WO2018203499A1 - 医薬品組成物及び化粧品組成物 - Google Patents

医薬品組成物及び化粧品組成物 Download PDF

Info

Publication number
WO2018203499A1
WO2018203499A1 PCT/JP2018/016738 JP2018016738W WO2018203499A1 WO 2018203499 A1 WO2018203499 A1 WO 2018203499A1 JP 2018016738 W JP2018016738 W JP 2018016738W WO 2018203499 A1 WO2018203499 A1 WO 2018203499A1
Authority
WO
WIPO (PCT)
Prior art keywords
stem cells
medium
raw material
supernatant
cells
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2018/016738
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
剛士 田邊
朗 伊達
健太 須藤
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
I Peace Inc
Original Assignee
I Peace Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by I Peace Inc filed Critical I Peace Inc
Priority to EP18794056.4A priority Critical patent/EP3607957A4/en
Priority to CN201880029436.XA priority patent/CN110621323B/zh
Priority to JP2019515707A priority patent/JP6647545B2/ja
Priority to CN202210686304.2A priority patent/CN114939097A/zh
Priority to US16/610,471 priority patent/US20200147146A1/en
Publication of WO2018203499A1 publication Critical patent/WO2018203499A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • 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
    • A61K8/99—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/10—Preservation of living parts
    • A01N1/12—Chemical aspects of preservation
    • A01N1/122—Preservation or perfusion media
    • A01N1/126—Physiologically active agents, e.g. antioxidants or nutrients
    • 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
    • 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
    • A61K35/54—Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
    • A61K35/545—Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
    • 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
    • A61K8/042—Gels
    • 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
    • A61K8/981—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • the present invention relates to a pharmaceutical composition and a cosmetic composition.
  • Embryonic stem cells are stem cells established from early embryos of humans and mice. ES cells have pluripotency capable of differentiating into all cells present in a living body. Currently, human ES cells are available for cell transplantation therapy for many diseases such as Parkinson's disease, juvenile diabetes, and leukemia. However, there are obstacles to transplantation of ES cells. In particular, transplantation of ES cells can elicit immune rejection similar to the rejection that occurs following unsuccessful organ transplantation. In addition, there are many criticisms and objections from the ethical point of view regarding the use of ES cells established by destroying human embryos.
  • An object of the present invention is to provide a pharmaceutical composition and a cosmetic composition that effectively utilize a medium for stem cells such as iPS cells.
  • the present inventors have found that the supernatant of a culture medium in which stem cells are maintained and cultured in an undifferentiated state becomes an active ingredient of pharmaceuticals or cosmetics.
  • a pharmaceutical composition or a pharmaceutical composition raw material comprising a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state for use as a pharmaceutical composition or a raw material for a pharmaceutical composition is provided.
  • the stem cell may be a pluripotent stem cell.
  • the pluripotent stem cell may be an iPS cell.
  • the pluripotent stem cell may be an ES cell.
  • the medium may be a gel medium.
  • the culture medium may contain gellan gum.
  • a therapeutic method comprising administering or applying to a subject a pharmaceutical composition containing a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the subject may be a human or non-human animal or plant.
  • an agent for preventing and improving any of skin spots, wrinkles and sagging comprising the above pharmaceutical composition.
  • a treatment method comprising administering or applying to a subject an agent for preventing and / or improving any one of skin spots, wrinkles and sagging, comprising the above pharmaceutical composition.
  • the subject may be a human or non-human animal.
  • a cosmetic composition or a cosmetic composition raw material comprising a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state for use as a cosmetic or cosmetic composition raw material is provided.
  • the stem cell may be a pluripotent stem cell.
  • the pluripotent stem cell may be an iPS cell.
  • the pluripotent stem cell may be an ES cell.
  • the medium may be a gel medium.
  • the culture medium may contain gellan gum.
  • an agent for preventing and improving any of skin spots, wrinkles and sagging comprising the cosmetic composition described above.
  • a treatment method comprising administering or applying to a subject an agent for preventing and / or improving any one of skin spots, wrinkles and sagging, comprising the cosmetic composition described above.
  • the subject may be a human or non-human animal.
  • a collagen production promoter or a collagen production promoter raw material comprising a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state for use in promoting collagen production is provided.
  • the stem cell may be a pluripotent stem cell.
  • the pluripotent stem cell may be an iPS cell.
  • the pluripotent stem cell may be an ES cell.
  • the medium may be a gel medium.
  • the culture medium may contain gellan gum.
  • a therapeutic method including administering or applying to a subject a collagen production promoter containing a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the subject may be a human or non-human animal.
  • a hyaluronic acid production promoter or a hyaluronic acid production promoter raw material containing a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state for use in promoting hyaluronic acid production is provided.
  • the stem cell may be a pluripotent stem cell.
  • the pluripotent stem cell may be an iPS cell.
  • the pluripotent stem cell may be an ES cell.
  • the medium may be a gel medium.
  • the culture medium may contain gellan gum.
  • a treatment method comprising administering or applying to a subject a hyaluronic acid production promoter containing a supernatant of a culture medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the subject may be a human or non-human animal.
  • a wound therapeutic agent or a wound therapeutic agent raw material comprising a supernatant of a culture medium in which stem cells are maintained and cultured in an undifferentiated state.
  • a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state for use in wound treatment is provided.
  • the stem cell may be a pluripotent stem cell.
  • the pluripotent stem cell may be an iPS cell.
  • the pluripotent stem cell may be an ES cell.
  • the medium may be a gel medium.
  • the culture medium may contain gellan gum.
  • a treatment method comprising administering or applying a wound treatment agent containing a supernatant of a culture medium in which stem cells are maintained and cultured in an undifferentiated state to a subject.
  • the subject may be a human or non-human animal.
  • an epidermal cell growth promoter or raw material for epidermal cell growth promoter comprising a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state for use in promoting the proliferation of epidermal cells is provided.
  • the stem cell may be a pluripotent stem cell.
  • the pluripotent stem cell may be an iPS cell.
  • the pluripotent stem cell may be an ES cell.
  • the medium may be a gel medium.
  • the culture medium may contain gellan gum.
