KR20240069664A - Composition for preventing or treating dementia comprising cannabidiol and taurine - Google Patents

Abstract

The present invention relates to a composition for preventing or treating dementia containing cannabidiol and taurine. The composition according to the present invention has an excellent effect in protecting brain nerve cells, controlling apoptosis-related factors, and suppressing inflammatory factors, and can effectively prevent or treat dementia. In addition, it is safe for the human body and has few side effects, so it can be used in a variety of materials such as medicines, quasi-drugs, or health functional foods.

Description

Composition for preventing or treating dementia comprising cannabidiol and taurine {COMPOSITION FOR PREVENTING OR TREATING DEMENTIA COMPRISING CANNABIDIOL AND TAURINE}

The present invention relates to a composition for preventing or treating dementia containing cannabidiol and taurine.

The proportion of the elderly population suffering from dementia, a degenerative brain disease, reaches approximately 10%, emerging as a serious social problem. Dementia is divided into Alzheimer's disease, cerebrovascular dementia, and Parkinson's disease. Among these, Alzheimer's disease is the most common cause of dementia, accounting for more than 70% of senile dementia patients.

Aβ excessively produced in brain tissue forms reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), superoxide anion, and hydroxyl radical. It is known to affect the mechanism of dementia by causing oxidative stress in cells and activating the apoptosis pathway, ultimately leading to synaptic damage.

Various drugs are used to treat dementia, but there is a constant need to search for substances that can replace them due to problems such as low bioavailability and hepatotoxicity.

Meanwhile, cannabidiol (CBD) is a substance isolated and extracted from cannabis and is the main physiologically active substance of cannabis along with THC, and has been reported to be effective in various diseases (Petr Jirasek et al., 2022). Cannabidiol (CBD), unlike THC, has little psychoactive effect, so it is used overseas for medical purposes to relieve symptoms such as pain, memory impairment, and anxiety. It is known to suppress excessive oil production and is used as an ingredient in cosmetics for acne-prone skin. Research is also being actively conducted.

Taurine is known to have many physiological functions. For example, taurine is now known to be involved in osmoregulation, membrane stabilization, calcium mobilization, neurotransmission, reproduction, and detoxification. In particular, taurine has been reported to provide anti-inflammatory effects and protect cells from the cytotoxic effects of inflammation.

The present inventors completed the present invention by experimentally confirming that the effect of treating cannabidiol (CBD) and taurine in combination is significantly superior to the effect of treating dementia when treated alone.

Republic of Korea Patent No. 10-1666969

The present invention provides a pharmaceutical composition for preventing or treating dementia containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.

Additionally, the present invention provides a quasi-drug composition for preventing or improving dementia containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.

The present invention also provides a food composition for preventing or improving dementia containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.

However, the technical problem to be achieved by the present invention is not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.

The present invention provides a pharmaceutical composition for preventing or treating dementia containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.

The cannabidiol may be represented by the following formula (1).

[Formula 1]

The taurine may be represented by the following formula (2).

[Formula 2]

The active ingredient can inhibit TNF-α, IL-1β and/or IL-6.

In addition, the present invention provides a quasi-drug composition for preventing or improving dementia containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.

Additionally, the present invention provides a food composition for preventing or improving dementia containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.

The composition according to the present invention has an excellent effect in protecting brain nerve cells, controlling apoptosis-related factors, and suppressing inflammatory factors, and can effectively prevent or treat dementia. In addition, it is safe for the human body and has few side effects, so it can be used in a variety of ways as a material for pharmaceuticals, quasi-drugs, or health functional foods.

Figure 1 shows the results of evaluating the brain nerve cell protective activity of candanibiol and taurine.
Figure 2 analyzes the effect of candaniviol and taurine on BAX and Bcl2, apoptosis-related factors, when treated alone or in combination.
Figure 3 analyzes the efficacy of inhibiting inflammation-related factors TNF-α, IL-1β, and IL-6 when treated alone or in combination with candanibiol and taurine.

The present inventors experimentally confirmed that the combined treatment of cannabidiol and taurine had a significantly superior effect in preventing or treating dementia, and completed the present invention.

Hereinafter, the present invention will be described in detail.

The present invention provides a composition for preventing or treating (or improving) dementia containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.

The active ingredient has the effect of suppressing inflammatory factors such as TNF-α, IL-1β or IL-6.

The composition may be a pharmaceutical composition, quasi-drug composition, food composition, or health functional food composition.

The composition may include cannabidiol:taurine at a concentration ratio of 1 to 20:200. Preferably, it may be included in a concentration ratio of 1 to 10:200, more preferably in a concentration ratio of 1 to 5:200.

