WO2023022414A1 - 아이리스 유래의 엑소좀을 유효성분으로 포함하는 새로운 조성물 - Google Patents
아이리스 유래의 엑소좀을 유효성분으로 포함하는 새로운 조성물 Download PDFInfo
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- WO2023022414A1 WO2023022414A1 PCT/KR2022/011554 KR2022011554W WO2023022414A1 WO 2023022414 A1 WO2023022414 A1 WO 2023022414A1 KR 2022011554 W KR2022011554 W KR 2022011554W WO 2023022414 A1 WO2023022414 A1 WO 2023022414A1
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- iris
- skin
- derived
- wound healing
- exosomes
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- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
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Definitions
- the present invention relates to a new composition containing iris-derived exosomes as an active ingredient, and more particularly, to improve skin elasticity, skin wrinkles, skin regeneration, skin tone or skin brightness containing iris-derived exosomes as an active ingredient It relates to a composition for improving, skin whitening, anti-inflammatory, wound healing and/or promoting wound healing.
- the present invention relates to a cosmetic composition for improving skin elasticity, improving skin wrinkles, skin regeneration, improving skin tone or brightness, and/or whitening, and a pharmaceutical composition for anti-inflammatory, wound healing, and/or promoting wound healing, including the above composition. it's about
- MMP matrix metalloproteinase
- Prostaglandin E2 Prostaglandin E2
- COX-2 an enzyme that produces inflammatory cytokines
- MMP muscle growth factor
- sunlight and ultraviolet rays are directly irradiated to the skin, a lot of free radicals are generated, and the antioxidant defense system of the skin is damaged by these free radicals, which accelerates skin aging by increasing wrinkles and relaxing the skin.
- Substances known to be effective in improving skin wrinkles include adenosine and retinoic acid, but adenosine has little clinical efficacy, and retinoic acid cannot be used for women of childbearing age and has side effects such as erythema.
- Human skin color is determined by the concentration and distribution of melanin in the skin. Melanin is synthesized through a non-enzymatic oxidation reaction after conversion from tyrosine to DOPA and dopaquinone by tyrosinase. When melanin is excessively produced, pigmentation occurs, and spots, dots, and freckles appear on the face, neck, and arms, making the appearance unattractive. Although skin whitening agents are being developed to improve blemishes, freckles, and dark skin tone, it is difficult to develop skin whitening agents that have excellent whitening effects and have no side effects. For example, a skin whitening agent that selectively attacks melanocytes that produce melanin has an excellent whitening effect, but has the side effect of skin toxicity.
- Inflammation is a defense reaction of a living body that appears in response to pathological conditions caused by physical or chemical trauma, infection by bacteria, fungi, or viruses, various allergens, and the like.
- the inflammatory response appears as part of the innate immune response.
- Various substances and physiological/chemical phenomena are involved in the inflammatory response, and recent studies have revealed that various inflammatory cytokines play an important role in the inflammatory response.
- IL-1 ⁇ , TNF- ⁇ , IL-6, IL-8, IL-12, and IFN- ⁇ are major cytokines involved in the inflammatory response, and their expression and secretion increase and activation are inflammatory mediators. It is associated with a series of complex physiological reactions such as secretion, immune cell infiltration, cell migration and tissue destruction, and symptoms such as erythema, edema, fever and pain.
- the inflammatory response does not become a major problem when the infectious agent is removed and the damaged tissue is regenerated, and the diseased area is restored to normal. cause inflammatory diseases.
- Immunosuppressants such as nonsteroidal anti-inflammatory drugs, steroidal anti-inflammatory drugs, neuropeptide antagonists, COX inhibitors, antihistamines, and cyclosporine A are used to alleviate or treat inflammatory reactions or inflammatory diseases caused by them, but skin atrophy, vasodilation, pigmentation There are problems causing side effects such as loss of blood, hypersensitivity, tolerance, and neutropenia. In addition, these drugs have limitations in helping control symptoms to an appropriate level rather than fundamental treatment.
- cell secretome contains various bioactive factors that regulate cell behavior. ' is included, and research on its ingredients and functions is actively underway.
- Extracellular vesicles are also referred to as cell membrane-derived vesicles, ectosomes, shedding vesicles, microparticles, exosomes, etc., and in some cases, they are used separately from exosomes.
- Exosomes are vesicles with a size of tens to hundreds of nanometers having a double-phospholipid membrane identical to the structure of a cell membrane, and contain proteins, nucleic acids (mRNA, miRNA, etc.) called exosome cargo inside. It is known that the exosome cargo contains a wide range of signaling factors, and these signaling factors are cell type-specific and differently regulated depending on the environment of the secreting cell. Exosomes are intercellular signaling mediators secreted by cells, and various cell signals transmitted through them regulate cell behavior including activation, growth, migration, differentiation, dedifferentiation, apoptosis, and necrosis of target cells. It is known.
- Exosomes contain specific genetic materials and bioactive factors depending on the nature and state of the derived cell. In the case of proliferating stem cell-derived exosomes, cell behaviors such as cell migration, proliferation, and differentiation are regulated, and characteristics of stem cells related to tissue regeneration are reflected (Nature Review Immunology 2002 (2) 569-579).
- exosomes called avatars of cells, contain bioactive factors such as growth factors similarly to cells, and play a role as a carrier for transporting bioactive factors between cells, that is, communication between cells.
