US20110028699A1 - Agent for Treating Skin Aging and Scars - Google Patents

Agent for Treating Skin Aging and Scars Download PDF

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US20110028699A1
US20110028699A1 US12/934,299 US93429909A US2011028699A1 US 20110028699 A1 US20110028699 A1 US 20110028699A1 US 93429909 A US93429909 A US 93429909A US 2011028699 A1 US2011028699 A1 US 2011028699A1
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skin
agent
scar
treating
aging
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Ichiro Ono
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LABO JUVERSA CO Ltd
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LABO JUVERSA CO Ltd
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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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1825—Fibroblast growth factor [FGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66—Enzymes
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
    • 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
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/91—Injection

Definitions

  • the present invention relates to an agent for preventing and treating aging of skin, and an agent for treating scars of skin.
  • scars of skin such as hypertrophic scars and keloid etc.
  • scars of skin also greatly influence the QOL of the patient, and it sometimes becomes an obstacle in social life depending on the degree or site (face, etc.) of the scar.
  • Scars are generated during the healing process of following injury, etc. Specifically, when skin is damaged by injuries generated by surgery, etc., wound healing mechanisms such as hemorrhagic phase and coagulation phase, inflammatory phase, proliferating phase, etc. function, and epidermalization ends after a certain period. Then, the wound is healed with scar remaining after a maturation phase during which scar matures. At that time, depending on conditions such as delayed healing, patient's age and body sites, etc.
  • the wound may form scars such as hypertrophic scar, scar contracture, keloid, atrophic scar, etc.
  • scars such as hypertrophic scar, scar contracture, keloid, atrophic scar, etc.
  • changes in thickness calm down with the passage of time, while symptoms such as reddening, pruritus, colic pain, etc. are severe in some cases, and the QOL of the patient can be significantly lowered for a long period of time. Further, wide scar or atrophic scar often remains even when the changes are calmed down, and the QOL of the patient was lowered for a long period of time in any of the cases.
  • Patent Document 1 discloses that wrinkles and sagging skin are treated by applying externally a skin care product comprising basic fibroblast growth factor (bFGF) as active ingredient to the skin.
  • bFGF basic fibroblast growth factor
  • bFGF is one kind of growth factor that has been found and identified by Grotendorst et al., which is a single chain polypeptide without sugar, having a molecular weight of about 17 K Dalton, and having a phospholipid affinity.
  • Patent Document 2 describes that an external preparation for skin comprising a fibroblast growth factor and epidermis growth factor exhibits an effect on improving wrinkles, pigmented spots, hair loss, etc.
  • skin care product nor skin external preparation could prevent and treat aging of skin sufficiently.
  • Patent Document 3 discloses that when administering subcutaneously a basic fibroblast growth factor (bFGF) additionally to a hepatocyte growth factor (HGF) to the skin just after the wound is formed, tissue regeneration in the wound site is promoted, or formation of scars after the healing of wound is suppressed.
  • bFGF basic fibroblast growth factor
  • HGF hepatocyte growth factor
  • the Patent Document 3 describes that in the mechanism of action, it is estimated that, first, the wounded healing action of bFGF functions during the early phase of injury, and then, during the scar maturation phase, HGF acts to suppress excessive growth and fibrosis of granulation tissue.
  • effect of bFGF without being combined with HGF when a scar has already been formed has not been reported yet.
  • Patent Document 4 discloses a pharmaceutical composition or veterinary composition for preventing and healing or treating organic diseases causing pathological and histological changes in vivo tissues, comprising ginsenoisides or their metabolic products, or salt thereof.
  • bFGF basic fibroblast growth factor
  • PDGF platelet derived growth factor
  • bFGF peptide factors
  • PDGF peptide factors
  • Patent Document 1 Japanese Laid-Open Patent Application No. 5-434442
  • Patent Document 2 Japanese Laid-Open Patent Application No. 2004-043313
  • Patent Document 3 Japanese Laid-Open Patent Application No. 2003-342194
  • Patent Document 4 Japanese Laid-Open Patent Application No. 2002-249498
  • the object of the present invention is to provide an agent for preventing and treating skin aging, and an agent for treating skin scars that can exert sufficient effect.
