WO2017146341A1 - Composition pour le traitement des plaies, contenant de la daphnine, et son utilisation - Google Patents

Composition pour le traitement des plaies, contenant de la daphnine, et son utilisation Download PDF

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Publication number
WO2017146341A1
WO2017146341A1 PCT/KR2016/012094 KR2016012094W WO2017146341A1 WO 2017146341 A1 WO2017146341 A1 WO 2017146341A1 KR 2016012094 W KR2016012094 W KR 2016012094W WO 2017146341 A1 WO2017146341 A1 WO 2017146341A1
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Prior art keywords
composition
daphnetin
wound
skin
glucoside
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PCT/KR2016/012094
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English (en)
Korean (ko)
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노주원
김명석
이희주
문길주
오상록
밧수렌둘람자브
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한국과학기술연구원
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Priority claimed from KR1020160039331A external-priority patent/KR101769545B1/ko
Application filed by 한국과학기술연구원 filed Critical 한국과학기술연구원
Publication of WO2017146341A1 publication Critical patent/WO2017146341A1/fr

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    • 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
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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
    • A61K8/60—Sugars; Derivatives thereof
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Definitions

  • a pharmaceutical composition for treating wounds a pharmaceutical composition for treating an inflammatory disease, a method for treating an individual's wound, a method for treating an inflammatory disease and a cosmetic composition for improving wounds, improving skin wrinkles, or preventing skin aging .
  • the skin acts as a shield to protect the body from the outside.
  • the blood fills the wound site by the natural healing action of the living body, the granule reduction of platelets and activation of the hageman factor are initiated, and the wound healing process proceeds.
  • Blood clotting is a temporary protective action that protects exposed wound tissues and provides a base for cells to migrate during the healing process.
  • the Wound healing and / or healing occurs in three major stages.
  • the first stage is the inflammatory phase, characterized by inflammation at the traumatic site.
  • the inflammatory stages can usually progress briefly in the absence of a serious infection.
  • the second stage is the proliferative phase, which is characterized by epithelialization, angiogenesis, granulation tissue formation and collagen deposition.
  • Angiogenesis involving new capillary formation is used to deliver nutrients and maintain granulation tissue formation. Without the formation of new capillaries into the wound, essential nutrients do not reach the wound, creating a wound that is not chronically cured.
  • As the surface of the damaged wound is covered by a layer of keratinocytes, new epidermis is produced and re-epithelialization occurs where the epithelial layer is rebuilt.
  • a series of processes are performed in which the wound area is reduced through the increase and reorganization of connective tissue.
  • the final stage of wound healing is the maturational phase where fibroblasts differentiate into collagen.
  • the convoluted cells and capillaries of the recovering tissues gradually disappear, and scarring can occur if the cells and capillaries of these tissues are hyperplastic or do not degrade normally.
  • the first aspect provides a pharmaceutical composition for treating a wound.
  • the second aspect provides a pharmaceutical composition for treating an inflammatory disease.
  • the third aspect provides a method of treating a wound in a subject.
  • a fourth aspect provides a method of treating an inflammatory disease in a subject.
  • a fifth aspect provides a cosmetic composition for improving wounds, improving skin wrinkles, or preventing skin aging.
  • the sixth aspect provides a cosmetic method for improving wounds, improving skin wrinkles, or preventing skin aging.
  • the first aspect is at least one compound selected from the group consisting of daphine, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetine, chamaechromene, and isoquarcitrin, pharmaceutically acceptable It provides a pharmaceutical composition for wound treatment comprising a possible salt or solvate as an active ingredient.
  • a second aspect is at least one compound selected from the group consisting of daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetine, chamaechromene, and isoquarcitrin, pharmaceutically acceptable
  • pharmaceutical compositions for treating inflammatory diseases comprising possible salts, or solvates as active ingredients.
  • the compound may be to increase the transcriptional activity of ⁇ -catenin, and / or to increase the expression of the collagen gene.
