Composition for alleviating stress comprising GABA and cistus incanus extract as active ingredients

Abstract

The present invention relates to a composition for alleviating stress, the composition comprising GABA and a Cistus incanus extract as active ingredients. In particular, the present invention relates to enhancing the efficacy of GABA by using a Cistus incanus extract.

Description

A composition for improving stress relief containing GABA and rock rose extracts as active ingredients

[0001] The present invention relates to a composition for improving stress comprising GABA and Cistus incanus extract as active ingredients. In particular, it relates to an invention that enhances the efficacy of GABA using Cistus incanus extract.

[0002] This invention is a result of a project supported by the Korea Bio-Specialized Center Association, and the project information is as follows.

[0003] Project No.: B0080207002074

[0004] Business No.: KBC-001

[0005] Ministry Name: Ministry of Trade, Industry and Energy

[0006] Name of Project Management Agency: Korea Institute for Industrial Technology Advancement (KIAT)

[0007] Research Project Title: Global Competitiveness Enhancement Project for Bioactive Agents

[0008] Project Period: March 8, 2024 – October 31, 2024

[0009] Describe GABA (gamma-aminobutyric acid):

[0010] GABA was discovered in mammalian brain extracts by the group of Roberts and Awapara in 1950 and identified as an inhibitory neurotransmitter in the elongation receptors of crustaceans. In addition to its nerve-calming effects, GABA is attracting attention as an excellent functional material possessing various physiological activities, such as inhibiting blood pressure elevation, anti-stress effects, promoting brain metabolism, improving liver function, and regulating growth hormones; it is currently widely used as a food additive both domestically and internationally. In particular, regarding its nerve-calming function, tablet-type products mixed with vitamins are predominant, and various forms of products ranging from cosmetics to pharmaceuticals are also being released and sold.

[0011]

[0012] Describe Myricetin:

[0013] Myricetin is a natural flavonol also known as 3,3',4',5,5',7-hexahydroxyflavone, cannabiscetin, myricetol, and myricitin. It is found in large quantities in the form of glycosides, mainly in tea, grapes, onions, broccoli, apples, and other foods. Pure myricetin is a yellow-beige crystalline powder.

[0014]

[0015] A review of the prior art literature reveals the following:

[0016] (Patent Document 1) is a registered publication of a patent held by the applicant. Upon examination, a method for enhancing erythropoietin using GABA is described. It relates to a method for enhancing EPO gene expression by administering GABA. (See Claim 1)

[0017] (Patent Document 2) is a registered publication of a patent held by the applicant. Upon examination, it relates to a feed composition for laying hens containing GABA and yeast extract as active ingredients for reducing stress and inhibiting the decrease in egg laying rate. (See Claim 1)

[0018] (Patent Document 3) relates to a composition for enhancing exercise performance containing myricetin as an active ingredient.

[0019] Problem 1 is to provide a method for converting the myricitrin component of rock rose extract into myricetin. Problem 2 is to provide a method for enhancing the efficacy of GABA by mixing processed rock rose extract with GABA. Problem 3 is to provide a composition for improving stress containing processed rock rose extract and GABA as active ingredients.

[0020] Solution 1 is,

[0021] A step of preparing a primary extract by chopping and extracting the leaves and stems of *Cistus incanus*; a step of preparing a *Cistus incanus* extract in which myricitrin is converted to myricetin by acid hydrolyzing the primary extract; and a step of preparing a *Cistus incanus* preparation for enhancing GABA efficacy comprising the *Cistus incanus* extract;

[0022] This is a method for manufacturing a Lacrose preparation to enhance the efficacy of GABA.

[0023] Solution 2 is,

[0024] Lacrose preparation of Solution 1;

[0025] and GABA; comprising as active ingredients,

[0026] This is a method for preparing a composition for stress improvement.

[0027] Solution 3 is,

[0028] In solution 2,

[0029] The Lacrose formulation is characterized by containing 1 / 10 to 1 / 5 of the GABA content,

[0030] This is a method for preparing a composition for stress improvement.

[0031] Solution 4 is,

[0032] It is a Lacrose preparation for enhancing the efficacy of GABA manufactured by Solution 1.

[0033] Solution 5 is,

[0034] It is a composition for stress improvement manufactured by the method of Solution Mean 2.

[0035] Effect 1 is that since rock rose extract is a food ingredient, the method according to the present invention or the composition according to the method has no side effects. Effect 2 is to provide a method for producing myricetin from rock rose extract. Effect 3 is to provide a composition that enhances the efficacy of GABA by mixing GABA with rock rose extract containing myricetin or myricetin isolated and purified from rock rose extract.

