such as stimulating the production of cytokines that damage the nerve and eventually attack, It is based on the action of reactive oxygen species (ROS). More than 95% of the brain is composed of fats and is oxidized by the attack of free radicals, where the beta-amyloid undergoes aggregation to form hydrogen peroxide, superoxide anion, and hydroxylradical, which act on macromolecules in vivo due to their high reactivity, which ultimately leads to active apoptosis in neurons.

Currently, reversible AChE inhibitors of the order of four (donepezil, galantamine, rivastigmine and tacrine) are approved for the treatment of mild to moderate Alzheimer's disease, Although it is known to delay the onset of behavioral and functional impairment, it is known to exhibit only moderate symptom relief, but there are side effects such as nausea, diarrhea, vomiting, anorexia, abdominal pain, and muscle twitching that are associated with a peripheral cholinergic effect on the gastrointestinal tract , Especially tacrine, has caused hepatotoxicity and is rarely used at present. Thus, the development of effective AchE inhibitors with fewer side effects may be of considerable help in improving and treating the quality of life and the pathology of Alzheimer's disease patients.

The primary symptom of dementia disease, memory and cognitive decline, is known to be closely related to the cholinergic nervous system, and reports have shown that scopolamine (an antagonist of the muscarinic receptor in postsynapse) ) Inhibits the binding of acetylcholine, a neurotransmitter liberated in presynapse, to muscarinic receptors, thereby temporarily interrupting the transmission of information, thereby damaging learning and memory. Lt; RTI ID = 0.0 > animal models. ≪ / RTI >

Medicine treats memory impairment as 'amnesia', and is good at forgetting the warrior and the message that he has done, so when treating things, I do not know about Sumi. The amnesia is caused by the deficit of the brain due to the deficiency of the nephrostomy (腦海 空虛), the damage of the seven chil- dren (七情 damage), the mind and body pylorus, the sympathetic conception (心 脾 陽虛) (瘀血 气 心) and 瘀血 심 心 (瘀血 头心) is caused by the cause and Daibo 气血 (宝 气), Anshin (yanfum), phlegm (phlegm) , Ibi (脾)), and the wise wolver (肝 肝 解压), etc.

On the other hand, Gwangsu is drink mixed with concentrated fruit juice and mixed with herbal medicine, and it is drink to drink in honey with honey by putting koji in the herbal medicine. In other words, drinking water when the thirsty drink is said to have a pharmacological effect.

Broccoli is a cassava trunk that has an unusual direction, its taste is spicy and its quality is hot. Broiler chest is made by treating loofahs with cold and loose knees and weakness, lack of ovaries, frequent urination, dilute stools, diarrhea, vomiting, menstrual irregularities, menstrual cramps, postpartum hemorrhagic abdominal pain, boils, skin ulcers, I write. Pharmacological actions have been reported to be central inhibition, sedation, pain relief, fever, increased coronary blood flow, and inhibiting skin fungi. Appearance is plate-like or sheath-like plate with inner side-dried plate, outer side is grayish brown with rough wrinkle, vertical wrinkle and lateral pore. Grayish white spots are in place, and the inner side is red or brown. A thin bark is called cinnamon, and a young branch is called anchovy.

Clove is an ash tree of dicotyledonous plant. It is distributed in Jeolla Province, Gyeongsang Province, North and Manchuria, and grows at the foot of a mountain. It grows up to about 3 m, has many branches, and has a branch. The leaves are opposite, oval or egg-shaped, or almost round, with flat edges. The flower blooms in May and runs on a cone flower, and the flower ear hangs on the old branch. Fruit is capillary, oval with a dull end, and has a lump. One flower is seen as a "dingo" on the side, and the flower has a scent, called clove, which is different from the cloves of tropical fatty acids. The buds are cloves, sour roots are cloves, cloves are cloves, cloves are cloves, fruits are cloves, and essential oils are cloves. Celadon blooming is a treatment for the middle-aged duck duck, the tucked sword, and toothache.

Amomi Cardamomi Fructus (Amomum cardamomum L.) is a blue perennial herb that uses its fruit as a medicinal material. Its fruit seed contains 2.4% essential oil. Its essential components are d-borneol and d- Campa, and is used in oriental pruritus medicine for digestion, vomiting, stomach ache.