  • Increasing the transcriptional activity of ⁇ -catenin is associated with promoting wound healing.
  • Fathke C et al., BMC Cell Biol. 2006 Jan 20; 7: 4 states that the ectopic activation of beta-catenin dependent Wnt signals by lithium chloride in wounds results in epithelial cysts and sometimes basic hair follicle structures in the dermis. Reported.
  • Bielefeld KA et al., Cell Mol Life Sci. 2013 Jun; 70 (12): 2059-81 report that the Wnt and / or beta-catenin signaling pathway plays an important role in wound healing.
  • the compound daphin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetin, chamaechromene, and isoquarcitrin each have the following structure: Can be.
  • Daphnetin-8- ⁇ -glucoside ,
  • the daphin may be 8-hydroxy-2-oxo-2H-chromen-7-yl- ⁇ -D-glucopyranoside.
  • Daphnetin may be 7,8-dihydroxycoumarin.
  • Rutarencin is 3-hydroxy-3-methyl-5-oxo-5-[[3,4,5-trihydroxy-6- [6-methoxy-2-oxo-3- (2-oxochromen) -7-yl) oxychromen-7-yl] oxyoxan-2-yl] methoxy] pentanoic acid.
  • Daphnoretin may be 7-hydroxy-6-methoxy-3- (2-oxochromen-7-yl) oxychromen-2-one.
  • Chamaecromone is (+)-3- [1- [bis (4-hydroxyphenyl) methyl] -2-oxo-2- (2,4,6-trihydroxyphenyl) ethyl] -5,7 -Dihydroxy-4H-1-benzopyran-4-one.
  • Isoquarcitrin is 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3-[(2S, 3R, 4S, 5S, 6R) -3,4,5-trihydroxy- 6- (hydroxymethyl) oxan-2-yl] oxychromen-4-oneyl.
  • the pharmaceutically acceptable salt is not particularly limited as long as it is pharmaceutically acceptable, but may preferably be an inorganic acid salt, an organic acid salt or a metal salt.
  • preferred inorganic acid salts include hydrochloride, phosphate, sulfate or disulfate
  • examples of preferred organic acid salts include maleate, maleic acid salt, citrate salt, fumarate salt, besylate salt, campylate salt or edyl salt salt.
  • examples include calcium salt, sodium salt, magnesium salt, strontium salt or potassium salt.
  • the term "wound” means that the tissue is cut, torn, broken, burned, or traumatized. Damage to a human body arising from a disorder or disease causing injury.
  • tissue refers to a mass of cells in the human body that collectively form a specific function. Tissues can include eyes, mucus, lungs, kidneys, heart, intestines, tendons, vascular tissues, bones, skin, connective tissue, and nerves such as the spinal cord.
  • the wound may be an open wound with an open surface or a closed wound with no open surface.
  • One example of such a wound may be an open wound in the skin.
  • the wound may include lesions, sores, necrosis, and ulcers.
  • the necrosis may be related to dead tissue resulting from infection, injury or infarction.
  • the ulcer may be a local defect or dent in the surface of an organ or tissue, produced by stripping of necrotic tissue.
  • wounds are an epidermis of the skin; Dermis; Epidermis and dermis; Or wounds with damaged epidermis, dermis and subcutaneous fat layers.
  • wounds include cuts, incisions (eg surgical incisions), abrasions, lacerations or lacerations, fractures, contusions, burns. Or amputations.
  • a “treat” provided by the present invention may be one that provides for the wound to heal at a shorter time compared to natural healing.
  • the treatment may include amelioration and / or alleviation of the wound.
  • the treatment may include both treatment of a wound and / or a disease associated with the wound. Said treatment may refer to healing and / or regeneration of damaged tissue resulting from the wound.
  • the wound treatment may include the meaning of skin regeneration.
  • the treatment may be to maintain the original composition of the damaged tissue.
