KR101106376B1 - A composition comprising the extract of dictyota coriacea treating and preventing neuro-degenerative disease - Google Patents

Abstract

PURPOSE: A pharmaceutical composition or health food containing Dictyota coriacea extract is provided to improve learning and space perception ability. CONSTITUTION: A pharmaceutical composition for preventing and treating Alzheimer dementia contains water and ethanol mixture extract of Dictyota coriacea as an active ingredient. A health food for preventing and treating Alzheimer dementia contains the extract as an active ingredient. The extract is isolated using water, low alcohol of C1-C4, or mixture solvent thereof. A health food for preventing and treating amnesia and neurodegenerative diseases contains the extract as an active ingredient.

Description

A composition comprising the extract of Dictyota coriacea treating and preventing neuro-degenerative disease}

The composition containing the extract of the bamboo shoots of the present invention as an active ingredient exhibits an excellent effect of improving the learning and spatial perception ability of the memory group induced by scopolamine to a high level, thereby improving forgetfulness and degeneration. It is useful for treating brain diseases.

Jin DQ et al, Anti-oxidant and anti-inflammatory activities of macelignan in murine hippocampal cell line and primary culture of rat microglial cells. Biochem Biophys Res Commun. 2005; 331: 1264-1269.

[2] Lim CS et al, Antioxidant and anti-inflammatory activities of the methanolic extract of Neorhodomela aculeate in hippocampal and microglial cells. Biol Pharm Bull. 2006; 29: 1212-1216.

Myhrer T. Neurotransmitter systems involved in learning and memory in the rat: a meta-analysis based on studies of four behavioral tasks. Brain Res Rev. 2003; 41: 268-87.

4 Blokland, A. Acetylcholine. a neurotransmitter for learning and memory. Brain research. Brain Res Rev. 1995; 21: 285-300.

Reference 5 Nobili L, Sannita WG. Cholinergic modulation, visual function and Alzheimer's dementia. Vision Res. 1997; 37 (24): 3559-71.

[Document 6] Lee Yong-pil, Jeju's Sea Horse, Academy Books, p.479, 2008

Kim, DH et al., (2007) Nodakenin, a coumarin compound, ameliorates scopolamine-induced memory disruption in mice. Life Sci . 80: 1944-1950.

The present invention relates to a composition for the treatment and prevention of forgetfulness and degenerative brain disease, including the extract of the bamboo shoots.

For modern people, memory is increasing in importance in rapidly changing life, and it is becoming a major concern from adolescents with a lot of social learning to old age. This deterioration in society is a social problem, and memory loss is a very important factor in the availability of social life in patients with degenerative diseases such as dementia in the elderly population. Dementia is a disease that causes a significant drop in quality of life, both personally and socially, and makes you and those around you unhappy. It is the fourth leading cause of death for the elderly, following cancer, heart disease, and stroke. Dementia is divided into Alzheimer's dementia and vascular dementia. Alzheimer's dementia is a form of dementia that is widely observed in the West, and is caused by the destruction of cholinergic neurons due to the accumulation of beta amyloid in certain parts of the brain. Vascular dementia is a dementia caused by hypertension, stroke, and hyperlipidemia due to abnormal blood vessels leading to the brain, which kills hippocampus and limbic system nerves. Although these two types of dementia have different causes, they have the same mechanism in that they cause damage to memory by reducing the action of acetylcholine, also known as memory transmission neurons.

