KR20170021409A - New tricin derivative and pharmaceutical use thereof - Google Patents
New tricin derivative and pharmaceutical use thereof Download PDFInfo
- Publication number
- KR20170021409A KR20170021409A KR1020150115492A KR20150115492A KR20170021409A KR 20170021409 A KR20170021409 A KR 20170021409A KR 1020150115492 A KR1020150115492 A KR 1020150115492A KR 20150115492 A KR20150115492 A KR 20150115492A KR 20170021409 A KR20170021409 A KR 20170021409A
- Authority
- KR
- South Korea
- Prior art keywords
- tricin
- derivative
- inflammatory
- cells
- derivative represented
- Prior art date
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- 229920001296 polysiloxane Polymers 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 230000004044 response Effects 0.000 description 1
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
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- 230000003595 spectral effect Effects 0.000 description 1
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- 239000012089 stop solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
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- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
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- 208000024891 symptom Diseases 0.000 description 1
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- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 description 1
- BHZYGNYHCAQMLT-VGSWGCGISA-N tricin 4'-O-(threo-beta-guaiacylglyceryl) ether Natural products COc1ccccc1O[C@H](CO)COc2c(OC)cc(cc2OC)[C@@H]3CC(=O)c4c(O)cc(O)cc4O3 BHZYGNYHCAQMLT-VGSWGCGISA-N 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 229940084600 vitamin b 12 0.1 mg Drugs 0.000 description 1
- 229940033203 vitamin b6 0.5 mg Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/352—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 condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- 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
-
- 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
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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
- A23V2200/314—Foods, ingredients or supplements having a functional effect on health having an effect on lung or respiratory system
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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
- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
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- Health & Medical Sciences (AREA)
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- Polymers & Plastics (AREA)
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- Mycology (AREA)
- Birds (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
The present invention relates to novel tricyclic derivatives isolated from Zizania latifolia and their uses.
Inflammation is generally a localized protective response of the body tissue to host infiltration by foreign substances or harmful stimuli. Causes of inflammation include infectious causes such as bacteria, viruses and parasites, physical causes such as burns or radiation, chemicals such as toxins, drugs or industrial preparations, immune responses such as allergies and autoimmune reactions, or conditions associated with oxidative stress Lt; / RTI >
Inflammation is regulated by complex processes such as nitric oxide (NO) produced by activated macrophages, cytokines, prostaglandins, and staged reactions of growth factors.
In congenital immunity, macrophages play an important role in initiating and expanding defense against pathogens. However, studies on effective inflammatory drugs that can reduce NO production because of NO produced by activated macrophages are exposed to endotoxin in other cells and cause rheumatoid arthritis, atherosclerosis, asthma and pulmonary fibrosis .
It is known that allergies cause abnormal immune function due to genetic and environmental factors, resulting in an abnormally excessive immune response to a harmless antigen, allergen. First, when the body is exposed to house dust mites, pollen, animal hair, cockroaches, fungi and food antigens, the allergen is recognized by circulating antigen presenting cells, Lt; / RTI > Differentiated Th2 cells secrete TNF-, IL-4, IL-5, IL-8 and IL-13, which are allergen-induced cytokines. They stimulate the development of acidic white blood cells in the bone marrow, Not only induces the migration of acidic white blood cells, but also acts on B cells to promote the production of immunoglobulin IgE and IgG1. The IgE produced by a series of mechanisms of action strongly binds to mast cells through the IgE receptor called FcR in tissues. Then, it is exposed again to the same allergen as the first, and binds to IgE bound to allergen-causing mast cells. The mast cells bind to allergic histamine, β-hexosaminidase, inflammatory prostaglandins, heparin and free radicals Which secrete various allergic disease symptoms, and these reactions lead to chronic inflammation.
The present invention is to provide a novel tricin derivative isolated from methanol extract of Zizania latifolia, which is effective for inflammation and allergy relief, and to provide it as a composition for treating an anti-inflammatory, anti-allergic or inflammatory allergic disease.
The present invention provides a tricine derivative represented by the following formula (1).
[Chemical Formula 1]
The present invention provides an anti-inflammatory agent containing the tricin derivative represented by the above formula (1) as an active ingredient.
The present invention provides an antiallergic agent containing the tricine derivative represented by the above formula (1) as an active ingredient.
The present invention provides a pharmaceutical composition for the prevention or treatment of inflammatory allergic diseases containing the tricin derivative represented by the above formula (1) as an active ingredient.
The present invention provides a cosmetic composition for preventing or improving an inflammatory allergic disease containing the tricin derivative represented by the general formula (1) as an active ingredient.
The present invention also provides a health food for preventing or ameliorating an inflammatory allergic disease containing the tricin derivative represented by the general formula (1) as an active ingredient.