  • bFGF is a pharmaceutical composition with which only topical application or topical spraying is possible, and it was considered that almost no effect or efficacy can be expected from a systemic administration such as intravenous administration. Specifically, it was thought that even by administering intradermally or subcutaneously bFGF per se, any diseases or symptoms could be prevented or treated significantly. Under such common knowledge of persons skilled in the art, the present inventors found out coincidentally that when intentionally administering intradermally or subcutaneously bFGF, and not using it for external application on the skin surface, it exerts a significant preventative and therapeutic effect on skin aging and a significant therapeutic effect on skin scars. They have thus completed the present invention based on this finding.
  • intradermal administration means to administer an agent (preferably by injection) into dermal tissue of the skin.
  • subcutaneous administration herein means to administer an agent (preferably by injection) into adipose tissue under the skin.
  • the present invention relates to:
  • the present invention relates to:
  • the present invention relates to:
  • FIG. 1 It is a figure showing the injection of the formulation of the present invention into the dermis, taking the injection into the lateral angle of right eye in Case 1 as an example.
  • FIG. 2 It is a figure showing the conditions of the target site to be treated of Case 1 (right lateral angle of eye) before and after the injection of the formulation of the present invention (before and after the treatment).
  • the upper left picture shows the condition before the treatment
  • the upper right picture shows the condition 1 month after the treatment
  • the lower left picture shows the condition 2 months after the treatment
  • the lower right picture shows the condition 3 months after the treatment.
  • FIG. 3 It is a figure showing the conditions of the target site to be treated in Case 2 (lateral angle of right eye and inferior eyelid) before and after the injection of the formulation of the present invention (before and after the treatment).
  • the upper left picture shows the condition before the treatment
  • the lower right picture shows the condition 2 months after the treatment.
  • FIG. 4 It is a figure showing the conditions of the target site to be treated in Case 3 (upper lip) before and after the injection of the formulation of the present invention (before and after the treatment).
  • the left picture shows the condition before the treatment
  • the right picture shows the condition 2 months after the treatment.
  • FIG. 5 It is a figure showing the conditions of the target site to be treated in Case 4 (between eyebrows) before and after the injection of the formulation of the present invention (before and after the treatment).
  • the left picture shows the condition before the treatment
  • the right picture shows the condition 3 months after the treatment.
  • FIG. 6 It is a figure showing the condition of the target site to be treated in Case 5 (dorsum of right hand) before and after the injection of the formulation of the present invention (before and after the treatment).
  • the left picture shows the condition before the treatment
  • the right picture shows the condition 3 months after the treatment.
  • FIG. 7 It is a figure showing the conditions of the target site to be treated in Case 6 (scar on the left shoulder part) before and after the injection of the formulation of the present invention (before and after the treatment).
  • the left picture shows the condition before the treatment
  • the right picture shows the condition 3 months after the treatment.
  • FIG. 8 It is a figure showing the conditions of the target site to be treated in Case 7 (scar on abdominal part) before and after the injection of the formulation of the present invention (before and after the treatment).
  • the left picture shows the condition before the treatment
  • the right picture shows the condition 3 months after the treatment.
  • FIG. 9 It is a graph showing the R2 average values of the dorsum of the hand of normal subjects in each age group.
  • FIG. 10 It is a graph showing the R2 average values of the dorsum of the hand in the non-treated group, and the R2 average values in the treated group on the Case.
  • the agent for preventing and treating skin aging of the present invention is not particularly limited, as long as it comprises bFGF for treating aging of skin, and is administered intradermally or subcutaneously. Further, the agent for treating skin scar of the present invention is not particularly limited, as long as it comprises bFGF for treating aging of skin, and is administered intradermally or subcutaneously.
  • bFGF used in the present invention is a substance that is widely and generally known, and that can also be obtained as a commercial product(e.g. bFGF commercial product “Trafermin” (genetically modified): KAKEN PHARMACEUTICAL CO., LTD., etc.)