- Exosomes are known to be released not only from animal cells such as stem cells, immune cells, fibroblasts and cancer cells, but also from cells of various organisms such as plants, bacteria, fungi, and algae. .
- exosomes can be isolated from cultures of cancer cells, immune cells, mesenchymal stem cells, etc., as well as plant cells or plant stem cell cultures.
- exosomes derived from plant cells or plant stem cells are still in its infancy, and most of them simply convert extracellular vesicles, which are mixed as a mixture in the filtrate of plant juice, into exosomes. It is a level that is being used for marketing. Therefore, more detailed characterization and function studies of exosomes derived from plant cells are required.
- Iris (Iris sp. ) is a perennial herbaceous plant belonging to the monocotyledonous lily order Iris family. Iris is distributed in various regions depending on the species. For example, Iris nertschinskia is distributed in Korea, Japan, northeastern China, and eastern Siberia, and is native to dry places at the foot of mountains. It has been reported that isoflavone-based substances in iris extracts exhibit anticancer or anti-inflammatory effects, but the components and action mechanisms of iris extracts have not been clearly identified. Therefore, it is necessary to accurately analyze the components of Iris and scientifically identify the pharmacological mechanism of action. The technology so far is at the level of using extracts obtained by hot water extraction or solvent extraction of iris flowers, leaves, stems, and roots as raw materials for cosmetics. However, the solvent extract has a problem of harmfulness to the human body in which the extraction solvent remains.
- callus which is called a stem cell of a plant
- a technology using callus culture obtained by culturing callus induced by scarring flowers and leaves of iris has been introduced. It is to the extent that the extract is used as a cosmetic ingredient.
- the callus culture contains growth regulators or callus inducers, it is difficult to say that it is a natural cosmetic raw material, and growth regulators contained in the culture may cause side effects such as skin trouble.
- the present inventors confirmed that Iris-derived exosomes are effective in improving skin elasticity, improving skin wrinkles, skin regeneration, improving skin tone or brightness, skin whitening, anti-inflammatory, wound healing and/or promoting wound healing, and A cosmetic composition containing exosomes as an active ingredient for skin elasticity improvement, skin wrinkle improvement, skin regeneration, skin tone or skin brightness improvement, and/or whitening, and a pharmaceutical composition for anti-inflammatory, wound healing, and/or promoting wound healing have been developed. .
- An object of the present invention is to provide a composition for improving skin elasticity, improving skin wrinkles, skin regeneration, improving skin tone or brightness, skin whitening, anti-inflammatory, wound healing, and/or promoting wound healing, comprising exosomes derived from iris as an active ingredient.
- an object of the present invention is a cosmetic composition for improving skin elasticity, improving skin wrinkles, skin regeneration, improving skin tone or skin brightness and / or whitening containing the composition, and a pharmaceutical composition for anti-inflammatory, wound healing and / or promoting wound healing to provide a composition.
- the present invention provides a composition for improving skin elasticity, improving skin wrinkles, skin regeneration, improving skin tone or brightness, skin whitening, anti-inflammatory, wound healing, and/or promoting wound healing, containing iris-derived exosomes as an active ingredient.
- the term "Iris” refers to a plant of the genus Iris ( Iris sp. ).
- the iris genus ( Iris sp. ) plants are iris ( Iris ensata ), dalmation iris ( Iris pallida ), blue flag iris ( Iris versicolor ), orris ( Iris florentina ), iris ( Iris nertschinskia ), yellow It may be iris ( Iris pseudacorus ), fan iris ( Iris setosa ), corkscrew iris ( Iris lactea ), jaman iris ( Iris germanica ) or yellow iris ( Iris odaesanensis ).
- exosomes refers to nano-sized vesicles having a membrane structure secreted or released from plant cells into the extracellular space, and may also be referred to as exosome-like vesicles or exosome-like particles. is defined
- skin elasticity refers to a property in which the skin deformed by an external force easily returns to its original shape when the external force is removed.
- Skin wrinkles refers to fine lines caused by skin deterioration, which can be caused by genes, reduction of collagen and elastin present in the skin dermis, external environment, and the like. Therefore, the term “improving skin wrinkles” as used herein means suppressing or inhibiting the formation of wrinkles on the skin, or alleviating wrinkles already formed.
- skin tone refers to a state in which the color of the skin is strong or weak.
- skin whitening includes increasing the brightness of the skin whose brightness has decreased due to excessive pigments such as melanin, or maintaining the brightness of the skin at a certain level.
- anti-inflammatory means to prevent, suppress, alleviate, improve or treat inflammation
- examples of inflammatory diseases that do not limit the present invention include dermatitis, atopic dermatitis, eczema, bacterial infection, virus Inflammation due to infection or fungal infection, burns, inflammation due to burns, wounds, inflammation due to wounds, and the like.
- wound or wound refers to a state in which a living body is damaged, and a tissue constituting an internal or external surface of a living body, such as skin, muscle, nerve tissue, bone, soft tissue, internal organs or blood vessels. It encompasses pathological conditions in which tissues are divided or destroyed.
- wounds or wounds include abrasion, laceration, cut, cut, avulsion, decubitus, sore, destruction of tissue by irradiation, penetrating wound, It includes gunshot wounds, burns, frostbite, surgical wounds, sutures after plastic surgery, chemical wounds, etc., and may include damage to any part of the subject.
