KR20170044394A - A composition comprising the extract of Cinnamomum cassia Blume for preventing, improving and treating brain disease - Google Patents
A composition comprising the extract of Cinnamomum cassia Blume for preventing, improving and treating brain disease Download PDFInfo
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- KR20170044394A KR20170044394A KR1020150144029A KR20150144029A KR20170044394A KR 20170044394 A KR20170044394 A KR 20170044394A KR 1020150144029 A KR1020150144029 A KR 1020150144029A KR 20150144029 A KR20150144029 A KR 20150144029A KR 20170044394 A KR20170044394 A KR 20170044394A
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- cinnamon
- extract
- disease
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- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
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Abstract
Description
The present invention relates to new uses for the prevention, improvement and treatment of degenerative brain diseases of cinnamon extracts.
Alzheimer's disease (AD) is usually chronic and progressive and represents a multiple disorder of brain function, including memory, thinking, comprehension, comprehension, learning, language and judgment. When we look at the pathology, the entire brain is atrophied, and a characteristic structure called neurofibrillary tangle and extracellular senile plaque is observed. The cerebral atrophy is caused by the death of cerebral cells. Meynert's basal ganglia, pyramidal cells, etc. are observed to die in large quantities. Especially, degenerative changes of cholinergic neurons cause dementia And is known to be highly related to.
In patients with Alzheimer's disease, the concentration of acetylcholine (Ach) is reduced due to the death of cholinergic nerve cells that produce neurotransmitters of basal ganglia cells, and choline acetyltransferase It is reported that the activity decreases and the cognitive ability decreases. Taking this into consideration, the development of a therapeutic agent for Alzheimer's disease is a method of activating the cholinergic action of the brain by administering a cholinergic agonist, acetylcholine precursor, and acetylcholinesterase (AChE) inhibitor to increase the concentration of acetylcholine Research. In particular, the AChE inhibitor (AChE inhibitor), which is being developed as a major drug, restores the activity of the cholinergic neurotransmitter by increasing the Ach level of the cerebrum by inhibiting the hydrolysis of ACh. Indeed, these AChE inhibitors are sold under the approval of the US Food and Drug Administration (FDA) and include tacrine, physostigmine, donepezil, metrifonate, galantamine galanthamine or rivastigmin. Recently, memantin has been used as a mechanism of action of NMDA (N-methyl-d-aspartate) receptor antagonist. However, AChE inhibitor drugs have problems with cholinergic side effects such as hepatotoxicity, nausea, vomiting, headache, and anorexia, and tacrine has already been withdrawn from the world market due to hepatotoxicity.
Inhibition of acetylcholinesterase does not eliminate the fundamental cause of dementia but inhibits the activity of this enzyme and inhibits the degradation of acetylcholine neurotransmitter in Alzheimer's dementia patients. Only. So far, there is no drug that can restore the cause of the disease called dementia to a normal state. Accordingly, in the development of a therapeutic agent for Alzheimer's disease, Alzheimer's disease requires a long-term use due to its characteristics, and since it is mostly taken by the elderly, there is a demand for a dementia treatment agent and a brain function improvement agent having more stable side effects.
On the other hand, cinnamon is a medicinal material made of bark of Cinnamomum cassia Blume belonging to the camphoraceae, and it is mainly consumed cinnamon in the form of cinnamon tea or cinnamon powder. Cinnamon has been known to be effective against various metabolic diseases because of the widely known antioxidant effect of cinnamon. The antioxidant activity of the cinnamon is believed to be effective for the prevention of degenerative brain diseases. Thus, the present inventors completed the composition for preventing, improving and treating the degenerative brain diseases of the present invention using the cinnamon extract.
The present invention provides a pharmaceutical composition for the prevention and treatment of degenerative brain diseases comprising cinnamon extract as an active ingredient, and a food composition for preventing and improving degenerative brain diseases comprising the extract.
The present invention also provides a pharmaceutical composition for inhibiting the activity of acetylcholinesterase (AChE) comprising 2,4-di-tert-butylphenol isolated from cinnamon as an active ingredient.
The inventors of the present invention found that cinnamon extract inhibits the activity of acetylcholinesterase during the study of natural substances against degenerative brain diseases and thus has an effect of preventing or treating degenerative brain diseases by increasing the level of acetylcholine in the cerebrum And completed the present invention.