Cannabidiol (CBD) is a phytocannabinoid discovered in 1940 and is one of 113 cannabinoids identified in Hemp plants. As of 2018, preliminary clinical studies of cannabidiol have included studies of anxiety, cognition, and movement disorders. In the United States, the drug Epidiolex, a cannabidiol drug, has been approved by the U.S. Food and Drug Administration for the treatment of epilepsy.

The structure of cannabidiol can be represented by the following formula (1).

[Formula 1]

Taurine is a sulfur-containing amine that exists in the cells and tissues of mammals, including humans, and is mainly found in fish and shellfish, especially oysters and scallops, and the dark red flesh of squid, octopus, and fish. Taurine is also known to have a very high level of safety, and one of the characteristics that differentiates it from other amino acids is that even if consumed in excessive amounts, decreased absorption, growth inhibition, or other side effects have not been reported.

The structure of taurine can be represented by the following formula (2).

[Formula 2]

The method for obtaining cannabidiol and taurine of the present invention is not particularly limited, and can be isolated from natural products, chemically synthesized using a known production method, or commercially available cannabidiol can be used.

In the present invention, cannabidiol and taurine may include hydrates, derivatives, etc. within the range of having the same efficacy, and may include solvates or stereoisomers thereof.

As used herein, “prevention” refers to any action that delays the onset of dementia by administration of the composition of the present invention, and “treatment” and “improvement” refers to the improvement or beneficial change in symptoms of dementia by administration of the composition of the present invention. It means all actions.

In the present invention, the term “pharmaceutically acceptable salt” or “salt thereof” may be an acid addition salt formed by a free acid. Acid addition salts can be prepared by conventional methods, for example, by dissolving the compound in an excess of aqueous acid solution and precipitating the salt using a water-miscible organic solvent, such as methanol, ethanol, acetone or acetonitrile. Additionally, equimolar amounts of the compound and an acid or alcohol (e.g., glycol monomethyl ether) in water can be heated, and the mixture can then be evaporated to dryness, or the precipitated salt can be filtered off with suction. The free acid may be an inorganic acid or an organic acid. Non-limiting examples of the inorganic acid include hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc., and these may be used alone or in a mixture of two or more types. The “pharmaceutically acceptable salt” or “salt thereof” may be an acid addition salt formed by a free acid. Acid addition salts can be prepared by conventional methods, for example, by dissolving the compound in an excess of aqueous acid solution and precipitating the salt using a water-miscible organic solvent, such as methanol, ethanol, acetone or acetonitrile. Additionally, equimolar amounts of the compound and an acid or alcohol (e.g., glycol monomethyl ether) in water can be heated, and the mixture can then be evaporated to dryness, or the precipitated salt can be filtered off with suction.

Unless otherwise indicated, the salts of cannabidiol and taurine may include all salts of acidic or basic groups that may be present in the compounds of cannabidiol and taurine. For example, the salts of cannabidiol and taurine may include sodium, calcium, and potassium salts of the hydroxy group, and other pharmaceutically acceptable salts of the amino group include hadrobromide, sulfuric acid, hydrogen sulfate, and phosphate. , hydrogen phosphate, dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, etc., which are known in the art. It can be produced through a known salt production method.

Pharmaceutical composition containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients

The compositions of the present invention can be prepared as pharmaceutical compositions.

When the composition of the present invention is prepared as a pharmaceutical composition, the pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier.

According to a preferred embodiment of the present invention, the composition of the present invention includes (a) a pharmaceutically effective amount of cannabidiol and taurine of the present invention described above; and (b) a pharmaceutically acceptable carrier. As used herein, the term “pharmaceutically effective amount” refers to an amount sufficient to achieve the efficacy or activity of cannabidiol and taurine described above.

Pharmaceutically acceptable carriers are commonly used, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrroli. Includes, but is not limited to, money, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition to the above ingredients, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical composition of the present invention can be administered orally or parenterally.

The appropriate dosage of the pharmaceutical composition of the present invention is prescribed in various ways depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity. It can be. The general dosage of the active ingredient included in the pharmaceutical composition of the present invention is within the range of 0.001-100 mg/kg for adults. Administration may be administered once a day, or may be administered in several divided doses. However, the scope of the present invention is not limited by the above dosage.

The pharmaceutical composition of the present invention is prepared in unit dosage form by formulating it using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily performed by those skilled in the art. Alternatively, it can be manufactured by placing it in a multi-capacity container. At this time, the formulation may be in the form of a solution, suspension, syrup or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, powder, granule, tablet or capsule, and may additionally contain a dispersant or stabilizer.

Quasi-drug composition containing cannabidiol and taurine, or pharmaceutically acceptable salts thereof, as active ingredients

The composition of the present invention may be provided as a quasi-drug composition.