According to the present invention, the novel trichine derivative, sarcocline D, isolated from natural herbicide, effectively inhibits excessive production of NO, which is a cause of inflammatory diseases, than the previously known trichine derivatives, It has been confirmed that the effect of inhibiting the release of? -Hexosaminidase is excellent, so that it can be provided as a composition for preventing or treating an anti-inflammatory, anti-allergic or inflammatory allergic disease.
FIG. 1 shows the chemical structure of Compound 1-5 isolated from Gochang Chol, wherein Compound 1 is tricine, Compound 2 is chalcone A, Compound 3 is chalcone B, Compound 4 is chalcone C and Compound 5 is chalcone D .
Figure 2 is the major gHMBC correlation diagram of
FIG. 3 shows the results of confirming cytotoxicity and NO production inhibitory effect of compounds isolated from goose chow in RAW 264.7 cells stimulated with LPS, and stimulated cells with LPS (100 ng / mL) for 24 hours and analyzed NO production , The values are expressed as the mean ± SEM of triplicate experiments, and the values in the other subscripts are significant differences (p <0.05) as determined by Duncan's multiple range test.
FIG. 4 shows DNP-specific IgE 450 ng / mL inhibition effect on β-hexosaminidase release of compounds isolated from goat supernatant in RBL-2H3 cells induced by IgE and DNP-BSA Stimulated with RBL-2H3 cells (2 × 10 5 cells) overnight, treated with various doses of compound for 10 minutes, stimulated with 10 μg / mL of DNP-BSA for 10 minutes, Hexosaminidase release was determined and the values were expressed as mean ± SEM of triplicate experiments and the values in the other subscripts were significant differences (p < 0.05).
The present invention can provide a tricine derivative represented by the general formula (1).
[Chemical Formula 1]
More specifically, the tricine derivative represented by the above formula (1) is a novel tricine derivative isolated from Zizania latifolia, and tricine-4'-O- [erythro-beta-guaiacyl- (7 & -O- methyl) -glyceryl] ether (tricin-4'-O- [erythro-beta -gaiaiacyl- (7 " -O- methyl) -glyceryl] ether.
The present invention can provide an anti-inflammatory agent containing the tricin derivative represented by the general formula (1) as an active ingredient, and the tricin derivative can inhibit the production of nitric oxide (NO).
According to one embodiment of the present invention, the treatment of RAW 264.7 cells stimulated with LPS, which is a tricine derivative of the above formula (1), inhibits NO production in a concentration-dependent manner as shown in FIG. 3B Especially at the concentration of 10 μg / mL, the inhibition of NO production was superior to that of other tricine derivatives.
From the above results, it was confirmed that the tricine derivative represented by the formula (1) of the present invention inhibits NO production and exhibits an anti-inflammatory effect.
The present invention can provide an antiallergic agent containing the tricine derivative represented by the above formula (1) as an active ingredient, and the tricine derivative can inhibit the release of? -Hexosaminidase.
According to another embodiment of the present invention, the tricine derivative of Salcocolin D represented by the above formula (1) inhibits the release of β-hexamidase from DNP-BSA-induced IgE-sensitized RBL-2H3 cells, Especially at the concentration of 1 μg / mL, β-hexaminidase release inhibitory effect was superior to other tricine derivatives.
From the above results, it was confirmed that the tricine derivative represented by the formula (1) of the present invention suppresses the release of? -Hexamidase and exhibits an anti-allergic effect.
In addition, it was confirmed that the present salacoline D is a safe compound having no cytotoxicity as shown in FIGS. 3A and 4A.
Accordingly, the present invention can provide a pharmaceutical composition for the prevention or treatment of inflammatory allergic diseases containing the tricin derivative represented by the general formula (1) as an active ingredient.
The inflammatory allergic disease may be selected from the group consisting of asthma, atopic dermatitis and allergic rhinitis.
The pharmaceutical composition may include, but is not limited to, 0.01 to 90 parts by weight of the tricine derivative represented by Formula 1, based on 100 parts by weight of the total amount of the pharmaceutical composition.
In one embodiment of the present invention, the pharmaceutical composition for preventing or treating an inflammatory allergic disease containing the tricin derivative represented by the general formula (1) as an active ingredient can be administered orally, parenterally, Any one of formulations selected from the group consisting of suppositories, gels, suspensions, emulsions, drops, and liquids can be used.
In another embodiment of the present invention, the pharmaceutical composition for the prevention or treatment of inflammatory allergic diseases containing the tricine derivative represented by the general formula (1) as an active ingredient may be formulated into a pharmaceutical composition containing an appropriate carrier, excipient, disintegrant, A lubricant, a lubricant, a flavoring agent, an antioxidant, a buffer, a bacteriostatic agent, a diluent, a dispersant, a surfactant, a binder and a lubricant.