Recently, efforts have been made to develop effective treatments and establish various treatment strategies to improve and improve cognitive and learning functions deteriorated due to dementia. Memory-improving drugs developed to date include acetylcholine precursors, receptor agonists, and acetylcholine esterase inhibitors. However, to date, no therapeutic agents have been developed to treat the underlying cause of Alzheimer's disease.Available as general therapeutic agents are Aricept, Pfizer's Aricept, Novartis's Exelon, and Janssen. And Lundbeck's Ebixa (Memantine), a mechanism of antagonists of Reminyl and the recently approved NMDA receptor by the US FDA. However, acetylcholine esterase inhibitors only improve the cognitive ability that has been impaired and do not cure the underlying cause of Alzheimer's disease. In addition, only a few patients have a temporary symptom relief effect, the drug does not last long, so it is difficult to be a fundamental treatment. In addition, the nature of the disease requires long-term administration, the drug is also accompanied by various side effects, including liver toxicity, vomiting, loss of appetite has also been revealed as a problem. Therefore, the development of a therapeutic agent that can prevent the progress of the disease is an urgent task. Many multinational pharmaceutical companies are investing heavily in research and development in this area, especially beta or gamma secretase inhibitors, which reduce the production of beta amyloid, which consists of about 40 amino acids that are believed to be the primary cause of Alzheimer's disease. Development is the dominant. In Korea, basic research on Alzheimer's disease has been conducted to some extent, but there is almost no case in developing dementia treatment itself.

As the standard of living improves and the life span of humans increases, interest in aging and various diseases related to aging is increasing, and oxidative stress has been found to be an important factor in degenerative brain diseases of the central nervous system such as Alzheimer's syndrome, Parkinson's syndrome, and Huntington's syndrome. (Jin DQ et al, Biochemical and Biophysical Research Communications, 331: 1264-1269, 2005; Lim CS et al, Biological and Pharmaceutical Bulletin, 29: 1212-1216, 2006).

Nervous systems related to memory are known as cholinergic nervous system, glutamatergic nervous system, GABAergic nervous system, serotonergic nervous system, and adrenergic nervous system, but especially cholinergic nervous system. It is known to be related to memory. Scopolamine blocks muscarinic receptors, one of the subtypes of cholinergic neurons, so the drugs that work in this model are thought to be efficacious via the cholinergic nervous system. Drugs developed to date include acetylcholine precursors, receptor agonists, and acetylcholinesterase inhibitors, but their effects are temporary, weak, and seriously toxic. There are many states. Currently used at home and abroad, the anti-memory treatments include anticholinergic drugs for symptom improvement, antidiarrheal drugs that promote non-specific metabolism, and blood circulation improvers that improve blood circulation, but the effects of these drugs are temporary and these drugs have parasympathetic nerve stimulation. It can cause side effects such as nausea, vomiting, and bronchial contraction, and may cause depression, insomnia, hypertension, and constipation (Myhrer T. Neurotransmitter systems involved in learning and memory in the rat: a meta-analysis based on studies of four behavioral tasks.Brain Res Rev. 2003; 41: 268-87 .; Blokland, A. Acetylcholine.a neurotransmitter for learning and memory.Brain research.Brain Res Rev. 1995; 21: 285-300 .; Nobili L, Sannita WG. Cholinergic modulation, visual function and Alzheimer's dementia.Vision Res. 1997; 37 (24): 3559-71).

Participation in Dictyota coriacea (Holmes)) refers to the plants, brown algae belonging to galjo door (Phaeophyceae), based on the net malmok (Dictyotales) and net basis Horse (Dictyotaceae). It is brown, thinly dented, divided into two branches several times, and grows into a fan shape. The roots are short strings, and the branches may be twisted or twisted one or two times, and the sides of the branches are narrow. It is a marine plant that grows up to 30 cm in the cross section of the branch and the cortex has two layers of chloroplasts. The water tissue is one layer of large cells, and grows in the southern coast or the sea near Jeju Island. Academy Books, p. 479, 2008).

Accordingly, the present inventors have studied the present invention to find a marine natural excellent in the improvement of dementia and forgetfulness, as a result, the extract of participating bamboo grass roots and the ability to enhance learning and spatial perception of the forgetful animal group induced by scopolamine It was confirmed that the recovery of the activity is superior to the existing therapeutic agent to confirm that it is useful for the treatment and prevention of degenerative brain diseases, and completed the present invention.

In order to solve the above object, the present invention provides a pharmaceutical composition for the treatment and prevention of forgetfulness and degenerative brain disease, containing the extract of the bamboo shoots as an active ingredient.

In another aspect, the present invention provides a health functional food for the prevention and improvement of forgetfulness and degenerative brain disease, containing the extract of the bamboo shoots as an active ingredient.