The above active ingredients may be added as is, or other components commonly used in quasi-drug compositions may be included. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment).

Quasi-drug compositions can be manufactured in any formulation commonly manufactured in the art. For example, it may be manufactured as an external preparation, patch, ointment, etc., but is not limited thereto.

In the composition of the present invention, the active ingredient is preferably contained at 0.005 to 90% by weight based on the total weight of the composition, but may be used in amounts above or below the above range depending on the intended use, as long as it has a dementia prevention or improvement effect and does not exhibit toxicity. You can.

A food composition containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.

The composition of the present invention may be provided as a food composition or health functional food composition. When the composition of the present invention is manufactured as a food composition, it includes not only the cannabidiol and taurine as active ingredients, but also ingredients commonly added during food production, such as proteins, carbohydrates, fats, nutrients, and seasoning. Includes agents and flavoring agents. Examples of the above-mentioned carbohydrates include monosaccharides such as glucose, fructose, etc.; Disaccharides such as maltose, sucrose, oligosaccharides, etc.; and polysaccharides, such as common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a flavoring agent, natural flavoring agents (thaumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is manufactured as a drink, in addition to the natural product extract of the present invention, citric acid, high fructose corn syrup, sugar, glucose, acetic acid, malic acid, fruit juice, Eucommia extract, jujube extract, licorice extract, etc. may be additionally included. there is.

The formulation of the food composition or health functional food composition can be in the form of powders, granules, pills, tablets, capsules, as well as general foods or beverages.

There are no particular restrictions on the type of food, and examples of foods to which the above substance can be added include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, and dairy products including ice cream. , various soups, beverages, teas, drinks, alcoholic beverages, and vitamin complexes, etc., and can include all foods in the conventional sense.

In general, when manufacturing food or beverages, the active ingredient can be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on 100 parts by weight of raw materials. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range, and since the present invention uses natural substances, there is no safety problem, so the amount above the above range. It can also be used.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples.

Example

Cannabidiol (CBD) was synthesized using olivetol and camphor according to a previously known synthesis method. (V. Vaillancourt and K.F. Albizati., 1992). Taurine was purchased and used from (Sigma-Aldrich, Korea).

Example 1. Evaluation of brain nerve cell protective activity

The brain neuron protection activity of CBD and Taurine was evaluated in mouse hippocampus-derived HT22 cell line (HT22 cell). By measuring the survival rate of nerve cells due to the toxicity of amyloid beta protein, the toxicity inhibition effect of treatment with CBD alone, taurine alone, or CBD and Taurine in combination was analyzed. Cultured cells were first treated with CBD 0.5, 1. 2.5 μg/mL or taurine 25, 50,100 μg/mL for 30 minutes, then treated with amyloid beta protein (Aβ1-42), and neuron survival rate was checked 24 hours later. The group treated only with Aβ1-42 showed a neuron survival rate of 50%, but when treated with CBD alone, the neuron survival rate was 53, 64, or 75%, which was significantly higher than the group treated with only Aβ1-42, and Taurine The group treated with Aβ1-42 alone showed a significantly higher neuronal survival rate of 50, 68, or 71% than the group treated with Aβ1-42 alone in a concentration-dependent manner. In a concentration-dependent manner, the group treated with CBD and Taurine in combination showed a higher neuron survival rate of 71, 88, and 97% than the group treated with CBD and Taurine alone (Figure 1).

Example 2. Analysis of effects on apoptosis-related factors and inflammation inhibition efficacy

The effects of CBD and Taurine on apoptosis-related factors, BAX and Bcl2, were analyzed. After treating HT22 cells with amyloid beta, the effects of CBD and Taurine treatment alone and in combination on BAX and Bcl2 were analyzed, and the results are shown in Figure 2. As a result of examining the inhibitory effect of BAX on apoptosis-related factors, it was confirmed that the expression of BAX was inhibited more when CBD and Taurine were combined than when CBD and Taurine were treated individually. Additionally, as a result of Bcl2 analysis, it was confirmed that Bcl2 expression increased more when CBD and Taurine were combined than when CBD and Taurine were treated individually. Therefore, it can be seen that the neuronal protection effect is better when CBD and Taurine are treated together than when CBD and Taurine are treated individually.

Afterwards, the anti-inflammatory effects of CBD and Taurine on TNF-α, IL-1β, and IL-6 related to the inflammatory mechanism were analyzed. After treating BV2 cells with amyloid beta, the anti-inflammatory effect of CBD and taurine alone and the combined treatment of CBD and taurine were analyzed (Figure 3). As a result of analyzing the inhibitory efficacy of TNF-α, IL-1β, and IL-6, when CBD and taurine were combined, TNF-α, IL-1β, and IL-6 were suppressed more than when CBD and taurine were treated alone. It was confirmed that this was suppressed more.

