[go: up one dir, main page]

WO2022035849A1 - Méthodes permettant de réduire la chute des cheveux et/ou d'augmenter la repousse des cheveux - Google Patents

Méthodes permettant de réduire la chute des cheveux et/ou d'augmenter la repousse des cheveux Download PDF

Info

Publication number
WO2022035849A1
WO2022035849A1 PCT/US2021/045377 US2021045377W WO2022035849A1 WO 2022035849 A1 WO2022035849 A1 WO 2022035849A1 US 2021045377 W US2021045377 W US 2021045377W WO 2022035849 A1 WO2022035849 A1 WO 2022035849A1
Authority
WO
WIPO (PCT)
Prior art keywords
fgf
hair
mutant
combinations
truncated
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/US2021/045377
Other languages
English (en)
Inventor
Adam NEDELLA
Robert Wayne BLACKBURN
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.)
Venturis Therapeutics Inc
Original Assignee
Venturis Therapeutics 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 Venturis Therapeutics Inc filed Critical Venturis Therapeutics Inc
Publication of WO2022035849A1 publication Critical patent/WO2022035849A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • 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
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • 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 in general to the field of treating hair loss and promoting hair growth.
  • U.S. Patent No. 10,470,992 issued to Sekhavat and entitled, “Compositions for reducing hair loss and/or increasing hair regrowth”.
  • This inventor teaches a composition comprising 2% to 5% minoxidil, 0.01% to 15% finasteride and 0.01% to 15% of a prostaglandin analog.
  • the prostaglandin analog is latanoprost
  • the composition comprises 5% minoxidil, 0.1% finasteride and 0.03% latanoprost.
  • the composition is said to reduce hair loss and/or increase regrowth of hair in a human subject.
  • Another such patent is U.S. Patent No.
  • the present invention includes a method for treating at least one of hair thinning or hair loss in a patient comprising administering at a site in need of hair growth a fibroblast growth factor-1 (FGF-1) in an amount effective to treat the hair thinning or hair loss.
  • FGF-1 is an FGF-1 mutant or a truncated FGF-1.
  • the truncated FGF-1 is an FGF-11 40, FGF-11 41, FGF-11454, or FGF-11455.
  • the mutant FGF-1 comprises 1, 2, 3, 4, or 5 amino acid changes, or combinations thereof, selected from K9A, K12V, S17R, N18R, N18K, H21Y, R35E, L44F, A66C, Y94V, N95V, H102Y, F108Y, N114R, N114K, Cl 17V, L133A.
  • the FGF-1 is administered subcutaneously, intradermally, or transcutaneous.
  • the FGF-1 is formulated in a pharmaceutical composition formulated for immediate release, sustained release, microneedle patch, transdermal enhancers, or combinations thereof.
  • the FGF-1 further comprises heparin, heparin like molecules, VEGF, TGF-a, TGF-J3, angiostatin, endostatin, and platelet-derived endothelial cell growth factor (PDGF), albumin, FGF-2, other growth factors that induce or enhance angiogenesis, or molecules that enhance the effects of FGF-1.
  • the FGF-1, FGF-1 mutant, truncated FGF-1, or combinations thereof is administered to the subject every 8, 12, 16, 24, 36, 48, 60, 72 days, or at least one of: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 weeks.
  • the FGF-1, FGF-1 mutant, truncated FGF-1, combinations thereof is repeatedly administered to the subject at least once per week for 3, 4, 5, 6, 7 or more weeks.
  • the FGF-1, FGF-1 mutant, truncated FGF-1, or combinations thereof is provided at 20, 50, 100, 200, 500 and 1,000 ug per injection site.
  • the FGF-1, FGF-1 mutant, truncated FGF-1, or combinations thereof is via direct injection into the scalp or surrounding tissues.
  • the FGF-1, FGF-1 mutant, truncated FGF-1, or combinations thereof increases hair growth more than 25, 30, 33, 35, 40, 45, or 50% when compared to a non-treated scalp tissue.
  • the FGF-1 is administered as a total of about 30 to about 60 subcutaneous injections, each in an amount about 0.05 to about 0.1 mL at intervals of about 1 cm to about 2 cm.
  • at least one of the hair thinning and hair loss of the patient is caused by conditions such as male pattern hair loss, female pattern hair loss, alopecia areata, or traction alopecia.