  • a treatment method comprising administering or applying to a subject an epidermal cell growth promoter comprising a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the subject may be a human or non-human animal.
  • a hair growth agent or a hair growth agent raw material comprising a supernatant of a culture medium in which stem cells are maintained and cultured in an undifferentiated state.
  • a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state for use in hair growth is provided.
  • the stem cell may be a pluripotent stem cell.
  • the pluripotent stem cell may be an iPS cell.
  • the pluripotent stem cell may be an ES cell.
  • the medium may be a gel medium.
  • the culture medium may contain gellan gum.
  • a treatment method including administering or applying to a subject a hair growth agent containing a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the subject may be a human or non-human animal.
  • a hair papilla cell activator or a hair papilla cell activator raw material containing a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state for use as an activator of hair papilla cells or a raw material for activators of hair papilla cells is provided.
  • the stem cell may be a pluripotent stem cell.
  • the pluripotent stem cell may be an iPS cell.
  • the pluripotent stem cell may be an ES cell.
  • the medium may be a gel medium.
  • the culture medium may contain gellan gum.
  • a treatment method comprising administering or applying to a subject dermal papilla cells containing a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the subject may be a human or non-human animal.
  • FGF fibroblast growth factor
  • the stem cells may be pluripotent stem cells.
  • the pluripotent stem cell may be an iPS cell.
  • the pluripotent stem cell may be an ES cell.
  • the medium may be a gel medium.
  • the culture medium may contain gellan gum.
  • a therapeutic method comprising administering or applying to a subject an FGF production promoter containing a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the subject may be a human or non-human animal.
  • a vascular endothelial growth factor (VEGF) production promoter or a VEGF production promoter raw material comprising a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state for use in promoting the production of VEGF is provided.
  • the stem cell may be a pluripotent stem cell.
  • the pluripotent stem cell may be an iPS cell.
  • the pluripotent stem cell may be an ES cell.
  • the medium may be a gel medium.
  • the culture medium may contain gellan gum.
  • a therapeutic method comprising administering or applying to a subject a VEGF production promoter containing a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the subject may be a human or non-human animal.
  • a cytoprotective agent or a cytoprotectant raw material that protects cells from stress, including the supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the stem cell may be a pluripotent stem cell.
  • the pluripotent stem cell may be an iPS cell.
  • the pluripotent stem cell may be an ES cell.
  • the medium may be a gel medium.
  • the culture medium may contain gellan gum.
  • a cell viability improver or a cell viability improver raw material that improves the survival rate of stressed cells, including the supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the stem cell may be a pluripotent stem cell.
  • the pluripotent stem cell may be an iPS cell.
  • the pluripotent stem cell may be an ES cell.
  • the medium may be a gel medium.
  • the culture medium may contain gellan gum.
  • At least one selected from the group consisting of a nucleic acid, a protein, a protein complex, a lipoprotein, a ribosome, and a biological membrane including a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • a biological material protecting agent or a biological material protecting agent raw material that protects a biological material from stress is provided.
  • the stem cell may be a pluripotent stem cell.
  • the pluripotent stem cell may be an iPS cell.
  • the pluripotent stem cell may be an ES cell.
  • the medium may be a gel medium.
  • the culture medium may contain gellan gum.
  • FIG. 1 It is a graph which shows the result of the proliferation test of the fibroblast which concerns on Example 4.
  • FIG. It is a graph which shows the result of the proliferation test of the fibroblast which concerns on Example 4.
  • FIG. It is a graph which shows the result of the collagen production test by the fibroblast which concerns on Example 5.
  • FIG. It is a graph which shows the result of the collagen production test by the fibroblast which concerns on Example 5.
  • FIG. It is a graph which shows the result of the hyaluronic acid production test by the fibroblast which concerns on Example 5.
  • FIG. It is a photograph which shows the result of the migration ability test of the epidermal cell which concerns on Example 6.
  • FIG. It is a graph which shows the result of the migration ability test of the epidermal cell which concerns on Example 6.
  • FIG. 10 is a graph showing the results of an FGF-7 production test using dermal papilla cells according to Example 8. It is a graph which shows the result of the VEGF production test by the dermal papilla cell concerning Example 8.
  • Each of the pharmaceutical composition, the pharmaceutical composition raw material, the cosmetic composition, and the cosmetic composition raw material according to the embodiment includes a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the stem cells are, for example, pluripotent stem cells such as induced pluripotent stem (iPS) cells and embryonic stem cells (ES cells).
  • iPS induced pluripotent stem
  • ES cells embryonic stem cells
  • the stem cell medium for example, a human ES / iPS medium such as TeSR2 (STEMCELL Technologies) can be used.
  • the medium for stem cells is not limited to this, and various stem cell culture media can be used.
  • Primate ES Cell Medium, Reprostem, ReproFF, ReproFF2, ReproXF (Reprocell), mTeSR1, TeSRE8, ReproTeSR (STEMCELL Technologies), PluriSTEM (registered trademark) MTM Medium for Human iPS and ES Cells, Pluriton reprogramming medium (Stemment), PluriSTEM (registered trademark), Stemfit AK02N, Stemfit AK03 (Ajinomoto), ESC-Sure (registered trademark) erum and feeder free medium for hESC / iPS (Applied StemCell), L7 (registered trademark) hPSC Culture System (LONZA), and Primate ES Cell Medium (ReproCELL) or the like may be utilized.
  • the stem cell medium is Dulbecco's Modified Eagle Medium / Ham F-12 (DMEM / F12) supplemented with alternative serum, L-glutamine, non-essential amino acid solution, 2-mercaptoethanol, and penicillin / streptomycin. Also good.
  • the medium for stem cells may contain a growth factor such as basic fibroblast growth factor (bFGF).
  • gel medium When stem cells are cultured in suspension, gel medium is used.
  • the gel medium is, for example, a gel medium such as a deacylated gellan gum in a stem cell medium with a final concentration of 0.5 wt% to 0.001 wt%, 0.1 wt% to 0.005 wt%, or 0.05 wt% % To 0.01% by weight.
  • gellan gum includes deacylated gellan gum.
  • Gel medium is composed of hyaluronic acid, rhamzan gum, diyutan gum, xanthan gum, carrageenan, fucoidan, pectin, pectic acid, pectinic acid, heparan sulfate, heparin, heparitin sulfate, keratosulfate, chondroitin sulfate, deltamann sulfate, rhamnan sulfate, and their It may contain at least one polymer compound selected from the group consisting of salts.
  • the gel medium may contain methyl cellulose and lipids such as lysophosphatidic acid and sphingosine-1-phosphate. By containing these substances, aggregation between cells is further suppressed.
