WO2016072821A1 - 줄기세포 유래 엑소좀을 함유하는 지방세포 분화유도, 지방조직 재생, 피부 미백 또는 주름개선용 조성물 - Google Patents
줄기세포 유래 엑소좀을 함유하는 지방세포 분화유도, 지방조직 재생, 피부 미백 또는 주름개선용 조성물 Download PDFInfo
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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
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/44—Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/48—Reproductive organs
- A61K35/51—Umbilical cord; Umbilical cord blood; Umbilical stem cells
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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
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
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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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Definitions
- the present invention relates to a composition for inducing differentiation of adipocytes from stem cells and / or adipose tissue regeneration using stem cell-derived exosomes containing adipocyte differentiation-inducing substances.
- the present invention also relates to a cosmetic composition for skin whitening, wrinkle improvement or regeneration containing exosomes extracted from stem cells.
- a regeneration treatment method for adipose tissue As a regeneration treatment method for adipose tissue, a three-dimensional culture of adipose tissue in a hydrogel is used as a substrate, and then a therapeutic agent including stem cells cultured with the substrate and growth factors secreted from the stem cells and extracellular matrix is used.
- a therapeutic agent including stem cells cultured with the substrate and growth factors secreted from the stem cells and extracellular matrix
- Stem cells have been widely used to restore damaged tissues that are limited by surgery or drug treatment, and biopolymers such as hyaluronic acid and collagen are used for stem cell transplantation.
- biopolymers such as hyaluronic acid and collagen are used for stem cell transplantation.
- the stem cells can be differentiated into various cells including adipocytes, the application field is wide, but when they enter the human body, the survival rate and engraftment rate is low because of low efficiency, and there is a risk that the undifferentiated stem cells can form tumors.
- stem cell differentiation-inducing material as described above is expensive and has a disadvantage in that it does not have a differentiation effect with only a single component to be mixed and treated with various substances, and the efficiency of cell differentiation is low.
- the culture solution obtained by culturing stem cells was intended to be used as a cosmetic.
- a culture medium containing an appropriate amount of antibiotics and serum is used.
- stem cell cultures developed as cosmetic compositions mostly use a general culture medium (Korea Patent No. 1237430), cosmetic compositions containing the stem cell culture solution in liposomes (Korea Patent No. 1047873), and allowed as a cosmetic raw material
- a cosmetic composition using a culture medium except for the non-constituent components Korean Patent No. 1413686
- a cosmetic composition containing a serum-free culture solution Kerean Patent No. 1108847
- the culture medium has been made very precisely with materials containing proteins, amino acids, hormones and growth factors for cell proliferation, but for research purposes only because the cell culture medium, antibiotics and serum are all at risk. It is forbidden to use.
- L-glutamine (glutamin) and the like are not allowed as a cosmetic raw material, the use of such a culture medium is not suitable as a cosmetic composition.
- the culture medium contains various proteins secreted by stem cells, cytokines, growth factors, etc., but also contains components such as waste products secreted as cells grow, antibiotics added to prevent contamination, and animal-derived serum. If used on the skin, it is likely to be exposed to various risks.
- the technique of encapsulating the culture medium with liposomes composed of lipids to increase the skin absorption rate of the stem cell culture medium also has limitations on the culture components to be used as cosmetics, and deterioration and contamination of the culture components during the inclusion process with liposomes, and the inclusion of liposomes. Processing is necessary.
- Stem cells are generally cultured in a medium containing antibiotics and serum.
- Bionanoparticles secreted from various cells in multicellular organisms, including humans, can be classified into exosomes and microvesicles according to differences in size and secretion mechanism.
- Exosomes are membrane vesicles secreted from different types of cells and are known to play a variety of roles, including binding to other cells and tissues to deliver membrane components, proteins, and RNA.
- Secretomes are obtained from cell culture supernatants.
- Stem cell-derived exosomes are currently used to extract cell secretions containing exosomes. There is a problem that complete purification is difficult due to interference by proteins in serum.
- the present inventors extracted the exosomes from the stem cells, and confirmed the stem cell differentiation, adipose tissue regeneration, whitening effect, wrinkle improvement effect, skin regeneration effect of the extracted exosomes to complete the present invention.
- Patent Document 1 Korean Registered Patent No. 1347190
- Patent Document 2 Korean Registered Patent No. 1237430
- Patent Document 3 Korean Registered Patent No. 1047873
- Patent Document 4 Korean Registered Patent No. 1413686
- Patent Document 5 Korean Registered Patent No. 1108847
- An object of the present invention is to provide a composition for inducing adipocyte differentiation or adipose tissue regeneration comprising exosomes extracted from stem cells that are differentiated into adipocytes as an active ingredient.
- Another object of the present invention is to provide a cosmetic composition
- a cosmetic composition comprising a composition for inducing adipocyte differentiation or regenerating adipose tissue containing an exosome extracted from stem cells differentiated into adipocytes as an active ingredient.
- Still another object of the present invention is to provide an adipocyte differentiation induction or adipose tissue regeneration medium composition containing exosomes extracted from stem cells differentiated into adipocytes as an active ingredient.
- Still another object of the present invention is to provide an injection including a composition for inducing adipocyte differentiation or adipose tissue regeneration and a hydrogel containing an exosome extracted from stem cells differentiated into adipocytes as an active ingredient.
- Still another object of the present invention is to provide a cosmetic composition for skin whitening, wrinkle improvement or regeneration containing exosomes extracted from stem cells as an active ingredient.
- One embodiment of the present invention provides a composition for inducing adipocyte differentiation or regenerating adipose tissue containing exosomes extracted from stem cells differentiated into adipocytes as an active ingredient.
- stem cells that are differentiated into adipocytes refers to stem cells in which stem cells are differentiated into adipocytes from adipose tissue-derived stem cells (ASCs) as shown in FIG. 1. From this, exosomes containing genetic information, proteins, and growth factors of adipocytes can be extracted.
- ASCs adipose tissue-derived stem cells
- the shape is significantly changed, wherein the exosomes are extracted. Therefore, it can be said that it is different from extracting exosomes from normal stem cells.
- exosome is a vesicle of membrane structure secreted from various types of cells, and is known to play various roles such as binding to other cells and tissues to deliver membrane components, proteins, RNA, etc. have.
- exosomes can be prepared using exosome extraction methods known in the art, for example
- 4) may be prepared by the step of separating and purifying the exosome, but is not limited thereto.
- Stem cells that are differentiated into adipocytes may be bone marrow stem cells, umbilical cord blood stem cells or fat-derived stem cells, but may be stem cells derived from a human body or animal-derived stem cells, but are not limited thereto.
