KR102532914B1 - Composition for preventing and treating dementia and Manufacturing method thereof - Google Patents

Abstract

The present invention relates to a composition for preventing or alleviating dementia and a method for manufacturing the same. More specifically, the present invention contains as an active ingredient a heated mixture of Conyza canadensis, Glycyrrhiza uralensis, Rheum rhabarbarum, Physalia physalis, and vinegar. According to the present invention, the composition is stable as it does not cause toxicity to cells, and has the advantage of being able to suppress the production of beta-amyloid, a known causative agent of dementia, especially Alzheimer's disease, so it can be effectively used in the prevention or treatment of dementia.

Description

Composition for preventing or improving dementia and manufacturing method thereof {Composition for preventing and treating dementia and Manufacturing method thereof}

The present invention relates to a composition for preventing or improving dementia and a method for preparing the same.

Due to the rapid increase in the elderly population in modern society, the occurrence of senile dementia has emerged as a serious social problem. Despite the high incidence of this disease, there is currently no clear treatment or prevention, causing enormous socio-economic loss.

In particular, Alzheimer's disease is a disease that is emerging as the most important among senile dementia, and accumulation of β-amyloid in the brain and resulting neurotoxicity are known to be important causes of onset (ProbstA et al, Brain Pathol, 1:229-239, 1991). In particular, beta-amyloid is known to cause plaques in which proteins accumulate and become entangled in the brain, thereby causing Alzheimer's disease (Breimer LH, et alNature, 326: 749-750, 1987).

The beta-amyloid (β-amyloid) is known to be produced by the continuous action of amyloid precursor protein (APP) of beta-secretase (BACE1) and gamma-secretase, which are membrane protein hydrolases. (Vassa and Citron, Neuron 27, 419-422, 2000). These beta-amyloids can be largely divided into two types, that is, Aβ40 and Aβ42 consisting of 40 or 42 amino acids. Among beta-amyloids, Aβ40 accounts for most of them, but Aβ42, which is produced relatively little, is pointed out as the most important etiological substance because it easily makes plaque (Selkoe, Science 298: 789-891, 2002).

Tacrine (Cognex, 1994) and donepezil (Aricept, 1996) have been approved by the US Food and Drug Administration (FDA) as typical dementia treatments known so far. The mechanism of action of these drugs prevents dementia by increasing the concentration of acetylcholine, a neurotransmitter, by inhibiting the activity of acetylcholinesterase (AChE), an enzyme that breaks down acetylcholine, which plays a central role in the central nervous system. And it is known to treat. However, the tacrine is expensive compared to its efficacy and has serious liver toxicity problems. Donepyzil has no hepatotoxicity, but stimulates the parasympathetic nerve to cause various side effects such as vomiting, nausea, and diarrhea.

Therefore, studies are being actively conducted to develop a new type of dementia treatment agent capable of causative treatment without the above side effects.

KR 10-1840451 B1 KR 10-1404566 B1

An object of the present invention is to provide a pharmaceutical composition for preventing or ameliorating dementia, which contains, as an active ingredient, heated water obtained by heating a mixture of geranium, licorice, rhubarb, swim bladder and vinegar.

Another object of the present invention is to provide a health functional food for the prevention or improvement of dementia, which contains, as an active ingredient, a heated water obtained by mixing and heating celery, licorice, rhubarb, swim bladder, and vinegar.

Another object of the present invention is to provide a method for producing a composition for preventing or ameliorating dementia, which includes heated water mixed with geranium, licorice, rhubarb, swim bladder and vinegar as an active ingredient.

The composition for preventing or improving dementia of the present invention for achieving the above object is characterized in that it comprises, as an active ingredient, a heated water mixed with gyeongje mango, licorice, rhubarb, swim bladder and vinegar.

The mixing ratio of the legal herb, licorice, rhubarb, swim bladder, and vinegar is 20 to 50 parts by weight, 10 to 50 parts by weight of licorice, 10 to 50 parts by weight of rhubarb, and 50 to 100 parts by weight of vinegar, based on 100 parts by weight of the swim bladder. characterized by denial.

The dementia is characterized in that it is at least one disease selected from the group consisting of Alzheimer's type dementia, cerebrovascular dementia and dementia caused by senile dementia.