Specific examples of carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. Solid formulations for oral administration may be in the form of tablets, pills, powders, granules, capsules These solid preparations can be prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc., into the composition. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, syrups and the like, and various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin which are commonly used simple diluents. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the suppository base, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.
According to one embodiment of the present invention, the pharmaceutical composition may be administered orally, intraarterally, intraperitoneally, intramuscularly, intraarterally, intraperitoneally, intrasternally, transdermally, nasally, inhaled, topically, rectally, ≪ / RTI > can be administered to the subject in a conventional manner.
The preferred dose of the tricine derivative may vary depending on the condition and body weight of the subject, the type and degree of disease, the type of drug, the route of administration and the period of time, and may be appropriately selected by those skilled in the art. According to one embodiment of the present invention, the daily dose may be 0.01 to 200 mg / kg, specifically 0.1 to 200 mg / kg, more specifically 0.1 to 100 mg / kg, though it is not limited thereto. The administration may be performed once a day or divided into several times, and thus the scope of the present invention is not limited thereto.
In the present invention, the 'subject' may be a mammal including a human, but is not limited thereto.
The present invention can provide a cosmetic composition for preventing or improving an inflammatory allergic disease comprising the tricin derivative represented by the general formula (1) as an active ingredient.
The cosmetic composition may contain conventional auxiliary agents such as stabilizers, solubilizers, vitamins, pigments and fragrances, and carriers in addition to the tricin derivative as an active ingredient.
The cosmetic composition may be prepared in any form conventionally produced in the art and may be in the form of a solution, suspension, emulsion, paste, gel, cream, lotion, powder, oil, powder foundation, emulsion foundation, Wax foundation, spray, and the like. However, the present invention is not limited thereto. More specifically, it can be manufactured in the form of a sun cream, a flexible lotion, a convergent lotion, a nutritional lotion, a nutritional cream, a massage cream, an essence, an eye cream, a pack, a spray or a powder.
When the formulation is a paste, cream or gel, an animal oil, a vegetable oil, a wax, a paraffin, a starch, a tracer, a cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component .
When the formulation 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, chlorofluorohydrocarbons, propane / Or propellants such as dimethyl ether.
When the formulation is a solution or an emulsion, a solvent, a solubilizing 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, - butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid esters of sorbitan.
When the formulation is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspension such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, a microcrystalline cellulose , Aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.
The present invention also provides a health food for preventing or ameliorating an inflammatory allergy disease containing the tricin derivative represented by the general formula (1) as an active ingredient.
The health food is used together with food or food additives other than the tricine derivative, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its use purpose, for example, prevention, health or therapeutic treatment.
The effective dose of the compound contained in the above-mentioned health food may be used in accordance with the effective dose of the therapeutic agent, but may be less than the above range for health and hygiene purposes or for long-term intake for health control purposes, It is clear that the component can be used in an amount of more than the above range since there is no problem in terms of safety.
There is no particular limitation on the type of the health food, and examples thereof include meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, Drinks, alcoholic beverages and vitamin complexes.
BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.
< Experimental Example 1> Materials and Methods
1. Plant sample
The dried ground portion of Zizania latifolia was purchased from Yeongcheon City, Gyeongbuk Province.
2. Appliances and reagents
LC-Forte / R, YMC, Japan) was performed using a YMC-DispoPack (ODS-25, 80 g, and 120 g, YMC, Japan) mesh, Merck, Germany) and Sephadex LH-20 (Merck, Germany).
Thin-layer chromatography (TLC) analysis was performed using a Kiesel gel 60F254 plate (Merck Co., Darmastdt, Germany) and RP-18 F254s plates (Merck Co., Darmastdt, Germany) UV lamp and 10% H 2 SO 4 solution.
1 H and 13 C NMR and 2D NMR data were obtained with Bruker AVANCE II 400 (1 H NMR at 400 MHz, 13 C NMR at 100 MHz) spectrometer (Bruker, Germany) using pyrimidine-d5 and TMS as internal controls.
ESI / MS was obtained with 6530 Accurate-Mass Q-TOF LC / MS (Agilent Technologies, Germany). All reagents were purchased from Sigma Chemical Co. (St. Louis, Mo., USA).
3. Separation of physiologically active substances
5 kg of dry solid powder was extracted with 45 L of 80% methanol (MeOH) at room temperature and the concentrated extract was washed successively with water (3 L), EtOAc (3 L × 3) and n-BuOH (3 L × 3) The EtOAc extract (97 g, ZLE), n-BuOH extract (240 g, ZLB) and H 2 O extract (57 g, ZLW) were obtained by fractionation.
The EtOAc extract was applied to silica gel and eluted with CHCl 3 : MeOH (50: 1 → 30: 1 → 20: 1 → 12: 1 → 10: 1 → 7: 1 → 5: 1 → 3: 1 → 1: L) to obtain 13 fractions (ZLE-1 to ZLE-13).