- the exosome is 1 to 150 ⁇ g, specifically 5 to 150 ⁇ g, more specifically 10 to 150 ⁇ g, more specifically 20 to 130 ⁇ g, more specifically 20 to 1 mL of the composition for inducing adipocyte differentiation or adipose tissue regeneration.
- Stem cells may be treated at a concentration of 100 ⁇ g, but are not limited thereto.
- induced adipocyte differentiation refers to inducing stem cells to differentiate into adipocytes.
- compositions containing exosomes extracted from stem cells differentiated from adipocytes according to one embodiment of the present invention as an active ingredient can differentiate the stem cells into adipocytes. Therefore, the composition can be used as a composition for inducing adipocyte differentiation.
- fat tissue regeneration refers to regeneration of adipose tissue by restoring damaged adipose tissue or by inducing the production of scarce adipose tissue.
- composition containing the exosomes extracted from the stem cells being differentiated into adipocytes according to an embodiment of the present invention as an active ingredient can regenerate adipose tissue. Therefore, the composition can be used as a composition for adipose tissue regeneration.
- composition for inducing adipocyte differentiation or adipose tissue regeneration may be used as a pharmaceutical composition.
- the pharmaceutical composition may include 0.001 to 10 parts by weight based on 100 parts by weight of the total composition.
- the pharmaceutical composition according to the above embodiment may be various oral or parenteral formulations.
- diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.
- Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin.
- lubricants such as magnesium stearate, talc and the like are also used.
- Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin, may be included.
- Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
- the pharmaceutical composition according to the above embodiment may be used as a non-aqueous solvent, a suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like.
- a suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like.
- injectable ester such as ethyl oleate, and the like.
- witepsol macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
- the dosage forms of the pharmaceutical compositions according to the above embodiments may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds as well as in a suitable collection.
- the salt is not particularly limited as long as it is pharmaceutically acceptable.
- hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, maleic acid, succinic acid, methanesulfonic acid , Benzene sulfonic acid, toluene sulfonic acid, naphthalene sulfonic acid and the like can be used.
- the pharmaceutical composition according to the above embodiment may be parenterally or orally administered as desired, and may be administered in one to several times so as to be administered in an amount of 0.1 to 500 mg and 1 to 100 mg per kg of body weight per day. Can be.
- the dosage for a particular patient may vary depending on the patient's weight, age, sex, health condition, diet, time of administration, method of administration, rate of excretion, severity of the disease, and the like.
- compositions according to the above embodiments may be powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral dosage forms, ointments, creams, external preparations, suppositories, and sterile injectable solutions, etc., according to conventional methods. It may be used in formulated in any form suitable for pharmaceutical formulations.
- the pharmaceutical composition according to the above embodiment may be administered to mammals such as rats, mice, livestock, humans by various routes such as parenteral, oral, and all modes of administration may be expected, but preferably oral, rectal Or by intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
- the pharmaceutical composition for inducing adipocyte differentiation or regenerating adipose tissue is used to differentiate stem cells into adipocytes (insulin), dexamethasone (dexamethasone), dehydroepiandrosterone (DHEA), histamine and iso It may further include a differentiation-inducing substance such as butylmethylxanthine (isobutylmethylxanthine), but is not limited thereto.
- another embodiment of the present invention provides a cosmetic composition for inducing adipocyte differentiation or regenerating adipose tissue containing exosomes extracted from stem cells differentiated into adipocytes as an active ingredient.
- the cosmetic composition may induce adipocyte differentiation and promote adipose tissue regeneration.
- the exosomes are contained in the cosmetic composition at a concentration of 1 to 150 ⁇ g, specifically 5 to 150 ⁇ g, more specifically 10 to 150 ⁇ g, more specifically 20 to 130 ⁇ g, and more specifically 20 to 100 ⁇ g per mL of the cosmetic composition. It may include, but is not limited to.
- the cosmetic composition according to the above embodiment is a fatty substance, an organic solvent, a dissolving agent, a thickening agent, a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, water, an ionic type or a non- With ionic emulsifiers, fillers, metal ion sequestrants, chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or any other ingredients commonly used in cosmetics It may contain adjuvants commonly used in the same cosmetic or dermatology field. Such adjuvants are introduced in amounts generally used in the cosmetic or dermatological arts.
- the appearance of the cosmetic composition according to the above embodiment contains a cosmetically or dermatologically acceptable medium or base.
- a cosmetically or dermatologically acceptable medium or base for example, emulsions, suspensions, microemulsions, microcapsules, microgranules or ionic (liposomes) obtained by dispersing the oil phase in solutions, gels, solids, pasty anhydrous products, aqueous phases, and It may be provided in the form of a nonionic vesicle dispersant and these compositions may be prepared according to conventional methods in the art.
- Cosmetic composition according to the embodiment is preferably applied in the form of being absorbed into the skin using a microneedle, etc., but is not limited thereto.
- a cosmetic composition for adipocyte differentiation or adipose tissue regeneration comprising exosomes extracted from stem cells differentiated into adipocytes as an active ingredient, insulin (dexulin), dexamethasone (dexamethasone) to differentiate stem cells into adipocytes
- insulin dihydroepiandrosterone (dehydroepiandrosterone, DHEA)
- dexamethasone dexamethasone
- DHEA dehydroepiandrosterone
- histamine histamine
- isobutylmethylxanthine isobutylmethylxanthine
- a stem cell differentiation medium composition containing exosomes extracted from stem cells that are differentiated into adipocytes according to another embodiment of the present invention as an active ingredient, inducing stem cells to differentiate into adipocytes.
- the exosome is 1 to 150 ⁇ g, specifically 5 to 150 ⁇ g, more specifically 10 to 150 ⁇ g, more specifically 20 to 130 ⁇ g, more specifically 20 to 100 ⁇ g per 1 mL of the stem cell differentiation medium composition As may be included in the stem cell differentiation medium composition, but is not limited thereto.
- the stem cell differentiation medium composition may further include a stem cell culture medium, but is not necessarily limited thereto.
- the medium composition for stem cell differentiation is used to differentiate stem cells into adipocytes. It may further include a differentiation-inducing substance such as, but is not limited thereto.
- Another embodiment of the present invention is a composition for inducing adipocyte differentiation or adipocyte regeneration comprising exosomes extracted from stem cells differentiated into adipocytes as an active ingredient; And it provides an injection comprising a hydrogel.
- the exosomes may be included in the injection at a concentration of 1 to 150 ⁇ g, specifically 5 to 150 ⁇ g, more specifically 10 to 150 ⁇ g, more specifically 20 to 130 ⁇ g, and more specifically 20 to 100 ⁇ g per mL of the injection.
- the present invention is not limited thereto.
- the hydrogel may be one or more hydrogels such as gelatin, alginate, chitosan, fibrin, elastin, hyaluronic acid, collagen, methylcellulose, and may be collagen and methylcellulose hydrogels, but are not limited thereto.