  • the present invention includes a method of treating at least one of hair thinning or hair loss in a patient comprising: identifying a patient with at least one of hair thinning or hair loss of the skin; administering at a site in need of hair growth a fibroblast growth factor- 1 (FGF-1) in an amount effective to treat the hair thinning or hair loss; and applying to the site in need of hair growth with the composition to treat a diminished microvascular blood flow of the scalp, wherein the FGF-1 at least one of hair thinning or hair loss, wherein the hair thinning or hair loss includes preventing additional hair loss, causing new hair growth, increasing the rate of growth, or increasing the thickness of hair.
  • FGF-1 fibroblast growth factor- 1
  • the FGF-1 is an FGF-1 mutant or a truncated FGF-1.
  • the truncated FGF-1 is an FGF-I1 40, FGF-1 M4i, FGF-1 M54, or FGF-11.155.
  • the mutant FGF-1 comprises 1, 2, 3, 4, or 5 amino acid changes, or combinations thereof, selected from K9A, K12V, S17R, N18R, N18K, H21Y, R35E, L44F, A66C, Y94V, N95V, H102Y, F108Y, N114R, N114K, C117V, L133A.
  • the FGF-1 is administered subcutaneously, intradermally, or transcutaneous.
  • the FGF-1 is formulated in a pharmaceutical composition formulated for immediate release, sustained release, microneedle patch, transdermal enhancers, or combinations thereof.
  • the FGF-1 further comprises heparin, heparin like molecules, VEGF, TGF-a, TGF-J3, angiostatin, endostatin, and platelet-derived endothelial cell growth factor (PDGF), albumin, FGF-2, other growth factors that induce or enhance angiogenesis, or molecules that enhance the effects of FGF-1.
  • PDGF platelet-derived endothelial cell growth factor
  • the FGF-1, FGF-1 mutant, truncated FGF-1, or combinations thereof is administered to the subject every 8, 12, 16, 24, 36, 48, 60, 72 days, or at least one of: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 weeks.
  • the FGF-1, FGF-1 mutant, truncated FGF-1, combinations thereof is repeatedly administered to the subject at least once per week for 3, 4, 5, 6, 7 or more weeks.
  • the FGF-1, FGF-1 mutant, truncated FGF-1, or combinations thereof is provided at 20, 50, 100, 200, 500 and 1,000 ug per injection site.
  • the FGF-1, FGF-1 mutant, truncated FGF-1, or combinations thereof is via direct injection into the scalp or surrounding tissues.
  • the FGF-1, FGF-1 mutant, truncated FGF-1, or combinations thereof increases hair growth more than 25, 30, 33, 35, 40, 45, or 50% when compared to a non-treated scalp tissue.
  • the FGF-1, FGF-1 mutant, truncated FGF-1, or combinations thereof are administered as a total of about 30 to about 60 subcutaneous injections, each in an amount about 0.05 to about 0.1 mL at intervals of about 1 cm to about 2 cm.
  • at least one of the hair thinning and hair loss of the patient is caused by conditions such as male patern hair loss, female patern hair loss, alopecia areata, or traction alopecia.
  • FIG. 1 is a photograph that shows the scalp of a subject on Day 0.
  • FIG. 2 is a photograph that shows the scalp of the subject 3 months later, which shows significant new hair growth.
  • FIG. 3 is a photograph that shows the scalp of the subject after over one year, showing that hair continued to remain and grow after at least one year.
  • Arteriogenesis is technically considered remodeling of pre-existing vascular channels (collaterals) or de novo artery formation, it can be stimulated by local changes in perfusion (shear stress), as well as cellular influx and proliferation, and associated with a 20-30 fold increase in blood flow.
  • Vasculogenesis is technically considered on the one hand to encompass embryonic vascular development, and on the other hand to include de novo formation or remodeling of pre-existing vascular channels initiated by circulating vascular precursor cells; furthermore; it is considered to be ischemia and injury initiated.
  • the term “angiogenesis” is meant to encompass all three technical terms.
  • Angiogenesis is known to occur physiologically during zygote implantation, embryogenesis, post-embryonic growth, and during tissue repair and remodeling.
  • angiogenesis is associated with a variety of diseases such as macular degeneration, diabetic retinopathy, inflammation, including arthritis and psoriasis, and cancer.
