KR101869353B1 - Novel Compound Isolated from Aruncus dioicus and Anti-inflammation Composition Using the Same - Google Patents
Novel Compound Isolated from Aruncus dioicus and Anti-inflammation Composition Using the Same Download PDFInfo
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- KR101869353B1 KR101869353B1 KR1020170106624A KR20170106624A KR101869353B1 KR 101869353 B1 KR101869353 B1 KR 101869353B1 KR 1020170106624 A KR1020170106624 A KR 1020170106624A KR 20170106624 A KR20170106624 A KR 20170106624A KR 101869353 B1 KR101869353 B1 KR 101869353B1
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- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/32—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
Abstract
The present invention inhibits the production of NO, PGE 2 , inflammatory cytokines (TNF-a and IL-6) and suppresses the production of iNOS and COX-2 in macrophages stimulated by lipopolysaccharide (LPS) (P38 MAPK), ERK1 / 2 (extracellular signal-regulated kinases 1/2) and JNK (c-Jun N-terminal kinase) And an anti-inflammatory composition using the same.
Description
The present invention relates to a novel compound isolated from Aruncus dioicus extract and an anti-inflammatory composition using the novel compound.
Inflammation is the defensive response of the body to external infectious diseases such as external physical and chemical stimuli, bacteria, fungi, viruses and allergens.
The inflammatory response is part of the innate immune response, and as in other animals, the innate immune response of humans begins by recognizing and attacking macrophages as non-self through a pattern of cell surfaces that are specific to the pathogen. During the inflammation reaction, plasma accumulates on the inflamed area, diluting the toxicities secreted by the bacteria, increasing the blood flow, and accompanied by symptoms such as erythema, pain, edema, and fever.
These inflammatory reactions involve a variety of biochemical events, in particular, cyclooxygenase (COX), which is associated with the nitric oxide synthase (NOS) and the biosynthesis of various prostaglandins, .
There are three isomers of NOS: endotoxin of bacteria such as calcium or camodanol-dependent eNOS (endothelial NOS), nNOS (neurotic NOS), and lipopolysaccharide (IL-1β, TNF-α, IL There are iNOS (inducible NOS) induced by various inflammatory cytokines such as IL-6, IL-8 and IL-12 and produce NO from L-arginine.
NO produced by eNOS or nNOS plays an important role in maintenance of homeostasis by performing various physiological responses related to blood pressure control, neurotransmission, learning, memory, etc. However, NO produced by iNOS is associated with arthritis, sepsis, (Moncade S. et al, Pharmacol. Rev., 1991, 43, 109, Nature Medicine, 2001, 7, 1138; Mu, S., et al., Immunoprecipitation, , MM, J. Endotoxic Res. 7, p341, 2001).
The COX enzyme synthesizes PGG 2 and PGH 2 from arachidonic acid with hydroperoxidase (HOX) activity together with the function of COX. These compounds include PGE 2 , PGF 2 , PGD 2 , prostacyclin and create a duplex thromboxane a 2 (thromboxane A2, TxA2) . Among the functions of COX, the function of PGH synthase is involved in the pain and inflammation reaction through synthesis of PGE 2 . There are two subtypes of COX and COX-1 is always expressed in most tissues, whereas COX-2 is rapidly induced by inflammatory cytokines and plays an important role in the inflammatory response.
Expression of iNOS and COX-2, which induce overproduction of NO and PGE 2 , is regulated by the nuclear factor kappa B (NF-κB), a nuclear transcription factor. NF-κB is a nuclear protein of the Rel gene family. In the cytoplasm, it binds to I-κB and is present in an inactive form. However, inflammatory cytokines, toxic compounds, bacterial infections, viral infections, The activation of the I-κB kinase by various external stimuli such as oxygen causes activation of I-κB by phosphorylation. NF-κB, composed of heterodimers of p50 and p65, is activated and induces gene expression of iNOS and COX-2, which translocates to the nucleus and induces an inflammatory response (Oh, GT et al., Atherosclerosis, 159 (1): 17-26, 2001). IκB binds to NIK (NF-κB-inducing kinase) and IKK (IB kinase) as well as MAPK p38 (p38 MAPK), extracellular signal-regulated
Bacterial endotoxins such as LPS (lipopolysaccharide) activate NF-κB, which is a transcription factor, by binding to TLR4 (toll-like receptor 4), and induce the expression of iNOS and COX-2 to produce NO, inflammatory cytokines, PGE 2 J Immunol., 170: 508-19, 2003; Ji Y, et al., ≪ RTI ID = 0.0 > et al., Cell Physiol Biochem., 25: 631-640, 2010). NO, Inflammatory cytokines such as TNF-α and IL-6 and PGE 2 have been implicated in arthritis (Jang CH et al., Rheumatology 2006, 45 (6): 703-710), fibromyalgia (Hernandez ME et al. (2009), 38 (5): 386-389), which is an important factor in the induction of inflammatory responses in patients with Sjogren's syndrome (Baturone R. et al., Scand J Rheumatol. Et al., BMC Res. Notes., 3 (1): 156, 2010; Baturone R. et < RTI ID = 0.0 > al., Scand J Rheumatol., 38 (5): 386-389, 2009).