Baekdugu is grown in Cambodia, Vietnam, Thailand and Indonesia and cultivated in the southern part of China. It removes fruit sack (bark) and fruit husk (peel) from mature fruit with yellow green and uses it in the sun. This medicine has a strong scent. The taste is similar to that of camphor and the weakness is spicy and warm. Baekdu-gu removes moisture from the stomach, and it is effective for dryness, digestion and abdominal pains, vomiting, pregnancy nausea, and nausea. Pharmacological actions have been reported to promote gastric secretion, excitement of the intestines, and directional structure.

Baekdugu is close to the circular shape, and its outer surface is pale yellowish white or yellowish brown, with three rows of dull ridge and several vertical lines, with the upper part depressed, and the lower part with the traces of bruising. The skin is thin, light and fibrous. The inside is divided vertically into three chambers by thin film, and each thread contains 7 ~ 10 seeds. The seed forms an irregular polyhedron, and its back has emerged like a bow. Tinnitus has a variety of organs, tetragonal, duo, white, and circle. Baekdugu is the fruit of Baekdugu which is an evergreen plant belonging to the ginger family. Ingredients are camphor, borneol, etc.

Signs (Ammomum xanthioides Wallich) are perennial herbs belonging to the genus Zingiberaceae. They are distributed in southern China, Southeast Asia and India. The medicinal form is elliptical or oval, with three dull edges, 15-20 mm in length, and 10-15 mm in diameter. It is recorded in Donguibogam that when the stomach is sick and the stomach is used, Known ingredients include essential oils of the seeds and their main constituents are Borneol, Bornyl-acetate, Linalool and Nerolidol.

Dipper (Citrus unshiu) is the mature fruit of the citrus fruit (Citrus unshiu, Citrus reticulata in China), which is an evergreen tree belonging to the genus Rutaceae. It is spicy, spicy, warm and directional, mainly active in the rain and lungs. Spicy tastes emanate and conduct, taste warm, and warm and dry (燥濕 去 寒). Ingredients include limonene, auraptin, and more than 90% of them are limonene. Flavonoid-based compounds include hesperidin, tangertin, nobiletin, etc. Among them, hesperidin contained in the white part of the skin mainly accounts for more than 90% . In addition, synephrine, citric acid, etc. are also contained. This product is an important medicinal agent for medicine, medicine, medicine, and medicine.

Accordingly, the inventors of the present invention have found that amelioration of amnesia is excellently achieved by using fresh water produced using Cinnamomum cassia, Syzygium aromaticum, Amomum cadamomum, Amomum villosum, and dermis (Citrus unshiu) Thereby confirming the completion of the present invention.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for preventing and treating diseases associated with forgetfulness and memory disorders, which comprises as an active ingredient, water.

In addition, the present invention provides a health functional food for preventing and ameliorating forgetfulness and memory disorder related diseases containing ginger or a health extract as an active ingredient.

As defined in the present application, water is added to Cinnamomum cassia, Syzygium aromaticum, Amomum cadamomum, Amomum villosum and Citrus unshiu in an amount of 1 to 20 times, Deg.] C for 1 hour to 5 hours, filtration, and concentration under reduced pressure, and the extract obtained by concentration can be lyophilized.

As defined herein, amnesia and memory disorder related disorders are selected from the group consisting of Alzheimer's disease, cerebrovascular dementia, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease , Dementia due to spinal cord injury or head injury, and the like, preferably dementia caused by Alzheimer's disease, cerebrovascular dementia or head injury, more preferably Alzheimer's disease.

Hereinafter, the method for obtaining the extract of the present invention will be described in detail.

The pharmaceutical composition containing gallate of the present invention contains the dry powder or the extract thereof in an amount of 0.1 to 50% by weight based on the total weight of the composition.

However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.

Since the extract of the present invention has little toxicity and side effects, it can be safely used even for long-term administration for the purpose of prevention.

The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.

The composition of the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions, Examples of the carrier, excipient and diluent which can be contained in the composition including the dry powder or extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate , Calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of the liquid preparation for oral administration include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As a base for suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.

The preferred dosage of the composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the composition of the present invention is preferably administered at 0.5 g / kg to 5 g / kg, preferably 1 g / kg to 3 g / kg per day. The administration may be carried out once a day or divided into several doses. Accordingly, the dosage is not limited in any way to the scope of the present invention.

The composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

The present invention also provides a health functional food for preventing and ameliorating forgetfulness and memory disorder related diseases containing ginger or a health extract obtained by the above production method as an effective ingredient.