- hydrogels such as gelatin, alginate, chitosan, fibrin, elastin, hyaluronic acid, collagen, methylcellulose, and may be collagen and methylcellulose hydrogels, but are not limited thereto.
- the injection may be, but is not limited to, injection of adipose cell differentiation or adipose tissue regeneration. That is, when the injection of the present invention is administered by the method of injecting the animal, it may be inducing adipocyte differentiation or adipose tissue regeneration effect.
- the hydrogel was prepared by adding methylcellulose powder to the collagen solution. Specifically, to the collagen solution dissolved in 0.02 N acetic acid at a concentration of 3 mg / mL, methylcellulose powder was added so that the final concentration of methylcellulose was 6% by weight, followed by stirring at 4 ° C for 1 hour. Collagen and methylcellulose hydrogels were prepared.
- the injection was prepared by supporting exosomes extracted from stem cells that are differentiated into adipocytes in collagen and methylcellulose hydrogel (collagen / methylcellulose hydrogel). Specifically, the exosomes extracted from the stem cells that are differentiated into adipocytes were loaded onto the hydrogel to have a final concentration of 50 ⁇ g / mL, and then dispersed in the hydrogel through pipetting.
- collagen and methylcellulose hydrogel collagen / methylcellulose hydrogel
- Injectables according to this embodiment may be administered by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection to mammals such as mice, mice, livestock, humans, and the like.
- the exosomes extracted from the stem cells differentiated into adipocytes according to the present invention is the expression rate of the bioactive factors affecting the differentiation into adipocytes Was excellent (FIGS. 4 and 5).
- exosomes extracted from stem cells differentiated into adipocytes according to the present invention are added.
- the adipocytes were differentiated to a level similar to that of the stem cells cultured in the differentiation medium at 7 days and thus oil was produced.
- the stem cells treated with the exosomes extracted from the proliferating stem cells did not differentiate into adipocytes but only proliferated (FIGS. 6 and 7).
- the exosomes extracted from stem cells differentiated into adipocytes according to the present invention on collagen / methylcellulose hydrogels are injected with exosomes extracted from proliferating stem cells. Adipose tissue regeneration effect was superior to that of injections (FIGS. 9 and 10).
- the composition for stem cell differentiation and adipose tissue regeneration includes exosomes containing genetic information, proteins, and growth factors of adipocytes related to the differentiation of adipocytes. Because of this, there is no need to add a complex and various growth factors for differentiation, so it is possible to effectively apply to stem cell differentiation.
- Stem cells are differentiated into adipocytes by exosomes extracted from stem cells differentiated into adipocytes of the present invention, and when applied in vivo, a beneficial effect on regeneration of adipose tissue is exerted.
- Exosomes extracted from stem cells that are differentiated into adipocytes of the present invention can be biocompatible as a cell-derived material to minimize the side effects of existing cell therapy, and the exosomes themselves can act as a carrier, so Because it can be easily applied to the human body, it can be applied as a stem cell differentiation inducing agent, injection for tissue regeneration, filler for cosmetic purposes, formulation for tissue engineering and the like.
- Another embodiment of the present invention is a cosmetic composition containing an exosome extracted from stem cells as an active ingredient, more specifically, a cosmetic composition for skin whitening, wrinkle improvement or regeneration containing exosomes extracted from stem cells as an active ingredient To provide.
- the exosomes extracted from the serum-free, antibiotic-free medium from stem cells contain extracellular matrix derivatives including collagen and growth factors effective for skin regeneration, which can be effectively applied to skin improvement.
- stem cells means stem cells that proliferate. From this, exosomes containing the genetic information, proteins, and growth factors of stem cells can be extracted.
- the stem cells may be bone marrow stem cells, umbilical cord blood stem cells or adipose derived stem cells, may be stem cells derived from the human body or animal or plant, for example, but may not be limited to human adipose derived stem cells.
- human adipose derived stem cells refers to stem cells derived from human adipose-derived stem cells. From this, exosomes containing genetic information, proteins, and growth factors of adipocytes can be extracted.
- the method for extracting the exosomes may be a method known in the art, but is not limited thereto.
- the exosomes were extracted during passage of human fat-derived stem cells. Specifically, the human adipose derived stem cells (passage 3 ⁇ 7) incubated in a general culture medium (Dulbecco Modified Eagle Medium, DMEM containing 10% fetal bovine serum, 1% penicillin / streptomycin), and then 24 hours to extract the exo Previously, serum-free, antibiotic-free medium and phenol red-free DMEM medium were replaced for 24 hours. After 24 hours, cell culture supernatants were recovered.
- DMEM Dulbecco Modified Eagle Medium
- the recovered cell culture supernatant was centrifuged at 300 xg for 10 minutes to remove cells, and then centrifuged at 2,000 xg for 30 minutes to remove cell secretions. Thereafter, the mixture was concentrated by centrifugation at 5,000 ⁇ g for 60 minutes using a centrifuge tube equipped with a filter having a molecular weight of 3,000.
- the supernatant obtained after concentration was mixed with exosome separation reagent in a ratio of 1: 0.5 and stored at 4 ° C. for one day.
- the exosome precipitate was obtained by centrifugation at 10,000 ⁇ g for 60 minutes, filtered through a 0.22 ⁇ m filter, and washed with phosphate-buffered saline (PBS).
- PBS phosphate-buffered saline
- the exosome is 1 to 150 ⁇ g, specifically 5 to 150 ⁇ g, more specifically 10 to 150 ⁇ g, more specifically 20 to 130 ⁇ g, more specifically 20 to 100 per 1 mL of the cosmetic composition for skin whitening, wrinkle improvement or regeneration It may be contained at a concentration of ⁇ g, but is not limited thereto.
- the wound recovery of human skin fibroblasts is excellent (Fig. 18), collagen Synthesis rate was excellent (Fig. 19), melanin synthesis was confirmed to decrease (Fig. 20).
- exosomes may be contained in the cosmetic composition in the form of liposomes in which the exosomes are enclosed in liposomes, but is not limited thereto and may be in any form suitable for use as a cosmetic composition, exosomes are not contained in liposomes It is possible to use itself.
- the exosome When the exosome is used in the form of a liposome encapsulated with an exosome, the exosome may be contained in an amount of 0.1 to 10.0% by weight based on the total weight of the liposome, and more specifically 0.1 to 1.0% by weight, but is not limited thereto.
- the liposome encapsulated with the exosome may be contained in an amount of 0.001 to 10.0% by weight, specifically, 0.001 to 1.0% by weight, and more specifically 0.01 to 1.0% by weight, based on the total weight of the total cosmetic composition. It may be contained, more specifically 0.01 to 0.1% by weight, but is not limited thereto.