  • the aspect of bFGF may be any of a naturally occurring type- or genetically modified type-bFGF, or a precursor protein thereof; a protein wherein one or more constituent amino acids of the naturally occurring type- or genetically modified type-bFGF has been substituted, deleted or inserted; a protein encoded by a cDNA that can hybridize under stringent conditions (65° C., 1 ⁇ SSC, 0.1% SDS or 0.1 ⁇ SSC, 0.1% SDS) to a naturally occurring type-human bFGF; a protein having a homology of 75% or more, preferably 80% or more, more preferably 85% or
  • the expression vector used for enhancing the introduction efficiency of the gene can be exemplified by any expression vector including viral vector. However, it is preferably an expression vector for mammalian cells.
  • the promoter contained in the expression vector used in the present invention is operably linked to bFGF gene, and is a functional promoter in mammalian (preferably human) cells.
  • This promoter is inductive or constitutive, and may be tissue specific according to need. Further, it is known that the rate of gene expression is different depending on the type of promoters, and for example, the expression rate of a gene under control of an immediate early promoter, an early promoter, and a late promoter is different from each other. Therefore, when administering bFGF as a gene to a mammal, the expression rate and sustainability of the bFGF protein can be adjusted by selecting appropriately the type of these promoters.
  • bFGF used in the present invention may be formulated into an appropriate formulation according to a common method.
  • the formulation maybe a solid formulation such as powder, granule, etc.
  • a liquid agent for injection such as a solution agent, emulsion, suspension agent, etc.; or a gelling agent for injection.
  • a method for producing the aforementioned liquid agent for example, a method comprising mixing bFGF with a solvent, and a method comprising further mixing bFGF with a suspending agent, or emulsifying agent can be preferably exemplified.
  • a method for producing the aforementioned gelling agent for example, a method of mixing bFGF with gelatin can be preferably exemplified.
  • an appropriate pharmaceutically acceptable carrier e.g. any component such as excipient, binding agent, solvent, solubilizing agent, suspending agent, emulsifying agent, tonicity agent, buffering agent, stabilizing agent, soothing agent, antiseptic agent, antioxidant agent, coloring agent, etc. may be compounded according to needs in formulation.
  • solvents examples include: hydrophilic solvent such as purified water, physiological saline, Ringer's solution, ethanol, propylene glycol, glycerin, polyethylene glycol, macrogol, etc.; lipophilic solvent such as olive oil, peanut oil, sesame oil, camellia oil, canola oil, fatty acid monoglyceride, fatty acid diglyceride, higher fatty acid ester, liquid paraffin, etc.
  • hydrophilic solvent such as purified water, physiological saline, Ringer's solution, ethanol, propylene glycol, glycerin, polyethylene glycol, macrogol, etc.
  • lipophilic solvent such as olive oil, peanut oil, sesame oil, camellia oil, canola oil, fatty acid monoglyceride, fatty acid diglyceride, higher fatty acid ester, liquid paraffin, etc.
  • suspending agent examples include: stearyl triethanol amine, sodium lauryl sulfate, lauryl aminopropionate, lecitin, benzalkonium chloride, benzethonium chloride, glyceryl monostearate, polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethyl cellulose, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polysolvates, polyoxyethylene hydrogenated castor oil, gum arabic, bentonite, etc.
  • examples of the above emulsifying agent include gum arabic, gelatin, lecithin, cholesterol, yolk, bentonite, Veegum, cetanol, glyceryl monostearate, methyl cellulose, sodium carboxymethyl cellulose, stearic acid, etc.
  • solubilizing agent examples include: polyethylene glycol, propylene glycol, D-mannitol, trehalose, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, sodium salicylate, sodium acetate, etc.
  • excipient examples include: lactose, white soft sugar, D-sorbitol, starch, pregelatinized starch, corn starch, D-mannnitol, dextrin, crystalline cellulose, gum arabic, low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, serum albumin, etc.
  • binding agent examples include: pregelatinized starch, sucrose, gelatin, gum arabic, methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, crystalline cellulose, white soft sugar, D-mannitol, trehalose, dextrin, pullulan, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol, etc.
  • Examples of the above tonicity agent include: sodium chloride, potassium chloride, glucose, fructose, mannitol, sorbitol, lactose, saccharose, glycerin, urea, etc.
  • examples of the above buffering agent include: sodium citrate, glycerin, etc.
  • examples of the above antiseptic agent include: paraoxy benzoic acid esters, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid, etc.
  • Examples of the above stabilizing agent include: polyethylene glycol, dextran sulfate sodium, amino acid, human serum albumin, etc.