  • the treatment may be to promote healing and / or regeneration of the damaged tissue while minimizing the complications and / or scarring of diseases associated with the wound.
  • the composition may be for promoting the previous stage of the wound healing process.
  • the composition may be to promote the proliferative and / or mature phase during the wound healing step.
  • the composition may be for treating a wound in the proliferative and / or mature phase.
  • the composition is 0.001% to 80% by weight, for example, 0.01% to 60%, 0.01% to 40%, 0.01% to 30%, 0.01% to 20% by weight relative to the total weight of the composition %, 0.01 wt% to 10 wt%, 0.01 wt% to 5 wt%, 0.05 wt% to 60 wt%, 0.05 wt% to 40 wt%, 0.05 wt% to 30 wt%, 0.05 wt% to 20 wt%, 0.05 wt% to 10 wt%, 0.05 wt% to 5 wt%, 0.1 wt% to 60 wt%, 0.1 wt% to 40 wt%, 0.1 wt% to 30 wt%, 0.1 wt% to 20 wt%, 0.1 wt% % To 10% by weight, or 0.1 to 5% by weight of the compound may be included.
  • the composition comprises 0.01 mg to 1,000 mg, for example, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 50 mg, 0.01 mg to 100 mg, 0.01 mg to 50 mg, 0.01 mg to 10 per unit of administration. mg, 0.01 mg to 1 mg, or 0.01 mg to 0.5 mg of the compound.
  • the composition may be one containing no compound other than the compound as an active ingredient.
  • the composition may comprise a pharmaceutically acceptable diluent or carrier.
  • the diluent may be lactose, corn starch, soybean oil, microcrystalline cellulose, or mannitol, and magnesium stearate as a lubricant, talc, or a combination thereof.
  • the carrier may be an excipient, a disintegrant, a binder, a lubricant, or a combination thereof.
  • the excipient may be microcrystalline cellulose, lactose, low-substituted hydroxycellulose, or a combination thereof.
  • the disintegrant may be calcium carboxymethyl cellulose, sodium starch glycolate, calcium dihydrogen phosphate, or a combination thereof.
  • the binder may be polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, or a combination thereof.
  • the lubricant may be magnesium stearate, silicon dioxide, talc, or a combination thereof.
  • the composition may be formulated in a parenteral dosage form.
  • the parenteral dosage form may be an injection or an external dermal preparation.
  • the topical skin preparation may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermal patch, mask pack, drug containing bandage, lotion, or a combination thereof.
  • the external skin preparations are commonly used in external preparations for cosmetics and medicines, such as aqueous components, oily ingredients, powder ingredients, alcohols, humectants, thickeners, ultraviolet absorbers, whitening agents, preservatives, antioxidants, surfactants, and fragrances. , Colorants, various skin nutrients, or combinations thereof, as appropriate.
  • the external skin preparations include metal blockers such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, belafamil, licorice extract, glablidine, and caline.
  • metal blockers such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, belafamil, licorice extract, glablidine, and caline.
  • Fruit hot water extract, various herbal medicines, drugs such as tocopherol acetate, glytilinic acid, tranexamic acid and derivatives thereof or salts thereof, vitamin C, magnesium ascorbic acid phosphate, ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, Sugars, such as trehalose, can also be mix
  • the composition may be for promoting expression of collagen gene in cells.
  • the composition can increase the expression of collagen or can increase the activity of collagen produced by the composition.
  • the composition may also increase the activity or expression of up-stream enzymes or proteins that produce collagen.
  • the composition may be one that has an effect of treating a wound by increasing expression and / or activity of collagen.
  • the collagen may be type 1 collagen (collagen, type I) or type 3 collagen (collagen, type III).
  • the gene encoding the collagen may be selected from the group consisting of COL1A1 and COL3A1.
  • the third aspect provides a method of treating a wound in an individual comprising administering to the individual an amount of the composition of the first aspect described above that is effective to treat the wound.