- Iontophoresis refers to a method of allowing ionized active ingredients to penetrate the skin with electrical repulsive force by changing the electrical environment of the skin by applying a potential difference by flowing a microcurrent through the skin to which the active ingredient is applied.
- Iontophoresis used in one embodiment of the present invention is a method in which a current from an external power source flows into an electrode patch on the skin and a microcurrent is introduced into the skin, and a battery is attached to the electrode patch itself to It may include a method in which microcurrent is introduced, a method in which microcurrent is introduced into the skin through a patch equipped with a reversed electrodialysis means that generates current through a difference in ion concentration between a high-concentration electrolyte solution and a low-concentration electrolyte solution, and the like.
- the present invention is not limited thereto, and various types of iontophoresis can be used, of course.
- exosomes derived from iris refers to, for example, iris plant cell culture medium, iris callus culture medium, iris plant stem cell culture medium, iris juice, or separated from biological solutions of iris equivalent thereto. or derived from iris plant cells or plant stem cells, eg secreted and/or released exosomes.
- the iris-derived exosomes may be separated and purified from a callus culture medium derived from the root of iris.
- composition comprising the iris-derived exosomes of one embodiment of the present invention as an active ingredient improves skin elasticity, improves skin wrinkles, regenerates skin, improves skin tone or brightness, whitens skin, anti-inflammatory, heals wounds and/or promotes wound healing. At least one efficacy may be exhibited.
- a composition comprising the exosomes derived from Iris of the present invention as an active ingredient may be a cosmetic composition or a pharmaceutical composition.
- the present invention provides a cosmetic composition for improving skin elasticity, improving skin wrinkles, regenerating skin, improving skin tone or brightness, and/or whitening, containing exosomes derived from iris as an active ingredient.
- the cosmetic composition includes shampoo, soap, rinse, surfactant-containing cleansing, cream, lotion, ointment, tonic, treatment, conditioner, suspension, emulsion, paste, gel, oil, wax, spray, aerosol, It may be a mist or powder, preferably a lotion or cream.
- the present invention provides a pharmaceutical composition for anti-inflammatory, wound healing and/or promotion of wound healing comprising an iris-derived exosome as an active ingredient.
- the pharmaceutical composition of one embodiment of the present invention may be administered or treated by injection, microneedling, iontophoresis, application, or a combination thereof.
- the pharmaceutical composition may be in the form of an injection, an injection, a spray, a liquid or a patch.
- composition of one embodiment of the present invention when used as a pharmaceutical composition, it may include a pharmaceutically acceptable carrier, excipient or diluent.
- the carriers, excipients and diluents include lactose, dextrose, trehalose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium carbonate, calcium silicate, cellulose , methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil, but are not limited thereto.
- the effective amount of the pharmaceutical composition of one embodiment of the present invention means an amount required for administration in order to expect anti-inflammatory, wound healing and / or wound healing promoting effects.
- the blending ratio of the pharmaceutical composition of one embodiment of the present invention can be appropriately selected according to the type, amount, form, etc. of the additional components as described above.
- the pharmaceutical composition of the present invention may be included in about 0.1 to 99% by weight, preferably about 10 to 90% by weight.
- a suitable dosage of the pharmaceutical composition of one embodiment of the present invention may be adjusted according to the severity of the disease, the type of formulation, the formulation method, the patient's age, sex, weight, health condition, diet, excretion rate, administration time and administration method can For example, when administering the pharmaceutical composition of one embodiment of the present invention to an adult, it may be divided into 1 to several times at a dose of 0.001 mg/kg to 100 mg/kg per day.
- composition of one embodiment of the present invention is prepared as a cosmetic composition
- components commonly used in cosmetic compositions within a range that does not impair the effects of the present invention for example, moisturizers, antioxidants, oily ingredients, ultraviolet absorbers, Emulsifiers, surfactants, thickeners, alcohols, powder components, coloring materials, aqueous components, water, various skin nutrients, etc. can be appropriately blended as needed.
- the cosmetic composition of one embodiment of the present invention has actions (eg, skin elasticity improvement, skin wrinkle improvement, skin regeneration, skin tone or brightness improvement, skin whitening, skin beauty, etc.) in addition to the iris-derived exosomes.
- actions eg, skin elasticity improvement, skin wrinkle improvement, skin regeneration, skin tone or brightness improvement, skin whitening, skin beauty, etc.
- Conventionally used skin improving agents, antioxidants, anti-aging agents, whitening agents, and/or moisturizing agents may be mixed and used as long as they are not damaged.
- the cosmetic composition of one embodiment of the present invention is, for example, a patch, mask pack, mask sheet, cream, tonic, ointment, suspension, emulsion, paste, lotion, gel, oil, pack, spray, aerosol, mist, foundation, It can be applied to various forms such as powder and oil paper.
- the cosmetic composition of one embodiment of the present invention may be used for purposes such as improving skin elasticity, improving skin wrinkles, regenerating skin, improving skin tone or brightness, and/or skin whitening
- the cosmetic formulation may be any formulation conventionally prepared in the art.
- patches, mask packs, mask sheets, softening lotion, nourishing lotion, astringent lotion, nourishing cream, massage cream, eye cream, cleansing cream, essence, eye essence, cleansing lotion, cleansing foam, cleansing water, sunscreen, lipstick , Soap, shampoo, surfactant-containing cleansing, bath additives, body lotion, body cream, body oil, body essence, body cleanser, hair dye, hair tonic, etc. can be formulated, but is not limited thereto.