Extracts as defined herein include water, lower alcohols of C ₁ to C ₄ or mixed solvents thereof, preferably extracts available in water or a mixed solvent of water and ethanol.

The degenerative brain disease is characterized by including stroke, stroke, dementia, Alzheimer's disease, Parkinson's disease, or Huntington's disease, specifically, vascular dementia and Alzheimer's dementia.

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

For example, the crude extract of the present invention is about 1 to 10 times the weight of the sample, preferably about 1 to 5 times (w / v) volume of water after washing and drying the participating bamboo grasses, C ₁ to C ₄ lower alcohols or mixed solvents thereof, preferably water or water and ethanol as an extraction solvent, and about 2 hours to a reaction temperature of about 10 to 120 ℃, preferably 30 to 90 ℃ 10 to 10 hours, preferably 4 to 8 hours, such as heating extraction, ultrasonic extraction, reflux extraction, such as conventional extraction method, preferably reflux extraction extraction method 1 to 10 times, preferably 1 to 5 times repeated extraction Step 2; A third step of filtering and extracting the extract obtained in the above step under reduced pressure; Participation of the present invention can be obtained through the step comprising the fourth step of the freeze-drying the concentrated extract of the present invention.

In another aspect, the present invention provides a pharmaceutical composition and health functional food for improving the forgetfulness and the treatment and prevention of degenerative brain disease, containing the extract of the present invention and the participating bamboo bark horse powder prepared by the manufacturing method as an active ingredient.

The above-mentioned extracts of the bark nettle horses are useful for the treatment and prevention of degenerative brain diseases by confirming that the scopolamine-induced learning and recovery of spatial perception ability of the amnesia animal group is superior to existing therapeutic agents. .

The composition of the present invention comprises 0.01 to 99% by weight of the herbal extract 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.

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

Compositions comprising extracts according to the invention are formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. The carriers, excipients and diluents that may be incorporated therein include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicates, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one or more excipients in the compound, at least cotton, starch, calcium carbonate, sucrose. Or lactose, gelatin, or the like is mixed. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Examples of the liquid preparation for oral use 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. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

Preferred dosages of the extracts of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the extract is preferably administered at 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg per day. The administration may be carried out once a day or divided into several doses. Therefore, the above dosage does not limit the scope of the present invention in any aspect.

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 can be expected, for example by oral and rectal or intravenous methods.

In another aspect, the present invention provides a health functional food for the prevention and improvement of forgetfulness and degenerative brain disease, containing the extract of the bamboo shoots as an active ingredient.

Health functional foods containing the extract of the present invention can be used in a variety of drugs, foods and drinks for the prevention and improvement of degenerative brain diseases. Examples of the food to which the extract of the present invention may be added include various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, and may be used in the form of powders, granules, tablets, capsules, or beverages. .

Therefore, the present invention also provides a food and food additive containing the extract of Participating bark foot meal, which has an effect of preventing and improving forgetfulness and degenerative brain disease.

Food forms to which the extract of the present invention can be added include various foods, beverages, gums, teas, vitamin complexes, or health supplements of candy.

Extract of the present invention may be added to food or beverages for the purpose of preventing and improving degenerative brain diseases. At this time, the amount of the extract in the food or beverage is generally added to the health food composition of the present invention to 0.01 to 15% by weight of the total food weight, the health beverage composition is 0.02 to 10 g based on 100 ml, preferably Can be added in a ratio of 0.3 to 1 g.

The health beverage composition of the present invention contains a mixture of the extract as an essential ingredient in the indicated ratio, and there is no particular limitation on the liquid component, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. have. 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. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract, for example rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. . The proportion of such natural carbohydrates 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, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation 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 fruit juice drinks and vegetable drinks. These components can 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.

Participants extract of the present invention is a high level of learning and spatial perception ability in the passive avoidance task and Y-maze test in the memory group of memory loss induced by scopolamine. The present invention provides a pharmaceutical composition or health functional food useful for improving forgetfulness and treating degenerative brain disease because it exhibits excellent efficacy.

1 is a view showing the results of performing a passive avoidance test;
2 is a diagram showing the results of the Y-maze test.