[0036] Figure 1 relates to a method for converting myricitrin contained in rock rose extract into myricetin by acid hydrolysis.

[0037] Solution Principle: Enhancing GABA efficacy with myricetin

[0038] GABA receptors are receptors that respond to GABA, a neurotransmitter that is a major inhibitory compound in the central nervous system of mature vertebrates. There are two classes of GABA receptors: GABAa and GABAb. GABAa receptors are also called ligand-gated ion channels or ionotropic receptors. GABAb receptors are G protein-coupled receptors, also known as metabotropic receptors.

[0039] Myricetin does not act directly on GABA receptors, and Ca 2+ Involved in channels, intracellular Ca 2+ It increases ions to activate CaMK-II (calcium / calmodulin-dependent protein kinase II), and CaMK-II phosphorylates GABAa receptors, thereby exposing intracellular GABAa receptors to the surface. The exposed GABAa receptors diffuse close to the presynapse, Cl - As ions increase within the cell, the cell membrane potential is maintained at a low level, thereby stabilizing the nerve.

[0040] The solution principle of the present invention is to further enhance the efficacy of GABA with myricetin by providing a method for preparing a composition containing both GABA and myricetin and a composition made by said method.

[0041]

[0042] Preparation Example 1. Processing of Rock Rose Extract: Conversion to Myricetin

[0043] FIG. 1 relates to a method for converting myricitrin contained in a rock rose extract into myricetin by acid hydrolysis. Myricetin is prepared using rock rose (Cistus incanus). Myricetin is prepared by concentrating an extract obtained from the leaves and stems of rock rose and then performing acid hydrolysis. Hot water or ethanol is used as the extraction solvent. In a preferred example, a primary extract is prepared by chopping the leaves and stems of rock rose and then extracting them in 10 times their weight in distilled water at 50 to 80°C for 3 to 4 hours. Next, the primary extract is acid hydrolyzed to prepare a rock rose extract in which myricitrin is converted into myricetin.

[0044]

[0045] Preparation Example 2. Preparation of a composition for stress improvement comprising GABA and rock rose extracts as active ingredients

[0046] GABA is a type of non-protein amino acid found in nature and is an inhibitory neurotransmitter that improves cerebral blood flow, increases oxygen supply, and promotes brain cell metabolic function. It is known to have nerve-calming effects, help relieve stress, improve memory, and alleviate insomnia, as well as effects on lowering blood pressure, alleviating depression, and preventing stroke and dementia.

[0047] The GABA used in the present invention may be natural GABA or synthetic GABA, but is not limited thereto. GABA can be administered to animals at a concentration of 20 to 500 ppm per 100g of body weight to enhance erythropoietin expression, preferably at 50 to 200 ppm, but is not limited thereto.

[0048] Preparation Example 2 according to the present invention is to prepare a composition comprising GABA and the processed rock rose extract of Preparation Example 1. A preferred example is to provide a composition comprising GABA and rock rose extract in an amount of 1 / 10 to 1 / 5 relative to the GABA content.

[0049]

[0050] Experimental Example 1. Analysis of Erythropoietin Enhancement

[0051] (Patent Document 1) is a registered patent held by the applicant. The analysis of EPO increase in rat serum described in (Patent Document 1) was used. During the rearing period, experimental groups were established in which GABA was consumed at a rate of 100 ppm per 100 g of body weight via drinking water for 3 weeks (100 ppm, G100), GABA was consumed together with a rock rose extract at a ratio of 1 / 10 of the GABA content (110 ppm, G100+R10), and GABA was consumed together with a rock rose extract at a ratio of 1 / 5 of the GABA content (120 ppm, G100+R20). After correcting the NC and G100 values ​​to the values ​​of (Patent Document 1), the EPO increase in the presence of rock rose extract was confirmed.

[0052] NCG100G100+R10G100+R20Erythropoietin (mIU / mL)0.390.630.660.68p value<0.05<0.05<0.05+ / - (%)61.569.274.3

[0053] As a result of the analysis, the composition containing 1 / 10 of the rock rose extract of Preparation Example 1 relative to the GABA content showed an improvement of 69.2% compared to the control group (NC), and the composition containing 1 / 5 additionally showed an improvement of 74.3%.