In addition, the method for producing a composition for preventing or improving dementia of the present invention includes the steps of adding water to licorice, rhubarb and air bladder and heating, adding vinegar to the heated water and heating, and the vinegar It is characterized in that it comprises the step of adding and heating the legal forget-me-not to the added heating water.

According to the composition for preventing or improving dementia and its manufacturing method according to the present invention, it does not induce toxicity to cells, is stable, and can inhibit the production of beta-amyloid, which is known as a causative agent of dementia, particularly Alzheimer's disease, thereby preventing dementia. Or it has the advantage that it can be effectively used for treatment.

1 is a graph showing the results of Test Example 1 according to the present invention.
Figure 2 is a graph showing the results of Test Example 2 according to the present invention.
3 and 4 are graphs showing the results of Test Example 3 according to the present invention.

Hereinafter, the present invention will be described in detail.

In general, dementia, as described in the prior art, refers to a disease in which cognitive impairment and personality change occur after maintaining a normal intellectual level during the growth period. Dementia is the destruction of brain nerves by various causes, resulting in overall disorders of mental function such as memory impairment, language impairment, urinary incontinence, paranoid thinking, and aphasia. In the process, psychiatric symptoms such as depression, personality disorder, and aggression may also accompany Although the medical community pays attention to the causality caused by aging and genetics, the exact cause and treatment have not yet been identified. Diseases classified as dementia may include, but are not limited to, any one of Alzheimer's type dementia, cerebrovascular dementia and senile dementia, and the composition provided in the present invention can treat, prevent, and improve such diseases. can include

The composition for preventing or ameliorating dementia according to the present invention comprises, as an active ingredient, heated water obtained by mixing fortification, licorice, rhubarb, swim bladder, and vinegar, and beta amyloid known as the cause of dementia due to the interaction of each component. By suppressing its production, it prevents or improves dementia, is good for the kidneys, and clears the head.

The legal forget-me-not is a refined product of sulfate mineral forget-me-not, and mainly contains sodium sulfate. When the filtrate obtained by dissolving and filtering by adding hot water to natural mangosteen is cooled, the crystal precipitated for the first time is called bakcho (朴硝), and the crystal obtained by repeated recrystallization is called legal mango mango. Conventionally, Mangcho was used a lot for the symptoms of constipation. In addition, the legal mangcho also acts as an analgesic.

In the present invention, the legal forget-me-not can be purchased and used commercially.

The licorice (Glycyrrhiza uralensis) is a perennial plant belonging to the leguminous family, and is native to or cultivated in northern China, Siberia, southern Italy, Manchuria, and Mongolia. Licorice is one of the herbs used as an antitussive and enters as a component to reduce toxicity in all herbal prescriptions (Rauchensteiner F. et al., JPharm BiomedAnal., 38(4), pp.594-600, 2005). It is also used to sweeten candies. According to recent research results, licorice alleviates kidney oxidative damage (Yokozawa T. etal., FreeRadic Res., 39(2), pp.203-211, 2005) and has the effect of protecting liver cells damaged by cadmium. (Kim SC. et al., Toxicology., 197(3), pp.239-251, 2004).

In the present invention, licorice is purchased and used commercially or directly collected or cultivated in nature, but is not limited thereto. In addition, it is not limited to the presence or absence of drying.

The rhizoma (Rhei Rhizoma) is a root and rhizome of a perennial herbaceous plant belonging to the rhubarb family and related plants of the same genus, and there are about 15 kinds of plants. In China, dry roots and rhizomes such as Rheum palmatum Linne, Pheum tanguticum Maxim, and medicinal rhubarb (Rheum offcinale Baill) are used as origins. there is. Studies on the components of rhubarb have been continued until recently, and reports such as sedative action by sennoside A, prevention of damage to the digestive tract mucosa, and antibacterial action of aloe-emodin and rhein have been reported. It has been published (中華本草編纂委: 中華本草, Shanghai Science Research Institute, Vol. 2. p710,715~716,1996). Rhubarb is also clinically applied to the treatment of dyspepsia, constipation, acute inflammation, infectious diseases, parasitic diseases, hemorrhage, thrombocytopenia, burns and skin diseases. Also, it has a great effect on treating boils and phlegm.