  • Examples of the above soothing agent include: glucose sugar, calcium gluconate, procaine hydrochloride, etc.
  • examples of the above antioxidant agent include: sulfite, ascorbic acid, etc.
  • examples of the above coloring agent include: tar pigment, caramel, colcothar, titanium dioxide, FD & C pigments such as FD & C blue No. 2, and FD & C red No. 40 from Ellis & Everard, etc.
  • bFGF used in the present invention may be formulated into a tissue extender, or sustained-release formulation, by using polysaccharides such as alginic acid, hyaluronic acid, chitin, carboxymethyl starch, carboxymethyl cellulose, etc., proteins such as gelatin, collagen, albumin, fibrin, etc., synthetic high molecules such as polyalanine, polyglycolic acid, polypropylene carbonate, etc., and carriers such as tricalcium phosphate, hydroxyapatite, etc.
  • polysaccharides such as alginic acid, hyaluronic acid, chitin, carboxymethyl starch, carboxymethyl cellulose, etc.
  • proteins such as gelatin, collagen, albumin, fibrin, etc.
  • synthetic high molecules such as polyalanine, polyglycolic acid, polypropylene carbonate, etc.
  • carriers such as tricalcium phosphate, hydroxyapatite, etc.
  • the agent for preventing and treating skin aging, or the agent for treating skin scar of the present invention can contain, besides bFGF, a substance having or expected to have an effect on preventing and treating skin aging or an effect to treat skin scar.
  • substances having or expected to have the above effect preferably include one or more selected from the group consisting of morphogens such as DPP (decapentaplegic), transforming growth factor beta, Hh (Hedgehog), shh (sonic Hedgehog), Wnt (Wingless int), bone morphogenetic protein (BMP), epidermal growth factor, and insulin-like growth factor (ILGF), etc; platelet derived growth factor (PDGF), vascular endothelial growth factor (VGEF), hepatocyte growth factor (HGF), etc.
  • those substances intradermally or subcutaneously in addition to the agent for preventing and treating skin aging, or the agent for treating skin scar of the present invention, they may be used in combination with the agent for preventing and treating skin aging, or the agent for treating skin scar of the present invention.
  • the method for administering the agent for preventing and treating skin aging of the present invention, or the agent for treating skin scar of the present invention intradermally or subcutaneously is not particularly limited as long as it is a method for administering the agent intradermally or subcutaneously to the site of skin aging or scar, or surrounding part theirof, being the target of prevention or treatment.
  • the dosage amount is not particularly limited, and generally, it can be administered in an amount of 0.1 ⁇ g to 1 mg, preferably 1 ⁇ g to 100 ⁇ g, more preferably 1 ⁇ g to 10 ⁇ g in terms of bFGF (freeze-dried) per 1 cm 2 of skin that is the target of prevention or treatment.
  • the frequency of administration is not particularly limited, and it can exert a sufficient effect by a single administration.
  • the agent for preventing and treating skin aging of the present invention or the agent for treating skin scar of the present invention is not particularly limited, and it is preferred to appropriately adjust the volume of the agent to be administered intradermally or subcutaneously to 0.1 to 0.3 ml, preferably 0.15 to 0.25 ml per 1 cm 2 of skin. Further, when administering the agent for preventing and treating skin aging of the present invention or the agent for treating skin scar of the present invention intradermally or subcutaneously, it is preferred to use a pressure injector, from the viewpoint of injecting the agent in a simple and accurate manner.
  • Aging of skin that is the target of the agent for preventing and treating skin aging of the present invention is not particularly limited as long as it is an aging of skin, and it may be a physiological change caused by increasing age, or a photoaging caused by irradiation of ultraviolet ray.
  • Specifically preferred examples include one or more selected from skin wrinkle, pigmented spot, sagging skin, rough skin, skin thinning and decrease of skin viscoelasticity.
  • scar of skin that is the target of the agent for treating skin scar of the present invention is not particularly limited as long as it is a scar of skin, and specifically preferred examples include one or more selected from keloid, hypertrophic scar, and scar contracture.
  • substances having a preventive effect to skin aging relate to those having an effect on decreasing any aging of skin in advance.
  • substances having a therapeutic effect on skin aging (skin aging therapeutic effect) in the present invention refer to those having an effect on ameliorating any aging of the skin
  • substances having a therapeutic effect on skin scar (skin scar therapeutic effect) in the present invention refer to those having an effect of ameliorating any of the skin scars.