  • the gel medium can be poly (glycerol monomethacrylate) (PGMA), poly (2-hydroxypropyl methacrylate) (PHPMA), Poly (N-isopropylacrylamide) (PNIPAM), amine terminated, carboxylic acid terminated, maleimide terminated, N-hydroxysuccinimide ( NHS) ester terminated, triethoxysilane terminated, Poly (N-isopropylacrylamide-co-acrylamide), Poly (N-isopropylacrylamide-co-acrylic acid), Poly (N-isopropylacrylamide-co-butylacrylate), Poly (N-isopropylacrylamide-co- It may contain a small number of temperature sensitive gels selected from methacrylic acid, Poly (N-isopropylacrylamide-co-methacrylic acid-co-octadecyl acrylate), and N-isopropylacrylamide.
  • PGMA poly (glycerol monomethacrylate)
  • a ROCK inhibitor is added to the gel medium so that the final concentration is 1000 ⁇ mol / L to 0.1 ⁇ mol / L, 100 ⁇ mol / L to 1 ⁇ mol / L, or 5 ⁇ mol / L to 20 ⁇ mol / L. Also good.
  • a ROCK inhibitor is added to the gel medium so that colony formation by stem cells is promoted.
  • the gel medium may not contain a growth factor such as bFGF, for example.
  • the gel medium may contain a growth factor such as bFGF at a low concentration of 400 ⁇ g / L or less, 100 ⁇ g / L or less, 40 ⁇ g / L or less, or 10 ⁇ g / L or less.
  • the gel medium may not contain TGF- ⁇ or may contain TGF- ⁇ at a low concentration of 600 ng / L or less, 300 ng / L or less, or 100 ng / L or less.
  • stem cells are decomposed into single cells before suspension culture, and the stem cells decomposed into single cells are placed in a gel medium.
  • the gel medium is not agitated.
  • Single cells grow while maintaining clonality and undifferentiated state and form colonies in gel medium. Whether or not the stem cells are kept in an undifferentiated state can be confirmed by examining whether or not the cells express an undifferentiated marker.
  • the temperature at which the stem cells are maintained and cultured is, for example, 37 ° C.
  • the concentration of carbon dioxide when maintaining the stem cells is 5%, for example.
  • the period for maintaining and culturing the stem cells is, for example, 1 day or more and 90 days or less, 2 days or more and 60 days or less, 5 days or more and 30 days or less, or 7 days or more and 21 days or less.
  • the stem cells may be removed from the supernatant of the culture medium in which the stem cells are maintained and cultured in an undifferentiated state by filtration, centrifugation, or the like.
  • the pharmaceutical composition according to the embodiment may be a skin coating composition.
  • the pharmaceutical composition according to the embodiment may be a skin disease therapeutic agent.
  • diseases treatable with the skin disease therapeutic agent according to the embodiment include acne vulgaris, psoriasis vulgaris, keloid, seborrheic dermatitis, contact dermatitis, atopic dermatitis, atopic dry dermatitis, Dermatoporosis, photoelastic fibrosis, actinic keratosis, ptosis, alopecia areata, scalp alopecia, hairy alopecia, melasma, senile pigmentation, sweat, freckles, slow Examples include onset bilateral Ota maternal, seborrheic keratosis, skin disease due to progeria, and herpes simplex.
  • Examples of states that can be improved or eliminated with the cosmetic composition according to the embodiment include spots, freckles, wrinkles, sagging, creaking, reduced skin elasticity, dullness, sensitive skin, dry skin, thinning hair, and the like. Is mentioned.
  • the effects of the cosmetic composition according to the embodiment include preparing the skin, adjusting the texture of the skin, keeping the skin smooth, preventing rough skin, tightening the skin, imparting moisture to the skin, and maintaining and maintaining moisture and oil in the skin. Keep skin soft, protect skin, prevent skin dryness, soften skin, give skin elasticity, give skin gloss, smooth skin, give skin elasticity, stains For example, to make it inconspicuous, to suppress wrinkles and to lighten the skin.
  • the effects on the scalp or hair of the cosmetic composition according to the embodiment include keeping the scalp healthy, preventing hair growth, preventing thinning hair, preventing itching, preventing hair loss, promoting hair growth, promoting hair growth, post-disease or postpartum
  • Examples include hair loss prevention and hair restoration.
  • the pharmaceutical composition according to the embodiment may be a wound therapeutic agent, an epidermal cell proliferation promoter, an epidermal turnover promoter, a hair growth agent, a hair growth agent, and a pilus alopecia therapeutic agent.
  • the pharmaceutical composition and cosmetic composition according to the embodiment include a collagen production promoter, a hyaluronic acid production promoter, a hair growth agent, a fibroblast growth factor (FGF) family production promoter, and a vascular endothelial growth factor (VEGF). It may be a production promoter.
  • hair growth During hair growth, the hair matrix cells of the hair root divide, and the cells generated from the hair make up the hair.
  • hair growth has a cycle called a hair cycle, and repeats a growth period, a regression period, and a rest period.
  • Papilla cells influence the growth and differentiation of hair follicle epithelial stem cells through the production and release of growth factors and control the hair cycle. It is said that the activation of hair papilla cells and hair matrix cells contributes to the mechanism of hair growth. Further, blood vessel remodeling is actively performed in the hair follicle according to the hair cycle. However, if there is a problem with angiogenesis at this time, the supply of nutrients and oxygen for hair formation becomes insufficient. Insufficient blood flow from the follicular vascular network is said to be involved in the pathogenesis of androgenetic alopecia (AGA).
  • AGA androgenetic alopecia
  • VEGF Vascular endothelial growth factor
  • AGA male pattern baldness
  • VEGFB competes and binds to VEGFR-1, which is a receptor that VEGF acts on.
  • VEGFB has vascular endothelial cell proliferation and permeability enhancement activity, but its effect on hair follicles is unknown.
  • the pharmaceutical composition and cosmetic composition according to the embodiment act directly on the hair papilla to increase the production of FGF-7, a hair growth promoting factor, and promote hair growth, thereby prolonging the growth period of the hair cycle. It has the effect of growing from thin and weak hair to thick and strong hair, enhances vascular endothelial growth factor (VEGF), is secreted from hair papilla cells, is involved in the growth of hair follicle blood vessels, and has the effect of growing hair papilla cells in autocrine is there.
  • VEGF vascular endothelial growth factor
  • compositions and cosmetic composition according to the embodiment are used as a hair restorer or hair growth agent
  • other active ingredients such as minoxidil, assembly, pantothenyl ethyl ether, tocopherol acetate, dipotassium glycyrrhizinate, and adenosine are added. May be included.
  • wounds that can be treated with the wound therapeutic agent according to the embodiment include burns, abrasions, lacerations, contusions, suture wounds, pressure sores, and skin defect wounds.
  • the pharmaceutical composition or cosmetic composition according to the embodiment may be a cytoprotective agent that protects cells from stress, including a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the pharmaceutical composition or cosmetic composition according to the embodiment stabilizes stressed cells including the supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state, and improves cell survival rate, for example, improves survival rate
  • An agent may be used.
  • the stressed cells are, for example, fibroblasts, epidermis cells, and hair papilla cells, but are not limited to these cells and may be any cells.