The present invention relates to a novel use for the prevention and treatment of degenerative brain diseases of cinnamon extracts, a pharmaceutical composition for the prevention and treatment of degenerative brain diseases comprising cinnamon extract as an active ingredient, a therapeutically effective amount of cinnamon extract, And a method for preventing and treating degenerative brain diseases.
In the following examples, the effect of improving the cognitive ability of mice after administration of cinnamon extract to mice was confirmed, and it was confirmed that the cinnamon extract inhibited the activity of acetylcholinesterase. Therefore, the cinnamon extract can be used as an active ingredient of a composition for the prevention and treatment of degenerative brain diseases.
In the present invention, the cinnamon extract includes all the extracts obtained by the compression method or the solvent extraction method.
In one embodiment of the invention, the cinnamon extract may be extracted from cinnamon using water, an organic solvent or a mixture thereof as an extraction solvent. The kind of the organic solvent used and the mixing ratio of water and the organic solvent are not particularly limited.
For example, the organic solvent may be one or more solvents selected from the group consisting of lower alcohols, hexane, acetone, ethyl acetate, chloroform and diethyl ether. The lower alcohol may be an alcohol having 1 to 6 carbon atoms. For example, as the lower alcohol, methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, 1-pentanol, 2-butoxyethanol or ethylene glycol can be used. The organic solvent may be a polar solvent such as acetic acid, dimethyl-formamide (DMFO), or dimethylsulfoxide (DMSO), acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, 2,2,4- Butene, 1-chloropentane, o-xylene, diisopropyl ether, 2-chloropropane, toluene, 1-chloropropane, chlorobenzene, A nonpolar solvent such as benzene, diethyl ether, diethyl sulfide, chloroform, dichloromethane, 1,2-dichloroethane, aniline, diethylamine, ether, carbon tetrachloride and THF (tetrahydrofuran) may be used.
In one embodiment, the cinnamon extract may be a hydrothermal extract or a lower alcohol extract of cinnamon. Preferably an ethanol extract of cinnamon. In another embodiment, the cinnamon extract may be a hexane extract of cinnamon. In the present specification, the extract of organic solvent includes organic solvent alone or extract obtained by using a mixed solvent of organic solvent and water as extraction solvent. For example, the ethanol extracts of cinnamon include not only extracts using ethanol alone but also extracts obtained by using a mixed solvent of water and ethanol.
For example, the cinnamon extract of the present invention is prepared by mixing 4 kg of cinnamon finely ground with a hand mixer in water of 3 to 10 times, preferably 5 times (v / v), ethanol, methanol, Preferably 70-120 占 폚, by a conventional extraction method such as a low temperature alcohol or a mixed solvent thereof, preferably water or 5 to 95% ethanol, such as a room temperature extraction method, a heating extraction method, an ultrasonic extraction method and a reflux extraction method, A first step of extracting at 80 to 110 DEG C for 1 to 6 hours, preferably 3 to 5 hours; A second step of filtrating and concentrating the extract obtained in the above step under reduced pressure; And then lyophilized at -50 캜 to -20 캜, preferably at -45 캜 to -20 캜 for 12 to 72 hours, preferably for 12 to 50 hours. An extract can be obtained.
In one embodiment, the cinnamon extract is blanched for about 5 minutes at about 100 < 0 > C before grinding the cinnamon to obtain a cinnamon extract for the prevention or treatment of an effective neurological disease, And deactivating the enzyme.
As used herein, the term " extract " also includes fractions obtained by further fractionating the extract. That is, the cinnamon extract includes not only those obtained by using the above-mentioned extraction solvent, but also those obtained by additionally applying a purification process thereto. Further, fractions obtained by passing the above extract or fractions 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 The fractions obtained through various purification methods were also included in the cinnamon extract of the present invention.
In one embodiment, the cinnamon extract may be a fraction in which the organic solvent extract of cinnamon is re-fractionated with a second organic solvent. In another embodiment, the cinnamon extract may be a fraction obtained by fractionating a lower alcohol extract of cinnamon with a second organic solvent. For example, the cinnamon extract may be a fraction obtained by fractionating the ethanol extract of cinnamon with hexane.