The ZLE-8 fraction (4.7 g) was analyzed using a prep-LC cartridge (YMC-DispoPack AT; ODS-25: 120 g, particle size: 25 μm). The fractions were run on a mobile phase consisting of A solvent containing 0.1% formic acid at a flow rate of 10 mL / min and B solvent containing 0.1% acetonitrile and analyzed by UV detector at 254 and 356 nm.
Min for 20 minutes and 0.2% / min for 30% B solvent at 0.2% / min rate, 30% B to 50% B at 0.2% / min and 50% B to 70% B for 20 minutes , And a gradient from 70% B to 90% B at a rate of 0.30% / min.
A total of 14 fractions (ZLE-8-14 in ZLE-8-1) were obtained and fraction ZLE-8 was obtained using a prep-LC cartridge (YMC-DispoPack AT; ODS-25: 80 g, particle size: -4 (327 mg). The mobile phase was flowed at a flow rate of 10 mL / min using a solvent A containing 0.1% formic acid and a solvent B containing 0.1% acetonitrile. The detector was maintained at 254 and 356 nm, and the gradient was 10% B The rate was 0.6% / min at 35% B and 0.5% / min at 35% B and 60% B at 35% B, respectively.
As a result, Compound 3 (27 mg, RT = 14.2 min), Compound 1 (21 mg, RT = 15.7 min) and Compound 2 (32 mg, RT = 17.8 min) were obtained.
The fraction ZLE-8-6 (231 mg) was also analyzed using a prep-LC cartridge (YMC-DispoPack AT; ODS-25: 80 g, particle size: 25 μm). The mobile phase was flowed at a flow rate of 10 mL / min using A solvent containing 0.1% formic acid and B solvent containing 0.1% acetonitrile, and the detector was maintained at 254 and 356 nm. The gradient was configured at a rate of 0.5% / min from 15% B to 40% B, and a rate of 0.6% / min from 40% B to 70% B.
As a result, Compound 4 (52 mg, RT = 21.1 min) and Compound 5 (21 mg, RT = 23.4 min) were obtained.
Tree Seen (Tricin; 1) Pale yellow powder (CH 3 OH); negative ESI / MS m / z 329 [MH] - ; IR (CaF2 plate) 3413, 2941, 2842, 1664, 1611 cm < -1 & gt ;; 1 H NMR (400 MHz, pyridined 5) δ 7.42 (2H, s, H-2 ', 6'), 7.01 (1H, s, H-3), 6.87 (1H, d, J = 2.0 Hz, H- 8), 6.74 (1H, d, J = 2.0 Hz, H-6), 3.84 (6H, s, OCH3 ', 5'). 13 C NMR (100 MHz, pyridine -d 5) δ 182.5 (C-4), 165.7 (C-7), 164.4 (C-2), 162.9 (C-5), 158.3 (C-9), 149.1 ( C-3 ', 5'), 141.1 (C-4 '), 121.1 (C-1'), 104.9 (C- 99.7 (C-6), 94.8 (C-8), 56.2 (C-3 ', 5'-OCH 3).
Salcolin A (2) yellow amorphous powder (CH 3 OH); negative ESI / MS m / z 525 [MH] - ; IR (CaF 2 plate) 3369, 2938, 1652, 1611, 1588, 1512, 1495, 1356, 1263, 1159, 1124, 841 cm -1 ; 1 H NMR (400 MHz, pyridine -d 5) δ7.59 (1H, br. S, H-2 "), 7.48 (1H, dd, J = 8.0, 1.2 Hz, H-6"), 7.31 (2H (1H, d, J = 2.0 Hz, 1H, s, H-2 ', 6'), 7.27 J = 6.0 Hz, H-7), 4.93 (1H, q, J = 6.0, Hz, H-8 "), 4.44 (1H, dd, J = 12.0, 4.0 Hz, H- 6H, s, OCH 3 ', 5'), 3.72 (3H, s, OCH 3 ''). 13C NMR (100 MHz, pyridine- d 5) δ183.9 (C-4), 167.3 (C-7), 165.0 (C-2), 163.9 (C-5), 159.8 (C-9), 155.1 ( C-3 ', C-3'), 149.6 (C-3 ''), 148.7 (C-3), 106.3 (C-10), 106.0 (C-2 ', 6'), 101.3 (C-6), 96.3 ( C-8), 90.4 (C-8 "), 74.9 (C-7"), 63.1 (C-9 "), 57.7 (C-3 ', 5'-OCH 3) , 57.0 (C-3 "-OCH 3).