  • tissue hypoxia In situations of tissue expansion, cells are typically dependent on the microvasculature for nutrients and oxygen supply, as well as removal of metabolic waste products. Accordingly, during tissue growth, cells begin to “sense” a lack of oxygen. This triggers a cascade of events that culminates in angiogenesis.
  • pathological conditions such as the conditions associated with hypoxic and/or ischemic intestinal disease, the lack of oxygen is induced through hypoperfusion. In some pathological conditions, the normal angiogenic response to hypoxia is absent or substantially diminished.
  • treatment does not necessarily mean total cure or abolition of the disease or condition, but rather, include any alleviation of any undesired signs or symptoms of a disease or condition, to any extent, can be considered treatment and/or therapy. It is entirely possible that “treatment” consists of a temporary improvement of the endplate vasculature that requires repeated treatment over time to continue the regenerative process. Furthermore, treatment may include acts that may worsen the patient's overall feeling of well-being or appearance.
  • the phrase “therapeutically effective amount” refers to a compound as used herein to indicate an amount of an active compound, or pharmaceutical agent, that elicits the biological or medicinal response indicated, e.g., FGF-1. This response may occur in a tissue, system, animal or human and includes alleviation of the symptoms of the disease being treated.
  • the exact formulation, route of administration and dosage for the composition and pharmaceutical compositions disclosed herein can be chosen by the individual physician in view of the patient's condition. (See e.g., Fingl et al. 1975, in “The Pharmacological Basis of Therapeutics”, Chapter 1, and updates thereof, or Remington's Pharmaceutical Sciences, Mace Publishing Company, Philadelphia, Pa., 17th ed.
  • Therapeutic treatments can be achieved with small molecule organic drugs or biologies, such as proteins.
  • the dose range of a small molecule therapeutic agent is administered from about 0.5 to 1000 pg/kg, or 1 to 500 pg/kg, or 10 to 500 pg/kg, or 50 to 100 pg/kg of the patient's body weight per dose.
  • the dose of a therapeutic protein growth factor can be administered to the patient intravenously or intraarterially as either a bolus dose or by infusion from about 0.1 to 100 pg/kg of the patient's body weight, or 0.3 to 30 pg/kg, or 1 to 3 pg/kg of the patient's body weight per dose.
  • FGF-1 can be injected either directly into or adjacent to the scalp.
  • Localized dose ranges can be from 10 ng/cm 3 to 1 mg/cm 3 , or 100 ug/cm 3 to 100 ug/cm 3 or 1 ug/cm 3 to 10 ug/cm 3 of target scalp tissue.
  • Local doses can be administered at each area in need of treatment for hair loss, such as the scalp, but also facial tissue.
  • the dosage may be a single one or a series of two or more given in the course of one or more weeks or months, as is needed by the patient.
  • FGF-1 refers to those native FGF-1, FGF-1 mutants or FGF-1 variants of FGF-1 that are still biologically active (that is, they activate FGF-1 receptors), but have a sequence that is altered from the natural FGF-1 that encodes a 154 or 155 amino acid protein of SEQ ID NO:2.
  • the present invention includes the use of FGF-1 15 ' 155 and mutants thereof. The skilled artisan will recognize that the mature form of FGF-1 has the first 14 amino acids cleaved after synthesis and prior to export.
  • truncated FGF-1 proteins for use with the present invention include: synthetic genes that encode a 140 or 141 amino acid protein of SEQ ID NO: 1, which is the mature form of human (i.e., the first 14 amino acids have been cleaved), also referred to as: FGF-1 1 ' 140 , FGF-1 1 ' 141 , FGF-1 10 ' 140 , FGF-1 10 ' 141 , FGF-1 1 ' 140 , FGF- 112-140, pGp_
  • the full length human FGF-1 is UniProtKB - P05230 (FGF1 HUMAN), Entrez Gene: 2246) SEQ ID NO: 2 MAEGEITTFT ALTEKF NLPP GNYKKPKLLY CSNGGHFLRI LPDGTVDGTRDRSDQHIQLQ LSAESVGEVY IKSTETGQYL AMDTDGLLYG SQTPNEECLF LERLEENHYN TYISKKHAEK NWFVGLKKNG SCKRGPRTHY GQKAILFLPL PVSSD (SEQ ID NO:2).
  • Mutant FGF-1 s with one or more amino acid insertions, deletions or substitutions are introduced by standard genetic engineering techniques, such as site-directed, deletion, and insertion mutagenesis.