The term " cinnamon extract " as used herein includes not only crude extract obtained by treating the cinnamon with an extraction solvent, but also processed products of cinnamon extract. For example, cinnamon extracts can be prepared in powder form by further processes such as vacuum distillation and lyophilization or spray drying.
The composition of the present invention may contain the cinnamon extract in an amount of 0.01 to 50% by weight based on the total weight of the composition. Such a composition is not limited thereto, and may vary depending on the concentration of the cinnamon extract, the state of the subject to which the composition of the present invention is administered, the type of disease and the degree of progression.
The term " comprising as an active ingredient " is meant herein to include an amount sufficient to achieve the efficacy or activity of the cinnamon extract. In one embodiment of the present invention, the cinnamon extract in the composition of the present invention may be administered in an amount of, for example, 0.01 mg / ml or more, preferably 0.05 mg / ml or more, more preferably 0.1 mg / ml or more, Gt; mg / ml < / RTI > Since the cinnamon extract has no adverse effect on the human body even when administered in an excessive amount as a natural product, the quantitative upper limit of the cinnamon extract contained in the composition of the present invention can be selected by a person skilled in the art within a suitable range.
The composition according to the present invention can be utilized as a pharmaceutical composition or a food composition.
The pharmaceutical composition of the present invention can be prepared by using pharmaceutically acceptable and physiologically acceptable adjuvants in addition to the above-mentioned active ingredients. Examples of the adjuvants include excipients, disintegrants, sweeteners, binders, coating agents, swelling agents, lubricants, A lubricant or a flavoring agent can be used.
The pharmaceutical composition may be suitably formulated into pharmaceutical compositions containing at least one pharmaceutically acceptable carrier in addition to the above-described effective ingredients for administration.
The pharmaceutical composition may be in the form of granules, powders, tablets, coated tablets, capsules, suppositories, liquids, syrups, juices, suspensions, emulsions, drops or injectable solutions. For example, for formulation into tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Also, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included as a mixture. Suitable binders include, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, natural and synthetic gums such as corn sweeteners, acacia, tracker candles or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum and the like.
Acceptable pharmaceutical carriers for compositions that are formulated into a liquid solution include sterile water and sterile water suitable for the living body such as saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, One or more of these components may be mixed and used. If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.
Further, it can be suitably formulated according to each disease or ingredient, using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.
The pharmaceutical composition of the present invention can be administered orally or parenterally. In the case of parenteral administration, the composition can be administered by intravenous injection, subcutaneous injection, muscle injection, intraperitoneal injection, transdermal administration, etc., .
The appropriate dosage of the pharmaceutical composition of the present invention varies depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate and responsiveness of the patient, Usually, a skilled physician can readily determine and prescribe dosages effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 0.0001 to 10 g / kg.
The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it with a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person skilled in the art to which the present invention belongs Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.
The present invention also provides a food composition for prevention and improvement of degenerative brain diseases comprising cinnamon extract as an active ingredient.
The food composition according to the present invention can be formulated in the same manner as the above pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, alcoholic beverages, confectioneries, diet bars, dairy products, meat, chocolates, pizza, ram noodles, other noodles, gums, ice cream, .
The food composition of the present invention may contain not only an extract of cinnamon as an active ingredient but also a component that is ordinarily added at the time of food production, for example, a protein, a carbohydrate, a fat, a nutrient, a seasoning agent and a flavoring agent. Examples of the above-mentioned carbohydrates are monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavorings such as tau martin and stevia extract (e.g., rebaudioside A and glycyrrhizin) and synthetic flavorings (saccharine, aspartame, etc.) can be used as flavorings. For example, when the food composition of the present invention is prepared from a drink and a beverage, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, juice, various plant extracts and the like may be further added in addition to the cinnamon extract of the present invention.
The present invention provides a health functional food comprising a food composition for preventing and improving degenerative brain diseases comprising the cinnamon extract as an active ingredient. A health functional food is a food prepared by adding a cinnamon extract to a food material such as beverage, tea, spice, gum or confection, or encapsulated, powdered or suspended, Meaning, unlike general medicine, there is an advantage that there is no side effect that can occur when a food is used as a raw material for a long time. The health functional food of the present invention thus obtained is very useful because it can be ingested routinely. The amount of the cinnamon extract added in such a health functional food can not be uniformly determined depending on the type of the health functional food to which it is added but may be added within a range that does not deteriorate the original taste of the food, To 50% by weight, preferably 0.1 to 20% by weight. In the case of health functional foods in the form of pills, granules, tablets or capsules, they may be added usually in the range of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the health functional food of the present invention may be in the form of a pill, tablet, capsule or beverage.