  • the present invention also encompasses use of bFGF in the manufacture of an agent for preventing and treating aging of skin; use of bFGF in the manufacture of an agent for treating scar of skin; a method for using bFGF in an agent for preventing and treating aging of skin; a method for using bFGF in an agent for treating scar of skin; use of bFGF in the prevention and treatment of aging of skin; use of bFGF in the treatment of scar of skin; a method for preventing and treating skin aging comprising administering intradermally or subcutaneously bFGF to mammals (particularly human); and a method for treating skin scar comprising administering intradermally or subcutaneously bFGF to mammals (particularly human).
  • the meaning of the terms or preferred embodiments in these uses or methods is as described in the above.
  • bFGF solution 500 ⁇ g of the freeze-dried commercial product of bFGF (Trafermin: KAKEN PHARMACEUTICAL CO., LTD.) was dissolved into 50 ml of distilled water for injection, to prepare 10 ⁇ g/ml of bFGF solution.
  • the bFGF solution was dispensed into sterilized polypropylene containers by 1 ml each, and was immediately cryopreserved in a freezer of ⁇ 70° C.
  • a bFGF solution prepared by naturally melting the cryopreserved product at room temperature was used as the formulation of the present invention (agent for preventing and treating skin aging, or agent for treating skin scar).
  • a total of 1.6 ml of the formulation of the present invention (0.2 ml per 1 cm 2 of the skin of the treatment site) was injected to the dermis of the two target sites to be treated (lateral angle of right eye and inferior eyelid) of a 66 years-old woman (Case 2).
  • the treatment sites were observed 2 months after the treatment, plural small wrinkles at the lateral angle of right eye which have been confirmed before the treatment ( FIG. 3 , upper left) had diminished as the skin tugor was improved ( FIG. 3 , lower right).
  • the eye areas were plumped up and the swelling in the inferior eyelid had diminished as compared with before the treatment, and the rejuvenating effect was confirmed ( FIG. 3 , lower right).
  • a total of 1.6 ml of the formulation of the present invention (0.2 ml per 1 cm 2 of the skin of the treatment site) was injected to the target site to be treated (upper lip) of a 56 years-old woman (Case 3), more specifically to the dermis of the entire width of the upper lip, which is 1 cm apart from the upper lip in the opposite direction of the bottom edge of the lip.
  • the treatment site was observed 2 months after the treatment, plural small wrinkles in the longitudinal direction in the upper lip which have been confirmed before the treatment ( FIG. 4 , left) had diminished as the upper lip was plumped up and became resilient( FIG. 4 , right). Further, 2 months after the treatment, the longitudinal length of the upper lip had become shorter as the upper lip was plumped up and became steric ( FIG. 4 , right).
  • the formulation of the present invention was shown to have a significant preventive and therapeutic effect to aging of skin.
  • the formulation of the present invention was shown to have a significant therapeutic effect to skin scar (keloid).
  • the correlation formula between the skin viscoelasticity of the dorsum of the hand of a normal subject without skin diseases, and the age of the normal subject was tried to be calculated.
  • a total of 60 normal subjects (10 subjects in 6 age groups (20s, 30s, 40s, 50s, 60s, and 70s to 90s)) was assembled and the skin viscoelasticity of the dorsum of the hand (20 hands for each age group; total 120 hands) was measured.
  • the R2 average values for each age group are shown in FIG. 9 .
  • the R2 average value of the dorsum of the hand in normal subject was 96.7% in the 20s (age 20 to 29), 93.1% in the 30s, 86.8% in the 40s, 76.2% in the 50s, 69.5% in the 60s and 64.3% in the 70s to 90s.
  • the R2 average value of the dorsum of the hand being the treated group and the R2 average value of the dorsum of the hand being the non-treated group are shown in FIG. 10 .
  • the R2 average value of the dorsum of the hand being the non-treated group (not treated) was 71.6% (corresponding to 61.0 years old), while the R2 average value of the dorsum of the hand being the treated group (after the treatment) was 90.8% (corresponding to 38.8 years old).
  • a significant effect that the skin viscoelasticity of the dorsum of the hand was improved by a condition corresponding to 22.2 years old has been obtained with the formulation of the present invention.
  • a physiologically preferred therapeutic effect i.e. rejuvenating effect of the skin can be obtained by the formulation of the present invention.
  • the agent for preventing and treating skin aging of the present invention exerts a significant effect on preventing and treating aging of skin such as skin wrinkle, pigmented spot, sagging skin, rough skin, skin thinning, decrease of skin viscoelasticity, etc. by an intradermal or subcutaneous administration. Further, the agent for treating skin scar of the present invention exerts a significant effect on treating an already formed skin scar by an intradermal or subcutaneous administration.