Salcolin B (3) yellow amorphous powder (CH 3 OH); negative ESI / MS m / z 525 [MH] - ; IR (CaF2 plate) 3364, 2933, 1649, 1607, 1590, 1495, 1457, 1358, 1121, 832 cm -1 ; 1 H NMR (400 MHz, pyridine -d 5) δ 7.54 (1H, d, J = 1.2 Hz, H-2 "), 7.38 (1H, dd, J = 8.0, 1.2 Hz, H-6"), 7.31 (2H, s, H-2 ', 6'), 7.27 (1H, d, J = 8.0 Hz, H- J = 4.8 Hz, H-8), 6.74 (1H, d, J = 2.0 Hz, H-6), 5.71 (1H, , 3.6 Hz, H-7 "), 4.65 (1H, dd, J = 12.0, 5.2 Hz, H- 3.82 (6H, s, OCH 3 ', 5'), 3.73 (3H, s,
Salcolin C (4) yellow amorphous powder (CH 3 OH); negative ESI / MS m / z 539 [MH] - ; IR (KBr) 3436, 2957, 2926, 2531, 1649, 1589, 1495, 1358 cm < -1 & gt ;; 1 H NMR (400 MHz, pyridine-d 5 )? 7.34 (2H, s, H-2 ', 6'), 7.33 (1H, d, J = 1.2 Hz, H- J = 8.0 Hz, H-5 "), 7.23 (1H, dd, J = 8.0, 1.6 Hz, H- J = 6.8 Hz, H-8), 6.75 (1H, d, J = 2.0 Hz, H-6), 5.08 , 4.0 Hz, H-8 "), 4.26 (1H, dd, J = 12.0, 3.6 Hz, H- 3.83 (6H, s, OCH 3 ', 5'), 3.59 (3H, s,
13 C NMR (100 MHz, pyridine -d 5) δ 183.6 (C-4), 167.1 (C-7), 165.0 (C-2), 164.0 (C-5), 159.5 (C-9), 154.8 ( C-3 '), 149.5 (C-3''), 148.9 (C-4''), 142.7 , 122.3 (C-6 "), 117.1 (C-5"), 112.7 (C-2 "), 106.6 (C-3), 105.9 , 101.0 (C-6), 96.0 (C-8), 87.9 (C-8 "), 86.0 3), 57.3 (C-3 "-OCH 3), 56.6 (C-7" -OCH 3).
Salcolin D (5) yellow amorphous powder (CH 3 OH); positive HRESI-MS m / z 541.1691 [M + H] +, calcd for m / z C 28 H 29 O 11 541.1704; IR (KBr) 3656, 2667, 2521, 2502, 1687, 1509, 1425, 1398, 1115 cm < -1 & gt ;; 1 H NMR (400 MHz, pyridine -d 5)) δ 7.33 (1H, d, J = 1.6 Hz, H-2 "), 7.29 (2H, s, H-2 ', 6'), 7.26 (1H, d, J = 8.4 Hz, H-5 "), 7.19 (1H, dd, J = 8.0, 1.6 Hz, H-6" = 2.0 Hz, H-8), 6.73 (1H, d, J = 2.0 Hz, H-6), 4.99 (1H, d, J = 4.0 Hz, H- 8H), 4.50 (1H, dd, J = 12.8, 2.8 Hz, H-9 "e), 4.25 (1H, dd, J = OCH 3 ', 5'), 3.76 (3H, s, OCH 3 '), 3.39 (3H, s, OCH 3 - 7'').
13 C NMR (100 MHz, pyridine -d 5) δ 183.9 (C-4), 167.4 (C-7), 165.1 (C-2), 164.3 (C-5), 159.8 (C-9), 155.2 ( C-3 ', C-3', C-3 '), 149.1 (C-4 "), 141.5 (C-6 "), 117.3 (C-5"), 113.3 (C-2 "), 107.0 (C-3), 106.3 C-6), 96.3 (C -8), 88.1 (C-8 "), 84.7 (C-7"), 62.5 (C-9 "), 58.3 (C-3 ', 5'-OCH 3), 57.6 (C-3 "-OCH 3 ), 57.0 (C-7" -OCH 3).
< Experimental Example 2> Cell culture
Mouse macrophage cell line RAW 264.7 cells and Rat Basophilic Leukemia cell line RBL-2H3 cells were purchased from Korean Cell Line Bank (KCLB, Seoul, Korea). RAW 264.7 cells were cultured in DMEM (Gibco-BRL, Rockville, MD, USA) containing 1% antibiotic (penicillin / streptomycin) and 10% inactivated fetal bovine serum (FBS, Gibco BRL, RBL-2H3 cells were cultured in MEM (Gibco BRL, NY, USA) containing 10% FBS and 1% penicillin / streptomycin.
Both cells were grown in an incubator at 37 ° C and 5
< Experimental Example 3> Cell viability Confirm
In order to confirm the cytotoxicity of the compounds, MTT analysis was performed to analyze the activity of mitochondria which reduced the penetrating formazan dye to MTT to confirm cell viability. Dividing the RBL-2H3 cells in 96-well plate at 3 × 10 4 cells per well in and from the next day 37 ℃ condition was treatment of the compound of 0.1 to 10 μg / mL concentration.