  • the wild type FGF-1 three-dimensional conformation is known to be marginally stable with denaturation occurring either at or near physiologic temperature. FGF-1 binding to heparin increases the thermal inactivation temperature by approximately 20°C, thus, in certain embodiments the mutant FGF-1 is combined with heparin.
  • the FGF-1 of the present invention can also be formulated with a therapeutically approved USP heparin, or a mutant heparin. The truncations, insertions, deletions or substitutions of the mutant FGF-1 tends to enhance half-life, which is further enhanced by the inclusion of heparin. Further, mutant heparins can also be used to further enhance the half-life or activity of the mutant FGF-1 used herein.
  • heparin is an anti-coagulant that can promote bleeding as a function of increasing concentration.
  • some individuals have been immunologically sensitized to heparin by previous therapeutic exposure, which can lead to heparin-induced thrombocytopenia and thrombotic events.
  • Mutations that extend the storage stability in vitro and biologic activity in vivo would allow FGF-1 to be formulated and dosed in the absence of exogenous heparin. These include mutations that decrease the rate of oxidative inactivation, such as replacement of one or more of the three cysteine residues by either serine or other compatible residues.
  • substitution of cysteine 117 by serine is known to substantially increase the half-life of human FGF-1 by decreasing the rate of oxidative inaction.
  • Other mutations have been described that increase conformational stability by making amino acid changes in internal buried and/or external exposed amino acid residues.
  • FGF-ls exhibiting greater stability and life-time might effectively decrease the frequency and number of repeated doses needed to achieve sustained exposure and greater efficacy.
  • These stabilized mutants would allow longer duration dosing from slow release polymeric matrices and delivery systems.
  • composition(s) of FGF-1, mutant FGF-1, truncated FGF-1 may be formulated for injection and administered by injection, e.g., intraperitoneal, intramuscular, or intravenous injection.
  • Such compositions can have a pH of between 6.5 and 8.5 or between 6.8 and 7.8.
  • Excipients/carriers/other ingredients can include a sterile aqueous buffer, an isotonizing agent, a microbicidal agent or preservative, a chelating agent, a solubility enhancing agent such as dimethylsulfoxide, and/or other ingredients.
  • the isotonizing agent can be, e.g., sorbitol, glycerine, polyethylene glycol, propylene glycol, glucose and sodium chloride.
  • the microbicidal agent/preservative can be, e.g., para-oxy benzoic acid esters, benzyl alcohol, para-chloro-meta-xylenol, chlorocresol, phenetyl alcohol, sorbic acid and salts thereof, thimerosal, chlorobutanol, etc.
  • the chelating agent can be, for example, sodium edetate, sodium citrate or the sodium salt of condensed phosphoric acid.
  • Other forms of FGF-1 may also be used, e.g., non-natural variants of FGF-1 that are still biologically active (activate FGF-1 receptors) but have a sequence that is not found in nature.
  • truncated mutant FGF-1 proteins for use with the present invention include: synthetic genes that encode a 140 or 141 amino acid protein of SEQ ID NO:1, which is the mature form of human, also referred to as: FGF-11 40, FGF-I1 41, FGF-110-140, FGF-110-141, FGF-11.140, FGF-112-140, FGF-I12- 141, and mature FGF-1 with point mutants including, for example, one or more of the following: K9A, K12V, S17R, N18R, N18K, H21Y, R35E, L44F, A66C, Y94V, N95V, H102Y, F108Y, N114R, N114K, Cl 17V, L133A of the mature form of the human FGF-1 (FGF-116-155).
  • the full length human FGF-1 is UniProtKB - P05230 and its gene sequence (FGF1 HUMAN), Entrez Gene: 2246, are incorporated herein by reference.
  • Mutant FGF-ls with one or more amino acid insertions, deletions or substitutions are introduced by standard genetic engineering techniques, such as site-directed, deletion, and insertion mutagenesis.
  • the wild type FGF-1 three- dimensional conformation is known to be marginally stable with denaturation occurring either at or near physiologic temperature.
  • FGF-1 binding to heparin increases the thermal inactivation temperature by approximately 20°C, thus, in certain embodiments the mutant FGF-1 is combined with heparin.
  • mutant FGF-1 of the present invention can also be formulated with a therapeutically approved USP heparin, or a mutant heparin.