The composition containing the ginger or health extract of the present invention can be used variously for medicines, foods and beverages for prevention and improvement of diseases related to forgetfulness and memory disorders. Examples of the food to which the ginger or the health extract of the present invention can be added include various foods, beverages, gums, tea, vitamin complexes, health supplement foods and the like, and may be in the form of powder, granule, tablet, capsule or beverage .

The amount of the extract in the food or beverage of the present invention can generally be from 1 to 5% by weight of the total food weight of the health food composition of the present invention, and the health beverage composition is preferably present in an amount of 0.02 to 10 g, Can be added at a ratio of 0.3 to 1 g.

The health beverage composition of the present invention contains not only the above-mentioned ginger or health extract as an essential ingredient in the indicated ratios but also the liquid ingredient, and contains various flavors or natural carbohydrates such as ordinary drinks as an additional ingredient . Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like Sugar, and sugar alcohols such as xylitol, sorbitol, and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 mL of the composition of the present invention.

In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like.

In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

The water of the present invention is excellent in ameliorating the amnesia in the scopolamine-induced amenity model, and can be usefully used as a remedy for amnesia and related diseases.

FIG. 1 is a graph showing the Y-maze test result in a scopolamine-induced amnesia model of fresh water.
FIG. 2 is a graph showing passive avoidance task results in a scopolamine-induced forgetfulness model of freshwater.
FIG. 3 is a graph showing Morris water maze test results in a scopolamine-induced forgetfulness model of fresh water.
4 is a graph showing the DPPH and ABTS free radical scavenging activity of Rice.

Hereinafter, the present invention will be described in detail by way of examples.

[ Example 1]  Produce

10 times water was added to 40 g of Cinnamomum cassia, 20 g of Syzygium aromaticum, 20 g of Amomum cadamomum, 20 g of Amomum villosum and 20 g of dermis (Citrus unshiu), followed by extraction at 80 ° C for 2 hours, After filtration with filter paper and concentration under reduced pressure, the extract was dried in a freeze dryer and used in the experiment. (Yield: 12.6%)

[ Example 2]  Confirmation of the amelioration effect

One. Experimental animal

Four-week-old ICR mice were used in a 12 h light / dark cycle in a feeding room maintained at temperature (22 ± 2 ° C) and humidity (50 ± 10%) from BioLink. Water and feed were freely consumed during the experiment.

2. Administration of drug

One hour before the start of the experiment, the rats were orally administered in 0.9% physiological saline solution and 30 minutes later scopolamine 1 mg / kg was intraperitoneally administered to the experimental animals to induce amnesia.

3. Y-maze test (Y-maze test)

The Y-maze test was used to assess the ability to act in a sequential manner as a measure of short-term memory. The measuring equipment consists of three branches, each branch having a length of 42 cm, a width of 3 cm, a height of 12 cm and three folding angles of 120 °. The device consisted of black polyvinyl plastic and the three branches were designated as A, B and C, respectively. The experimental animals were added to each branch for 8 minutes, and the number of times the animals entered the branch until the tail of the animal and the number of turns in each branch were given 1 point (actual change). The alternation behavior is defined as entering all three without overlap, and is calculated by the following equation:

Change Actual Power (%) = actual alternation / maximum alternation × 100 (highest change: total number of entries 2)

The results are shown in Fig.

As shown in FIG. 1, spontaneous alterations (%) were significantly decreased in the model in which the memory capacity was decreased by the scopolamine administration, and 800 mg / kg in the control group. Increasing the change behavior means that learning and memory are restored. On the other hand, the total number of mice entering each branch showed no change, indicating that they were not caused by changes in the activity of the mice.

4. Passive avoidance task

Experiments were conducted using a manual evasive box to measure the working memory of experimental animals. The manual evasive box is divided into a dark room and a bright room. When a laboratory animal is placed in a bright room, the room is moved to a dark room. At that moment, 0.5mA is applied for 3 seconds. When the test animals were placed in a bright room the day after the electric shock was applied, the electric shock in the dark room was remem- bered and stayed in the bright room. The memory was evaluated by measuring the step-through latency.

The results are shown in Fig.