Forty-eight hours later, 100 μL of MTT (5 mg / mL) was added to each well and cultured at 37 ° C for 4 hours. Then, 100 占 퐇 of DMSO was added to each well to dissolve the cells. Plates were maintained at room temperature for 5 minutes and absorbance was measured at 550 nm using a multiwell spectrophotometer (Molecular Devices, Sunnyvale, Calif.).
In addition, cytotoxicity of compounds in IgE-sensitive RBL-2H3 cells was confirmed by MTT assay. The IgE-sensitive RBL-2H3 cells were plated at 3 × 10 4 cells per well and the compounds were incubated overnight with 450 ng / mL DNP-specific IgE before treatment, at 37 ° C.
< Experimental Example 4> By LPS Identification of induced NO products
RAW 264.7 cells were plated in 96-well plates at 1 × 10 5 cells per well and cultured overnight, and various concentrations of test compounds were treated in the presence of LPS (final concentration, 100 ng / mL).
After LPS stimulation for 24 hours, the NO production in the cell culture medium was measured with a Griess Reagent System.
To 100 μL of the culture supernatant was added 10% of the same amount of a 2.5% phosphoric acid solution containing Griess reagent [1% sulfanilamide and 0.1% naphthylethylendiamine] for 10 minutes, and the absorbance at 540 nm And the NO concentration was calculated from the NaNO 2 standard curve.
The NO production inhibitory activity of the compound was expressed by the IC 50 value (the concentration required to inhibit NO production by 50%).
< Experimental Example 5 > antigen-induced < RTI ID = 0.0 & Hexosaminidase ( hexosaminidase ) Release confirmation
The inhibitory effect of the extract on the release of? -Hexosaminidase was confirmed in RBL-2H3 cells. First, dividing the RBL-2H3 cells in a 24-well plate at 2 × 10 5 cells per well and it was stimulated overnight with anti-37 ℃ -DNP IgE (450 ng / mL) .
The cells were then washed with Siraganian buffer and incubated for 20 min at 37 ° C with the addition of 160 μL of incubate buffer. 20 μL of the extract was then treated for 10 min with 20 μL of antigen (DNPBSA, 10 μg / mL) Was added to stimulate the cells to form granules at 37 占 폚 for 10 minutes. Thereafter, the reaction was stopped by soaking in an ice water bath for 10 minutes.
Transfer 25 μL of the supernatant to a 96-well plate and add 25 μL of 0.1 M citrate buffer (pH 4.5) in which the substrate (1 mM p-nitrophenyl-Nacetyl-β-D-glucosaminide) And reacted for 1 hour. Then, 200 μL of stop solution (0.1 M Na2CO3 / NaHCO3, pH 10.0) was added to stop the reaction and absorbance was measured at 405 nm using a microplate reader.
The inhibitory activity of the compound for β-hexosaminidase release was expressed by the IC 50 value (the concentration required to inhibit 50% inhibition of β-hexosaminidase release).
< Example 1> tricine ( tricin ) Isolation and Identification of Derivatives
The aerial parts extract with 80% methanol and the concentrated extract was partitioned successively using EtOAc, n-BuOH and H 2 O.
The EtOAc fractions were subjected to sequential repeated SiO 2 and ODS-A column chromatography to purify four kinds of flavonolignans including flavone and novel flavonolignan, (3), tricin-4'-O- (threo-β-guaiacylglyceryl) ether, salcolin A (2), tricin-4'-O- (erythro-β -guaiacylglyceryl ether, salcolin B (3), and tricin-4'-O- [threo-β-guaiacyl- (7 "-O-methyl) -glyceryl] ether and salcolin C (4). All of these compounds are the first to be isolated in Z.latifolia.
The compound (5), which is a yellow amorphous powder, was identified by TLC, followed by spraying with 10% H 2 SO 4 and heating to a dark yellow color.
It was expected that the molecular weight would be 540 as the false molecular ion peak in the negative ESI / MS results for this molecule was identified as m / z 539 [MH] - .
Further, 1 H NMR spectral results showed that 1,2,4-trisubstituted benzene rings and five olefinic methine proton signals [δ 7.29 (2H, s, H-2 ', 6'), 6.99 7.33 (1H, d, J) because of 1H, s, H-3), 6.85 (1H, d, J = 2.0Hz, H-8) and 6.73 = 1.6 Hz, H-2 "), 7.26 (1H, d, J = 8.4 Hz, H-5") and 7.19 (1H, dd, J = 8.0, 1.6 Hz, H- ) A flavonoid moiety such as a methine proton signal was identified.