- the cosmetic composition of one embodiment of the present invention includes components commonly used in cosmetic compositions, and may include, for example, antioxidants, stabilizers, solubilizers, vitamins, pigments, and conventional adjuvants such as fragrances and carriers.
- other ingredients may be appropriately selected and blended without difficulty by a person skilled in the art according to the type or purpose of use of the cosmetic composition.
- Another embodiment of the present invention provides a cosmetic method for controlling the skin condition of a mammal, except for treatment, using the cosmetic composition.
- skin condition control means improving skin condition and/or preventively controlling skin condition
- skin condition improvement means visual and/or tactile perception of the appearance and feel of the skin. It means positive change that can be made.
- improvement of skin condition may include improvement of skin elasticity, improvement of skin wrinkles, skin regeneration, improvement of skin tone or brightness, and/or skin whitening.
- step (a) directly applying the cosmetic composition to the skin of a mammal (b) applying a patch, mask pack or mask sheet on which the cosmetic composition is applied or deposited to the skin of a mammal It includes contacting or attaching to, or sequentially proceeding with (a) and (b) above.
- a lotion or cream may be used as a cosmetic composition.
- step (c) after step (b), the patch, mask pack or mask sheet is removed from the skin of the mammal, and the cosmetic composition is applied to the skin of the mammal.
- An application step may be further included.
- a lotion or cream may be used as a cosmetic composition.
- the mammal may be a human, dog, cat, rodent, horse, cow, monkey, or pig.
- the present invention relates to inflammation treatment, wound treatment or promotion of wound healing, including the step of administering a therapeutically effective amount of the pharmaceutical composition to a mammal, or applying the pharmaceutical composition to the skin, inflammatory site or wound site ( It provides a method for accelerating wound healing.
- the mammal may be a human, dog, cat, rodent, horse, cow, monkey, or pig.
- composition of the present invention is less likely to contain impurities such as residual solvents and growth regulators than conventional hot water extracts or solvent extracts of iris, filtrates of these extracts, and iris callus culture solutions, and improves skin elasticity, improves skin wrinkles, and regenerates skin. , skin tone or skin brightness improvement, skin whitening, anti-inflammatory, wound healing or wound healing promotion effects are excellent.
- FIG. 1 is a graph showing the particle size distribution and particle number obtained by performing NTA (nanoparticle tracking analysis) on the iris-derived exosomes of the present invention.
- FIG. 2 is a cell fluorescence microscopy image confirming the transfer of fluorescently-stained iris-derived exosomes to human dermal fibroblasts (green: exosomes delivered into cells, blue: cell nuclei).
- Figure 3 is a graph showing the relative amount of collagen increased after treating human skin fibroblasts with iris-derived exosomes.
- FIG. 4 is a graph showing the increase in migration of human skin fibroblasts after treating iris-derived exosomes with Scratch-Wound.
- 5 is a fluorescence microscopy image of a cell confirming that fluorescently stained iris-derived exosomes are delivered to melanoma cells (green: exosomes delivered into cells, blue: cell nuclei).
- 6 is a graph showing that the amount of melanin produced is decreased in a concentration-dependent manner in exosomes when melanoma cells are treated with iris-derived exosomes.
- FIG. 8 is a graph showing that IL-6 induced by LPS was reduced in a concentration-dependent manner when RAW 264.7 cells were treated with Iris-derived exosomes.
- Example 1 Preparation of iris callus culture medium
- callus derived from the root of iris is induced, and the induced iris callus is cell cultured.
- callus in a good growth state is selected and cultured in large quantities to prepare an iris callus culture medium.
- An iris callus culture medium ( Iris germanica callus culture medium) prepared in the same manner as in Example 1 was obtained from Biospectrum Co., Ltd. (an iris callus culture medium supplier located in Gyeonggi-do, Korea). The iris callus culture medium was filtered through a 0.22 ⁇ m filter to remove impurities such as cell debris, waste products, and giant particles. Iris-derived exosomes were isolated from the filtered culture medium using a tangential flow filtration (TFF).
- TMF tangential flow filtration
- NTA nanoparticle tracking analysis
- Example 3 Iris-derived exosomes confirmation of skin fibroblast transmissibility
- PKH67 fluorescent dye
- a fluorescent dye PKH67 purchased from Sigma-Aldrich
- the reaction solution was fractionated with a MiniTrap-25 (purchased from Cytiva) column to remove free PHK67 (free PKH67) fluorescent dye not stained on the exosome membrane.
- PKH67 fluorescent dye was reacted with a buffer solution and then fractionated using a MiniTrap-25 column.
- Exosomes stained with PKH67 were cultured with human skin fibroblasts prepared by culturing in advance, and then intracellular delivery of exosomes over time was observed using a fluorescence microscope. Hoechst fluorescent dye (purchased from Thermo Fisher) was used to stain the cell nucleus, and CellMask Orange fluorescent dye (purchased from Thermo Fisher) was used to stain the cytoplasm. As a result of confirming whether the exosomes were intracellularly delivered, it was confirmed that the fluorescently stained exosomes were delivered into the cells and green fluorescence was accumulated inside the cells over time (FIG. 2).