  • the pharmaceutical composition or cosmetic composition according to the embodiment includes a group consisting of a nucleic acid, a protein, a protein complex, a lipoprotein, a ribosome, and a biological membrane, including a supernatant of a culture medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the biological material protective agent which protects at least 1 biological material selected from stress from stress may be sufficient.
  • the biological membrane includes a cell membrane.
  • the pharmaceutical composition and the cosmetic composition according to the embodiment include an effective amount of a supernatant of a medium in which stem cells are maintained and cultured in an undifferentiated state.
  • the effective amount means an amount capable of exerting the effect as a pharmaceutical composition or a cosmetic composition.
  • the effective amount is appropriately set according to the age of the patient, the target disease, the presence or absence of other successful ingredients, and the amount of other formulations.
  • the pharmaceutical composition and cosmetic composition according to the embodiment include a pharmaceutically acceptable carrier, excipient, disintegrant, buffer, emulsifier, suspending agent, soothing agent, stabilizer, preservative, preservative, and It may contain physiological saline or the like.
  • excipients include lactose, starch, sorbitol, D-mannitol, and sucrose.
  • disintegrant include carboxymethyl cellulose and calcium carbonate.
  • buffering agents include phosphate, citrate, and acetate.
  • emulsifiers include gum arabic, sodium alginate, and tragacanth.
  • suspending agents include glyceryl monostearate, aluminum monostearate, methylcellulose, carboxymethylcellulose, hydroxymethylcellulose, and sodium lauryl sulfate.
  • soothing agents include benzyl alcohol, chlorobutanol, and sorbitol.
  • stabilizers include propylene glycol and ascorbic acid.
  • preservatives include phenol, benzalkonium chloride, benzyl alcohol, chlorobutanol, and methyl paraben. Examples of preservatives include benzalkonium chloride, paraoxybenzoic acid, and chlorobutanol.
  • the pharmaceutical composition and cosmetic composition according to the embodiment include water, alcohol, surfactant (cation, anion, nonion, amphoteric surfactant, etc.), humectant (glycerin, 1,3-butylene glycol, Propylene glycol, propanediol, pentanediol, polyquaternium, amino acids, urea, pyrrolidone carboxylates, nucleic acids, monosaccharides, oligosaccharides, and derivatives thereof), thickeners (polysaccharides, polyacrylates, Carboxyvinyl polymer, polyvinylpyrrolidone, polyvinyl alcohol, chitin, chitosan, alginic acid, carrageenan, xanthan gum, methylcellulose, and the like, and derivatives thereof), wax, petrolatum, hydrocarbon saturated fatty acid, unsaturated fatty acid, silicone oil, and the like, and Their derivatives, tri (Caprylic / Capric acid)
  • Natural and synthetic neutrophil elastase inhibition and MMP-1 and MMP-2 inhibitory activity Ingredients etc.), titanium oxide, talc, mica, silica, zinc oxide, iron oxide, silicon, and powders obtained by processing these, etc., to achieve the purpose of the pharmaceutical composition and cosmetic composition according to the embodiment Can be blended within.
  • the component that can be added to the pharmaceutical composition and the cosmetic composition according to the embodiment is not limited to the above, and any component that can be used for the pharmaceutical composition and the cosmetic composition can be freely selected.
  • a base such as kaolin and bentonite
  • a gelling agent such as polyacrylate and polyvinyl alcohol
  • sulfate, bicarbonate, borate, pigment, and moisturizer are appropriately blended within a range that achieves the purpose, powder type, liquid agent It may be prepared in a type.
  • the pharmaceutical composition and the cosmetic composition according to the embodiment can be produced by a method commonly used in the technical field.
  • Example 1 Preparation of supernatant of medium in which stem cells were maintained and cultured
  • 5 mL L-glutamine (25030-081, Invitrogen) 5 mL non-essential amino acid solution (11140-050, Invitrogen), 1 mL 2-mercaptoethanol (21985-023, Invitrogen), 2.5 mL penicillin / streptomycin (15140) -122, Invitrogen) was added DMEM / F12 (10565-018, Invitrogen) and alternative serum (KSR: KnockOut Serum Replacement, registered trademark, 10828028, Invitrogen) to make a total volume of 500 mL.
  • KSR KnockOut Serum Replacement
  • bFGF basic fibroblast growth factor, R and D
  • human iPS cells were cultured for adhesion maintenance on feeder cells on a petri dish for adhesion culture. Human iPS cells were passaged every week. At the time of passage, human iPS cells were treated with a stripping solution containing 0.25% trypsin, 0.1 mg / mL collagenase IV, 1 mmol / L CaCl 2 , and 20% KSR.
  • the human iPS cells maintained and maintained as described above were detached from the adhesion culture dish using an ES cell dissociation solution (TrypLE Select, registered trademark, ThermoFisher).
  • the detached human iPS cells were seeded on a dish coated with laminin (Nippi). Thereafter, human iPS cells were cultured for 1 week using TeSR2 medium (Stem cell) supplemented with 10 ⁇ mol / L ROCK inhibitor. The medium was changed every day.
  • the medium was replaced with a medium for stem cells, and the supernatant of the medium for stem cells was recovered two days later.
  • the collected supernatant of the stem cell medium is centrifuged at 1500 rpm for 5 minutes, and the supernatant of the medium is collected again and then centrifuged at 3000 rpm for 3 minutes.
  • the supernatant of the stem cell medium after centrifugation is filtered with a 0.22 ⁇ m filter. Filtered.
  • the supernatant of the stem cell medium after filtration was used as the supernatant solution according to Example 1.
  • iPS cells maintained in culture were positive for undifferentiated markers NANOG, OCT3 / 4, and TRA 1-60.
  • Example 2 Preparation of supernatant of medium in which stem cells were maintained and cultured
  • human iPS cells were maintained and cultured. Thereafter, in the same manner as in Example 1, human iPS cells were detached from the petri dish for adhesion culture and divided into single cells. Next, human iPS cells were seeded in a stem cell medium gelled with gellan gum and 10 ⁇ mol / L ROCK inhibitor (Selleck), and the human iPS cells were cultured in suspension for 21 days. Meanwhile, the incubator was replenished with the gelled stem cell medium once every two days.
  • the gelled stem cell culture medium in which human iPS cells are suspended was filtered with a mesh filter to remove the cell mass. Furthermore, the filtered medium for gelled stem cells is centrifuged at 1500 rpm for 5 minutes to precipitate cells and gel, and the supernatant of the centrifuged stem cell medium is collected again, and then centrifuged at 3000 rpm for 3 minutes. The supernatant of the stem cell medium was filtered through a 0.22 ⁇ m filter. The supernatant of the medium for stem cells after filtration was used as the supernatant solution according to Example 2.
  • iPS cells maintained in culture were positive for undifferentiated markers NANOG, OCT3 / 4, and TRA 1-60.
  • Example 3 Preparation of supernatant of culture medium in which stem cells were maintained and cultured
  • human iPS cells were maintained and cultured. Thereafter, in the same manner as in Example 1, human iPS cells were detached from the petri dish for adhesion culture and divided into single cells. Next, human iPS cells were seeded in a medium for stem cells gelled with gellan gum and 100 ⁇ mol / L ROCK inhibitor (Selleck), and the human iPS cells were cultured in suspension for 14 days. Meanwhile, the incubator was replenished with the gelled stem cell medium once every two days.