  • a fourth aspect provides a method of treating an inflammatory disease in an individual comprising administering to the individual an amount of the composition of the second aspect described above that is effective to treat the inflammatory disease.
  • composition is the same as described above.
  • Administration can be by any method known in the art. Administration can be administered directly to the subject by any means, for example by intravenous, intramuscular, transdermal, mucosal, intranasal, intratracheal or subcutaneous administration. .
  • the administration can be administered systemically or locally. The administration may be to be administered locally to the site where the wound is present.
  • the subject may be a mammal, for example a human, a cow, a horse, a pig, a dog, a sheep, a goat, or a cat.
  • the administration of the compound may comprise 0.1 mg to 1,000 mg, for example 0.1 mg to 500 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 1 mg to 1,000 mg, 1 mg per individual.
  • a fifth aspect is at least one compound selected from the group consisting of daphine, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetine, chamaechromene, and isoquarcitrin, pharmaceutically acceptable
  • a cosmetic composition for improving wounds, improving skin wrinkles, or preventing skin aging, including a possible salt or solvate as an active ingredient.
  • the compound is the same as described above.
  • the term "improving a wound” may include the use of lowering or alleviating the extent of a wound.
  • the wound amelioration may be to lower or alleviate the extent of a wound that has already occurred.
  • the compound promotes the production of collagen in fibroblasts.
  • Collagen is a major component of the dermal layer of the skin. It is an elastic protein that has a strong binding property with moisture. That is, collagen has a property of imparting elasticity to the skin, and thus has an effect of preventing wrinkles from occurring. As a person ages, the amount of collagen in the skin decreases, and the skin undergoes an aging process that causes loss of elasticity and wrinkles. Therefore, the composition of the claimed invention comprising the compound can be used as a cosmetic composition for improving skin wrinkles or preventing skin aging.
  • the cosmetic composition may be provided in any formulation suitable for topical application.
  • a formulation suitable for topical application for example, in the form of an emulsion obtained by dispersing an oil phase in a solution, an aqueous phase, an emulsion obtained by dispersing an aqueous phase in an oil phase, a suspension, a solid, a gel, a powder, a paste, a mask pack or a sheet, a foam, or an aerosol composition.
  • Compositions of such formulations may be prepared according to conventional methods in the art.
  • the cosmetic composition may further include a moisturizer, an emulsifier, a ultraviolet absorber, a preservative, a fungicide, an antioxidant, a pH adjuster, organic and inorganic pigments, fragrances, coolants or limiting agents.
  • a moisturizer an emulsifier, a ultraviolet absorber, a preservative, a fungicide, an antioxidant, a pH adjuster, organic and inorganic pigments, fragrances, coolants or limiting agents.
  • the blending amount of the additional components such as the moisturizing agent can be easily selected by those skilled in the art within the range that does not impair the object and effect of the present invention, the blending amount is 0.01 to 5% by weight, specifically 0.01 to 3 based on the total weight of the composition Weight percent.
  • the composition is 0.001% to 80% by weight, for example, 0.01% to 60%, 0.01% to 40%, 0.01% to 30%, 0.01% to 20% by weight relative to the total weight of the composition %, 0.01 wt% to 10 wt%, 0.01 wt% to 5 wt%, 0.05 wt% to 60 wt%, 0.05 wt% to 40 wt%, 0.05 wt% to 30 wt%, 0.05 wt% to 20 wt%, 0.05 wt% to 10 wt%, 0.05 wt% to 5 wt%, 0.1 wt% to 60 wt%, 0.1 wt% to 40 wt%, 0.1 wt% to 30 wt%, 0.1 wt% to 20 wt%, 0.1 wt% % To 10% by weight, or 0.1 to 5% by weight of the compound may be included.
  • a sixth aspect provides a method for making up skin, comprising applying a cosmetic composition for improving wounds, improving skin wrinkles, or preventing skin aging according to the fifth aspect to the skin of an individual.