Hereinafter, the present invention will be described in detail by the following Reference Examples and Experimental Examples.

However, the following Reference Examples and Experimental Examples are merely illustrative of the present invention, the content of the present invention is not limited by the following Reference Examples and Experimental Examples.

Example  One. Participation  Preparation of 70% Ethanol Extract

After drying the outposts of dried bark horses taken from Jeju sea, 20 kg of the sample was heat-extracted three times for six hours with 60 liters of 30% of 70% ethanol at 60 ° C. It was filtered and the filtrate was concentrated in a vacuum concentrator (BR-205, V-805, BLabortechnik AG, Flawil, Switzerland). The concentrate was lyophilized in an lyophilizer (Eyela Model FD-1, Tokyo Rikaikikai Co., LTD, Japan) to obtain a granular final extract (hereinafter referred to as "CP") and used as a sample of the following experimental example.

Reference Example  1. Drugs and reagents

Scopolamin (S1875), tacrine (A3773) are described in Sigma-Aldrich Chemistry Co. The reagents were purchased from and used, and the best reagents commercially available were used. Participants were taken from Jeju sea and used.

Reference Example  2. Preparation of experimental animals

10-week-old SD rats (240-260 g male) were supplied from Hallim Experiment Animal Co., Ltd. (Hwaseong, Korea).

The herbal extract (CP) prepared in Example 1 was administered intraperitoneally 30 minutes prior to laboratory administration of scopolamine (Sigma-Aldrich Co.) at a dose of 1 mg / kg, and the experimental animals were divided into four groups. Leather net ground extract or Tacrine (Tacrine; Sigma-Aldrich Co.) was administered orally once in the doses listed in Table 1 40 minutes before behavioral observation.

Drug nonadministration
Bamboo Extract Extract (mg / kg) Tacrine (mg / kg)
0
50
100
10
0
50
100
10

Reference Example  3. Statistical Processing

The data were analyzed by means ± SEM and one-way analysis of variance (ANOVA) was used to test statistical significance. The Post hoc test was applied to the Newman-Keuls test and judged to be a significant difference at * p <0.05.

Experimental Example  1. Observation of memory change in passive avoidance experiment

In order to confirm the effect in the passive avoidance experiment of the Participated Horsetail Extract (CP) obtained in the above Examples, the experiment was performed as follows (Kim, DH et al., (2007) ) Nodakenin, a coumarin compound, ameliorates scopolamine-induced memory disruption in mice. Life Sci . 80: 1944-1950).

1-1. Experiment method

It consists of two chambers, a bright room and a dark room, with a grid of 2 mm spacing on a 20 × 20 × 20 cm floor made of black polyvinyl plastic. The bright room is equipped with a 50W bulb and the dark room is connected to an electrical stimulator to allow electricity to flow along the grid. Rats were placed in brightly lit compartments, and after 20 seconds of search time, the guillotine doors were opened to enter the dark compartments. After 24 hours, the rats were placed in the illuminated bright compartment again and after 20 seconds of search time allowed the guillotine door to enter the dark compartment and the latency time for all four rounds to enter the dark was measured. Mice that did not migrate to the second space, which remained dark until 40 seconds after opening of the guillotine-type entrance, were excluded from the experiment.

1-2. Experiment result

Passive avoidance tests were performed on the scopolamine-induced forgetful animal model for each of the Participating bark horsetail extract (CP) prepared in the above examples.

Each group used 10 mice. In all experiments, the retention time of the scopolamine-only group was significantly reduced compared to the control group, indicating that a memory loss model was produced. In the dose-dependent experiment of CP extract, the retention time of the scopolamine-only group, as shown in FIG. 1, averaged 74 seconds before moving to the light-free space by learning. In the case of administration and administration of polyamine, it was confirmed that the movement occurred in an average of 18.3 seconds. After scopolamine pretreatment, the mean value was 51 seconds with 50 mg of joktang powder extract, 68 seconds with 100 mg of extract, and 63 seconds with 10 mg / kg of tacrine. Participating bamboo batter confirmed better memory improvement than tacrine.