  • the gelled stem cell culture medium in which human iPS cells are suspended was filtered with a mesh filter to remove the cell mass. Furthermore, the filtered medium for gelled stem cells is centrifuged at 1500 revolutions to precipitate cells and gels, and the supernatant of the centrifuged stem cell culture medium is collected again, and then centrifuged at 3000 revolutions for 3 minutes, and after centrifugation, for stem cells The supernatant of the medium was filtered with a 0.22 ⁇ m filter. The supernatant of the medium for stem cells after filtration was used as the supernatant solution according to Example 3.
  • iPS cells maintained in culture were positive for undifferentiated markers NANOG, OCT3 / 4, and TRA 1-60.
  • Human iPS cells were cultured according to the examples described in JP-A-2016-128396. That is, using the same medium for stem cells as in Example 1, human iPS cells were cultured for adhesion maintenance on feeder cells on a petri dish for adhesion culture. Human iPS cells were passaged every week. At the time of passage, human iPS cells were treated with a stripping solution containing 0.25% trypsin, 0.1 mg / mL collagenase IV, 1 mmol / L CaCl 2 , and 20% KSR.
  • the human iPS cells cultured as described above were detached from the adhesion culture dish using an ES cell dissociation solution (TrypLE Select, registered trademark, ThermoFisher).
  • the detached human iPS cells were suspended in a non-gelled human iPS cell in a non-adhesive culture dish for 1 week.
  • an embryoid body (EB) was formed.
  • the formed embryoid body was seeded on a petri dish for adhesion culture and grown for 1 week in DMEM containing 10% FBS.
  • the cells were detached from the adhesion culture dish using a 0.05% trypsin-EDTA solution, and the cells divided into single cells were seeded in a new adhesion culture dish. Thereafter, the cells were cultured for one week using DMEM containing 10% FBS as a medium.
  • the medium was replaced with a serum-free medium (DMEM not containing FBS), and after culturing for 2 days, the supernatant of the medium was collected.
  • the collected medium supernatant was centrifuged at 1500 rpm for 5 minutes, the medium supernatant was collected again, then centrifuged at 3000 rpm for 3 minutes, and the medium supernatant was collected again with the supernatant solution according to the comparative example. did.
  • the cultured cells were negative for the undifferentiation markers NANOG, OCT3 / 4, and TRA 1-60, confirming that they were differentiated cells.
  • Example 4 Fibroblast proliferation test
  • growth medium A DMEM medium supplemented with 10% FBS and 1% penicillin-streptomycin was prepared.
  • normal human fibroblasts derived from adults KF-4109, Strain No. 01035, Kurabo Industries
  • growth medium A normal human fibroblasts derived from adults (KF-4109, Strain No. 01035, Kurabo Industries) were suspended in growth medium A so that the concentration was 5 ⁇ 10 3 cells / 0.1 mL / well, and a 96-well plate was obtained. And cultured for 1 day in a CO 2 incubator (5% CO 2 , 37 ° C.).
  • test medium A DMEM medium supplemented with 1% FBS and 1% penicillin-streptomycin was prepared. Next, each of the supernatant solutions according to Examples 1 to 3 and the comparative example and the test medium A were mixed at a volume ratio of 10.00: 90.00, and the concentration was 10.00 v / The supernatant-added medium A according to Examples 1 to 3 and Comparative Example of v% was obtained. The growth medium A in some wells was replaced with each of the supernatant-added medium A according to Examples 1 to 3 and the comparative example.
  • the growth medium A in some wells was replaced with a DMEM medium (no addition test medium A) to which 1% FBS and 1% penicillin-streptomycin were not added.
  • DMEM medium no addition test medium A
  • some wells were added to diluted test medium A obtained by mixing DMEM / F12 and test medium A to a volume ratio of 10.00: 90.00. Medium A was replaced.
  • Fibroblasts are cultured in the replaced medium for 1 day and 3 days, and using a viable cell count reagent SF (Cat. No. 07553-15, Nacalai Tesque) and a plate reader (Varioscan MicroPlate Reader, Thermo Scientific) Thus, the number of viable cells was measured by the WST-8 method.
  • the results are shown in FIGS.
  • the supernatant-added medium A according to Examples 1 to 3 having a concentration of 10.00 v / v% was used, the non-added test medium A, the diluted test medium A, and the supernatant-added medium A according to the comparative example were used. Compared to the case, it was confirmed that fibroblasts proliferated predominantly.
  • the supernatant of the stem cell medium is effective in increasing the cell viability. Furthermore, when exfoliating from a petri dish at the time of passage, or when divided into single cells, physical stress such as pressure and chemical stress are applied to the cells by a release agent. However, since these stressed cells grew in the supernatant-added medium according to the example, the supernatant-added medium according to the example alleviates the stress received by the cell and protects the cell from the stress. These results suggest that the cells are stabilized and the survival rate is improved.
  • the supernatant-added medium protects nucleic acids, proteins, protein complexes, lipoproteins, ribosomes, and biological membranes contained in the cells.
  • the biological membrane includes a cell membrane.
  • Example 5 Type I collagen and hyaluronic acid production test by fibroblasts
  • Example 4 adult-derived normal human fibroblasts were cultured in growth medium A for 1 day. Thereafter, the growth medium A in a part of the wells was changed to Example 1 except that the concentration was 1.00 v / v%, 10.00 v / v%, or 100.0 v / v%. To 3 and each of the supernatant-added medium A according to the comparative example.
  • growth medium A in some wells was not replaced.
  • growth medium A in some wells was replaced with additive-free test medium A.
  • the growth medium A in some wells was replaced with a diluted test medium A prepared in the same manner as in Example 4.
  • fibroblasts were cultured for 3 days, and the supernatant of the medium was collected and stored at ⁇ 80 ° C. Thereafter, the supernatant of the medium was thawed, and the concentration of type I collagen in the supernatant of the medium was measured with a human collagen type 1 ELISA kit (Cat. No. EC1-E105). Moreover, the hyaluronic acid concentration in the supernatant of the culture medium was measured using DueSet Hyaluronan (Cat. No. DY3614, R & D Systems). The results are shown in FIG. 3, FIG. 4 and FIG.
  • the corrected bar on the right side shows data that has been corrected to exclude the amount of collagen originally contained in the medium before culturing fibroblasts.
  • the raw data bar on the left indicates data before correction.
  • the supernatant-added medium A according to Example 1 having a concentration of 1.0 v / v% was used, the non-added test medium A, the growth medium A, the diluted test medium A, and the comparative example Compared with the case of using such a supernatant-added medium A, the amount of type I collagen produced was significantly increased. As shown in FIG.
  • the corrected bar on the right side shows data that has been corrected to exclude the amount of hyaluronic acid originally contained in the medium before culturing fibroblasts.
  • the raw data bar on the left indicates data before correction.