- the present invention after dispersing 3% by weight of lecithin in an aqueous phase containing 0.01% by weight of exosomes extracted from stem cells at room temperature (15 °C), reverse micelle using supercritical carbon dioxide An emulsion (hydroxyl / cold carbon dioxide) was formed. Then, the reaction was stopped and the supercritical carbon dioxide was evaporated under reduced pressure to remove the supercritical carbon dioxide phase, thereby obtaining a low temperature liposome suspension containing exosomes.
- the cosmetic composition was prepared by containing 5% by weight of the liposome encapsulated with the exosome thus prepared based on the total weight of the cosmetic composition.
- Exosome according to the embodiment is similar to the conventional techniques in that the culture medium obtained during the culturing process of human adipose derived stem cells, but extracts the exosomes of the nanovesicle form present in the culture medium without using the culture medium as it is It is different in that it is used as a cosmetic after purification.
- stem cell exosomes only regeneration-related proteins, collagen derivatives and various growth factors supported on exosomes can be effectively used, thereby solving problems caused by media components including antibiotics and serum.
- Exosome according to the embodiment is not only carried the genetic information, protein, growth factor of the stem cell, the exosomes themselves may serve as a carrier.
- Exosomes consisting of lipids of about 50-150 nm in size are biocompatible because they are cell-derived materials, and the uptake of cells is also very good. Therefore, there is no need for a separate process of encapsulating the culture solution in liposomes as in the prior art, and there is an advantage that it can be easily applied to the skin.
- the cosmetic composition containing the exosomes extracted from the stem cells can be used as a scar improvement agent.
- Stem cell-derived exosomes contain proteins and growth factors that induce cell proliferation, differentiation, and skin regeneration, which can be applied to old wounds and acne scars to relieve scarring. Therefore, when used as a scar improvement agent, it is possible to apply in the form of a spray, gel-type ointment, patch, etc. containing exosomes extracted from stem cells.
- another embodiment of the present invention provides a pharmaceutical composition containing exosomes extracted from stem cells as an active ingredient, more specifically, a pharmaceutical composition for skin regeneration containing exosomes extracted from stem cells as an active ingredient. do. Therefore, the cosmetic composition for skin regeneration containing exosomes extracted from stem cells according to one embodiment of the present invention as an active ingredient may also be used as a pharmaceutical composition.
- the stem cells may be bone marrow stem cells, umbilical cord blood stem cells or adipose derived stem cells, may be stem cells derived from the human body or animal or plant, for example, but may not be limited to human adipose derived stem cells.
- the size of the exosomes is about 69nm exo extracted from human skin keratinocytes Smaller than human forderkin fibroblasts (F-EXO) extracted from human epidermal keratinocytes (K-EXO) or human skin fibroblasts (FIG. 13).
- Stem-EXO promotes and degrades collagen synthesis.
- MCP-1, -3 Monocyte chemoattractant protein
- CCL-5 chemokine ligand 5
- TRIP-1 collagenase inhibitors associated with mechanisms that inhibit inhibitor of metalloproteinase-1
- IGF interleukin-6, -8 (whitening) related to whitening
- HGF hepatocyte growth factor
- PAI-1 minogen activator inhibitor-1
- angiogenin angiogenin
- angiopoietin-1 were overexpressed compared to K-EXO and F-EXO (FIGS. 15 to 17).
- Stem-EXO is treated with K-EXO or when treated at a concentration of 10, 30, 50 ⁇ g / mL Compared with F-EXO, it was confirmed that the transfer effect of dermal fibroblasts was excellent and the wound healing effect was excellent (FIG. 18).
- Exosome according to an embodiment of the present invention has an excellent expression rate of the bioactive factors affecting the differentiation into adipocytes compared to the exosomes extracted from the proliferating stem cells and has the effect of differentiating stem cells into adipocytes. Accordingly, the present invention can be applied to stem cell differentiation inducing agent, injection for tissue regeneration, filler for cosmetic purposes, preparation for tissue engineering and the like.
- the exosome according to an embodiment of the present invention is an exosome secreted during the proliferation of stem cells, and contains a gene, protein, growth factor, etc. associated with cell proliferation, differentiation and regeneration of stem cells. It can also induce skin regeneration without other additives such as growth factors.
- the present invention can be applied to functional cosmetic compositions including skin whitening, wrinkle improvement or regeneration, scar improvement agents for cosmetic purposes, and the like.
- 1 is a schematic diagram of exosomes extracted from stem cells differentiated into adipocytes and their applications.
- FIG. 2 is a schematic diagram of a method for extracting exosomes from stem cells that are differentiated into adipocytes.
- Figure 3 is a diagram of the characteristics of exosomes from stem cells differentiated into extracted adipocytes; A: structure and shape of exosomes (transmission electron microscope), B: size of exosomes (nanoparticle analyzer, dynamic light scattering), C: exosome membrane surface marker (western blot).
- Figure 4 is a diagram showing the fat-associated bioactive factors in exosomes through microarrays; A: exosomes (hASC-EXO) extracted from proliferating stem cells, B: exosomes (D-EXO) extracted from stem cells differentiated into adipocytes, C: adipocaine array map .
- Exosomes extracted from proliferating stem cells hASC-EXO
- exosomes extracted from stem cells differentiated into adipocytes D-EXO
- Figure 6 is the result of inducing differentiation of human adipose derived stem cells into adipocytes;
- A human adipose derived stem cells (hASCs)
- B positive control group (DM), exosomes extracted from stem cells differentiated into adipocytes (D-EXO), exosomes extracted from proliferating stem cells (hASC- EXO).
- A human adipose derived stem cells (hASCs)
- B positive control group (DM)
- exosomes extracted from stem cells differentiated into adipocytes D-EXO
- exosomes extracted from proliferating stem cells hASC- EXO
- A Collagen / methylcellulose hydrogel (Gel)
- B Hydrogel carrying exosomes (hASC-EXO) extracted from proliferating stem cells
- C Exosomes extracted from stem cells differentiated into adipocytes ( Hydrogel carrying D-EXO).
- h-ASC-EXO exosome extracted from the proliferating stem cells
- D-EXO exosome extracted from stem cells that are differentiated into adipocytes in the subcutaneous gel of nude mice Hematoxylin-eosin staining; A, C, E: 40 magnification; B, D, F: 100 magnifications.
- hASC-EXO subcutaneous injection of a mouse and exosomes extracted from proliferating stem cells and a exosomes (D-EXO) extracted from stem cells differentiated into adipocytes
- D-EXO exosomes
- Figure 11 is a schematic diagram of a method for extracting exosomes from the proliferating human adipose derived stem cells.
- FIG. 12 is a microscopic image of human adipose-derived stem cells, human epidermal keratinocytes, and human foreskin fibroblasts.