These findings suggest that inhibition of NO production Drugs that inhibit the production of inflammatory cytokines such as TNF-α and IL-6, and drugs that inhibit the expression of iNOS or COX-2 have potential as effective anti-inflammatory agents (Karin M. et al., Cold Spring Harb Perspect Biol., 1, pp1-14, 2009).
Non-steroidal anti-inflammatory drugs (NSAIDS), which are now widely used as anti-inflammatory drugs, are known to cause serious side effects such as gastrointestinal disorders, hepatic impairment and renal failure (Rainsford KD., Subcell biochem., 42: 3 -27, 2007, Guruprasad P. Aithal., Rheumatology., 7: 139-150, 2011, Praveen PN Rao et al., Pharmaceuticals., 3: 1530-1549, 2010).
Therefore, it is still necessary to develop new drugs that have anti-inflammatory activity, have fewer side effects, and continue to be effective.
The present invention discloses novel compounds and their anti-inflammatory activity isolated from edible pear-riding.
It is an object of the present invention to provide a novel compound separated from a pomegranate horse extract.
It is another object of the present invention to provide an anti-inflammatory composition using the compound.
Other and further objects of the present invention will be described below.
As shown in the following examples and experimental examples, the present invention is a method for isolating and identifying a novel compound of the following formula (1) from a tear extract of horse mackerel and determining whether the compound is NO, PGE 2 , P38 (p38 MAPK), and ERK1 / 2 (NF-κB), which inhibit the production of inflammatory cytokines (TNF-α and IL-6) and inhibit the production of iNOS and COX- extracellular signal-regulated
In view of the foregoing, in one aspect, the present invention relates to a compound of Formula 1, an isomer of the compound, a prodrug thereof, a hydrate of the compound, or a solvate of the compound.
≪ Formula 1 >
In the present invention, the isomers of the compounds are not only inherently pure diastereomers, but also conformation isomers, position isomers (especially tautomers) or geometric isomers (optical isomers) And includes geometric isomers (e. G., Cis-trans isomers).
In the present invention, "prodrug" refers to a drug which does not exhibit physiological activity itself but can be converted into an original drug by chemical or enzymatic action in the body after administration, It is manufactured for the purpose of controlling physical and chemical properties. In some cases, prodrugs may be used to facilitate administration. For example, some drugs can not ferment the drug efficacy by oral administration, but the prodrug can ferment the drug efficacy by oral administration. Prodrugs may also be prepared to increase the solubility of the drug. For example, prodrugs may be in the form of esters that facilitate the passage of cell membranes, where the solubility in water is detrimental to portability but is once hydrolyzed to the carboxylic acid that is active by metabolism in cells with favorable water solubility. Another example of a prodrug may be a short peptide in which the peptide is attached to an acid group that is converted by metabolism to reveal the active site.
In the present invention, "hydrate" means a compound in which water is bonded, and includes a containing compound having no chemical bonding force between water and the compound. The hydrate may contain 1 equivalent or more, preferably 1 to 5 equivalents of water. Such a hydrate may be prepared by crystallizing the compound of the present invention, a pharmaceutically acceptable salt thereof, or an isomer thereof from a solvent containing water or water.
In the present invention, "solvate" means a compound formed between a molecule or ion of a solute and a molecule or ion of a solvent. Such solvates may include stoichiometric or non-stoichiometric amounts of a solvent that is bound by noncovalent intermolecular forces. Preferred solvents include ethanol, methanol, propanol, methylene chloride, etc., which are non-volatile and do not exhibit toxicities that are acceptable to humans.