The invention also provides the use of said cinnamon extract for the manufacture of a medicament or food for the prevention, amelioration and treatment of degenerative brain diseases. As described above, the cinnamon extract can be used for prevention, improvement and treatment of degenerative brain diseases.
The present invention also provides a method of preventing, ameliorating, and treating a degenerative brain disease comprising administering an effective amount of cinnamon extract to a mammal.
As used herein, the term " mammal " refers to a mammal that is the subject of treatment, observation, or experimentation, preferably a human.
The term " effective amount " as used herein refers to the amount of active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human, as contemplated by a researcher, veterinarian, physician or other clinician, ≪ / RTI > inducing a reduction of the symptoms of the disease or disorder. It will be apparent to those skilled in the art that the effective amount and the administration frequency of the active ingredient of the present invention will vary depending on the desired effect. Thus, the optimal dosage to be administered can be readily determined by those skilled in the art and will vary with the nature of the disease, the severity of the disease, the amount of active and other ingredients contained in the composition, the type of formulation, and the age, The age, body weight, sex, diet, time of administration, route of administration and fraction of the composition, duration of treatment, concurrent medication, and the like. In the prevention, treatment or improvement method of the present invention, in the case of an adult, it is preferable to administer the cinnamon extract at a dose of 0.001 mg / kg to 10 g / kg once to several times a day.
In the therapeutic method of the present invention, the composition comprising the cinnamon extract as an active ingredient can be administered orally, rectally, intravenously, intraarterally, intraperitoneally, intramuscularly, intrasternally, transdermally, topically, Lt; / RTI >
The composition of the present invention can be applied to the prevention, amelioration and treatment of diseases caused by a decrease in acetylcholine concentration due to the activity of acetylcholinesterase. The composition of the present invention can be applied to prevention, improvement and treatment of degenerative brain diseases, but the present invention is not limited thereto, and may include Alzheimer's disease, dementia, Parkinson's disease and Huntington's disease.
Also, the present invention provides a pharmaceutical composition for inhibiting acetylcholinesterase (AChE) activity comprising 2,4-di-tert-butylphenol isolated from cinnamon as an active ingredient.
In one embodiment, 2,4-di-tert-butylphenol isolated from the cinnamon is obtained by refluxing cinnamon ethanol extracts with hexane, chloroform and ethyl acetate to obtain the respective solvent fractions; Fractionating the fractions by silica gel open column chromatography with a mixed solvent of chloroform and ethanol; Performing thin layer chromatography (TLC) on the fraction having the highest acetylcholinesterase inhibiting activity among the above-mentioned small fractions to obtain an active band; And separating the active band by HPLC to obtain 2,4-di-tert-butylphenol.
The pharmaceutical and food compositions of the present invention inhibit the hydrolysis of acetylcholine to increase the level of acetylcholine in the cerebrum, thereby restoring the activity of the cholinergic neurotransmitter, so that it can be effectively used for preventing or treating degenerative brain diseases have.
Figure 1 shows the results of AChE inhibition of the ethanol extract of cinnamon.
FIG. 2 is a graph showing the AChE inhibitory effect of the organic solvent fraction treatment of the cinnamon extract. FIG.
Figure 3 is a graph showing the AChE inhibition of the first open-column chromatographic fraction-treated group of the cinnamon-chloroform fraction (C2).
Figure 4 is a graph showing the AChE inhibition of the second open-column chromatographic fraction-treated group for CHCl 3 : EtOH = 90: 10-2 small fractions.
Figure 5 is a graph showing the AChE inhibition of the third open-column chromatographic fraction-treated group for CHCl 3 : EtOH = 94: 6 fractions.
Figure 6 is a graph showing the AChE inhibition of band treatment groups obtained using TLC for CHCl 3 : EtOH = 96: 4 fractions.