Experimental Example  2. Y maze test (Y- maze test Learning and memory effects

In order to confirm the effect in the Y labyrinth experiment of the participated bamboo grass extract (CP) obtained in the above example, the experiment was conducted as follows (Kim, DH et al., (2007) ) Nodakenin, a coumarin compound, ameliorates scopolamine-induced memory disruption in mice. Life Sci . 80: 1944-1950).

2-1. Experiment method

The herbal extract (CP) prepared in Example 1 was subjected to a Y maze test on a scopolamine-induced forgetful animal model.

Experimental device consisting of three branches (A, B, C) made of black polyvinyl plastic, each arm is 50 cm long, 10 cm wide, 20 cm high and has an angle of three arms contacting 120 degrees The animals were carefully placed and allowed to move freely for 8 minutes, and then recorded the branches. One point (actual alteration) was given to each of three different branches in turn, and the alteration behavior was calculated by Equation 1 below.

2-2. Experiment result

The altered behavior of normal animals was 67 points, but decreased to 45.5 points by the administration of scopolamine. The change behavior was restored to 52.1 points by 50mg administration of JJK extract, and further increased to 55.9 by 100mg extract. The administration of taclean 10 mg / kg, an existing dementia treatment, increased to 54.4 points. In addition, the behavior of alteration was confirmed to be better in memory than tacrine.

Hereinafter, a preparation example of a composition containing an extract of the present invention will be described, but the present invention is not intended to be limited thereto but only to be described in detail.

Formulation example  One. Powder  Produce

CP 200 mg

Lactose 100 mg

Talc 10 mg

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

Formulation example  2. Preparation of Tablets

CP 200 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

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

Formulation example  3. Manufacture of capsule

CP 200 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium stearate 0.2 mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

Formulation example  4. Preparation of injections

CP 200 mg

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO _{4 ,} 12H ₂ O 26 mg

According to the conventional method for preparing an injection, it is prepared in the amount of the above ingredient (2) per ampoule.

Formulation example  5. Liquid  Produce

CP 200 mg

10 g per isomer

5 g of mannitol

Purified water

After dissolving each component in purified water according to the usual method of preparing a liquid solution, adding a proper amount of lemon aroma, and then mixing the above components, adding purified water and adjusting the whole to 100 ml by adding purified water and filling into a brown bottle. The solution is prepared by sterilization.

Formulation example  6. Manufacture of health food

CP 1000 mg

Vitamin mixture proper amount

Vitamin A Acetate 70

Vitamin E 1.0

Vitamin B1 0.13

Vitamin B2 0.15

Vitamin B6 0.5

Vitamin B12 0.2

Vitamin C 10

Biotin 10

Nicotinamide 1.7

Folic acid 50

Calcium Pantothenate 0.5

Mineral mixture

Ferrous Sulfate 1.75

Zinc Oxide 0.82

Magnesium Carbonate 25.3

Potassium Phosphate Monobasic 15

Dicalcium Phosphate 55

Potassium Citrate 90

Calcium Carbonate 100

Magnesium chloride 24.8

The composition ratio of the above-mentioned vitamin and mineral mixture is mixed with a composition suitable for a health food in a preferred embodiment, but the compounding ratio may be arbitrarily modified. The granules may be prepared and used for preparing a health food composition according to a conventional method.

Formulation example  7. Manufacture of health drinks

CP 1000 mg

Citric Acid 1000

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water is added to the total 900

After mixing the above components according to a conventional healthy beverage production method, and stirred and heated at 85 for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2l container, sealed sterilization and refrigerated and then stored in the present invention Used to prepare healthy beverage compositions.

Although the composition ratio is a composition that is relatively suitable for the preferred beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

Claims (5)

A pharmaceutical composition for treating and preventing Alzheimer's dementia, containing 60-80% water and an ethanol mixed solvent (ethanol in water, v / v) extract as an active ingredient of Dictyota coriacea from Jeju.
delete delete delete Jeju Functional Dictyota coriacea A dietary supplement for the prevention and improvement of Alzheimer's dementia containing 60 to 80% water and an ethanol mixed solvent (ethanol in water, v / v) extract as an active ingredient.

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