In another aspect, the present invention relates to an anti-inflammatory composition comprising the compound of formula (I) as an active ingredient.
As used herein, the term " active ingredient "alone means an ingredient which exhibits the desired activity or which can exhibit activity together with a carrier which is itself inactive.
As used herein, "anti-inflammatory" is meant to include improvement of an inflammatory disease (alleviation of symptoms), treatment, inhibition or delay of onset of such a disease as defined below.
In the present specification, the term "inflammatory disease" refers to an inflammatory disease caused by an external physicochemical stimulus or infection of an external infectious source such as bacteria, fungi, viruses, various allergenic substances, or a local or systemic defense against autoimmunity It may be defined as a pathological symptom. These inflammatory reactions include activation of various inflammatory mediators and enzymes associated with immune cells such as iNOS and COX-2, secretion of inflammatory mediators such as NO, TNF-, and IL-6 secretion, Migra- tion, and tissue destruction, and manifest externally by symptoms such as erythema, pain, swelling, fever, deterioration or loss of specific functions of the body. The inflammatory disease may be acute, chronic, ulcerative, allergic or necrotic, so long as it is included in the definition of inflammatory diseases as above, it may be acute, chronic, ulcerative, allergic, Whether it is necrotic or not. Specifically, the inflammatory diseases include asthma, allergic and non-allergic rhinitis, chronic and acute rhinitis, chronic and acute gastritis or enteritis, ulcerative gastritis, acute and chronic nephritis, acute and chronic hepatitis, chronic obstructive pulmonary disease, Inflammatory bowel syndrome, inflammatory pain, migraine headache, headache, back pain, fibromyalgia, fascia disease, viral infection (e.g., C type infection), bacterial infection, fungal infection, burn, wound due to surgical or dental surgery, Rheumatoid arthritis, ankylosing spondylitis, Hodgkin's disease, pancreatitis, conjunctivitis, iritis, scleritis, uveitis, dermatitis (including atopic dermatitis), eczema, multiple sclerosis, etc. Will be included.
The anti-inflammatory composition or the like of the present invention may be contained in any amount (effective amount) as long as it can exhibit the activity of improving the inflammatory diseases intended to be treated according to the purpose of use, formulation, blending purpose, etc., An effective amount will be determined within the range of from 0.001% to 15% by weight based on the total weight of the composition. The term "effective amount" as used herein refers to an amount of an effective amount of a compound of the present invention to be administered to a mammal, preferably a human, to which the composition of the present invention is administered during a period of administration, / Delay " refers to the amount of active ingredient that can exhibit an intended medical pharmacological effect. Such effective amounts can be determined experimentally within the ordinary skill of those skilled in the art.
The anti-inflammatory composition of the present invention may further contain, in addition to the active ingredient, any compound or natural extract known to have safety and anti-inflammatory activity for enhancing anti-inflammatory effects and the like. Specific examples of such compounds or extracts include MSM (dimethylsulfonylmethane), N-acetylglucosamine, glucosamine, and individual approval under the Health Functional Foods Act Complex extracts of CMO-containing complex extracts such as FAT (Fatty acid Complex) and Gassiogarifolia, complex extracts such as turmeric extract, chicken breast cartilage powder, rosehip powder, boswellia extract, beeswax alcohol, , Green lipped mussel extract oil, hop extract, and gold extract. Such compounds or natural extracts may be included in the anti-inflammatory compositions of the present invention in combination with one or more of their effectiveness.
The anti-inflammatory composition and the like of the present invention can be grasped as a food composition in a specific aspect.
The food composition of the present invention can be produced in any form and can be used in various forms such as beverages such as tea, juice, carbonated drink, ionic drink, processed oil such as milk and yogurt, gum, rice cake, Korean confectionery, A food, a health food, a food, a tablet, a capsule, a ring, a granule, a liquid, a powder, a slice, a paste, a syrup, a gel, a jelly and a bar. In addition, the food composition of the present invention may be classified into any product category as long as it is in compliance with the regulations on the time of manufacture and distribution in terms of the function of the law. For example, it may be a health functional food according to the Act on Health Functional Foods, or a confectionery, bean curd, fermented beverages, special-purpose foods, etc. according to each type of food in the food revolution (food standard, .