7 is a graph showing the HPLC results of the Rf value 0.64 band portion.
FIG. 8 is a table summarizing the purification process of cinnamon extracts through Examples 1 and 2. FIG.
FIG. 9 shows the results of the Y-maze test showing that memory learning ability reduced by TMT injection is increased again in the group consuming cinnamon extract.
FIG. 10 shows the result of the passive avoidance test showing that memory learning ability reduced by TMT injection is increased again in the group consuming cinnamon extract.
FIG. 11 shows the results of the Y-maze test showing that memory learning ability reduced by TMT injection is increased again in the group taking 2,4-di-tert-butylphenol.
Figure 12 shows the result of a passive avoidance test showing that memory learning ability reduced by TMT injection is increased again in the group taking 2,4-di-tert-butylphenol.
Advantages and features of the present invention and methods of achieving them will become apparent with reference to the embodiments described in detail below. The present invention may, however, be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Is provided to fully convey the scope of the invention to those skilled in the art, and the invention is only defined by the scope of the claims.
[Experimental Example 1] AChE inhibition of cinnamon extract
1) Preparation of cinnamon ethanol extract
4 kg of cinnamon finely ground with a hand mixer was shaken with 5 times volume of ethanol (v / v) for 24 hours, and then extracted five times, followed by concentration under reduced pressure to prepare a cinnamon ethanol extract.
2) Measurement of AChE inhibitory effect of cinnamon extract
(Ellman, GL, Courtney, KD, Andres, V. Jr. and Featherstone, RM (1961) A new and Ellman's method to determine whether the cinnamon ethanol extract prepared in 1) rapid colorimetric determination of acetylcholinesterase activity, Biochem. Pharmacol., Vol. 7, pp. 88-95). (5-dithio-bis (2-nitrobenzoic acid)) (DTNB) were all purchased from Sigma Chemical Co. and sodium phosphate buffer pH 8.0 was used as a buffer solution. Respectively. Substrate solution was prepared by adding 500 M acetylthiocholine and 1 mM (5,5-dithio-bis (2-nitrobenzoic acid)) (DTNB) to 50 mM sodium phosphate buffer (pH 8.0). The instrument used for the reaction was a Bio-Rad microplate reader model 550. 50 μl of the buffer, 10 μl of the sample, 10 μl of the acetylcholinesterase enzyme, and 70 μl of the substrate solution were placed in a 96-well plate, followed by reaction at 37 ° C for 15 minutes in an incubator. Then, the inhibition activity was measured by the following equation at the value measured at 405 nm. When the AchE inhibitory activity of the cinnamon extract was measured, tacrine was used as a control group with a concentration of 300 nM. The results are shown in Fig.
[Mathematical Expression]
As shown in FIG. 1, the AChE inhibitory activity was higher than that of 300 nM tacrine at a concentration of 1.0 mg / ml of ethanol extract of cinnamon.
[Experimental Example 2] Separation of AChE inhibitor
1) Separation by solvent
The organic extracts prepared in Example 1 were completely dispersed in water, and then hexane fraction (H1, H2, H3), chloroform fraction (C1, C2, C3) and ethylacetate fractions (E1, E2, E3) were measured. As a result, as shown in FIG. 2, the second chloroform fraction (C2) showed excellent AChE inhibitory activity.
2) Separation by silica gel open column chromatography
The first open column chromatography was performed on the second chloroform fraction (C2) after solvent fractionation. The separated fractions (chloroform: ethanol = 100: 0, 90:10, 80:20, 70:30, 60:40, 50:50, 40:60, 30:70, 20:80, 10:90, 0 (CHCl 3 : EtOH = 90: 10-2), which had the highest inhibitory activity as shown in FIG. 3, was used to measure the AChE inhibitory activity Respectively.
A second open column chromatography was performed with CHCl 3 : EtOH = 90: 10-2 small fractions. Separate fractions (chloroform: ethanol = 100: 0, 98: 2, 96: 4, 94: 6, 92: 8, 90: : 20; 1 time each, total 11 fractions) were used to measure the AChE inhibitory activity, and the fraction of CHCl 3 : EtOH 94: 6 having the highest inhibitory activity was selected as shown in FIG.