In the present invention, the rhubarb may be purchased and used commercially or directly collected or cultivated in nature, but is not limited thereto. In addition, it is not limited to the presence or absence of drying.

The swim bladder refers to air sacs in fish, and is used as a raw material for isinglass, a high-quality glue. In the present invention, as the bladder, it is most preferable to use a croaker bladder, but this is not necessarily limited.

The vinegar is a fermented food that has been used for a long time in both the East and the West, and contains about 60 organic acids, and is effective in recovering from fatigue, preventing adult diseases, and increasing appetite. In the present invention, the type of vinegar is not limited, and any commercially available vinegar may be purchased and used. In addition, as a method of fermenting and aging grains, it is also possible to prepare and use vinegar.

At this time, the mixing ratio of the marijuana, licorice, rhubarb, swim bladder and vinegar is 20 to 50 parts by weight of marijuana, 10 to 50 parts by weight of licorice, 10 to 50 parts by weight of rhubarb and 50 to 50 parts by weight of vinegar, based on 100 parts by weight of the swim bladder. It is preferably 100 parts by weight, because such a ratio can exhibit the most excellent effect in preventing or improving dementia.

The composition of the present invention may be a pharmaceutical composition, and the composition may include the above mixed powder alone, or may include one or more pharmaceutically acceptable carriers, excipients, or diluents.

In the present invention, the pharmaceutically effective amount of the mixed powder is 0.5 to 100 mg/day/kg of body weight, preferably 0.5 to 5 mg/day/kg of body weight. However, the pharmaceutically effective amount may be appropriately changed depending on the degree of dementia symptoms, the patient's age, weight, health condition, sex, administration route, treatment period, and the like.

In addition, the term pharmaceutically acceptable herein refers to a composition that is physiologically acceptable and does not cause allergic reactions such as gastrointestinal disorders and dizziness or similar reactions when administered to humans. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In addition, fillers, anti-coagulants, lubricants, wetting agents, flavoring agents, emulsifiers and preservatives may be further included.

In addition, the compositions of the present invention can be formulated using methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. The dosage form may be any one of the form of powder, granule, tablet, pill, emulsion, syrup, soft or hard gelatin capsule.

The composition according to the present invention is preferably administered orally, and the dosage of the active ingredient may be appropriately selected depending on various factors such as the route of administration, age, sex, weight, and severity of the patient.

In addition, since the composition for preventing or improving dementia of the present invention can be added to food for the purpose of preventing or improving symptoms of dementia, the composition of the present invention can be used as a composition for food for preventing or improving symptoms of dementia. there is. Therefore, the composition for food for preventing and improving dementia of the present invention can be easily utilized as a food effective in preventing or improving dementia symptoms, for example, as a main ingredient, supplementary ingredient, food additive, functional food or beverage of food.

Foods to which the composition for preventing and improving symptoms of dementia according to the present invention can be added include, for example, various foods, beverages, chewing gum, tea, vitamin complexes, and functional foods. In addition, in the present invention, food includes special nutritional food (eg, formula milk, infant food, baby food, etc.), processed meat product, fish meat product, tofu, jelly, noodles (eg, ramen, noodles, etc.), bread, health supplement food, seasoning Foods (eg, soy sauce, soybean paste, gochujang, mixed paste, etc.), sauces, confectionery (eg, snacks), candies, chocolates, chewing gum, ice cream, dairy products (eg, fermented milk, cheese, etc.), other processed foods, kimchi, It includes, but is not limited to, pickled foods (various types of kimchi, pickled vegetables, etc.), beverages (eg, fruit drinks, vegetable drinks, soy milk, fermented beverages, etc.), and natural seasonings (eg, ramen soup, etc.). The food, beverage or food additive may be prepared by a conventional manufacturing method.

In addition, the functional food is a food group or food composition that has added value so that the function of the food acts for a specific purpose by using physical, biochemical, or bioengineering methods, etc. It refers to food designed and processed to sufficiently express the body's regulatory function related to the back, and specifically, it may be a health functional food. The functional food may include food additives that are acceptable in food science, and may further include appropriate carriers, excipients, and diluents commonly used in the manufacture of functional foods.

In the food containing the composition for preventing and improving dementia symptoms of the present invention, the amount of the composition according to the present invention may be included in 0.001% to 100% by weight of the total weight of the food.

