An anti-inflammatory composition containing plum squeezed juice as an active ingredient

Abstract

The present invention relates to an anti-inflammatory composition containing ume squeezed juice as an active ingredient, and the feed composition is further added with aogiri extract, false acacia extract, butterbur extract, cinnamon extract and asparagus extract, so that it is harmless to the human body and has excellent efficacy in suppressing various inflammatory symptoms. Therefore, it can be used as a therapeutic agent for various inflammatory diseases such as colitis, arthritis, hepatitis, cystitis, nephritis, dermatitis, a food for improving symptoms, a cosmetic, and the like.

Description

Technical Field

[0001] The present invention relates to an anti-inflammatory composition containing ume squeezed juice as an active ingredient.

Background Art

[0002] The mechanism by which an inflammatory reaction occurs is that macrophages react to pathogens to generate pro-inflammatory cytokines such as TNF-α (tumor necrotic factor-α), IL-6 (interleukin-6), and IL-1β, and synthesize iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) to generate nitric oxide (NO) and PGE2 (prostaglandin E2). Physiologically, NO plays various roles such as removing bacteria and tumors, regulating blood pressure, and mediating neurotransmission. However, when an inflammatory reaction occurs, the expression of iNOS increases in related cells to generate a large amount of NO, and the excessively generated NO induces tissue damage, gene mutation, nerve damage, etc., and increases vascular permeability to promote inflammatory reactions such as edema. PGE2 is an inflammatory factor mainly involved in pain and fever, and is generated by COX-2 of macrophages when an inflammatory reaction occurs. Therefore, among the substances generated in an inflammatory reaction, it is possible to confirm the anti-inflammatory effect by confirming the suppression of the generation of substances such as NO and PGE2.

[0003] On the one hand, the activation process of macrophages by LPS is mediated by TLR (toll-like receptor) and occurs via a pathway that activates NF-κB (nuclear factor-κB), a transcription factor. LPS is present on the cell outer wall of Gram-negative (-) bacteria and is composed of a polysaccharide region consisting of a core region and an O-polysaccharide region, and a lipid region known as lipid A. It is known that lipid A of LPS plays an important role in the pathophysiology of Gram-negative bacteria. When TLR-4 on the surface of macrophages is stimulated by lipid A of LPS, a signal is transmitted to the TOLL / IL-1R (TIR) domain in the cytoplasm. The signal thus transmitted into the macrophage induces ligation with MyD88 (myeloid differentiation primary-response protein 88) and induces IRAK4 (IL-1R-associated kinase 4) into the signal transduction pathway. This IRAK-4 phosphorylates IRAK1, causing TRAF6 (tumour-necrosis-factor-receptor-associated factor 6) to also converge into the signal transduction system. The phosphorylated IRAK1 and TRAF6 are separated from the receptor complex and, via other mechanisms at the cell membrane, reactivate TAK1 (transforming-growth-factor-β-activated kinase) in the cytoplasm. The activated TAK1 phosphorylates the MAP (mitogen-activated protein) kinase and the IKK (inhibitor of nuclear factor-κB (IκB)-kinase complex) complex, inducing the degradation of IκB and NF-κB. The separated NF-κB moves to the nucleus of the macrophage and induces the expression of inflammation-related genes, thereby generating various cytokines and proteins.

[0004] Ume has been used since ancient times for the prevention and treatment of food poisoning, infectious diseases, etc. Even now, it is widely studied for purposes such as food preservation, and particularly contains a lot of citric acid, malic acid, etc. Its bactericidal power is well known.

[0005] While conducting various studies on anti-inflammatory related compositions using such ume, the present inventors have found that the ume squeezed juice suppresses the production of NO in macrophages activated by LPS, and have thus completed the present invention.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Summary of the Invention

Problems to be Solved by the Invention

[0007] An object of the present invention is to provide an anti-inflammatory composition containing ume squeezed juice as an active ingredient.

Means for Solving the Problems

[0008] The present invention relates to an anti-inflammatory composition characterized by containing ume squeezed juice, mugwort extract, false acacia extract, butterbur extract, cinnamon extract and asparagus extract.

[0009] The anti-inflammatory composition may contain 20 to 30 parts by weight of mugwort extract, 5 to 14 parts by weight of false acacia extract, 20 to 30 parts by weight of butterbur extract, 3 to 15 parts by weight of cinnamon extract, and 10 to 20 parts by weight of asparagus extract with respect to 100 parts by weight of ume squeezed juice.