A third open column chromatography was performed with CHCl 3 : EtOH = 94: 6 small fractions. AChE inhibitory activity was measured using each of the separated fractions (chloroform: ethanol = 97: 3, 96: 4, 95: 5, 94: 6, 93: 7, 92: measured, too, the with a high inhibitory activity, such as CHCl 3 5: 4 were finally selected for the small fraction: 96 of EtOH.
3) Isolation by TLC
2), the 96: 4 fraction of CHCl 3 : EtOH, which showed the highest inhibitory effect, was subjected to thin layer chromatography (TLC) using a preparative silica-gel plate (aluminum, 100 × 100 mm). Selected fractions were dissolved in ethanol at a concentration of 902.8 mg / ml and dried by spotting 4 times with 0.5 μl each. After developing with chloroform and ethanol (90:10, v / v), the band was separated and the AChE inhibitory activity was measured. As a result, as shown in FIG. 6, the ninth band (Rf value = 0.64) out of the total 12 bands showed the highest inhibitory activity.
4) Isolation by HPLC
3), the HPLC assay was performed to isolate the active component of the 9th band. The HPLC conditions were as shown in Table 1 below and the results as shown in FIG. 7 were obtained. As a result, a significant peak was observed at a wavelength of 290 nm at 31 minutes, and the AChE inhibitor was identified as 2,4-di-tert-butylphenol.
The process of extracting cinnamon extract from Example 2 is shown in FIG.
Example 3: Measurement of cognitive ability improvement effect in vivo
1) Measuring the improvement effect of cinnamon extract on cognitive ability
ICR male mice (4 weeks old) were housed in a 12 hr photoperiod chamber with a relative humidity of 30 ~ 70% at 20 ~ 24 ℃, and ethanol extracts of cinnamon were added to the feeds (400, 800, 1200 ㎎ / Kg body weight per day) for about 3 weeks. On the 21st day after the start of the diet, trimethyltin (TMT), a dementia inducing substance, was injected and Y-maze test and passive avoidance experiment were conducted.
In order to measure the alternation behavior, behavioral experiments were conducted in the Y-maze with three arms, A, B, and C, respectively. The Y-maze was 32.5 cm in length, 15 cm in height, and 4 cm in width, and each arm was defined as A, B, The mice were placed in a maze and allowed to move freely for 8 minutes without any stimulation, and then the number of the two hind paws in the arm except for the tail was measured and calculated. The results are shown in Fig. 9 and Fig. 9, and 10, the control group was fed with only normal diet, TMT was treated with TMT after feeding, and C400, C800 and C1200 were treated with 400, 800 and 1200 mg / kg per day And TMT treated group.
As a result, as shown in FIG. 9, it was confirmed that the TMT group causing dementia was reduced by about 17% as compared with the control group, but the memory was improved in the group to which the cinnamon extract was supplied. In particular, TMT was blocked in the 800 and 1200 ㎎ / ㎏ concentration groups and almost recovered to control level of brain activity. There was no significant difference in the number of times of entry into Arms, so TMT and cinnamon extract did not affect the exercise capacity of mice.
The passive avoidance experiment was conducted by training the mouse in the same place as the memory box, and then conducting a behavioral test the day before the actual experiment. All the mice were subjected to adaptive training (light room, light room, light room, shock) in the experimental box, and after 24 hours, For 300 sec.
As a result, as can be seen from FIG. 10, the learning ability of the TMT-treated group was remarkably decreased, but the effect of protecting the learning ability and enhancing the effect of the extract of cinnamon extract was shown. Especially, the group that consumed 1,200 mg / kg of cinnamon extract showed better learning effect than the control group.
2) Experiment to measure cognitive improvement effect of AChE inhibitor
For memory experiments, ICR male mice (4 weeks old) were housed in a 12 hr photoperiod chamber with a relative humidity of 30-70% at 20-24 ℃, and 2,4-di-tert-butylphenol was added to the feed (5, 10, 20, and 40 mg / kg body weight per day) for about 3 weeks. On the 21st day after the start of the diet, trimethyltin (TMT), which is a dementia inducing substance, was injected and Y-maze test and passive avoidance experiment were performed as in 1) above. The results are shown in Figs. 11 and 12. Fig. 12, 12, and 12, control was performed in the control group, and TMT was the group treated with TMT only after feeding the normal diet. BP5, BP10, BP20 and BP40 were 2,4-di-tert-
As can be seen in Fig. 11, the Y-maze results showed that the TMT group was reduced by about 20% as compared with the control group, but the decrease was inhibited in the group to which the sample was supplied. In particular, the 2,4-di-tert-butylphenol group at 20 and 40 mg / kg showed the recovery effect in mice induced amnesia. The number of times of entry into the arms did not show any significant difference between the groups, so TMT and 2,4-di-tert-butylphenol did not affect the motor performance.