Hereinafter, the method for preparing the composition according to the present invention will be described in detail.

The method for producing a composition according to the present invention includes the steps of adding water to licorice, rhubarb and bure and heating, adding vinegar to the heated water and heating it, and formulating the heated water to which the vinegar is added. It is characterized in that it comprises the step of heating by adding forget-me-not.

licorice, rhubarb And adding water to the swim bladder and heating it.

Add water to licorice, rhubarb and air bladder, and heat at 80-100℃ for 20-80 minutes. At this time, the amount of water used is not limited, and 2 to 10 times the weight of the mixture of licorice, rhubarb and air bladder is sufficient.

the heated to heating water Heating by adding vinegar

Then, vinegar is added to the heated water and heated again at 80 to 100° C. for 10 to 20 minutes.

The vinegar was added to heating water Step of heating by adding marijuana

Next, the vinegar is added to the heated water to which the vinegar is added and heated at 80 to 100 ° C. for 3 to 8 minutes.

And it is cooled at room temperature.

The composition prepared as described above may be taken as it is or formulated. At this time, the additional formulation method is not limited.

In addition, it can also be manufactured in the form of a dry matter as needed.

That is, the solids in the heated water to which the legal forget-me-nots are added are pulverized so that they are about 100 to 300 msh, and dried. At this time, the drying method is not limited.

The reason for drying after pulverization in the present invention is to consider material properties such as air bladder, and it is because there is difficulty in powdering when pulverized after drying.

The composition prepared as described above may be taken in powder form, taken as it is, or formulated into pills, liquids, etc., and additional formulation methods are not limited.

Here, the amount of use of each material is preferably 20 to 50 parts by weight of marigold, 10 to 50 parts by weight of licorice, 10 to 50 parts by weight of rhubarb, and 50 to 100 parts by weight of vinegar, based on 100 parts by weight of the air bladder, which is To increase prevention and improvement effect.

On the other hand, the composition of the present invention has the advantage of being excellent in treatment or prevention of epilepsy as well as dementia.

Hereinafter, the present invention will be described in detail through specific examples.

(Example 1)

After mixing 300 g of dried licorice, 300 g of dried rhubarb, and 1000 g of crucian carp bladder, 5 L of water was added thereto and heated at 90° C. for 30 minutes. Next, 1000 g of vinegar was added thereto, and after heating at 90° C. for 15 minutes, 350 g of Forget-me-not-forget-me-not was added and heated at 90° C. for 5 minutes. And it was left at room temperature for 10 minutes.

Next, the above heated material was pulverized so that the solid material in the heated material was about 200 mesh, and then lyophilized to obtain a powdered form.

(Test Example 1)

In order to examine the effect of inhibiting beta-amyloid production of the sample, a human-derived amyloid precursor protein (APP)-transfected HeLa cell line was cultured in DMEM medium (Cat # 11995, Gibco, USA) used

Specifically, the sample was added to the cell culture medium in which the cell line was cultured, then incubated at 37 ° C. for 8 hours, and the amount of beta-amyloid secreted into the culture medium was measured. Human β-Amyloid [1-42] (Aβ42) Colorimetric ELISA kit (#KHB3442; BioSource International, Inc, USA) was used to quantify Aβ42 among the two types of β-amyloid. And the results are shown in Figure 1. The case where the sample was not treated was used as a control group.

As shown in FIG. 1, it was found that Example 1 inhibited Aβ42 in a concentration-dependent manner.

(Test Example 2)

In order to measure the effect of the sample on cell death, a known MTT Cell Proliferation assay method was used. Specifically, samples of various concentrations were treated with cultured HeLa cells in the same manner as in Test Example 1 for 8 hours, and viable cells were quantified, and the results are shown in FIG. 2 . The case where the sample was not treated was used as a control group.

As shown in the attached FIG. 2, Example 1 was confirmed to be safe for the human body by confirming that almost no cells died even when all were administered at a concentration of 5 μg/ml. In addition, it was confirmed that the inhibition of Aβ42 in Test Example 1 was not caused by apoptosis.