- Human dermal fibroblasts (Human Dermal Fibroblast; purchased from ATCC) dispersed in DMEM medium containing fetal calf serum were seeded in a multi-well plate and cultured for 24 hours. Thereafter, the iris callus culture medium prepared in Example 1 and the iris-derived exosomes prepared in Example 2 were diluted in a serum-free medium, respectively, and treated with human skin fibroblasts, and the human skin fibroblasts were cultured for 24 hours. To confirm the efficacy of collagen production using human skin fibroblasts, the experimental groups were classified as follows.
- Negative control group (indicated by “N.C.” in FIG. 3): an experimental group treated only with serum-free medium;
- Iris callus culture solution treatment group (indicated as “Iris Callus CM” in FIG. high concentration: 240 ⁇ g/mL);
- Iris-derived exosome treatment group (indicated as “Iris Exosome” in FIG. 3): Experimental group treated by diluting the Iris-derived exosome prepared in Example 2 in a serum-free medium (treatment concentration - low concentration: 60 ⁇ g) /mL, high concentration: 240 ⁇ g/mL).
- Each of the above experimental groups was cultured for 24 hours after treatment with human skin fibroblasts, and the culture medium was collected and centrifuged, and then the centrifuged culture medium was prepared.
- the amount of collagen synthesized from human skin fibroblasts and accumulated in the culture medium was measured using an EIA kit (purchased from Takara) for procollagen type I C-peptide (PIP).
- the relative amount of collagen was determined by normalization by dividing by the total number of cells measured via the MTT assay kit (purchased from Sigma-Aldrich).
- the iris callus culture solution-treated group had no effect of increasing collagen synthesis in human skin fibroblasts, whereas the iris-derived exosomes of the present invention increased collagen synthesis in human skin fibroblasts, In particular, it was confirmed that collagen synthesis in human skin fibroblasts was remarkably increased when Iris-derived exosomes were treated at a high concentration (FIG. 3).
- the iris-derived exosomes of the present invention are superior in collagen synthesis increasing efficacy, that is, skin elasticity improvement, wrinkle improvement and/or skin regeneration efficacy, compared to the iris callus culture medium.
- the exosomes derived from iris of the present invention have a useful functional activity as a cosmetic for skin elasticity improvement, wrinkle improvement and/or skin regeneration, that is, an activity to increase collagen synthesis. Therefore, the iris-derived exosomes of the present invention can be usefully used as an active ingredient in a cosmetic composition for skin elasticity improvement, wrinkle improvement and/or skin regeneration.
- Example 2 In order to evaluate whether the exosomes prepared in Example 2 promote wound healing in human dermal fibroblasts (purchased from ATCC), a scratch-wound assay was performed. Human dermal fibroblasts dispersed in DMEM medium containing fetal bovine serum were dispensed at a density of 5,000 cells/well on a culture plate for wound induction (ImageLock Plate; purchased from EssenBio) and incubated for 24 hours under 5% CO 2 and 37°C conditions. After culturing and confirming the density of 90% or more, scratches were induced using a WoundMaker (purchased from EssenBio). To confirm the skin regeneration effect using human skin fibroblasts, the experimental groups were classified as follows.
- Negative control group (indicated by “N.C.” in FIG. 4): an experimental group treated only with serum-free medium;
- Positive control group (indicated as “P.C.” in FIG. 4): an experimental group treated with a culture medium containing 10% fetal bovine serum;
- Iris callus culture solution treatment group (indicated as "Iris Callus CM” in FIG. 4): Experimental group treated by diluting the iris callus culture solution prepared in Example 1 in a serum-free medium (treatment concentration - low concentration: 50 ⁇ g / mL, high concentration: 200 ⁇ g/mL);
- Iris-derived exosome treatment group (indicated as “Iris Exosome” in FIG. 4): Experimental group treated by diluting the Iris-derived exosome prepared in Example 2 in a serum-free medium (treatment concentration - low concentration: 50 ⁇ g) /mL, high concentration: 200 ⁇ g/mL).
- the iris callus culture medium did not increase the migration of human skin fibroblasts compared to the negative control group, whereas the iris-derived exosome of the present invention increased the migration of human skin fibroblasts compared to the negative control group. It was confirmed that increased (Fig. 4).
- the iris-derived exosomes of the present invention are superior in the migration promoting effect of human skin fibroblasts, that is, the wound healing ability or skin regeneration effect, compared to the iris callus culture medium.
- the iris-derived exosome of the present invention can be usefully used as an active ingredient in a cosmetic composition for skin elasticity improvement, wrinkle improvement and/or skin regeneration, and a pharmaceutical composition for wound healing or promoting wound healing.
- Example 6 Iris-derived exosomes confirm melanoma cell delivery ability
- the following assay was performed to confirm whether the iris-derived exosomes were delivered into mouse melanoma (B16F10; purchased from ATCC).
- a fluorescent dye PKH67 purchased from Sigma-Aldrich.
- the reaction solution was fractionated with a MiniTrap-25 (purchased from Cytiva) column to remove free PHK67 (free PKH67) fluorescent dye not stained on the exosome membrane.
- PKH67 fluorescent dye was reacted with a buffer solution and then fractionated using a MiniTrap-25 column.
- Example 7 Melanin production inhibitory effect of iris-derived exosomes
- the whitening effect of the iris-derived exosomes was confirmed through inhibition of melanin production in melanoma cells.