As shown in FIG. 2, the latency time of the model in which the memory was decreased by the scopolamine administration was statistically significantly decreased in the test trial as compared with the control group. This indicates that the memory decay model with scopolamine was well developed and that 200, 400, and 800 mg / kg of diets were administered to 200 and 800 mg / kg groups, respectively The time can be seen to increase significantly. On the other hand, the time spent in the training trials did not show any difference between the groups, indicating that the experiments were carried out with the individual differences of the experimental animals minimized.

5. Morris water maze test (Morris water maze test)

In the underwater labyrinth experiment, the animal animal memorizes four markers around the water tank using the EthoVision Maze test system (Noldus Information Technology, Wageningen, Netherlands) It is an experiment to measure the escape latency, which is the time it takes to get to the platform when staying. Experiments were conducted on 4 occasions, 4 times a day, four times a day, and the mean value was defined as mean escape latency. In addition, the platform was removed on the last day, and the animals were swam for 120 seconds. The swimming time was measured in the area where the platform was placed and the memory was compared.

The results are shown in Fig.

As shown in FIG. 3, water maze experiments were performed to measure the spatial perception ability and short-term and long-term memory of experimental animals. Comparing the mean escape latency time for the animals to reach the hidden platform in the water for 4 days, the control group decreased the time to reach the platform over time, whereas the scopolamine administration decreased the memory The model could hardly find the platform. At 200 and 800 mg / kg, the mean escape time was reduced, indicating that the damaged memory was restored. On the last day, the platform was removed to perform the memory test, and then free swimming was performed for 120 seconds, and the time spent in the zone where the platform was located was measured through the Ethovision program. The results showed that the scopolamine - depressed model showed a significant decrease compared to the control group, and the time spent in the zone where the platform was in the 200, 400, and 800 mg / kg group, which was administered with water, was significantly increased.

6. Antioxidant Scatters  Measure

( 1) DPPH  Anti-oxidant Scatters  Measure

DPPH free radical scavenging was measured using the Blois method using DPPH, a relatively stable free radical. The sample was completely dissolved in water, and 100 μl of the solution was added to a 96-well plate. 100 μl of the DPPH solution was added, and the solution was left at room temperature for 30 minutes and absorbance was measured at 570 nm. The free radical scavenging performance was calculated as the percentage difference between the absorbance of the sample and non - irradiated samples. As a positive control, ascorbic acid (Sigma, USA) was used.

( 2) ABTS  Anti-oxidant Scatters  Measure

ABTS free radical scavenging was measured by the method of Van den Berg et al. 7 mM ABTS and 2.4 mM potassium persulfate were reacted in the dark for one day to form ABTS · ⁺ , and the absorbance was measured at 734 nm to dilute the absorbance value to 0.7. 100 μl of the diluted ABTS · ⁺ solution was added to the sample 100 ul, and the absorbance was measured after a reaction in a dark room for 7 minutes. The values of absorbance difference of sample and non - irradiated samples were calculated as percentage (%) and ascorbic acid (Sigma, USA) was used as positive control.

( 3) Conclusion

The results are shown in Fig.

As shown in FIG. 4, the various oxidative products produced by oxidation affect the memory and cognitive ability, and the antioxidative effects of DPPH and ABTS were measured in order to measure the antioxidative effect to suppress them.

DPPH showed 69.8% antioxidant activity in 1 mg / ml of water and 88.9% of ascorbic acid (Vit C) 0.1 mg / ml in the positive control group. ABTS assay showed 1 mg / ml of antioxidant activity of 96.9% and ascorbic acid (Vit C) of 0.1 mg / ml as a positive control was 100% effective.

8. Statistical processing

All the test results were statistically analyzed using one way analysis of variance. When the significance was recognized, the Student-Newman-Keuls test was used to test for significance at p <0.05 or less Respectively.

Claims (4)

A pharmaceutical composition for the prevention and treatment of amnesia and memory disorder related diseases, which comprises as an active ingredient, water. The composition according to claim 1, wherein the water is produced using Cinnamomum cassia, Syzygium aromaticum, Amomum cadamomum, Amomum villosum, and dermis (Citrus unshiu). The method of claim 1, wherein the amnesia and memory disorder related diseases are selected from the group consisting of Alzheimer's disease, cerebrovascular dementia, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, Pick's disease, Creutzfeldt- Jakob disease, A pharmaceutical composition which is dementia due to a disease, spinal cord injury or head injury A food composition for prevention and improvement of amenorrhea and memory disorder related diseases, which comprises as an active ingredient, water.

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