  • the supernatant-added culture medium A according to Examples 1 to 3 having concentrations of 10.0 v / v% and 100.0 v / v% is used, the test medium A without addition, the dilution test medium A, and the comparative example Compared with the clear addition medium A, the production amount of hyaluronic acid was remarkably increased. Therefore, it was suggested that the supernatant of the stem cell medium promotes the production of hyaluronic acid and is effective in preventing and improving the formation of wrinkles and sagging due to the decrease in hyaluronic acid.
  • Growth medium B includes growth additives (10 ⁇ g / mL insulin, 0.1 ng / mL hEGF, 0.67 ⁇ g / mL hydrocortisone, 4 ⁇ L / mL bovine pituitary extract BPE) and antibacterial agent (50 ⁇ g / mL).
  • growth additives (10 ⁇ g / mL insulin, 0.1 ng / mL hEGF, 0.67 ⁇ g / mL hydrocortisone, 4 ⁇ L / mL bovine pituitary extract BPE) and antibacterial agent (50 ⁇ g / mL).
  • test medium B a medium prepared by adding an antibacterial agent (50 ⁇ g / mL gentamicin and 50 nm / mL amphotericin) to 500 mL of epidermal cell medium was prepared. Next, each of the supernatant solutions according to Examples 1 to 3 and the comparative example and the test medium B were mixed so that the volume ratio was 10.0: 90.0 and 1.0: 99.0. Thus, supernatant-added medium B according to Examples 1 to 3 and Comparative Example was obtained. The growth medium B on some plates was replaced with each of the supernatant-added medium B according to Examples 1 to 3 and the comparative example.
  • an antibacterial agent 50 ⁇ g / mL gentamicin and 50 nm / mL amphotericin
  • the growth medium B on some plates was replaced with an epidermal cell culture medium (no addition test medium B) to which no growth additive was added.
  • DMEM / F12 and test medium B were diluted test medium B obtained by mixing volume ratios of 10.0: 90.0 and 1.0: 99.0. The growth medium B on some plates was replaced.
  • epidermal cells migrate toward the wound and the wound contracts. In this example, it was analyzed using a plate reader whether or not epidermal cells migrated where they were blocked by the stopper. Specifically, 23 hours after the medium was replaced, the epidermal cells were stained with a live cell staining reagent (Calcein AM, Cat. NO. 341-07901, DOJINDO), and a plate reader (Varioscan MicroPlate Reader, Thermo Scientific). Was used to measure fluorescence at a wavelength of 538 nm against excitation light at a wavelength of 485 nm.
  • a live cell staining reagent Calcein AM, Cat. NO. 341-07901, DOJINDO
  • a plate reader Varioscan MicroPlate Reader, Thermo Scientific
  • the supernatant of the stem cell medium is effective in stabilizing the cells and increasing the survival rate. Furthermore, when exfoliating from a petri dish at the time of passage, or when divided into single cells, physical stress such as pressure and chemical stress are applied to the cells by a release agent. However, since these stressed cells grew in the supernatant-added medium according to the example, the supernatant-added medium according to the example alleviates the stress received by the cells, protects the cells from stress, It has been suggested to stabilize cells and improve viability.
  • the supernatant-added medium protects nucleic acids, proteins, protein complexes, lipoproteins, ribosomes, and biological membranes contained in the cells.
  • the biological membrane includes a cell membrane.
  • Growth medium C is a medium exclusively for hair papilla cells (Cat. No. TMTPGM-250) with a special additive (fetal bovine serum, insulin / transferrin / triiodothyronine mixed solution, bovine pituitary extract, cyproterone acetate) added. , TOYOBO).
  • a special additive fetal bovine serum, insulin / transferrin / triiodothyronine mixed solution, bovine pituitary extract, cyproterone acetate
  • TOYOBO normal human hair papilla cells
  • the growth medium C in some wells was replaced with a hair papilla cell-free medium (additive test medium C) to which no additive was added.
  • DMEM / F12 and additive-free test medium C were mixed with diluted test medium C obtained by mixing at a volume ratio of 30.0: 70.0. Growth medium C was replaced.
  • the dermal papilla cells were cultured for 3 days in the replaced medium, and the number of viable cells was measured by the WST-8 method. The results are shown in FIG.
  • the supernatant-added medium C according to Examples 1 to 3 having a concentration of 30.0 v / v% is used, the dermal papilla cells are superior to the case where the non-added test medium C and the diluted test medium C are used. It was confirmed that it proliferated. Therefore, it was suggested that the supernatant of the stem cell medium has hair growth and hair growth effects such as treatment of hair thinning, prevention of hair loss, hair growth promotion, and hair growth promotion.
  • Example 8 FGF-7 and VEGF production test by dermal papilla cells
  • normal human hair papilla cells were cultured in growth medium C for 1 day. Thereafter, the growth medium C in a part of the wells was changed to the examples in the same manner as in Example 7 except that the concentration was 0.3 v / v%, 30.0 v / v%, or 100.0 v / v%.
  • the supernatant was added to each of 1 to 3 and the supernatant-added medium C according to the comparative example.
  • the growth medium C in some wells was replaced with an additive-free test medium C and a diluted test medium C, respectively.
  • the growth medium C of some wells was added to an adenosine-added medium in which 100 ⁇ mol / L adenosine was added to a hair papilla cell-dedicated medium, and adenosine added to 30 ⁇ mol / L minoxidil in a hair papilla cell-dedicated medium. Replaced with each of the supplemented media.
  • the growth medium C in some wells was replaced with a DMSO-added medium in which 0.1% DMSO was added to a hair papilla cell-dedicated medium.
  • the corrected bar on the right side shows the corrected data excluding the amount of FGF-7 originally contained in the medium before culturing hair papilla cells.
  • the raw data bar on the left indicates data before correction.
  • the supernatant-added medium C according to Examples 1 to 3 having a concentration of 0.3 v / v% was used, the non-added test medium C, the diluted test medium C, and the supernatant-added medium C according to the comparative example were used. As compared with the case, it was confirmed that the production amount of FGF-7 was significantly increased.
  • the corrected bar on the right side shows data that has been corrected excluding the amount of VEGF originally contained in the medium before culturing hair papilla cells.
  • the raw data bar on the left indicates data before correction.
  • the supernatant-added medium C according to Examples 1 to 3 having a concentration of 30.0 v / v% and 100.0 v / v% was used, the dilution test medium C and the supernatant-added medium C according to the comparative example were used. Compared with the case, it was confirmed that the production amount of VEGF increased significantly.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Cell Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Zoology (AREA)
  • Reproductive Health (AREA)
  • Birds (AREA)
  • Biotechnology (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Biomedical Technology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Environmental Sciences (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Cosmetics (AREA)
  • Biophysics (AREA)
  • Physiology (AREA)
PCT/JP2018/016738 2017-05-02 2018-04-25 医薬品組成物及び化粧品組成物 Ceased WO2018203499A1 (ja)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP18794056.4A EP3607957A4 (en) 2017-05-02 2018-04-25 PHARMACEUTICAL COMPOSITION AND COSMETIC COMPOSITION
CN201880029436.XA CN110621323B (zh) 2017-05-02 2018-04-25 医药品组合物及化妆品组合物
JP2019515707A JP6647545B2 (ja) 2017-05-02 2018-04-25 医薬品組成物及び化粧品組成物
CN202210686304.2A CN114939097A (zh) 2017-05-02 2018-04-25 医药品组合物及化妆品组合物
US16/610,471 US20200147146A1 (en) 2017-05-02 2018-04-25 Pharmaceutical composition and cosmetic composition