- the melanoma cells are cells derived from mouse melanoma (B16F10; purchased from ATCC) and secrete a black pigment called melanin. After dispensing 8,000 melanoma cells per unit area in a 48-well plate, they were cultured for 24 hours under 5% CO 2 and 37°C conditions.
- the iris callus culture medium prepared in Example 1 and the iris-derived exosomes prepared in Example 2 were diluted in a culture medium mixed with a-MSH, a melanin synthesis stimulant, and then treated with melanoma cells. time incubated.
- the experimental groups were classified as follows.
- Negative control group (indicated by “N.C.” in FIG. 6): an experimental group treated with a culture medium mixed with a-MSH, a melanin synthesis stimulator;
- Iris callus culture solution treatment group (indicated as "Iris Callus CM" in FIG. 6): Experimental group treated with a culture medium mixed with the iris callus culture solution prepared in Example 1 and a-MSH, a melanin synthesis stimulator (treatment concentration - low concentration: 100 ⁇ g/mL, high concentration: 200 ⁇ g/mL);
- Iris-derived exosome treatment group (indicated as “Iris Exosome” in FIG. 6): Experimental group treated with a culture medium in which Iris-derived exosome prepared in Example 2 and a-MSH, a melanin synthesis stimulator, were mixed ( Treatment concentration - low concentration: 100 ⁇ g/mL, high concentration: 200 ⁇ g/mL).
- the recovered melanoma culture medium and CCK-8 assay reagent purchased from Dojindo
- the supernatant was transferred to a 96-well plate and the total cell number was measured by measuring the absorbance at 450 nm.
- the washed melanoma cells were treated with 1N NaOH (purchased from Merck-Milipore) mixed with 10% DMSO, and then the plate was sealed and incubated at 85°C.
- the melanin in the melanoma cells was extracted by heating for 20 minutes. The extracted melanin measured the absorbance at 405 nm to calculate the amount of melanin, and normalized to the absorbance value measured through the CCK-8 assay.
- the iris-derived exosomes of the present invention had an effect of inhibiting melanin synthesis in melanoma cells in a concentration-dependent manner compared to the negative control group, and that the melanin synthesis inhibitory effect was superior to that of the iris callus culture medium (Fig. 6).
- the cosmetic composition containing the iris-derived exosomes of the present invention as an active ingredient has a whitening effect, and the iris-derived exosomes of the present invention are effective in cosmetic compositions for skin tone improvement, skin brightness improvement and/or skin whitening. It can be usefully utilized as a component.
- Example 8 Iris-derived exosomes confirmation of macrophage delivery ability
- the membrane of the iris-derived exosome prepared in Example 2 was reacted with a fluorescent dye PKH67 (purchased from Sigma-Aldrich) in order to fluorescently stain the membrane.
- PKH67 purchased from Sigma-Aldrich
- the reaction solution was fractionated with a MiniTrap-25 (purchased from Cytiva) column to remove free PHK67 (free PKH67) fluorescent dye not stained on the exosome membrane.
- PKH67 fluorescent dye was reacted with a buffer solution and then fractionated with a MiniTrap-25 column.
- Exosomes stained with PKH67 were cultured with previously prepared mouse macrophages, and then intracellular delivery of exosomes over time was observed using a fluorescence microscope. Hoechst fluorescent dye (purchased from Thermo Fisher) was used to stain the cell nucleus, and CellMask Orange fluorescent dye (purchased from Thermo Fisher) was used to stain the cytoplasm. As a result of confirming whether the exosomes were intracellularly delivered, it was confirmed that the fluorescently stained exosomes were delivered into the cells and green fluorescence was accumulated inside the cells over time (FIG. 7).
- Example 9 Evaluation of anti-inflammatory efficacy of exosomes derived from iris
- the effect of the iris-derived exosomes on the amount of IL-6 produced in mouse macrophage RAW 264.7 cells was confirmed.
- RAW 264.7 cells suspended in DMEM medium containing 10% FBS were dispensed into each well of a 48-well plate to have a confluency of 80 to 90%.
- the iris callus culture medium prepared in Example 1 and each of the iris-derived exosomes prepared in Example 2 were mixed in a new LPS-containing medium [DMEM medium containing 1% FBS and 200 nM LPS (lipopolysaccharide)] to obtain RAW 264.7 cells
- RAW 264.7 cells were cultured for 24 hours.
- Experimental groups for anti-inflammatory efficacy evaluation were classified as follows.
- Negative control group (indicated by “N.C.” in FIG. 8): an experimental group in which only LPS medium was treated with RAW 264.7 cells;
- Positive control group (indicated as “P.C.” in FIG. 8): an experimental group treated with RAW 264.7 cells by mixing LPS medium with dexamethasone (final concentration: 200 ⁇ M);
- Iris callus culture solution treatment group (shown as "Iris Callus CM" in FIG. 8): Experimental group treated with RAW 264.7 cells by diluting the iris callus culture solution prepared in Example 1 in LPS medium (treatment concentration - low concentration: 50 ⁇ g) /mL, high concentration: 200 ⁇ g/mL);
- Iris-derived exosome treatment group Experimental group treated with RAW 264.7 cells by diluting the iris-derived exosome prepared in Example 2 in LPS medium (treatment concentration - low concentration: 50 ⁇ g / mL, high concentration: 200 ⁇ g / mL).
- IL-6 an inflammatory cytokine present in the culture supernatant
- IL-6 ELISA kit purchased from R&D systems
- the amount of production of IL-6 (inflammatory cytokine) in the group treated with only LPS and dexamethasone, iris callus culture medium and iris-derived exosomes were mixed with LPS medium.