- Figure 13 is a diagram of the characteristics of exosomes extracted from human adipose derived stem cells (Stem-Exo). Exosomes extracted from human skin keratinocytes (K-Exo) and human skin fibroblasts (F-Exo) were used as controls.
- the structure and shape of the exosomes (transmission electron microscope) and the size of the exosomes (nanoparticle analyzer, dynamic light scattering) were respectively shown; A: Stem-Exo (Scale bars represent 50 nm (black) and 100 nm (white), respectively), B: K-Exo (Scale bars represent 50 nm (black) and 100 nm (white), respectively), And C: F-Exo (Scale bars represent 50 nm (black) and 200 nm (white), respectively).
- FIG. 14 shows exosomes (Stem-EXO) extracted from human adipose derived stem cells using microarrays, exosomes extracted from human keratinocytes (K-EXO), and exosomes extracted from human skin fibroblasts (F -EXO) is a diagram comparing the amount of expression of the bioactive factors contained in; A: microarray table, B: microarray results, C and D: graph showing relative expression levels of bioactive factors.
- FIG. 15 shows bioactive factors related to wrinkle improvement in exosomes using microarrays (A: PDGF-AA, B: PDGF-AB, C: PDGF-BB, D: FGF-6, E: MCP-1, F: MCP-3, G: Eotaxin, H: CCL-5, I: TIMP-1).
- Stem-EXO exosomes extracted from proliferating human adipose derived stem cells
- K-EXO exosomes extracted from human skin keratinocytes
- F-EXO exosomes extracted from human skin fibroblasts.
- FIG. 16 is a diagram showing the expression level of the whitening-related bioactive factors (A: TGF-beta, B: TNF-alpha, C: IL-6, D: IL-8) in exosomes using a microarray; Stem-EXO: exosomes extracted from proliferating human adipose derived stem cells, K-EXO: exosomes extracted from human skin keratinocytes, F-EXO: exosomes extracted from human skin fibroblasts.
- A TGF-beta
- B TNF-alpha
- C IL-6
- D IL-8
- Stem-EXO exosomes extracted from proliferating human adipose derived stem cells
- K-EXO exosomes extracted from human skin keratinocytes
- F-EXO exosomes extracted from human skin fibroblasts.
- FIG. 17 shows bioactivators related to skin regeneration and microvascular formation in exosomes using microarrays (A: EGF, B: HGF, C: PAI-1, D: VEGF, E: Angiogenin, F: Angiopoietin-1) It is a figure which shows the expression amount of; Stem-EXO: exosomes extracted from proliferating human adipose derived stem cells, K-EXO: exosomes extracted from human skin keratinocytes, F-EXO: exosomes extracted from human skin fibroblasts.
- FIG. 18 is a diagram showing the effect of human adipose derived stem cell exosomes (Stem-EXO) on the movement of human fibroblasts; GM: stem cell growth medium, SFM: serum-free medium, Stem-EXO: exosomes extracted from proliferating human adipose derived stem cells, K-EXO: from human keratinocytes Extracted exosomes, F-EXO: Exosomes extracted from human dermal fibroblasts.
- stem-EXO human adipose derived stem cell exosomes
- FIG. 19 is a diagram showing the effect of human adipose derived stem cell exosomes (Stem-EXO) on the collagen synthesis of human fibroblasts; SFM: serum-free medium, Stem-EXO: exosomes extracted from proliferating human adipose derived stem cells, K-EXO: exosomes extracted from human skin keratinocytes, F-EXO: human skin Exosomes extracted from fibroblasts.
- SFM serum-free medium
- Stem-EXO exosomes extracted from proliferating human adipose derived stem cells
- K-EXO exosomes extracted from human skin keratinocytes
- F-EXO human skin Exosomes extracted from fibroblasts.
- FIG. 20 is a diagram showing the effect of human adipose derived stem cell exosomes (Stem-EXO) on the melanin synthesis of mouse melanocyte (melanocyte) cells; GM: stem cell growth medium, SFM: serum-free medium, Stem-EXO: exosomes extracted from proliferating human adipose derived stem cells, K-EXO: from human keratinocytes Extracted exosomes, F-EXO: Exosomes extracted from human dermal fibroblasts.
- stem-EXO human adipose derived stem cell exosomes
- differentiation was induced into adipocytes by culturing stem cells in differentiation medium. Differentiation into adipocytes resulted in the formation of lipid droplets in the cytoplasm as the stem cells gradually enlarged.
- the differentiated stem cells were replaced with serum-free medium and maintained for 48 hours, after which the cell culture supernatants were recovered.
- the recovered cell culture supernatant was centrifuged at 300 xg for 10 minutes to remove cells and centrifuged at 2,000 xg for 30 minutes to remove cell secretions.
- Exosomes extracted from Example 1-1 were checked for size and shape using a transmission electron microscope and dynamic light scattering, and Western blots were used to detect specific proteins. The surface protein of the exosomes was confirmed.
- the extracted exosomes as shown in Figure 3A could be confirmed by transmission electron microscope, the size was confirmed that the average of about 50.75-58.77 nm from Figure 3B.
- exosome-specific markers expressed on the surface of the exosomes as shown in Figure 3C was confirmed through the antibody reaction.
- Microarrays were used to analyze exosomes extracted from stem cells differentiated into adipocytes and fat related bioactive factors present in exosomes extracted from proliferating stem cells. Microarrays were performed through antigen-antibody reactions, and fluorescence (Streptavidin-Cy3) expression was measured by a laser scanner (GenePix 4000B).
- MCSF macrophage colony stimulating factor
- TNF- tumor necrosis factor- ⁇
- ⁇ leptin
- insulin angiopoietin1
- ANGPT1 angiopoietin1
- Adrp30 adipocyte complement-related protein of 30 kDa
- exosomes (hASC-EXO) extracted from stem cells proliferating as shown in Figures 4A to 4C and Table 1 and fats present in exosomes (D-EXO) extracted from stem cells differentiated into adipocytes It was confirmed that there is a difference in the type of related bioactive factors, it was confirmed that there is a significant difference in the expression rate of the bioactive factors affecting the differentiation into adipocytes (Fig. 5).
- a medium composition comprising each of exosomes extracted from proliferating stem cell culture medium and exosomes extracted from stem cells differentiated into adipocytes was used. .
- the medium composition was used in addition to the exosome 30, 50, 100 ⁇ g / mL concentration to the stem cell culture medium.
- the culture medium composition was replaced every 14 days for 3 days.
- Positive controls were 5% fetal bovine serum, 1 ⁇ M dexamethasone, 1 ⁇ g / mL insulin, 100 ⁇ M indomethacin, 0.5 mM 3-isobutyl-1-methylxanthine
- DMEM high glucose (Dulbecco's Modified Eagle's Medium high glucose) medium containing 3-isobutyl-1-methylxanthine were used.