(1H, d, J = 12.8, 2.8 Hz, H-7) and 4.97 (1H, m, H- (6H, s, OCH 3 ') and two methoxy proton signals [δ 3.79 (6H, s, OCH 3 ' , 5 '), 3.76 (3H, s, OCH 3 '), 3.39 (3H, s, OCH 3 7 ")] was confirmed.
The relative arrangement of the asymmetric carbons of C-7 "and C-8" in
The J H -7 "and 8" binding constants of proton resonance in the guaiacylglyceryl moiety were used to distinguish between erythro and threo types, with J values of 4.0-5.0 and 6.0-7.0 Hz, respectively.
In addition, 13 C NMR spectrum in the 4-methoxy-carbon [δ58.3 (C-3 ', 5'-OCH 3), 57.6 (C-3''- OCH 3), 57.0 (C-7''- OCH 3 )],
The conjugated ketone carbon δ183.9 (C-4) and the seven oxygenated olefine quaternary carbons [δ167.4 (C-7), 165.1 (C-2), 164.3 ), 159.8 (C-9), 155.2 (C-3 ', 5'), 141.5 10) and five olefinic carbon atoms [? 107.0 (C-3), 106.0 (C-2 ', 6'), 101.3 (C-6), 96.3 From these signals the presence of a flavone moiety was confirmed.
In addition, two oxygenated olefinic quaternary carbons [? 149.8 (C-3 "), 149.1 (C-4")], one olefinic quaternary carbon [? 131.7 (C-8 "), 84.7 (C-8 "), 7 ")] and one oxygenated methylene carbon 62.5 (C-9 ") signal were confirmed, and the presence of phenylpropanoid moiety was confirmed through these signals.
In the HMBC spectrum, the oxygenated methine protons δH 4.97 (1H, m, H-8 ") showed accurate cross-peaks with the oxygenated olefin quaternary δC 141.5 (C-4 '), The phenylpropanoid moiety was found to be connected via an ether bond between δC C-8 "and δC C-4 ', and the oxygenated methine proton signal δH 4.99 (1H, d, J = 4.0 Hz, H- 7 ") and the methoxy carbon signal of delta C 57.0 was confirmed by the fact that the methoxy group was connected to the C-7 " hydroxyl of the phenylpropanoid moiety.
From the above results, the structure of
The high resolution positive ESI-MS showed a false positive peak [M + H] + at m / z 541.1691, which was 541.1704, confirming C 28 H 29 O 11 .
The structure of the
< Example 2> From Zizania latifolia Identification of inhibitory effect of isolated components on NO production
In order to confirm the anti-inflammatory effect of the components isolated from Zizania latifolia, NO production and cytotoxicity were confirmed in RAW 264.7 cells stimulated with LPS.
RAW 264.7 cells were treated with LPS (100 ng / mL) in the presence of
As a result, it was confirmed that the NO production was suppressed depending on the concentration of all the compounds as shown in FIG. 3B. In particular, the cells treated with 0.1, 1, 5 and 10 μg / 3.18, 13.86 ± 2.51, 21.47 ± 2.62 and 59.14 ± 0.78%, respectively.
In other words, tricine (1), salicolin A (2), salcolin B (3), salcolin C (4) and salcolin D (5) at concentrations of 10 μg / mL were 23.29 ± 3.21, 32.23 (IC 50 = 0.24 μg / ml) in the IC 50 values required to inhibit NO production by 50%, while the inhibition of NO production by the IC 50 values was ± 1.93, 34.25 ± 2.76, 43.76 ± 2.82 and 59.14 ± 0.78% tree Seen (IC 50 = 12.51 μg / ml ), live Colin A (IC 50 = 4.91 μg / ml), live Colin B (IC 50 = 5.18 μg / ml) and live Colin C (IC 50 = 0.69 μg / ml) And showed excellent effect as compared with those of Comparative Example.
Further, as a result of confirming cell viability through MTT analysis, it was confirmed that NO production inhibition was not related to cell death. From the results, it was found that the test compound and 0.1% DMSO did not affect cell survival Respectively.
< Example 3> From Zizania latifolia The β- Hexosaminidase (β-hexosaminidase) release inhibitory effect
The inhibitory effect of each extract on β-hexosaminidase release was confirmed in DNP-BSA-induced IgE-sensitized RBL-2H3 cells and the value obtained from the DNP-BSA-treated group was used as a control.