The food composition of the present invention may contain food additives in addition to the active ingredients thereof. Food additives are generally understood to be substances that are added to foods and mixed or infiltrated into food in the manufacture, processing or preservation of food, and their safety must be ensured since they are taken daily with food and for long periods. Food additives according to the Food Hygiene Act (food additives notification, food additive standards and standards) are limited by the classification of safe synthetic food additives as chemical synthetic products, natural additives and mixed preparations.
These functional food additives can be classified into sweeteners, flavors, preservatives, emulsifiers, acidifiers, and thickeners.
A sweetener is used to impart a sweet taste suitable for foods, and natural or synthetic sweeteners can be used. Preferably, natural sweeteners are used. Examples of natural sweeteners include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose and maltose.
Flavors may be used to enhance taste or flavor, both natural and synthetic. Preferably, a natural one is used. When using natural ones, the purpose of nutritional fortification can be performed in addition to the flavor. Examples of natural flavoring agents include those obtained from apples, lemons, citrus fruits, grapes, strawberries, peaches, and the like, or those obtained from green tea leaves, Asiatica, Daegu, Cinnamon, Chrysanthemum leaves and Jasmine. Also, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, banks and the like can be used. The natural flavoring agent may be a liquid concentrate or a solid form of extract. Synthetic flavors may be used depending on the case, and synthetic flavors such as esters, alcohols, aldehydes, terpenes and the like may be used.
As the preservative, calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate and EDTA (ethylenediaminetetraacetic acid) can be used. As the emulsifier, acacia gum, carboxymethyl cellulose, Pectin and the like. As the acidulant, math, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid and the like can be used. The acidulant may be added so that the food composition has a proper acidity for the purpose of inhibiting the growth of microorganisms other than the purpose of enhancing the taste.
Examples of the thickening agent include suspending agents, sedimentation agents, gel-forming agents, bulking agents and the like.
The food composition of the present invention may contain physiologically active substances or minerals which are known in the art and which are stable as a food additive in addition to the above-mentioned food additives in order to supplement and supplement functional and nutritional properties.
Examples of such physiologically active substances include catechins contained in green tea and the like, vitamins such as vitamin B1, vitamin C, vitamin E and vitamin B12, tocopherol, dibenzoyl thiamine, etc. Examples of minerals include calcium preparations such as calcium citrate, magnesium stearate , Iron preparations such as iron citrate, chromium chloride, potassium iodide, selenium, germanium, vanadium, zinc and the like.
The food composition of the present invention may contain an appropriate amount of the above-mentioned food additives according to the product type so as to achieve the purpose of addition thereof.
With regard to other food additives that can be included in the food composition of the present invention, reference may be made to the Food Code or the Food Additive Code.
The composition for anti-inflammation of the present invention and the like may be regarded as a pharmaceutical composition in another specific embodiment.
The pharmaceutical composition of the present invention may be prepared into oral formulations or parenteral formulations according to the route of administration by conventional methods known in the art, including pharmaceutically acceptable carriers in addition to the active ingredient. The term "pharmaceutically acceptable" as used herein means that the application (prescribing) subject does not have the above-mentioned toxicity that is adaptable without inhibiting the activity of the active ingredient.
When the pharmaceutical composition of the present invention is prepared into an oral formulation, it may be formulated into powder, granules, tablets, pills, sugar tablets, capsules, solutions, gels, syrups, suspensions, wafers And the like. Examples of suitable pharmaceutically acceptable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, xylitol, starch such as corn starch, potato starch and wheat starch, cellulose, methylcellulose, ethylcellulose, Cellulose derivatives such as sodium carboxymethyl cellulose and hydroxypropylmethyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, And the like. In case of formulation, a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and / or an excipient may be formulated according to need.
When the pharmaceutical composition of the present invention is prepared into a parenteral dosage form, it may be formulated in the form of an injection, transdermal drug delivery, nasal aspirate and suppository together with a suitable carrier according to methods known in the art. Examples of suitable carrier in the case of formulation with an injectable preparation include sterilized water, ethanol, polyol such as glycerol and propylene glycol, or a mixture thereof. Preferably, the carrier is selected from the group consisting of Ringer's solution, phosphate buffered saline containing triethanolamine, Water, or isotonic solution such as 5% dextrose may be used. When formulated with a transdermal drug, it can be formulated in the form of an ointment, a cream, a lotion, a gel, a solution for external use, a pasta, a liniment, or an air-roll. The nasal inhalant may be formulated in the form of an aerosol spray using a suitable propellant such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, etc. When formulated as a suppository, witepsol, tween 61, polyethylene glycols, cacao butter, laurin, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, and sorbitan fatty acid esters.