- the positive control group used stem cells treated with exosomes extracted from proliferating stem cells. Then, for 14 days, the stem cells induced differentiation into adipocytes were analyzed for cell morphology and differentiation using a microscope and Oil-red O staining.
- adipocytes were differentiated to levels similar to those of human adipose-derived stem cells on day 7 (FIG. 6), thereby producing oil. It could be confirmed that (Fig. 7). However, it was confirmed that stem cells treated with exosomes (hASC-EXO) extracted from proliferating stem cells only proliferated without being differentiated into adipocytes.
- liposomes containing exosomes extracted from stem cells differentiated into adipocytes were prepared. Specifically, 3% by weight of lecithin at room temperature (15 ° C) is dispersed in an aqueous phase containing 0.01% by weight of exosomes extracted from stem cells differentiated into adipocytes, and then reverse micelle using supercritical carbon dioxide. ) Emulsion (water phase / cold carbon dioxide) was formed. Then, the reaction was stopped and the supercritical carbon dioxide was evaporated under reduced pressure to remove the supercritical carbon dioxide phase, and a low temperature process liposome suspension containing exosomes extracted from stem cells differentiated into adipocytes was obtained. At this time, the temperature of the reaction process proceeded to 4 °C or less.
- the cosmetic composition was prepared using the composition shown in Table 2 below using the liposome encapsulated in the exosome.
- exosomes extracted from proliferating stem cells and exosomes extracted from stem cells differentiated into fat cells Were each supported on a collagen / methylcellulose hydrogel.
- the hydrogel was prepared by adding methyl cellulose powder to the collagen solution to prepare a collagen / methyl cellulose hydrogel. That is, to the collagen solution dissolved in 0.02 N acetic acid at a concentration of 3 mg / mL, methyl cellulose powder was added so that the final concentration of methyl cellulose was 6% by weight, and then stirred at 4 ° C. for 1 hour. Prepared. The exosomes extracted from stem cells differentiated into exosomes or adipocytes extracted from stem cells growing on collagen / methylcellulose hydrogel thus prepared were carried.
- the exosomes were loaded on the collagen / methylcellulose hydrogel so as to have a final concentration of 50 ⁇ g / mL, and then dispersed in the hydrogel through pipetting.
- the hydrogel loaded with exosomes was injected subcutaneously in nude mice and observed for 3 weeks. Negative control group was used hydrogel (Gel) does not contain exo, positive control group was used hydrogel containing exosomes (hASC-EXO) extracted from the proliferating stem cells (Fig. 8). After 3 weeks, hematoxylin-eosin staining and oil red O staining were performed to check whether adipose tissue was regenerated in the implanted hydrogel.
- Exosome was extracted in the process of propagating human fat-derived stem cells to passage 7. That is, exosomes were extracted from proliferating human adipose derived stem cells.
- human adipose derived stem cells (passage 3 ⁇ 7) was cultured in a general culture medium (Dulbecco Modified Eagle Medium, DMEM containing 10% fetal bovine serum, 1% penicillin / streptomycin). Then, 24 hours before the exosomes were extracted and replaced with DMEM medium without phenol red (serum-free, antibiotic-free medium) and maintained for 24 hours. After 24 hours, cell culture supernatants were recovered. The recovered cell culture supernatant was centrifuged at 300 xg for 10 minutes to remove cells, and then centrifuged at 2,000 xg for 30 minutes to remove cell secretions.
- DMEM Dulbecco Modified Eagle Medium
- Exosome extracted in the process of proliferating stem cells up to passage 7 was used in the following experiment. Derived from human fat In order to compare the efficacy of stem cell exosomes, exosomes were similarly extracted from human skin keratinocytes and human skin fibroblasts through the above method (FIG. 12).
- Exosome (Stem-Exo) extracted from human adipose derived stem cells of Example 2-1, exosomes (K-Exo) extracted from human skin keratinocytes and exosomes (F-Exo) extracted from human skin fibroblasts ) was checked for size and shape using a transmission electron microscope and dynamic light scattering.
- the shapes of the extracted exosomes were confirmed by transmission electron microscope.
- the size of the exosomes is about 69 nm exosomes extracted from human adipose derived stem cells, about 79.7 nm exosomes extracted from human skin keratinocytes, about 94.6 nm exosomes extracted from human skin fibroblasts With the size, it was confirmed that the size of the human adipose derived stem cell exosomes (Stem-Exo) is the smallest (FIGS. 13A to 13C).
- 14C and 14D graphs show the relative expression levels of the bioactive factors
- the horizontal axis indicates human adipose derived stem cell exosomes
- the vertical axis indicates skin keratinocytes and fibroblast exosomes, respectively.
- the upper line and the lower line centered on the middle line of the graph represent 1.5 times increase / decrease.
- 15A to 15I show bioactive factors related to the anti-wrinkle effect in exosomes
- FIG. 16A to 16D show bioactive factors related to the whitening effect in exosomes
- FIGS. 17A to 17F show skin regeneration in exosomes and The microvascular generation related bioactive factors are shown.
- exosomes Stem-EXO
- K-EXO exosomes extracted from human skin keratinocytes
- F-EXO exosomes extracted from human skin fibroblasts
- exosomes (Stem-EXO) extracted from human adipose derived stem cells are monocyte chemoattractant protein-1, -3 (MCP-1) related to mechanisms that promote collagen synthesis and inhibit degradation.
- chemokine ligand 5 CCL-5
- TGF tissue inhibitor of metalloproteinase-1
- IL interleukin
- HGF hepatocyte growth factor
- PAI-1 plasminogen activator inhibitor-1
- angiogenin angiopoy related to skin regeneration and angiogenesis
- proliferating human fat A medium composition comprising exosomes (Stem-EXO) extracted from stem cell culture medium, exosomes (K-EXO) extracted from human skin keratinocytes and exosomes (F-EXO) extracted from human skin fibroblasts, respectively.
- stem-EXO exosomes extracted from stem cell culture medium
- K-EXO exosomes extracted from human skin keratinocytes
- exosomes F-EXO
- DMEM medium containing 10% serum was used as a positive control, and DMEM serum-free medium was used as a negative control.
- Human dermal fibroblasts were labeled with green fluorescence dye, and then dispensed into 24 well plates at 1 ⁇ 10 5 cells / well and culture medium (DMEM containing 10% fetal bovine serum, 1% penicillin / streptomycin). Incubated for 72 hours at. After incubation, the center of the plate bottom to which cells were attached was made artificially at regular intervals by using a sterile pipette tip, and the medium composition containing exosomes was treated to each cell. .