Hereinafter, an example of manufacturing a medicine or food containing the CBD and taurine as active ingredients according to the present invention will be described, but the present invention is not intended to be limited, but merely explained in detail. Using the above active ingredients, the pharmaceutical or food composition of Preparation Example 1 or 2 was prepared according to a conventional method according to the composition ingredients and composition ratios as follows.

[Preparation Example 1] Preparation of pharmaceutical composition

<1-1> Production of powder

CBD and taurine 20mg

Lactose hydrate 100 mg

Talc 10 mg

The above ingredients were mixed and filled into an airtight bubble to prepare a powder.

<1-2> Preparation of tablets

CBD and taurine 10mg

Corn starch 100 mg

Lactose hydrate 100 mg

Magnesium stearate 2 mg

After mixing the above ingredients, tablets were manufactured by tableting according to a conventional tablet manufacturing method.

<1-3> Production of capsules

CBD and taurine 10mg

Microcrystalline cellulose 3 mg

Lactose hydrate 14.8 mg

Magnesium stearate 0.2 mg

After mixing the above ingredients, a capsule was prepared by filling a gelatin capsule according to a typical capsule preparation method.

<1-4> Preparation of injections

CBD and taurine 10mg

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Sodium monohydrogen phosphate 26 mg

After mixing the above ingredients, it was prepared with the above ingredient content per 1 ampoule (2 mL) according to a typical injection preparation method.

<1-5> Preparation of liquid

CBD and taurine 10mg

10 mg of isomerized sugar

Mannitol 5mg

Proper amount of purified water

Lemon flavor appropriate amount

The above ingredients are dissolved in purified water according to the usual manufacturing method, an appropriate amount of lemon flavor is added, then purified water is added to adjust the total to 100 mL, then sterilized and filled into a brown bottle to prepare a liquid.

[Manufacture Example 2] Manufacture of health functional food

<2-1> Manufacturing of health supplements

CBD and taurine 10mg

Vitamin mixture dosage

Vitamin A acetate 70 μg

Vitamin E 1.0 mg

Vitamin B ₁ 0.13 mg

Vitamin B ₂ 0.15 mg

Vitamin B ₆ 0.5 mg

Vitamin B ₁₂ 0.2 ㎍

Vitamin C 10 mg

Biotin 10 μg

Nicotinamide 1.7 mg

Folic acid 50 μg

Calcium pantothenate 0.5 mg

mineral mixture Appropriate amount

Ferrous sulfate 1.75 mg

Zinc oxide 0.82 mg

Magnesium Carbonate 25.3 mg

Monobasic Potassium Phosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium citrate 30 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

The composition ratio of the above vitamin and mineral mixture is a mixture of components relatively suitable for health food in a preferred embodiment, but the mixing ratio may be modified arbitrarily. The above ingredients are mixed according to a typical health food manufacturing method, and then , granules can be manufactured and used to manufacture health food compositions according to conventional methods.

<2-2> Manufacturing of health drinks

10 mg CBD and taurine

15 g of vitamin C

Vitamin E (powder) 100 g

19.75 g iron lactate

3.5 g zinc oxide

Nicotinamide 3.5 g

Vitamin A 0.2 g

Vitamin B1 0.25 g

Vitamin B2 0.3 g

Purified water quantification

After mixing the above ingredients according to a typical health drink manufacturing method, stirring and heating at 85° C. for about 1 hour, the resulting solution was filtered, obtained in a sterilized 2-liter container, sealed, sterilized, and refrigerated, followed by the present invention. It is used in the production of health drink compositions.

The composition ratio is a preferred embodiment of mixing ingredients that are relatively suitable for beverages of preference, but the mixing ratio may be arbitrarily modified depending on regional or ethnic preferences such as demand class, country of demand, and intended use.

The description of the present invention described above is for illustrative purposes, and those skilled in the art will understand that the present invention can be easily modified into other specific forms without changing the technical idea or essential features of the present invention. will be. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive.

Claims (6)

A pharmaceutical composition for preventing or treating dementia comprising cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
In claim 1,
The cannabidiol is a pharmaceutical composition for preventing or treating dementia, characterized in that it is represented by the following formula (1).
[Formula 1]

In claim 1,
The taurine is a pharmaceutical composition for preventing or treating dementia, characterized in that it is represented by the following formula (2).
[Formula 2]

In claim 1,
A pharmaceutical composition for preventing or treating dementia, wherein the active ingredient inhibits TNF-α, IL-1β or IL-6.
A quasi-drug composition for preventing or improving dementia comprising cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
A food composition for preventing or improving dementia comprising cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.