[0010] The anti-inflammatory composition may contain ume sugar extract. The ume sugar extract can be mixed in an amount of 10 to 30 parts by weight with respect to 100 parts by weight of ume squeezed juice.

[0011] Each of the above extracts can be obtained by preparing each raw material sample and extracting the raw material sample using water, C1-C4 alcohol or a mixed solution thereof as a solvent. As the solvent, it is most preferable to use water.

[0012] Hereinafter, the present invention will be described in detail. The ume squeezed juice used in the present invention is characterized by being obtained by pulverizing fresh ume, squeezing (juicing) it, and then heating the resulting liquid phase. Yellow ume or green ume can be used. Also, the liquid phase obtained by pulverizing fresh ume, squeezing it to extract juice, heating it primary, centrifuging it, filtering it with a microfilter, and then heating it secondary can be used. The centrifugation is preferably carried out at 4 to 10 °C and 8000 to 10000 rpm for 5 to 30 minutes, and the primary or secondary heating can be carried out at 70 to 125 °C for 0.5 to 48 hours. As the microfilter, one with a pore size of 0.2 to 0.45 μm can be used.

[0013] The composition of the present invention may further contain an ume sugar extract. The ume sugar extract used in the present invention can be the liquid phase obtained by removing the residue from the mixture obtained by allowing the mixture of ume and saccharides to stand still for osmotic extraction as it is. The ume sugar extract can be the liquid phase obtained by removing the residue from the mixture obtained by allowing the mixture of 50 to 200 parts by weight of saccharides and 100 parts by weight of ume to stand still for osmotic extraction for 3 to 6 months as it is. The extraction temperature of the ume sugar extract is preferably 4 to 37 °C, and more preferably 15 to 30 °C. Any saccharide that produces a sweet taste can be used as the saccharide, but one or more selected from the group consisting of granulated sugar, sugar powder, oligosaccharide, agave syrup, maple syrup, cactus sugar, and honey can be used. At this time, if the amount of saccharide mixed is less than 50 parts by weight per 100 parts by weight of ume, it is likely to rot without fermentation. Also, if the amount of saccharide mixed exceeds 200 parts by weight per 100 parts by weight of ume, the saccharide component may not be mixed with the juice extracted from ume due to over-addition of the saccharide component. Also, if the extraction period is less than 3 months, it is likely to rot thereafter, and if the extraction period exceeds 6 months, acetic acid fermentation or alcohol fermentation may proceed, or rotting may proceed depending on the storage location or environment.

[0014] As the aogiri used in the present invention, one or more selected from branches, fruits, and leaves can be contained, and as the false acacia (acacia), the xylem can be used.

[0015] Each solvent extract can be mixed with ume squeezed juice after freeze-drying in the anti-inflammatory composition. When the extract is extracted with water, it may be immediately mixed with ume squeezed juice. Preferably, the solvent extract may be a liquid phase obtained by adding 5 to 20 parts by weight of water to the raw material sample, heating and extracting at 70 to 90 °C for 1 to 10 hours, and then removing the residue.

[0016] As the solvent extract used in the present invention, the extract of Artemisia princeps Pamp., the extract of Albizia julibrissin Durazz., the extract of Petasites japonicus (Thunb.) Koidz., the extract of Cinnamomum cassia Presl, and the extract of Asparagus officinalis L. can be produced by the following method. For this purpose, each raw material sample is prepared, and the raw material sample can be extracted using water, an alcohol having 1 to 4 carbon atoms, or a mixed solution thereof as a solvent. The alcohol having 1 to 4 carbon atoms can be selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, and isobutanol.

[0017] The extraction conditions of the raw material sample may be 20 to 100°C for 1 minute to 48 hours. The above process can be repeated 1 to 4 times. At this time, as the extraction equipment to be used, ordinary extraction equipment, ultrasonic crushing extractor or fractionator can be used. The solvent extract produced in this way can remove the solvent by hot air drying, vacuum drying or freeze drying. Further, the solvent extract can be purified using column chromatography and then used. The solvent extract can be fractionated or purified and used by using a known method used for the separation and extraction of plant components, such as extraction with an organic solvent (alcohol, ether, acetone, etc.), partition of hexane and water, and a method using column chromatography, alone or in a suitable combination, according to a conventional method. The chromatography can be selected from silica gel column chromatography, LH-20 column chromatography, ion exchange resin chromatography, medium pressure liquid chromatography, thin layer chromatography (TLC), silica gel vacuum liquid chromatography and high performance liquid chromatography.