(Test Example 3)

Experimental animals were male ICR mice (10 weeks old, 34 to 36 g,) adjusted to a temperature of 23 ± 1 ° C, humidity of 60 ± 10%, and day and night for 12 hours each, and were acclimatized in an animal room for 7 days while providing sufficient water and general diet. After that, it was used in the experiment. 100 mg/kg of the composition of Example 1 was orally administered five times a day for 3 days, and on the third day of drug administration, 0.4 μg of kainic acid was directly injected into the lateral ventricle of the brain to induce epilepsy.

In this test example, we tried to confirm the effect of delaying the seizure latency period and reducing the frequency of seizure occurrence by the treatment of Example 1 of the present invention using an animal model in which epilepsy was induced by kainic acid.

Seizure latency delay effect

Behavioral seizure stages are identified in five stages, each of which includes stage 1; facial movement, stage 2; head nodding and myoclonic twitching, stage 3; forelimb clonus with lordotic posture, stage 4; forelimb clonus with reared posture, stage 5; There is a behavioral type of tonic-clonic seizures without postural control. The onset of seizure occurrence was set at the time of stage 3 (forelimb clonus with lordotic posture) among the types of seizure behavior induced by kainic acid treatment, and the time at which stage 3 seizure behavior occurred after kainic acid treatment was set. recorded. The rats treated with kainic acid were video-recorded for 6 hours while measuring the seizure onset time by kainic acid treatment, and through this, the effect of delaying the latency of seizure onset by the treatment of Example 1 was measured. Observed.

The results are shown in Figure 3.

As shown in FIG. 3, it was confirmed that the occurrence of epileptic seizures was significantly delayed in the test group compared to the control group.

Seizure frequency reduction effect

Spontaneous recurrent seizures (SRS) were observed by videotaping for 2 weeks (9 hours a day, 6 days a week, a total of 108 hours within 2 weeks) from the 3rd week after treatment with kinic acid. did In the case of seizure behavior of stages 3 to 5 during the imaging period, it was recorded that spontaneous recurrent epilepsy occurred and the frequency was measured, and through this, the effect of reducing the seizure frequency by the treatment of Example 1 was confirmed.

The results are shown in FIG. 4 .

As shown in FIG. 4, it was confirmed that the incidence of spontaneous epileptic seizures was significantly reduced in the test group compared to the control group.

In the above, the present invention has been described in detail using preferred embodiments, but the scope of the present invention is not limited to specific embodiments, and should be interpreted according to the appended claims. In addition, those skilled in the art should understand that many modifications and variations are possible without departing from the scope of the present invention.

Claims (7)

A pharmaceutical composition for the prevention or improvement of dementia, characterized in that it comprises as an active ingredient a heated water mixed with geranium, licorice, rhubarb, swim bladder and vinegar.
According to claim 1,
The mixing ratio of the legal forget-me-not, licorice, rhubarb, swim bladder and vinegar,
A pharmaceutical composition for preventing or improving dementia, characterized in that 20 to 50 parts by weight of the bladder, 10 to 50 parts by weight of licorice, 10 to 50 parts by weight of rhubarb, and 50 to 100 parts by weight of vinegar, with respect to 100 parts by weight of the bladder.
According to claim 1 or 2,
The dementia is
A pharmaceutical composition for preventing or improving dementia, characterized in that it is one or more diseases selected from the group consisting of Alzheimer's dementia, cerebrovascular dementia and senile dementia.
A food composition for the prevention or improvement of dementia, characterized in that it contains as an active ingredient a heated water mixed with gyeongjemangcho, licorice, rhubarb, swim bladder and vinegar.
According to claim 4,
The mixing ratio of the legal forget-me-not, licorice, rhubarb, swim bladder and vinegar,
With respect to 100 parts by weight of the air bladder, 20 to 50 parts by weight of marijuana, 10 to 50 parts by weight of licorice, 10 to 50 parts by weight of rhubarb and 50 to 100 parts by weight of vinegar A food composition for preventing or improving dementia.
According to claim 4 or 5,
The dementia is
A food composition for preventing or improving dementia, characterized in that it is one or more diseases selected from the group consisting of Alzheimer's dementia, cerebrovascular dementia and senile dementia.
Injecting water into licorice, rhubarb and bladder and heating;
Heating by adding vinegar to the heated water;
Method for producing a composition for preventing or improving dementia, characterized in that it comprises the step of adding and heating the vinegar-added heating water.

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