[0054]

[0055] Example 1. Various formulations of GABA efficacy-enhancing agents and compositions for stress improvement

[0056] The processed rock rose extract of Preparation Example 1 can be provided as a preparation that enhances GABA efficacy. Additionally, a preparation can be provided that is formulated into a pharmaceutical unit dosage form by including the composition of Preparation Example 2 as an active ingredient and adding pharmaceutically acceptable carriers, excipients, or diluents. Here, carriers, excipients, and diluents may include toz, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

[0057] In addition, the above pharmaceutical dosage form may also be used in the form of a pharmaceutically acceptable salt, and may also be used alone, in combination with other pharmaceutically active compounds, or in a suitable combination. Furthermore, when formulating the above active ingredient, it may be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. In addition, the above pharmaceutical dosage form may be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, as well as topical preparations, suppositories, and sterile injectable solutions, each according to conventional methods.

[0058] The above solid formulation for oral administration may be prepared by mixing at least one excipient with the formulation or composition, for example, starch may be prepared by mixing calcium carbonate, sucrose or lactose, gelatin, etc. In addition, lubricants such as magnesium stearate and talc may also be used in addition to simple excipients.

[0059] The above-mentioned formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, and suppositories. The above-mentioned non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.

[0060] Witepsol, Macrogol, Tween 61, Cacao, Laurin, Glycerozelatin, etc. can be used as bases for suppositories.

[0061]

[0062] The preferred dosage of the formulations and compositions of the present invention varies depending on the patient's condition and weight, the severity of the disease, age, gender, drug form, route of administration, and duration, but can be appropriately selected by those skilled in the art.

[0063] The formulations and compositions of the present invention may be administered to mammals, such as rats, mice, livestock, and humans, by various routes. Any mode of administration may be anticipated, for example, by oral, rectal, or intravenous, intramuscular, or subcutaneous injection.

[0064] A health functional food composition can be provided by adding a food auxiliary additive to the active ingredient of the present invention.

[0065] Foods to which the above active ingredient can be added include, for example, various types of food products, beverages, chewing gum, tea, vitamin complexes, health functional foods, etc.

[0066] The amount of the above-mentioned active ingredient in the food or beverage may be added in an amount of 0.01 to 20 weight percent of the total weight of the food or beverage, and the health beverage composition may be added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g, based on 100 ml.

[0067] The health functional beverage composition of the present invention has no particular limitations on other ingredients other than those containing the above-mentioned formulation or composition, and may contain various flavoring agents or natural carbohydrates, etc., as additional ingredients, as in ordinary beverages. Examples of the above-mentioned natural carbohydrates are monosaccharides, e.g., glucose, fructose; disaccharides, e.g., maltose, sucrose, etc.; polysaccharides, e.g., dextrin, cyclodextrin, etc., and other common sugars; and sugar alcohols such as xylitol, sorbitol, erythritol, etc. In addition to those mentioned above, natural flavoring agents (taumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) may be advantageously used as flavoring agents. The proportion of the above-mentioned 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.

[0068] In addition to the above, the formulations and compositions of the present invention may contain various nutritional agents, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc.

[0069] In addition, the formulations and compositions of the present invention may contain fruit pulp for the production of natural fruit juices, fruit juice beverages, and vegetable beverages. These ingredients may be used independently or in combination. Although the proportion of these additives is not particularly important, it is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the formulation or composition of the present invention.

[0070] When the formulation of the present invention is a solution or an emulsion, a solvent, a solubilizing agent, or an emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan.

[0071] In the case where the formulation of the present invention is a suspension, liquid diluents such as water, ethanol, or propylene glycol, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracanthese may be used as carrier components.

[0072] In the case where the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, it may additionally include a propellant such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether.

Claims

1. A step of preparing a primary extract by chopping and extracting the leaves and stems of *Cistus incanus*; a step of preparing a *Cistus incanus* extract in which myricitrin is converted to myricetin by acid hydrolyzing the primary extract; and a step of preparing a *Cistus incanus* preparation for enhancing GABA efficacy comprising the *Cistus incanus* extract; comprising Method for manufacturing a Lacrose preparation for enhancing the efficacy of GABA.

2. The lacrose preparation of Claim 1; and GABA; comprising as active ingredients, A method for preparing a composition for improving stress.

3. In Claim 2, The Lacrose formulation is characterized by containing 1 / 10 to 1 / 5 of the GABA content, A method for preparing a composition for improving stress.

4. A lacrose preparation for enhancing GABA efficacy manufactured by the method of Claim 1.

5. A composition for improving stress prepared by the method of Claim 2.

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