The formulation of pharmaceutical compositions is well known in the art and can be specifically described in Remington ' s Pharmaceutical Sciences (19th ed., 1995). This document is considered part of this specification.
The preferred dosage of the pharmaceutical composition of the present invention is 0.001 mg / kg to 10 g / kg per day, preferably 0.001 mg / kg to 1 g / day, depending on the patient's condition, body weight, sex, age, / kg < / RTI > The administration can be carried out once or several times a day. Such dosages should in no way be construed as limiting the scope of the invention.
In another specific embodiment, the composition for anti-inflammation of the present invention can be identified as a cosmetic composition. When the anti-inflammatory composition of the present invention is identified as a cosmetic composition, its use can be understood as a relief of inflammatory skin irritation.
The cosmetic composition of the present invention may contain, in addition to its active ingredient, conventional additives such as stabilizers, solubilizing agents, surfactants, vitamins, colorants and antioxidants, and carriers commonly used in cosmetic compositions.
The cosmetic composition of the present invention can be prepared into any of the formulations conventionally produced in the art and can be used in the form of solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, , Oil, powder foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, it can be manufactured in the form of a soft lotion, a nutritional lotion, a nutritional cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder.
When the formulation of the present invention is a paste, cream or gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .
When 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. In the case of a spray, in particular, / Propane or dimethyl ether.
When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.
In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.
When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component is selected from aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters.
The cosmetic composition of the present invention can be manufactured according to a method for producing a cosmetic composition which is conventionally performed in the art, except that it contains the active ingredient exhibiting anti-inflammatory activity and the like.
As described above, according to the present invention, it is possible to provide a composition for anti-inflammation using the compound of formula (1) isolated from a tear extract.
The anti-inflammatory composition of the present invention can be produced into pharmaceutical compositions, food compositions or cosmetic compositions.
FIG. 1 is a schematic diagram showing the separation of the compound of
2 is an LC-MS spectrum of the compound of the formula (1).
FIG. 3 shows 13 C NMR spectrum and 1 H NMR spectrum data of the compound of the formula (1).
4 is a DEPT 135 NMR spectrum of the above formula (1).
5 shows the < 1 > H NMR spectrum of the formula (1).
6 shows the HMBC spectrum of the formula (1).
7 is a HMQC spectrum of the formula (1).
Fig. 8 shows experimental results on the NO production inhibitory activity and cytotoxicity of the compound of the formula (1).
FIG. 9 shows experimental results on the PGE 2 inhibitory activity of the compound of formula (1).
FIGS. 10 to 12 are experimental results on the inhibitory activity of the compounds of the formula (I) for the production of inflammatory cytokines (TNF-.alpha., IL-6 and IL-1 beta).
Figure 13 shows the iNOS and COX-2 Western blot results of the compound of formula (I).
14 and 15 are graphs showing the activity of IκB, p38 (p38 MAPK), extracellular signal-regulated
Hereinafter, the present invention will be described with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited to these examples and experimental examples.
< Example > Preparation of pearl riding extract and isolation of active ingredients
Example 1 Preparation of 70% Ethanol Extract on the Surface of a Tiger Ridge
The dried powder of the top part of the top of the tiger pupae was added with 20 times the weight of 70% ethanol, and the mixture was left at room temperature for 24 hours. The mixture was repeatedly extracted three times and filtered. The filtrate was concentrated under reduced pressure and lyophilized to obtain a solid pomegranate extract.
Example 2 Isolation of Active Ingredients from Pig Horse Equestrian Extract
First, 50 g of the solid extract was suspended in 10 L of distilled water, and then the fractions were sequentially fractionated with an equal amount of normal hexane, dichloromethane, ethyl acetate and normal butanol, and then concentrated under reduced pressure to obtain the respective fractions . 4.1 g of the ethyl acetate fraction having excellent dual antitumor activity was subjected to column chromatography (mobile phase: normal hexane, dichloromethane, ethyl acetate, butanol and methanol) on a glass column (5 x 50 cm) packed with Celite 545, And divided into five fractions. The ethyl acetate fraction, which had excellent anti-inflammatory activity, was concentrated in the following five fractions and was completely dried and purified by vacuum liquid chromatography (VLC) on a glass column (10 × 3 cm) packed with silica gel (mobile phase: n-hexane, dichloromethane , Ethyl acetate, methanol; mobile phase transfer rate = 60 mL / min). The
The
≪ Experimental Example > The anti-inflammatory activity of the separated active ingredients of the pearl riding extract and fractions thereof
1. Samples and Experimental Methods
1.1 Cell culture
RAW 264.7 was purchased from the American Type Culture Collection (ATCC, Rockville, Md., USA), and 10% fetal bovine serum (FBS), penicillin (100 units / mL), and streptomycin (100 g / mL) was added and stored in Dulbeccos Modified Eagles Medium (DMEM; GIBCO Inc.). These cells were cultured at 37 ° C in a subconfluence condition of 95% air, 5% CO 2 humidified air, and subcultured every 3 days.