  • the method may be to improve the wound, to improve skin wrinkles, or to prevent skin aging.
  • the cosmetic composition is applied in numerous treatments, in particular cosmetic treatments of the skin, lips and hair, including the scalp.
  • composition for treating a wound according to one aspect, it can be used to efficiently treat a wound in a subject.
  • composition for treating an inflammatory disease it can be used to effectively treat an inflammatory disease in an individual.
  • the individual's wound can be efficiently treated.
  • the method for making up the skin it is possible to efficiently improve the wound, improve the skin wrinkles, or prevent skin aging.
  • Figure 2 is an electrophoresis picture showing the effect of seven compounds on the expression of COL1A1 and COL3A1 gene in fibroblasts.
  • Figure 3 shows the effect of the seven compounds on the expression of the COL1A1 gene in fibroblasts.
  • FIG. 4 is a diagram showing the effect of the seven compounds on the expression of the COL3A1 gene in fibroblasts.
  • FIG. 6 shows the presence of seven compounds, namely daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetine, chamaechromene, and isoquarcitrin to promote migration of keratinocytes. This is the result of checking.
  • FIG. 7 shows the presence of seven compounds, namely daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetin, chamaechromene, and isoquarcitrin to the expression level of MMP-1. This is the result of checking the impact.
  • Figure 8 Expression of daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetin, chamaechromone, and isoquarcitrin in type 1 procollagen in UVB irradiated human fibroblasts The result of measuring the extent to which it affects is shown.
  • DMSO dimethylsulfoxide
  • FIG. 1 shows the presence of seven compounds, namely daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetin, chamaechromene, and isoquarcitrin, affect beta-catenin activity in cells. It is a figure which shows the effect.
  • A, B, C, D, E, F, and G are daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetine, chamaechromone, and iso, respectively. Quercitrin is shown.
  • Human fibroblast Hs68 was placed in a well of a 6-well microtiter plate containing 2 ml of DMEM (Dulbecco's Modified Eagle's Media: Hyclone) medium containing 2.5 (v / v) fetal calf serum. 2 ⁇ 10 6 cells / well were added and incubated under the same conditions as above until the confluency reached 80%.
  • DMEM Dulbecco's Modified Eagle's Media: Hyclone
  • Figure 2 is an electrophoresis picture showing the effect of seven compounds on the expression of COL1A1 and COL3A1 gene in fibroblasts.
  • Figure 3 shows the effect of the seven compounds on the expression of the COL1A1 gene in fibroblasts.
  • 4 and 5 are the results analyzed from the electrophoresis picture of FIG.
  • Figure 5 shows the effect of the seven compounds on the expression of the COL3A1 gene in fibroblasts.
  • daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetine, chamaechromene, and isoquarcitrin are involved in the expression of COL3A1 gene, a collagen synthesis-related factor. It was found that the effect of activating is remarkable.
  • macrophage (macrophage) was confirmed the effect of the production of prostaglandin E 2 which is an inflammation promoting factor.
  • RAW 264.7 ATCC TIB-71. These cells are made from Abelson murine leukemia virus-induced tumors of mice, have mononuclear and macrophage morphology, and attach and grow.
  • RAW 264.7 cells were placed in a well of a 24-well microtiter plate containing Dulbecco's Modified Eagle's Media: Hyclone (DMEM) medium containing 10 (v / v) Fetal Bovine Serum for 24 hours. Cultured under the same conditions as described above. Each of the seven compounds was then added to the medium at the indicated concentrations (uM) and incubated at the same conditions for 24 hours.
  • DMEM Dulbecco's Modified Eagle's Media
  • FIG. 9 shows the effect of seven compounds on prostaglandin E2 production in macrophages.
  • the vertical axis shows the amount of prostaglandin E 2 released into the culture.
  • seven compounds significantly inhibited the production of prostaglandin E2 compared to the control.