- the amount of IL-6 produced in the treated experimental group was confirmed (FIG. 8).
- the exosomes derived from Iris of the present invention had excellent anti-inflammatory efficacy. Therefore, the iris-derived exosomes of the present invention can be usefully used as an active ingredient of a pharmaceutical composition for anti-inflammatory, wound healing and/or promoting wound healing.
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Abstract
Description
Claims (18)
- 아이리스 유래의 엑소좀을 유효성분으로 포함하는, 피부탄력개선, 피부주름개선, 피부재생, 피부톤이나 피부밝기 개선 또는 미백용 화장료 조성물.
- 제1항에 있어서,샴푸, 비누, 린스, 계면활성제-함유 클렌징, 크림, 로션, 연고, 토닉, 트리트먼트, 컨디셔너, 현탁액, 유탁액, 페이스트, 젤, 오일, 왁스, 스프레이, 에어졸, 미스트, 또는 파우더인, 피부탄력개선, 피부주름개선, 피부재생, 피부톤이나 피부밝기 개선 또는 미백용 화장료 조성물.
- 제2항에 있어서,크림 또는 로션인, 피부탄력개선, 피부주름개선, 피부재생, 피부톤이나 피부밝기 개선 또는 미백용 화장료 조성물.
- 제1항 내지 제3항 중 어느 한 항에 있어서,상기 아이리스 유래의 엑소좀은 아이리스 식물세포 배양액, 아이리스 캘러스 배양액, 아이리스 식물줄기세포 배양액, 아이리스 착즙물, 또는 이들과 동등한 아이리스의 생물학적 용액으로부터 분리되거나, 아이리스 식물세포 또는 식물줄기세포로부터 유래된 것인, 피부탄력개선, 피부주름개선, 피부재생, 피부톤이나 피부밝기 개선 또는 미백용 화장료 조성물.
- 제4항에 있어서,상기 아이리스 유래의 엑소좀은 아이리스의 뿌리 유래 캘러스 배양액으로부터 분리 정제된 것인, 피부탄력개선, 피부주름개선, 피부재생, 피부톤이나 피부밝기 개선 또는 미백용 화장료 조성물.
- 아이리스 유래의 엑소좀을 유효성분으로 포함하는, 항염증, 상처 치유 또는 상처 치유 촉진용 약학 조성물.
- 제6항에 있어서,주사, 마이크로니들링, 이온토포레시스, 도포, 또는 이들의 조합에 의해 투여 또는 처리되는, 항염증, 상처 치유 또는 상처 치유 촉진용 약학 조성물.
- 제6항에 있어서,주사제형, 주입제형, 분무제형, 액상제형 또는 패취제형인, 항염증, 상처 치유 또는 상처 치유 촉진용 약학 조성물.
- 제6항 내지 제8항 중 어느 한 항에 있어서,상기 아이리스 유래의 엑소좀은 아이리스 식물세포 배양액, 아이리스 캘러스 배양액, 아이리스 식물줄기세포 배양액, 아이리스 착즙물, 또는 이들과 동등한 아이리스의 생물학적 용액으로부터 분리되거나, 아이리스 식물세포 또는 식물줄기세포로부터 유래된 것인, 항염증, 상처 치유 또는 상처 치유 촉진용 약학 조성물.
- 제9항에 있어서,상기 아이리스 유래의 엑소좀은 아이리스의 뿌리 유래 캘러스 배양액으로부터 분리 정제된 것인, 항염증, 상처 치유 또는 상처 치유 촉진용 약학 조성물.
- 아이리스 유래의 엑소좀을 유효성분으로 포함하는 화장료 조성물을 이용하여, 치료용을 제외한 포유동물의 피부탄력개선, 피부주름개선, 피부재생, 피부톤이나 피부밝기 개선 또는 피부 미백을 하는 미용방법.
- 제11항에 있어서,(a) 상기 화장료 조성물을 포유동물의 피부에 직접 도포하는 것, (b) 상기 화장료 조성물이 도포되거나 침적된 패취, 마스크팩 또는 마스크시트를 포유동물의 피부에 접촉 또는 부착하는 것, 또는 상기 (a) 및 (b)를 순차적으로 진행하는 것을 포함하는, 미용방법.
- 제12항에 있어서,상기 (a) 단계에서는 화장료 조성물로서 로션이나 크림이 사용되는, 미용방법.
- 제12항 또는 제13항에 있어서,(c) 상기 (b) 단계 이후에 상기 패취, 마스크팩 또는 마스크시트를 상기 포유동물의 피부로부터 제거하고, 상기 화장료 조성물을 포유동물의 피부에 도포하는 단계를 더 포함하는, 미용방법.
- 제14항에 있어서,상기 (c) 단계에서는 화장료 조성물로서 로션이나 크림이 사용되는, 미용방법.
- 제11항 내지 제13항 중 어느 한 항에 있어서,상기 포유동물은 인간, 개, 고양이, 설치류, 말, 소, 원숭이, 또는 돼지인, 미용방법.
- 아이리스 유래의 엑소좀을 유효성분으로 포함하는 약학 조성물의 치료학적으로 유효한 양을 인간을 제외한 포유동물에게 투여하는 단계, 또는 아이리스 유래의 엑소좀을 유효성분으로 포함하는 약학 조성물을 인간을 제외한 포유동물의 피부, 염증 부위 또는 상처 부위에 도포하는 단계를 포함하는, 염증치료, 상처 치료 또는 상처 치료 촉진을 위한 방법.