1.2 NO ( Nitric oxide ) Production inhibition efficacy evaluation
RAW 264.7 cells were adjusted to 1.5 × 10 5 cells / mL using DMEM supplemented with 10% FBS, and then inoculated into a 24-well plate. LPS (1 μg / mL) Lt; / RTI > The amount of produced NO Griess reagent [1% (w / v) sulfanilamide, 0.1% (w / v) naphylethylenediamine in 2.5% (v / v) phosphoric acid] by using the NO 2 present in the cell culture - in the form of Respectively. 100 L of cell culture supernatant and 100 L of Griess reagent were mixed and reacted on 96-well plates for 10 minutes, and the absorbance was measured at 540 nm. The amount of NO produced was compared with sodium nitrite (NaNO 2 ) as standard.
1.3 Cytotoxicity Assessment - LDH assay
RAW 264.7 cells (1.5 × 10 5 cells / mL) were co-treated with DMEM medium and LPS (1 μg / mL) in a DMEM medium for 24 hours, followed by culture at 3,000 rpm for 5 minutes. LDH (lactate dehydrogenase) assay was performed using a non-radioactive cytotoxicity assay kit (Promega). 50 L of the culture medium obtained by centrifugation on a 96-well plate and 50 L of the reconstituted substrate mix were added and reacted at room temperature for 30 minutes After the addition of 50 L stop solution, the absorbance was measured at 490 nm using a microplate reader (Bio-TEK Instruments Inc., Vermont, WI, USA). The average absorbance values for each sample group were determined and compared with the absorbance values of the control (LDH control, 1: 5000) to evaluate cytotoxicity. The results showed the mean ± SD of three independent experiments.
1.4 PGE 2 ( Prostaglandin E 2 ) Production inhibition efficacy evaluation
RAW 264.7 cells were adjusted to 1.5 × 10 5 cells / mL using DMEM medium, inoculated into 24-well plates, and incubated 18 hours before in a 5% CO 2 incubator. Then, the medium was removed and a new medium containing the sample of Example and LPS (1 / / mL) was treated and cultured under the same conditions as the pre-culture. After 24 hours, the supernatant was obtained by centrifuging the culture medium (12,000 rpm, 3 min) to measure PGE 2 . PGE 2 was quantified using a PGE 2 ELISA kit (R & DS Systems Inc., Minneapolis, MN, USA). The r 2 value of the standard curve for the standard was 0.99 or more. The results showed the mean ± SD of three independent experiments.
1.5 Inflammatory cytokines ( TNF -α, IL -6 and IL-1?)
RAW 264.7 cells (1.5 × 10 5 cells / mL) were inoculated into 24-well plates using DMEM medium and cultured for 18 hours in a 5% CO 2 incubator. Then, the medium was removed and a new medium containing both the sample and LPS (1 / / mL) was treated and cultured under the same conditions as the pre-culture. After 24 hours, the amount of pro-inflammatory cytokines produced in the supernatant obtained by centrifuging the culture medium (12,000 rpm, 3 minutes) was measured. All samples were stored at -20 ° C or lower before quantification. Quantification of pro-inflammatory cytokines was quantitated using a mouse enzyme-linked immunosorbent assay (ELISA) kit (R & D Systems Inc., Minneapolis, MN, USA). The results showed the mean ± SD of three independent experiments.