  • the inhibitory effect of daphnoretin, chamaechromone, and daphnetin was particularly excellent.
  • the seven compounds namely daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetin, chamaechromene, and isoquarcitrin, migrate to human keratinocytes. Whether to increase was confirmed as follows.
  • HaCaT human keratinocytes were placed in a well of a 24-well microtiter plate containing 1 ml of DMEM (Dulbecco's Modified Eagle's Media: Hyclone) medium containing 2.5 (v / v) Fetal Bovine Serum. Added to 2 ⁇ 10 5 cells / well. Next, the keratinocytes were incubated in a 37 ° C. and 5% CO 2 incubator until the confluency reached 80%, and then the cell monolayer in the medium was scraped with a p10 pipette tip to induce “scratch-damage”. .
  • DMEM Dynamic Eagle's Media
  • Hyclone Hyclone
  • FIG. 6 shows the presence of seven compounds, namely daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetine, chamaechromene, and isoquarcitrin to promote migration of keratinocytes. This is the result of checking.
  • Collagen degrading enzyme-1 of the seven compounds namely daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetine, chamaechromene, and isoquarcitrin (Matrix Metalloproteinase-1, The inhibitory efficacy of production of MMP-1) was measured.
  • the level of MMP-1 in the supernatant was measured using the collagen MMP-1 ELISA kit (QIA55, Merck & Co., USA) from the supernatant.
  • the supernatant was added to a well of a 96-well plate uniformly coated with a mouse anti-MMP-1 antibody as a primary antibody, and incubated at room temperature for 2 hours to form an antigen-antibody complex. .
  • anti-MMP-1 antibody conjugated with horseradish peroxidase as a chromophore was placed in a well of a 96-well plate and incubated for 1 hour.
  • FIG. 7 shows the presence of seven compounds, namely daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetin, chamaechromene, and isoquarcitrin to the expression level of MMP-1. This is the result of checking the impact.
  • daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, dafnoretin, daphnetin, chamaechromene, and isoquarcitrin are excellent in inhibiting MMP-1 production. It can be seen that it has an effect. In particular, isoquarcitrin was confirmed to be the most effective.
  • Epigallocatechin gallate (EGCG) was used as a positive control.
  • the seven compounds namely daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetine, chamaechromene, and isoquarcitrin are Type-1 procollagen. It was confirmed whether to promote the expression of.
  • DMEM Dulbecco's Modified Eagle's Media
  • mouse anti-PIP monoclonal antibody conjugated with horseradish peroxidase (POD) to a well of 96-hole plate uniformly coated with mouse anti-PIP monoclonal antibody.
  • antibody-POD conjugate conjugated with horseradish peroxidase (POD)
  • POD horseradish peroxidase
  • the cell culture and standard solution were added respectively and left at 37 ° C. for 3 hours.
  • the wells were then washed and a substrate solution containing hydrogen peroxide and tetramethylbenzidine was added and incubated for 15 minutes at room temperature. Thereafter, a stop solution was added to the well to stop the reaction, and the absorbance was measured at 450 nm using a plate reader.
  • Figure 8 Expression of daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetin, chamaechromone, and isoquarcitrin in type 1 procollagen in UVB irradiated human fibroblasts The result of measuring the extent to which it affects is shown. As a result, as shown in FIG. 8, seven compounds promoted the expression of type 1 procollagen, and in particular, daphnin, isoquarcitrin, daphnetin-8- ⁇ -glucoside, and rutalensin were largely type 1 pro Collagen expression was promoted. Daphnetin-8- ⁇ -glucoside most greatly promoted type 1 procollagen expression.
  • seven compounds namely daphnin, daphnetin-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetin, chamaechromone, and isoquarcitrin, promote wound healing and inflammation
  • the inhibitory effect was excellent.