- exosomes extracted from stem cells To investigate the effect of exosomes extracted from stem cells on collagen synthesis of human dermal fibroblasts, exosomes (Stem-EXO) extracted from proliferating stem cell culture medium, exosomes extracted from human skin keratinocytes ( K-EXO) or a medium composition containing exosomes (F-EXO) extracted from human dermal fibroblasts, respectively.
- Stem-EXO was added to the DMEM serum-free culture medium at 10, 30, and 50 ⁇ g / mL concentration, and K-EXO and F-EXO were added to the DMEM serum-free culture medium at 50 ⁇ g / mL concentration.
- DMEM serum-free medium was used as a negative control.
- Human dermal fibroblasts were dispensed in 48 well plates at 5 ⁇ 10 4 cells / well, and cultured in culture medium (DMEM containing 10% fetal bovine serum, 1% penicillin / streptomycin) for 72 hours, followed by phosphate buffered saline. Was washed and the medium composition containing the exosomes was treated to each cell.
- culture medium DMEM containing 10% fetal bovine serum, 1% penicillin / streptomycin
- the culture solution of each well was recovered and centrifuged at 25 ° C. and 3000 rpm for 10 minutes, and then the supernatant was taken and used for extraction and quantification of soluble collagen.
- PBS was added to each well of the plate from which the culture solution was removed and washed, and then cells were separated from the bottom by trypsin (tyrpsin-EDTA) and the number of cells was measured.
- Sircol collagen assay kit Biocolor, UK was used for quantification of soluble collagen.
- the obtained supernatant was treated with polyethylene glycol-mixed Tris-HCl (pH 7.6) buffer and maintained at 4 ° C. for at least 12 hours. Then, the collagen was concentrated by centrifugation at 12,000 rpm for 10 minutes. After removing the supernatant, 1 mL of the collagen adsorbed dye (sircol dye reagent) was added to the collagen pellet and shaken for 30 minutes.
- the pellet was washed with acid-salt buffer, and treated with alkali reagent to dissolve the dye adsorbed to collagen and the absorbance was measured at a wavelength of 555 nm.
- the amount of water-soluble collagen in the wells to which Stem-EXO, K-EXO, F-EXO and negative control were added was calculated by substituting absorbance into the formula of the standard curve. Synthesis rate was calculated by substituting the corrected amount of collagen into the equation.
- the water-soluble collagen synthesis rate of the Stem-EXO group was increased depending on the exosome concentration compared to the negative control group (0.138 ⁇ g), especially in the 50m / mL Stem-EXO group, 2.59 ⁇ g
- the same amount of K-EXO (1.4 ⁇ g) or F-EXO (0.8 ⁇ g) was significantly increased.
- exosomes extracted from human adipose derived stem cells are judged to have an effect of promoting collagen synthesis of skin fibroblasts (FIG. 19).
- Melanoma cells were seeded in 1 ⁇ 10 5 concentrations in 96 well plates and attached to the cells, followed by incubation for 3 days by replacing with medium containing Stem-EXO, K-EXO, F-EXO. After 3 days, the medium was recovered, centrifuged at 4,500 rpm for 10 minutes, and the absorbance was measured at 405 nm to calculate the amount of melanin released out of the cells. Cells attached to the plate were removed by trypsin-EDTA treatment, and then the number of cells was measured and centrifuged to recover the cells. The cells were washed once with PBS and centrifuged to obtain cell pellets.
- Exosomes extracted from human adipose derived stem cells were treated with the melanoma cells at concentrations of 10, 30, and 50 ⁇ g / mL, and the melanin synthesis was observed. Exosomes extracted from stem cells were melanin at all concentrations. It was confirmed that the synthesis was reduced (FIG. 20).
- a liposome encapsulated with an exosome extracted from human adipose derived stem cells proliferating according to Example 2-1 was prepared.
- the cosmetic composition was prepared using the composition shown in Table 3 below using the liposome encapsulated in the exosome.
- a liposome encapsulated with the exosomes extracted from the proliferating stem cells obtained by the method of Example 2-7 to prepare a nutrient lotion (lotion) with a composition as shown in Table 5.
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Abstract
Description
배합성분 | 함량 ( 중량% ) |
스테아린산 | 2 |
세틸알코올 | 2 |
라놀린 알코올 | 2 |
액상파라핀 | 7 |
사이클로메치콘 | 5 |
폴리옥시에틸렌 모노올레익산 에스테르 | 2 |
헥산디올 | 2 |
글리세린 | 3 |
트리에틸아민 | 5 |
카보머 | 0.2 |
본 발명의 실시예1-1에 따른 엑소좀이 포접된 리포좀 | 0.01 |
정제수 | to 100 |
배합성분 | 함량 ( 중량% ) |
스테아린산 | 2 |
세틸알코올 | 2 |
라놀린 알코올 | 2 |
액상파라핀 | 7 |
사이클로메치콘 | 5 |
폴리옥시에틸렌 모노올레익산 에스테르 | 2 |
헥산디올 | 2 |
글리세린 | 3 |
트리에틸아민 | 5 |
카보머 | 0.2 |
본 발명의 실시예2-1에 따른 엑소좀이 포접된 리포좀 | 0.01 |
정제수 | to 100 |
배합성분 | 함량 ( 중량% ) |
본 발명의 실시예2-1에 따른 엑소좀이 포접된 리포좀 | 0.01 |
에탄올 | 10 |
글리세린 | 3 |
부틸렌글리콜 | 3 |
소듐 히알루로네이트 | 0.1 |
트리에탄올아민 | 0.1 |
항산화제 | 0.1 |
방부제, 향, 색소 | 0.1 |
정제수 | to 100 |
배합성분 | 함량 ( 중량% ) |
본 발명의 실시예2-1에 따른 엑소좀이 포접된 리포좀 | 0.01 |
글리세린 | 5 |
미네랄오일 | 4 |
밀납 | 4 |
폴리솔베이트-60 | 1.5 |
카르복시비닐폴리머 | 0.1 |
부틸렌글리콜 | 3 |
스쿠알란 | 5 |
트리에탄올아민 | 0.15 |
방부제, 향, 색소 | 0.1 |
정제수 | to 100 |
Claims (12)
- 지방세포로 분화되고 있는 줄기세포로부터 추출된 엑소좀을 유효성분으로 함유하는 지방세포 분화 유도 또는 지방조직 재생용 조성물.
- 제 1항에 있어서, 상기 지방세포로 분화되고 있는 줄기세포는 골수 줄기세포, 제대혈 줄기세포 또는 지방 유래 줄기세포인 지방세포 분화 유도 또는 지방조직 재생용 조성물.
- 제 2항에 있어서, 상기 골수 줄기세포, 제대혈 줄기세포 또는 지방 유래 줄기세포는 인체, 동물 또는 식물 유래 줄기세포인 지방세포 분화 유도 또는 지방조직 재생용 조성물.