- 제17항에 있어서,상기 포유동물은 개, 고양이, 설치류, 말, 소, 원숭이, 또는 돼지인, 염증치료, 상처 치료 또는 상처 치료 촉진을 위한 방법.
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Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0930954A (ja) * | 1995-05-17 | 1997-02-04 | Shiseido Co Ltd | 美白用皮膚外用剤 |
KR19980079285A (ko) * | 1996-06-28 | 1998-11-25 | 후쿠하라요시하루 | 외부 피부 처리 조성물 |
US6224850B1 (en) * | 1996-03-27 | 2001-05-01 | Societe L'oreal S.A. | Antiwrinkle cosmetic/pharmaceutical compositions comprising iridaceae extracts |
KR20070002133A (ko) * | 2005-06-30 | 2007-01-05 | (주)아모레퍼시픽 | 피부 외용제 조성물 |
KR20070115507A (ko) * | 2006-06-02 | 2007-12-06 | 주식회사 에스티씨나라 | 독일붓꽃, 병풀, 캐모마일, 달맞이꽃 및 어성초 추출물을함유하는 여드름 피부 개선을 위한 피부 외용제 조성물 |
KR20160086253A (ko) * | 2015-01-08 | 2016-07-19 | 한양대학교 에리카산학협력단 | 줄기세포로부터 추출된 엑소좀을 함유하는 피부 미백, 주름개선 또는 재생용 화장료 조성물 |
KR102058444B1 (ko) * | 2018-07-26 | 2019-12-23 | 주식회사 엑소코바이오 | 장미 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 화장료 조성물 |
KR102257524B1 (ko) * | 2020-08-18 | 2021-05-31 | 주식회사 바이오에프디엔씨 | 피부 진정 및 재생효과를 지니는 병풀 유래 엑소좀 함유 피부 개선용 화장료 조성물 |
KR102348510B1 (ko) * | 2021-08-27 | 2022-01-07 | 주식회사 에이바이오머티리얼즈 | 붓꽃 구근 유래 엑소좀을 유효성분으로 함유하는 화장료 조성물 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100491102B1 (ko) | 2003-01-15 | 2005-05-24 | 박은필 | 아이리스의 조직배양방법 |
KR100973839B1 (ko) | 2008-05-20 | 2010-08-04 | 경상북도(관련부서:경상북도산림생태과학원) | 노랑무늬붓꽃의 잎 절편을 이용한 캘러스의 대량증식방법및 노랑무늬붓꽃의 대량분화방법 |
-
2022
- 2022-08-04 CN CN202280049207.0A patent/CN117881391A/zh active Pending
- 2022-08-04 JP JP2023577484A patent/JP2024526557A/ja active Pending
- 2022-08-04 WO PCT/KR2022/011554 patent/WO2023022414A1/ko active Application Filing
- 2022-08-04 KR KR1020220097115A patent/KR102490802B1/ko active IP Right Grant
- 2022-08-04 EP EP22858652.5A patent/EP4342448A1/en active Pending
-
2023
- 2023-12-27 US US18/397,644 patent/US20240180816A1/en active Pending
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0930954A (ja) * | 1995-05-17 | 1997-02-04 | Shiseido Co Ltd | 美白用皮膚外用剤 |
US6224850B1 (en) * | 1996-03-27 | 2001-05-01 | Societe L'oreal S.A. | Antiwrinkle cosmetic/pharmaceutical compositions comprising iridaceae extracts |
KR19980079285A (ko) * | 1996-06-28 | 1998-11-25 | 후쿠하라요시하루 | 외부 피부 처리 조성물 |
KR20070002133A (ko) * | 2005-06-30 | 2007-01-05 | (주)아모레퍼시픽 | 피부 외용제 조성물 |
KR20070115507A (ko) * | 2006-06-02 | 2007-12-06 | 주식회사 에스티씨나라 | 독일붓꽃, 병풀, 캐모마일, 달맞이꽃 및 어성초 추출물을함유하는 여드름 피부 개선을 위한 피부 외용제 조성물 |
KR20160086253A (ko) * | 2015-01-08 | 2016-07-19 | 한양대학교 에리카산학협력단 | 줄기세포로부터 추출된 엑소좀을 함유하는 피부 미백, 주름개선 또는 재생용 화장료 조성물 |
KR102058444B1 (ko) * | 2018-07-26 | 2019-12-23 | 주식회사 엑소코바이오 | 장미 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 화장료 조성물 |
KR102257524B1 (ko) * | 2020-08-18 | 2021-05-31 | 주식회사 바이오에프디엔씨 | 피부 진정 및 재생효과를 지니는 병풀 유래 엑소좀 함유 피부 개선용 화장료 조성물 |
KR102348510B1 (ko) * | 2021-08-27 | 2022-01-07 | 주식회사 에이바이오머티리얼즈 | 붓꽃 구근 유래 엑소좀을 유효성분으로 함유하는 화장료 조성물 |
Non-Patent Citations (1)
Title |
---|
NATURE REVIEW IMMUNOLOGY, no. 2, 2002, pages 569 - 579 |
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KR102490802B1 (ko) | 2023-01-20 |
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