  • the seven compounds namely daphnin, daphnetine-8- ⁇ -glucoside, rutarencin, daphnoretin, daphnetine, chamaechromeone, and iso under UV-irradiated conditions Quercitrin has been shown to reduce the expression of MMP-1 and promote collagen expression from human fibroblasts. That is, the seven compounds promoted the expression of collagen while reducing the expression of collagenase under the condition of UV irradiation in human fibroblasts. Thus, the seven compounds can promote collagen synthesis in tissues including human fibroblasts, for example in the skin, thereby maintaining and promoting elasticity of the tissues.
  • the seven compounds are effective in improving tissues including human fibroblasts, such as skin wrinkles, or preventing skin aging.

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une composition pharmaceutique pour le traitement des plaies, contenant de la daphnine ; une composition pharmaceutique pour le traitement des maladies inflammatoires ; une méthode de traitement des plaies chez un sujet ; une méthode de traitement des maladies inflammatoires ; et une composition cosmétique pour le traitement des plaies, l'atténuation des rides cutanées et la prévention du vieillissement de la peau.
PCT/KR2016/012094 2016-02-24 2016-10-26 Composition pour le traitement des plaies, contenant de la daphnine, et son utilisation WO2017146341A1 (fr)

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KR20160022153 2016-02-24
KR10-2016-0022153 2016-02-24
KR10-2016-0039331 2016-03-31
KR1020160039331A KR101769545B1 (ko) 2016-02-24 2016-03-31 다프닌을 포함하는 상처 치료용 조성물 및 그의 용도

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3666250A1 (fr) * 2018-12-10 2020-06-17 ETH Zurich Préparations cosmétiques comprenant des extraits de daphné
US11110075B2 (en) * 2019-08-14 2021-09-07 Xi'an Jiaotong University Use of daphnetin in improving function of aortic endothelial cell

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060193789A1 (en) * 2002-10-25 2006-08-31 Foamix Ltd. Film forming foamable composition

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060193789A1 (en) * 2002-10-25 2006-08-31 Foamix Ltd. Film forming foamable composition

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
AHN, J. Y. ET AL.: "Effect of Taxifolin Glycoside on Atopic Dermatitis-like Skin Lesions in NC/Nga Mice", PHYTOTHERAPY RESEARCH, vol. 24, no. 7, 29 December 2009 (2009-12-29), pages 1071 - 1077, XP018502987 *
SUNTAR, I. ET AL.: "Daphne Oleoides Schreber ssp. Oleoides Exhibits Potent Wound Healing Effect: Isolation of the Active Components and Elucidation of the Activity Mechanism", RECORDS OF NATURAL PRODUCTS, vol. 8, no. 2, 19 March 2014 (2014-03-19), pages 93 - 109, XP055409688 *
SUNTAR, I. ET AL.: "Efficacy of Daphne Oleoides Subsp. Kurdica Used for Wound Healing: Identification of Active Compounds through Bioassay Guided Isolation Technique", JOURNAL OF ETHNOPHARMACOLOGY, vol. 1, no. 3, 10 April 2012 (2012-04-10), pages 1058 - 1070, XP028502678 *
WITAICENIS, A. ET AL.: "Antioxidant and Intestinal Anti-inflammatory Effects of Plant-derived Coumarin Derivatives", PHYTOMEDICINE, vol. 21, no. 3, 2014, pages 240 - 246, XP055409690 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3666250A1 (fr) * 2018-12-10 2020-06-17 ETH Zurich Préparations cosmétiques comprenant des extraits de daphné
WO2020120451A1 (fr) 2018-12-10 2020-06-18 Eth Zurich Préparations cosmétiques comprenant des extraits de daphne
US11896707B2 (en) 2018-12-10 2024-02-13 Eth Zurich Cosmetic preparations comprising Daphne extracts
US11110075B2 (en) * 2019-08-14 2021-09-07 Xi'an Jiaotong University Use of daphnetin in improving function of aortic endothelial cell

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