1.6 Western blot
Cells were harvested and washed twice with phosphate buffered saline (PBS). Cell lysis buffer (50 mM Tris-HCl, pH 7.5, 150 mM NaCl, 1% Nonidet P-40, 2 mM EDTA, After incubation for 30 min at 4 ° C, the cells were incubated at 4 ° C and 15,000 rpm for 1 min at room temperature. The cells were incubated at 37 ° C for 1 h, For 15 minutes to remove cell membrane components and the like. Protein concentrations were quantified by standardizing bovine serum albumin (BSA) using the Bio-Rad Protein Assay Kit. 20 ~ 30 ㎍ of the separated proteins were separated by 4-12% NuPAGE Tris-Acetate mini gel and transferred to PVDF (polyvinylidene difluoride) membrane iBlot gel transfer (Invitrogen, La Jolla, CA, USA) for 7 minutes. Blocking of the membranes was performed in TTBS (0.1
2. Experimental results
2.1 NO production inhibition
The NO production inhibitory activity of 70% ethanol extract (100 ㎍ / mL) and each fraction (100 ㎍ / mL) (normal hexane, dichloromethane, ethyl acetate and normal butanol) and the new active components (10, 20 and 40 uM) 8.
Among the fractions, the dichloromethane fraction had the highest inhibitory activity, and the fresh active ingredient isolated from the dichloromethane fraction showed a concentration - dependent NO production inhibitory activity.
2.2 Cytotoxicity
The results of the cytotoxicity of the 70% ethanol extract and each fraction (normal hexane, dichloromethane, ethyl acetate and normal butanol) and the new active ingredient are shown in FIG.
Among the fractions, the ethyl acetate fraction showed slight cytotoxicity, and the new active component showed slight cytotoxicity at 40 uM.
2.3 PGE 2 Generation inhibition
The activity of the novel active ingredient to inhibit PGE 2 production is shown in FIG. The new active components (10, 20 and 40 uM) inhibited PGE 2 production in a concentration-dependent manner.
2.4 Inhibition of the production of inflammatory cytokines
The activity of inhibiting the production of inflammatory cytokines (TNF-a, IL-6 and IL-l [beta]) of the novel active ingredient is shown in Fig. 10 to Fig. The new active components (10, 20 and 40 uM) inhibited the production of inflammatory cytokines (TNF-a, IL-6 and IL-l [beta]) in a largely dose-dependent manner.
2.5 Western blot results
iNOS and COX-2 Western blot results are shown in Fig. The new active components (10, 20 and 40 uM) inhibited the production of iNOS and COX-2 in a concentration-dependent manner.
Western blot results of IκB, p38 (p38 MAPK), ERK1 / 2 (extracellular signal-regulated
Claims (5)
[Chemical Formula 1]
[Chemical Formula 1]
Wherein the composition is a pharmaceutical composition.
Wherein the composition is a food composition.
Wherein the composition is a cosmetic composition.
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KR20210002399A (en) | 2020-12-18 | 2021-01-08 | 경상대학교산학협력단 | A method for preparing ethyl acetate fraction from Aruncus dioicus var. kamtschaticus and the composition comprising the same as the effective ingredient |
KR102389900B1 (en) | 2021-12-14 | 2022-04-25 | 주식회사 코씨드바이오팜 | Cosmetic Composition for Improvement of Sensitive Skin Comprising extract of Aruncus dioicus |
KR20230115035A (en) | 2022-01-26 | 2023-08-02 | (주)유스케어팜 | Composition for preventing or treating anti-inflammatory diseases comprising a composite extract of Ocimum basilicum, Cirsium nipponicum(Maxim.) Makino and Aruncus dioicus as an active ingredient |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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KR20210002399A (en) | 2020-12-18 | 2021-01-08 | 경상대학교산학협력단 | A method for preparing ethyl acetate fraction from Aruncus dioicus var. kamtschaticus and the composition comprising the same as the effective ingredient |
KR102389900B1 (en) | 2021-12-14 | 2022-04-25 | 주식회사 코씨드바이오팜 | Cosmetic Composition for Improvement of Sensitive Skin Comprising extract of Aruncus dioicus |
KR20230115035A (en) | 2022-01-26 | 2023-08-02 | (주)유스케어팜 | Composition for preventing or treating anti-inflammatory diseases comprising a composite extract of Ocimum basilicum, Cirsium nipponicum(Maxim.) Makino and Aruncus dioicus as an active ingredient |
WO2023146123A1 (en) * | 2022-01-26 | 2023-08-03 | (주)유스케어팜 | Composition for preventing or treating inflammatory diseases comprising composite extract of ocimum basilicum, cirsium nipponicum (maxim.) makino, and aruncus dioicus as active ingredient |
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