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US12/934,299 2008-03-28 2009-03-24 Agent for Treating Skin Aging and Scars Abandoned US20110028699A1 (en)

Applications Claiming Priority (3)

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JP2008-085952 2008-03-28
JP2008085952 2008-03-28
PCT/JP2009/001303 WO2009119073A1 (ja) 2008-03-28 2009-03-24 皮膚の老化や瘢痕の治療剤

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PCT/JP2009/001303 A-371-Of-International WO2009119073A1 (ja) 2008-03-28 2009-03-24 皮膚の老化や瘢痕の治療剤

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US13/233,315 Continuation US8518878B2 (en) 2008-03-28 2011-09-15 Method for treating skin aging by administration of bFGF

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US12/934,299 Abandoned US20110028699A1 (en) 2008-03-28 2009-03-24 Agent for Treating Skin Aging and Scars
US13/233,315 Active US8518878B2 (en) 2008-03-28 2011-09-15 Method for treating skin aging by administration of bFGF
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US20120004173A1 (en) 2012-01-05
CA2718296A1 (en) 2009-10-01
ES2659437T3 (es) 2018-03-15
WO2009119073A1 (ja) 2009-10-01
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JP5553284B2 (ja) 2014-07-16
KR20100126396A (ko) 2010-12-01
EP2263683B1 (en) 2017-09-20
JPWO2009119073A1 (ja) 2011-07-21
US8518878B2 (en) 2013-08-27
KR20160003269A (ko) 2016-01-08
KR20150116922A (ko) 2015-10-16
CA2718296C (en) 2016-08-23
DK2263683T3 (en) 2017-12-11
US20130231285A1 (en) 2013-09-05
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RU2010138655A (ru) 2012-05-10
EP2263683A1 (en) 2010-12-22

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