As a result, the cells treated with tricine (1), salicolin A (2), salcolin B (3), salcolin C (4) and salcolin D (5) Inhibition of β-hexosaminidase release was observed at 24.34 ± 2.89, 25.06 ± 1.36, 27.69 ± 5.61, 70.55 ± 0.60, and 89.43 ± 2.36%, respectively, and especially at concentrations of 0.1, 1 and 10 μg / Inhibited the release of? -Hexosaminidase by 42.83 ± 3.15, 89.43 ± 2.36 and 82.97 ± 6.96%, respectively, in the treated cell group. Also, β- hexyl sosami is the choline Kinase-emitting live in IC 50 value represents the concentration needed to inhibit 50% D (IC 50 = 0.45 μg / ml) is a new tree (IC 50 = 11.99 μg / ml ), choline live A (IC 50 = 5.18 μg / ml), salcolicin B (IC 50 = 4.91 μg / ml) and salcolin C (IC 50 = 0.69 μg / ml).
From the above results, it was confirmed that the effect of inhibiting? -Hexosaminidase release of sarcolin D was the most excellent.
In addition, as shown in FIG. 4A, the compounds did not show cytotoxicity on IgE-sensitized RBL-2H3 cells under the same conditions as described above. From the results, it was confirmed that the compounds did not show toxicity to cells.
Meanwhile, the tricine derivative according to the present invention can be formulated into various forms according to the purpose. Hereinafter, some formulation methods in which the tricine derivative according to the present invention is contained as an active ingredient are exemplified, and the present invention is not limited thereto.
Formulation Example 1 Prescription Example of Pharmaceutical Composition
≪ Formulation Example 1-1 > Preparation of injection
10 mg of SALCOLINE D, 3.0 mg of sodium metabisulfite, 0.8 mg of methylparaben, 0.1 mg of propylparaben and an appropriate amount of sterile distilled water for injection are mixed and made to a final volume of 2 mL by a conventional method, The ampoules were filled and sterilized to prepare an injection.
≪ Formulation Example 2-1 > Preparation of tablet
10 mg of salacoline D, 100 mg of lactose, 100 mg of starch and an appropriate amount of magnesium stearate, and tableted according to a conventional tablet preparation method.
≪ Formulation Example 3-1 > Preparation of capsules
10 mg of saccharin D, 50 mg of lactose, 50 mg of starch, 2 mg of talc, and magnesium stearate were mixed and filled in gelatin capsules according to a conventional capsule preparation method to prepare capsules.
≪ Formulation Example 4-1 > Preparation of ointment preparation
After mixing 100 mg of salcolin D, 250 mg of PEG-4000, 650 mg of PEG-400, 10 mg of white petrolatum, 1.44 mg of methyl p-hydroxybenzoate, 0.18 mg of propyl pamooxybenzoate and the remaining amount of purified water, .
≪ Formulation Example 2 > Formulation Example of Cosmetic Composition
≪ Formulation Example 2-1 > Preparation of nutrition lotion
3.0 parts by weight of propylene glycol, 0.1 part by weight of carboxy polymer, purified water of a small amount of preservative and remaining amount were heated to 80 to 85 ° C while stirring and mixing, and then charged into a manufacturing part. Then, an emulsifying agent was allowed to act. 1.0 part by weight of
<Formulation Example 2-2> Preparation of nutritional cream
0.3 parts by weight of carboxy polymer, 5.0 parts by weight of butylene glycol, 3.0 parts by weight of glycerin
And a remaining amount of purified water were heated to 80 to 85 占 폚 while being mixed and stirred. Then, the mixture was put into a production part and then an emulsifier was allowed to react. 2.0 parts by weight of stearic acid, 2.0 parts by weight of cetyl alcohol, 2.0 parts by weight of glyceryl monostearate, 0.5 part by weight of tanninostearate, 0.5 part by weight of sorbitan sesquioleate, 1.0 part by weight of glyceryl monostearate / glyceryl stearate / polyoxyethylene stearate, 1.0 part by weight of wax, 4.0 parts by weight of liquid paraffin, And 4.0 parts by weight of caprylic / capric triglyceride were heated to 80 to 85 占 폚 and then added with 0.5 part by weight of triethanolamine to emulsify. After the emulsification was completed, the mixture was cooled to 35 DEG C with stirring using an agitator, and then chalcone D was added thereto, followed by cooling to 25 DEG C and aging.
≪ Formulation Example 3 > Preparation of health food
Vitamin B 12, vitamin B 12 0.1 mg,
While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereby. something to do. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.
Claims (9)
[Chemical Formula 1]
[Chemical Formula 1]
[Chemical Formula 1]
[Chemical Formula 1]
[Chemical Formula 1]
[Chemical Formula 1]
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JP7315278B1 (en) | 2023-03-15 | 2023-07-26 | マスダ商事株式会社 | Method for producing skin disease improving agent |
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CN114601828B (en) * | 2021-12-17 | 2023-10-03 | 中国科学院西北高原生物研究所 | Arenaria kansuensis extract and application thereof in preparing anti-inflammatory drugs |
JP7315278B1 (en) | 2023-03-15 | 2023-07-26 | マスダ商事株式会社 | Method for producing skin disease improving agent |
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