As shown in FIG. 12, it was confirmed that the cognitive ability of the sample group was recovered according to the concentration by protecting the memory learning ability inhibition effect (inducing loss of cognitive ability and learning ability) of the TMT, , Indicating a cognitive ability of the control group in the 2,4-di-tert-butylphenol group at a concentration of 40 mg / kg, thereby normally protecting brain cell signaling.
Hereinafter, formulation examples of the composition containing the extract of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.
[Formulation Example 1] Preparation of powders
Cinnamon extract 20mg
Lactose 100mg
Talc 10mg
The above components are mixed and filled in airtight bags to prepare powders.
[Formulation Example 2] Preparation of tablet
Cinnamon extract 10 mg
1 mg of magnesium stearate
Microcrystalline cellulose 84 mg
After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.
[Formulation Example 3] Preparation of capsules
Cinnamon extract 10 mg
Lactose 14.8 mg
Magnesium stearate 0.2 mg
The above components are mixed in accordance with a conventional method for producing a capsule, and filled in a gelatin capsule to prepare a capsule.
[Formulation Example 4] Preparation of injections
Cinnamon extract 10 mg
180 mg mannitol
Sterile sterilized water for injection 2974 mg
Na 2 HPO 4 , 12H 2 O 26 mg
(2 ml) per ampoule in accordance with the usual injection method.
[Formulation Example 5] Preparation of liquid agent
Cinnamon extract 20 mg
10 g per isomer
5 g mannitol
Purified water quantity
Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.
[Formulation Example 6] Preparation of health food
Cinnamon extract 1000 mg
Vitamin mixture quantity
70 [mu] g of vitamin A acetate
Vitamin E 1.0 mg
0.13 mg vitamin B1
0.15 mg of vitamin B2
0.5 mg vitamin B6
0.2 [mu] g vitamin B12
10 mg vitamin C
Biotin 10 μg
Nicotinic acid amide 1.7 mg
50 ㎍ of folic acid
Calcium pantothenate 0.5 mg
Mineral mixture quantity
1.75 mg of ferrous sulfate
0.82 mg of zinc oxide
Magnesium carbonate 25.3 mg
15 mg of potassium phosphate monobasic
Secondary calcium phosphate 55 mg
Potassium citrate 90 mg
100 mg of calcium carbonate
24.8 mg of magnesium chloride
Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.
[Formulation Example 7] Preparation of health drink
Cinnamon extract 1000 mg
Citric acid 1000 mg
100 g of oligosaccharide
Cinnamon concentrate 2 g
Taurine 1 g
Purified water was added to a total of 900 ml
The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >
Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.
Claims (15)
Wherein the cinnamon extract is an extract of cinnamon water, an organic solvent or a mixture thereof.
Wherein the organic solvent is at least one solvent selected from the group consisting of lower alcohols, hexane, acetone, ethyl acetate, chloroform, and diethyl ether.
Wherein the cinnamon extract is a lower alcohol extract of cinnamon.
Wherein the cinnamon extract is an ethanol extract of cinnamon.
Wherein the cinnamon extract is a hexane extract of cinnamon.
Wherein said degenerative brain disease is at least one selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease and Huntington's disease.
Wherein the cinnamon extract is an extract of cinnamon water, an organic solvent or a mixture thereof.
Wherein the organic solvent is at least one solvent selected from the group consisting of lower alcohols, hexane, acetone, ethyl acetate, chloroform, and diethyl ether.
Wherein the cinnamon extract is a lower alcohol extract of cinnamon.
Wherein the cinnamon extract is an ethanol extract of cinnamon.
Wherein the cinnamon extract is a hexane extract of cinnamon.
Wherein the degenerative brain disease is at least one selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease and Huntington's disease.
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