- 제 1항에 있어서, 상기 엑소좀은 상기 지방세포 분화 유도 또는 지방조직 재생용 조성물 1mL 당 1 내지 150 μg의 농도로 줄기세포에 처리되는 것인 지방세포 분화 유도 또는 지방조직 재생용 조성물.
- 제 1항 내지 제 3항 중 어느 한 항에 따른 지방세포 분화 유도 또는 지방조직 재생용 조성물을 포함하는 화장료 조성물.
- 제 1항 내지 제 3항 중 어느 한 항에 따른 지방세포 분화 유도 또는 지방조직 재생용 조성물을 포함하는 지방세포 분화 유도용 배지 조성물.
- 제 1항 내지 제 3항 중 어느 한 항에 따른 지방세포 분화 유도 또는 지방조직 재생용 조성물; 및 하이드로젤;을 포함하는 주사제.
- 줄기세포로부터 추출된 엑소좀을 유효성분으로 함유하는 피부 미백, 주름개선 또는 재생용 화장료 조성물.
- 제 8항에 있어서, 상기 줄기세포는 골수 줄기세포, 제대혈 줄기세포 또는 지방 유래 줄기세포인 피부 미백, 주름개선 또는 재생용 화장료 조성물.
- 제 9항에 있어서, 상기 골수 줄기세포, 제대혈 줄기세포 또는 지방 유래 줄기세포는 인체, 동물 또는 식물 유래 줄기세포인 피부 미백, 주름개선 또는 재생용 화장료 조성물.
- 제 8항에 있어서, 상기 엑소좀은 피부 미백, 주름개선 또는 재생용 화장료 조성물 1mL 당 1 내지 150 μg의 농도로 함유되는 것인 피부 미백, 주름개선 또는 재생용 화장료 조성물.
- 제 8항에 있어서, 상기 화장료는 스킨로션, 스킨소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스쳐 로션, 영양로션, 마사지크림, 영양크림, 모이스처크림, 핸드크림, 파운데이션, 에센스, 영양에센스, 팩, 비누, 클렌징폼, 클렌징로션, 클렌징크림, 바디로션, 바디클렌저, 세안제, 트리트먼트, 미용액, 미용팩, 연고제, 겔제, 리니멘트제, 액제, 패치 및 분무제로 구성된 군으로부터 선택된 어느 하나의 제형인 것인 피부 미백, 주름개선 또는 재생용 화장료 조성물.
Priority Applications (13)
Application Number | Priority Date | Filing Date | Title |
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BR112017007892-9A BR112017007892A2 (ko) | 2014-11-07 | 2015-11-09 | Induced adipocyte-derived stem cells, some containing exo differentiation, local tissue regeneration, skin whitening or anti-wrinkle composition |
JP2017523534A JP6683700B2 (ja) | 2014-11-07 | 2015-11-09 | 幹細胞由来のエキソソームを含有する脂肪細胞分化誘導、または脂肪組織の再生用組成物の製造方法 |
CN202410228746.1A CN118161444A (zh) | 2014-11-07 | 2015-11-09 | 用于成脂分化诱导、脂肪组织再生、皮肤美白或改善皱纹的包含干细胞来源外泌体的组合物 |
CN202410228742.3A CN118161529A (zh) | 2014-11-07 | 2015-11-09 | 用于成脂分化诱导、脂肪组织再生、皮肤美白或改善皱纹的包含干细胞来源外泌体的组合物 |
EP15857147.1A EP3189828B1 (en) | 2014-11-07 | 2015-11-09 | Composition for differentiation induction of adipocyte containing stem cell-derived exosome, regeneration of adipose tissue, and skin whitening or wrinkle improvement |
CN202010527869.7A CN111773173B (zh) | 2014-11-07 | 2015-11-09 | 用于成脂分化诱导、脂肪组织再生、皮肤美白或改善皱纹的包含干细胞来源外泌体的组合物 |
CN201580060480.3A CN107106613B (zh) | 2014-11-07 | 2015-11-09 | 用于成脂分化诱导、脂肪组织再生、皮肤美白或改善皱纹的包含干细胞来源外泌体的组合物 |
EP18200218.8A EP3453382B1 (en) | 2014-11-07 | 2015-11-09 | Composition including stem cell-derived exosome for skin whitening or wrinkle improvement |
AU2015343845A AU2015343845B2 (en) | 2014-11-07 | 2015-11-09 | Composition for differentiation induction of adipocyte containing stem cell-derived exosome, regeneration of adipose tissue, and skin whitening or wrinkle improvement |
RU2017116138A RU2710373C2 (ru) | 2014-11-07 | 2015-11-09 | Композиция, включающая экзосому, полученную из стволовых клеток, для индукции адипогенной дифференцировки, регенерации жировой ткани, отбеливания кожи или коррекции морщин |
US15/429,493 US10071050B2 (en) | 2014-11-07 | 2017-02-10 | Cosmetic composition containing exosomes extracted from stem cell for skin whitening, antiwrinkle or regeneration |
US15/429,462 US20170152484A1 (en) | 2014-11-07 | 2017-02-10 | Composition including Stem Cell-Derived Exosome for Inducing Adipogenic Differentiation and Adipose Tissue Regeneration |
AU2017202287A AU2017202287B2 (en) | 2014-11-07 | 2017-04-06 | Composition for differentiation induction of adipocyte containing stem cell-derived exosome, regeneration of adipose tissue, and skin whitening or wrinkle improvement |
Applications Claiming Priority (8)
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KR20140154410 | 2014-11-07 | ||
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KR20150002660 | 2015-01-08 | ||
KR10-2015-0002660 | 2015-01-08 | ||
KR1020150134689A KR101663912B1 (ko) | 2015-01-08 | 2015-09-23 | 줄기세포로부터 추출된 엑소좀을 함유하는 피부 미백, 주름개선 또는 재생용 화장료 조성물 |
KR10-2015-0134689 | 2015-09-23 | ||
KR10-2015-0137635 | 2015-09-30 | ||
KR1020150137635A KR101629151B1 (ko) | 2014-11-07 | 2015-09-30 | 줄기세포 유래 엑소좀을 포함하는 지방세포 분화유도 및 지방조직 재생용 조성물 |
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US15/429,462 Continuation US20170152484A1 (en) | 2014-11-07 | 2017-02-10 | Composition including Stem Cell-Derived Exosome for Inducing Adipogenic Differentiation and Adipose Tissue Regeneration |
US15/429,493 Continuation US10071050B2 (en) | 2014-11-07 | 2017-02-10 | Cosmetic composition containing exosomes extracted from stem cell for skin whitening, antiwrinkle or regeneration |
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