[0018] The present invention relates to a pharmaceutical composition for preventing or treating an inflammatory disease, comprising the anti-inflammatory composition. The inflammatory disease may be selected from the group consisting of atopic dermatitis, edema, dermatitis, allergy, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, systemic lupus erythematosus, fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, periarthritis of shoulder, tendinitis, tenosynovitis, myositis, hepatitis, cystitis, nephritis, Sjogren's syndrome and multiple sclerosis.

[0019] The pharmaceutical composition can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injection solutions by ordinary methods. Examples of carriers, excipients, and diluents that can be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginates, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. When formulating, it is usually prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. Such solid preparations are prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, or lactose, gelatin, etc., into the anti-inflammatory composition of the present invention. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, internal solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, such as wetting agents, sweeteners, fragrances, preservatives, etc., can be included. Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. As non-aqueous solvents and suspensions, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate can be used. As the base of suppositories, witepsol, macrogol, Tween 61, cacao butter, laurin fat, glycerogelatin, etc. can be used.

[0020] The dosage of the pharmaceutical composition of the present invention varies depending on the age, sex, weight of the subject to be treated, the specific disease or pathological condition to be treated, the severity of the disease or pathological condition, the route of administration, and the judgment of the prescriber. Determination of the dosage based on such factors is within the level of those skilled in the art. Generally, the dosage ranges from 0.01 mg / kg / day to approximately 2000 mg / kg / day. A more preferred dosage is from 1 mg / kg / day to 500 mg / kg / day. Administration may be once a day or divided into several times. The above dosage does not limit the scope of the present invention in any way.

[0021] The pharmaceutical composition of the present invention can be administered to mammals such as mice, livestock, and humans by various routes. All modes of administration are predictable. For example, it can be administered orally, rectally, or by intravenous, intramuscular, subcutaneous, intrauterine epidural, or intracerebrovascular injection.

[0022] The present invention provides a health functional food for preventing or improving inflammatory diseases, which contains the above anti-inflammatory composition. In addition, the anti-inflammatory composition can be added to the health functional food of the present invention in an amount of 0.001 to 100% by weight. The health functional food of the present invention includes forms such as tablets, capsules, pills, or liquids. Examples of foods to which the anti-inflammatory composition of the present invention can be added include various drinks, meats, sausages, bread, candies, snacks, noodles, ice cream, dairy products, soups, ion drinks, drinking water, alcoholic beverages, gums, teas, and vitamin complexes.

[0023] In another aspect, the present invention can provide a cosmetic composition containing the anti-inflammatory composition. As the dosage form of the cosmetic composition, it can be manufactured into any dosage form usually produced in the art, such as essence, lotion, emulsion, pack, hand cream, foot cream, lip balm, lipstick, eyeshadow, eyeliner, eyebrow pencil, blusher, highlighter, general lotion, skin lotion, cream, serum, beauty soap, softening lotion, medicinal lotion, body wash, cleansing foam, cleansing lotion, gel, cleansing oil, cleansing cream, shampoo, conditioner, hair treatment, hair lotion, cleansing tissue, and cleansing water.

[0024] The cosmetic composition of the present invention can further contain components selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high molecular weight peptides, high molecular weight polysaccharides, sphingolipids, and seaweed extracts, or ordinary excipients for cosmetics.

Advantages of the Invention

[0025] The present invention relates to an anti-inflammatory composition containing ume squeezed juice as an active ingredient. By further adding a bluebottle extract, a false acacia extract, a butterbur extract, a cinnamon extract, and an asparagus extract to the feed composition, it is harmless to the human body and has excellent efficacy in suppressing various inflammatory symptoms. Therefore, it can be used as a therapeutic agent for various inflammatory diseases such as colitis, arthritis, hepatitis, cystitis, nephritis, dermatitis, a food for improving symptoms, a cosmetic, and the like.

Examples

[0026] Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, it is provided to fully convey the idea of the present invention to those skilled in the art so that the content introduced here is thorough and complete.

[0027] <Examples 1 to 6. Production of Anti-Inflammatory Composition> Fresh ume plums were crushed and juiced, and then heated at 90 °C for 1 hour for the first time. The heated liquid phase was centrifuged at 8000 rpm for 30 minutes at 4 °C, filtered through filter paper, and then heated for the second time under the same conditions as the first time. Thereafter, it was filtered through a 0.2 μm filter to obtain ume plum juice extract.