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762500117P 2017-05-02 2017-05-02
US62/500,117 2017-05-02

Publications (1)

Publication Number Publication Date
WO2018203499A1 true WO2018203499A1 (ja) 2018-11-08

Family

ID=64017009

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2018/016738 Ceased WO2018203499A1 (ja) 2017-05-02 2018-04-25 医薬品組成物及び化粧品組成物

Country Status (5)

Country Link
US (1) US20200147146A1 (enExample)
EP (1) EP3607957A4 (enExample)
JP (3) JP6647545B2 (enExample)
CN (2) CN110621323B (enExample)
WO (1) WO2018203499A1 (enExample)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2020218579A1 (enExample) * 2019-04-26 2020-10-29
WO2021144843A1 (ja) * 2020-01-14 2021-07-22 株式会社ハーバーリンクスジャパン バイオ化粧品組成物
CN116725927A (zh) * 2023-08-09 2023-09-12 美出莱(杭州)化妆品有限责任公司 一种含牡丹活性成分的空间结构组合物及其制备方法与应用
JPWO2023176187A1 (enExample) * 2022-03-15 2023-09-21
WO2024176985A1 (ja) * 2023-02-20 2024-08-29 アイ ピース， インコーポレイテッド 組成物

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018203499A1 (ja) * 2017-05-02 2018-11-08 剛士 田邊 医薬品組成物及び化粧品組成物
CN114504636B (zh) * 2022-01-27 2023-09-26 华南理工大学 一种杏仁油烫伤膏及其制备方法与应用
JPWO2023149408A1 (enExample) * 2022-02-02 2023-08-10
CN117180149B (zh) * 2023-08-16 2024-04-30 宝萃生物科技有限公司 一种舒缓组合物及其制备方法与应用

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005062791A2 (en) * 2003-12-20 2005-07-14 Jeffrey Sebastian Utilization of stem cell and fibroblast combined products and nutrients in topical compositions
JP4183742B1 (ja) 2005-12-13 2008-11-19 国立大学法人京都大学 誘導多能性幹細胞の製造方法
JP2009527475A (ja) * 2006-02-16 2009-07-30 バーンハム インスティトゥート フォー メディカル リサーチ ヒト胚性幹細胞又は他の前駆細胞により馴化された培地、及びその使用
WO2011118795A1 (ja) * 2010-03-26 2011-09-29 国立大学法人名古屋大学 損傷部治療用組成物
WO2013118877A1 (ja) * 2012-02-10 2013-08-15 株式会社ジャパニック 非ヒト幹細胞の培養上清を原材料とする化粧品又は皮膚再生促進剤、及びタンパク質のイオン導入方法
US20140093486A1 (en) * 2012-10-01 2014-04-03 Taipei Veterans General Hospital Method for preparing induced pluripotent stem cells and its applications
JP2016128396A (ja) 2015-01-09 2016-07-14 上田　実 ｉＰＳ細胞培養上清を含む医薬組成物およびその製造方法、化粧品およびその製造方法、抗加齢組成物、疾患発症抑制方法、疾患治療方法、組織異常治療方法ならびに美容方法
WO2016164915A1 (en) 2015-04-09 2016-10-13 Neostem Oncology, Llc Stem cell compositions for cosmetic and dermatologic use

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1950498A (zh) * 2004-03-10 2007-04-18 加利福尼亚大学董事会 培养胚胎干细胞的组合物和方法
CA2718830C (en) * 2008-03-31 2017-04-18 Kyoto University Method for proliferation of pluripotent stem cells
CN101538553A (zh) * 2009-02-06 2009-09-23 叶尚勉 从人类早期流产的胎儿组织分离纯化和培养增殖全能干细胞的方法
JP5902092B2 (ja) * 2009-10-19 2016-04-13 セルラー ダイナミクス インターナショナル， インコーポレイテッド 心筋細胞の生成
WO2011058558A2 (en) * 2009-11-12 2011-05-19 Technion Research & Development Foundation Ltd. Culture media, cell cultures and methods of culturing pluripotent stem cells in an undifferentiated state
EP2601289B1 (en) * 2010-08-04 2017-07-12 Cellular Dynamics International, Inc. Reprogramming immortalized b cells
KR102482184B1 (ko) * 2010-12-22 2022-12-28 페이트 세러퓨틱스, 인코포레이티드 단세포 분류 및 iPSC의 증강된 재프로그래밍을 위한 세포 배양 플랫폼
JP2012143229A (ja) * 2010-12-24 2012-08-02 Chiba Univ 多能性幹細胞培養用組成物およびその用途
KR101293637B1 (ko) * 2011-01-14 2013-08-13 서울대학교병원 줄기세포의 부유배양용 조성물
RU2018129432A (ru) * 2012-07-24 2019-03-14 Ниссан Кемикал Индастриз, Лтд. Композиция культуральной среды и способ культивирования клетки или ткани с использованием указанной композиции
CN104955939B (zh) * 2013-01-31 2018-07-27 味之素株式会社 用于进行多能性干细胞的稳定的未分化维持增殖的培养方法
KR101655383B1 (ko) * 2013-07-27 2016-09-08 고려대학교 산학협력단 소분자 화합물을 포함하는 만능성 줄기세포의 염색체 안정성 유지용 조성물
WO2015098111A1 (ja) * 2013-12-26 2015-07-02 国立大学法人広島大学 ｉＰＳ細胞の樹立方法および幹細胞の長期維持方法
US10316292B2 (en) * 2014-01-23 2019-06-11 Nissan Chemical Industries, Ltd. Material for undifferentiated state-maintaining culture
CN103976929A (zh) * 2014-05-07 2014-08-13 王浩 一种具有iPS活细胞液和生物多肽美白的化妆品
JP6113133B2 (ja) * 2014-11-06 2017-04-12 日本メナード化粧品株式会社 幹細胞の未分化状態維持剤及び増殖促進剤
CN106244652B (zh) * 2016-08-17 2019-11-08 广州宏柯源生物科技有限公司 一种人间充质干细胞培养上清液冻干粉的制备方法及制得的冻干粉
WO2018203499A1 (ja) 2017-05-02 2018-11-08 剛士 田邊 医薬品組成物及び化粧品組成物