[0028] For kogiri, samples were prepared by mixing branches, fruits, and leaves in the same weight. For false acacia (Acacia), the xylem of branches and trunks was prepared. For cinnamon, the bark of cinnamon trees was prepared. Kogiri, false acacia, butterbur (fruits), cinnamon, and asparagus were prepared in their raw state. For each raw material from kogiri to cinnamon, 10 kg of water was added per 1 kg, and heated and extracted at 80 °C for 5 hours. The liquid phase obtained after removing the residue was cooled and used as it was.

[0029] A mixture of ume plums and sugar in the same weight was left standing at 25 °C in a cool and shaded room temperature for 3 months. After sufficient juice was extracted from the ume plums, the residue was removed and the liquid phase was collected to obtain ume plum sugar extract.

[0030] Next, based on 100 g of the ume plum juice extract, it was mixed as shown in Table 1 below to produce an anti-inflammatory composition.

Table 1

[0031] <Comparative Examples 1 - 6. Preparation of Anti-Inflammatory Composition under Comparative Conditions> Comparative anti-inflammatory compositions were prepared under the conditions shown in Table 2. Each raw material and manufacturing method were the same as in Example 1.

Table 2

[0032] <Experimental Example 1. Confirmation of Cytotoxicity> 96-well plate (1.5×10 3Raw264.7 cells inoculated into each well were treated with each anti-inflammatory composition at different concentrations. After culturing for 24 hours, the WST-8 reagent (manufactured by Dojindo Laboratories) was added to the medium at 37°C for 1 hour. The absorbance was measured at 450 nm using a microplate reader (manufactured by BioTek). Thereafter, the absorbance was measured every 24 hours to confirm the cell viability.

[0033] The cell viability for each sample was calculated by converting the value when the cell state of the control group (the group without sample treatment) was set to 100%, and the viability is shown in Table 3 below.

Table 3

[0034] <Experimental Example 2. Confirmation of anti-inflammatory efficacy> RAW264.7 cells were dispensed into 60 mm plates at a density of 2×10 6 cells / dish and allowed to adhere to the plates for 24 hours. To induce an inflammatory response, the cells were treated with a new medium containing 1 μg / ml of LPS (lipopolysaccharide) and each anti-inflammatory composition and cultured for 24 hours.

[0035] The level of NO present in the culture medium produced by RAW264.7 cells was measured using a NO detection kit (Detection Kit, 21021 from Intron) based on the Griess reaction. 100 μl of the culture medium presumed to contain NO was dispensed into a 96-well plate, then 50 μl of N1 buffer (sulfanilamide) was added and reacted at room temperature for 10 minutes. Next, 50 μl of N2 buffer (naphthylethylenediamine) was added and reacted at room temperature for 10 minutes, and then the absorbance was measured at 540 nm. Each NO production amount was calculated using a standard calibration curve obtained using a nitrite standard. LPS was used as the positive control group (positive control).

[0036]

Table 4

Claims

1. An anti-inflammatory composition characterized by containing ume squeezed juice as an active ingredient.

2. The anti-inflammatory composition according to claim 1, characterized in that the composition contains mugwort extract, mimosa extract, butterbur extract, cinnamon extract and asparagus extract.

3. The anti-inflammatory composition according to claim 2, characterized in that the composition contains ume sugar extract.

4. The anti-inflammatory composition according to claim 1, characterized in that the ume squeezed juice is obtained by pulverizing fresh ume, squeezing it, and then heating the obtained liquid phase.

5. A pharmaceutical composition for preventing or treating inflammatory diseases, characterized by containing the composition according to claim 1.

6. The pharmaceutical composition for preventing or treating inflammatory diseases according to claim 5, characterized in that the inflammatory disease is selected from the group consisting of atopic dermatitis, edema, dermatitis, allergy, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, pharyngolaryngitis, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, systemic lupus erythematosus, fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, periarthritis of shoulder, tendinitis, tenosynovitis, myositis, hepatitis, cystitis, nephritis, Sjogren's syndrome and multiple sclerosis.

7. A health functional food for preventing or improving inflammatory diseases, characterized by containing the composition according to claim 1.

8. The health functional food for preventing or improving inflammatory diseases according to claim 7, characterized in that the inflammatory disease is selected from the group consisting of atopic dermatitis, edema, dermatitis, allergy, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, pharyngolaryngitis, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, systemic lupus erythematosus, fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, periarthritis of shoulder, tendinitis, tenosynovitis, myositis, hepatitis, cystitis, nephritis, Sjogren's syndrome and multiple sclerosis.

9. An anti-inflammatory cosmetic composition characterized by containing the composition according to claim 1.

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