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005062791A2 (en) * 2003-12-20 2005-07-14 Jeffrey Sebastian Utilization of stem cell and fibroblast combined products and nutrients in topical compositions
JP4183742B1 (ja) 2005-12-13 2008-11-19 国立大学法人京都大学 誘導多能性幹細胞の製造方法
JP2009527475A (ja) * 2006-02-16 2009-07-30 バーンハム インスティトゥート フォー メディカル リサーチ ヒト胚性幹細胞又は他の前駆細胞により馴化された培地、及びその使用
WO2011118795A1 (ja) * 2010-03-26 2011-09-29 国立大学法人名古屋大学 損傷部治療用組成物
WO2013118877A1 (ja) * 2012-02-10 2013-08-15 株式会社ジャパニック 非ヒト幹細胞の培養上清を原材料とする化粧品又は皮膚再生促進剤、及びタンパク質のイオン導入方法
US20140093486A1 (en) * 2012-10-01 2014-04-03 Taipei Veterans General Hospital Method for preparing induced pluripotent stem cells and its applications
JP2016128396A (ja) 2015-01-09 2016-07-14 上田　実 ｉＰＳ細胞培養上清を含む医薬組成物およびその製造方法、化粧品およびその製造方法、抗加齢組成物、疾患発症抑制方法、疾患治療方法、組織異常治療方法ならびに美容方法
WO2016164915A1 (en) 2015-04-09 2016-10-13 Neostem Oncology, Llc Stem cell compositions for cosmetic and dermatologic use

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
AMIRTHALINGAM, MUTHUKUMAR ET AL.: "Stem Cell Derived Cosmetic Products: An overview", MANIPAL J. MED. SCI., vol. 1, no. 2, 2016, pages 46 - 52, XP055560679 *
GAZDHAR, AMIQ ET AL.: "The secretome of induced pluripotent stem cells reduces lung fibrosis in part by hepatocyte growth factor", STEM CELL RES. THER., vol. 5, 2014, pages 1 - 11, XP021206649 *
PAWITAN, JEANNE ADIWINATA: "Prospect of Stem Cell Conditioned Medium in Regenerative Medicine", BIOMED. RES. INT., vol. 2014, 2014, pages 1 - 14, XP055365351 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2020218579A1 (enExample) * 2019-04-26 2020-10-29
WO2020218579A1 (ja) * 2019-04-26 2020-10-29 国立大学法人京都大学 分化誘導のために馴化された多能性幹細胞の作製方法
WO2021144843A1 (ja) * 2020-01-14 2021-07-22 株式会社ハーバーリンクスジャパン バイオ化粧品組成物
JPWO2023176187A1 (enExample) * 2022-03-15 2023-09-21
WO2023176187A1 (ja) * 2022-03-15 2023-09-21 アイ ピース， インコーポレイテッド 医薬品及び化粧品、並びにそれらの提供方法
WO2024176985A1 (ja) * 2023-02-20 2024-08-29 アイ ピース， インコーポレイテッド 組成物
CN116725927A (zh) * 2023-08-09 2023-09-12 美出莱(杭州)化妆品有限责任公司 一种含牡丹活性成分的空间结构组合物及其制备方法与应用
CN116725927B (zh) * 2023-08-09 2023-11-17 美出莱(杭州)化妆品有限责任公司 一种含牡丹活性成分的空间结构组合物及其制备方法与应用

Also Published As

Publication number Publication date
CN114939097A (zh) 2022-08-26
JP6647545B2 (ja) 2020-02-14
CN110621323B (zh) 2022-10-14
JPWO2018203499A1 (ja) 2020-01-23
EP3607957A1 (en) 2020-02-12
JP2020040996A (ja) 2020-03-19
EP3607957A4 (en) 2020-12-16
JP7222471B2 (ja) 2023-02-15
US20200147146A1 (en) 2020-05-14
CN110621323A (zh) 2019-12-27
JP2023038330A (ja) 2023-03-16

Similar Documents

Publication Publication Date Title
JP7222471B2 (ja) 医薬品組成物及び化粧品組成物
KR101806115B1 (ko) 피부재생 또는 주름개선 효과를 가지는 인간 지방유래 줄기세포의 배양 농축액 및 이의 용도
US20250339471A1 (en) Pharmaceutical composition and cosmetic composition
JP7518513B2 (ja) 医薬品組成物及び化粧品組成物
WO2024176985A1 (ja) 組成物
US10842735B2 (en) Hair growth-promoting composition
HK40074090A (en) Pharmaceutical composition and cosmetic composition
HK40015995A (en) Pharmaceutical composition and cosmetic composition
HK40015995B (en) Pharmaceutical composition and cosmetic composition
US20250195584A1 (en) Pharmaceutical and cosmetic and method for providing same
WO2024046329A1 (en) Composition comprising amniotic fluid stem cells or derivatives thereof and use thereof
US20240319171A1 (en) Method for screening substance, system for screening substance, method for producing a clump from stem cells, and method for producing differentiated cells
KR101589869B1 (ko) 단백질 키나아제 C 억제제(Protein Kinase C Inhibitor)로 인한 인간 지방 유래 중간엽 줄기세포의 미백효과 및 항산화효과 관련 성장인자 발현 제어 및 분비를 촉진하는 성장인자 대량 생산방법
HK40044917A (en) Pharmaceutical composition and cosmetic composition
HK40044917B (zh) 医药品组合物以及化妆品组合物
KR20160003512A (ko) 저분자 화합물로 인한 인간 골수유래 중간엽 줄기세포 성장인자의 발현 제어 및 분비를 촉진하는 성장인자 대량 생산방법

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18794056

Country of ref document: EP

Kind code of ref document: A1

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
ENP Entry into the national phase

Ref document number: 2019515707

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2018794056

Country of ref document: EP

Effective date: 20191107