  • the truncations, insertions, deletions or substitutions of the mutant FGF-1 tends to enhance half-life, which is further enhanced by the inclusion of heparin.
  • mutant heparins can also be used to further enhance the half-life or activity of the mutant FGF-1 used herein.
  • heparin is an anti-coagulant that can promote bleeding as a function of increasing concentration.
  • some individuals have been immunologically sensitized to heparin by previous therapeutic exposure, which can lead to heparin-induced thrombocytopenia and thrombotic events.
  • Mutations that extend the storage stability in vitro and biologic activity in vivo would allow FGF-1 to be formulated and dosed in the absence of exogenous heparin.
  • mutations that decrease the rate of oxidative inactivation such as replacement of one or more of the three cysteine residues by either serine or other compatible residues.
  • substitution of cysteine 117 by serine is known to substantially increase the half-life of human FGF-1 by decreasing the rate of oxidative inaction.
  • Other mutations have been described that increase conformational stability by making amino acid changes in internal buried and/or external exposed amino acid residues.
  • FGF-ls exhibiting greater stability and life-time might effectively decrease the frequency and number of repeated doses needed to achieve sustained exposure and greater efficacy. These stabilized mutants would allow longer duration dosing from slow release polymeric matrices and delivery systems.
  • angiogenesis-stimulating protein for administration in a therapeutically effective amount.
  • Said protein may be selected from proteins known to stimulate angiogenesis, including but not limited to TPO (thyroid peroxidase), SCF (stem cell factor), IL-1 (interleukin 1), IL-3, IL-6, IL-7, IL-11, flt-3L (fms-like tyrosine kinase 3 ligand), G-CSF (granulocyte-colony stimulating factor), GM-CSF (granulocyte monocyte-colony stimulating factor), EPO (erythropoietin), FGF-1, FGF-2, FGF-4, FGF-5, FGF-20, IGF (insulin-like growth factor), EGF (epidermal growth factor), NGF (nerve growth factor), LIF (leukemia inhibitory factor), PDGF (platelet-derived growth factor), BMPs (bone morphogenetic protein), activin-A,
  • TPO thyroid peroxidase
  • a carrier solution or containing/metering device may be desired.
  • Appropriate carrier solutions may be selected based on properties such as viscosity, ease of administration, ability to bind solution over a period of time, and general affinity for the agent delivered.
  • Said solutions may be modified or additives incorporated for modification of biological properties.
  • Starting solutions may include certain delivery polymers known to one who is skilled in the art.
  • polylactic acid poly- L-lactic acid
  • PDLA poly-D-lactic acid
  • polyglycolide polyglycolic acid
  • PGA polyglycolic acid
  • PLA polylactide-co-glycolide
  • polydioxanone polygluconate
  • polylactic acid-polyethylene oxide copolymers polyethylene oxide, modified cellulose, collagen, polyhydroxybutyrate, polyhydroxpriopionic acid, polyphosphoester, poly (alpha-hydroxy acid), polycaprolactone
  • polycarbonates polyamides, polyanhydrides, polyamino acids, polyorthoesters, polyacetals, polycyanoacrylates, degradable urethanes, aliphatic polyester polyacrylates, polymethacrylate, acryl substituted cellulose acetates, non-degradable polyurethanes, polystyrenes, polyvinyl fluoride, polyvinyl imidazole, chlorosulphonated polyolefin,
  • transdermal enhancer refers to compounds that increase permeability and/or accelerate the delivery of the FGF-1, mutants or variants taught herein through the skin at a location in need of treatment for hair thinning or hair loss.
  • transdermal enhancer examples include: alcohols including ethyl, isopropyl, butyl and benzyl alcohols; dihydric alcohols including ethylene glycol, diethylene glycol, or propylene glycol dipropylene glycol and trimethylene glycol; polyhydric alcohols including glycerin, sorbitol and polyethylene glycol; polyethylene glycol ethers of aliphatic alcohols (including cetyl, lauryl, oleyl and stearyl) polyoxyethylene-4-lauryl ether, polyoxyethylene-2-oleyl ether and polyoxyethylene-10-oleyl ether; vegetable, animal and fish fats and oils including cotton seed, com, safflower, olive and castor oils, squalene, and lanolin; fatty acid alcohols including oleyl alcohol and its derivatives; fatty acid amides including oleamide and its derivatives; urea and urea derivatives such as allantoin; polar solvents including di
  • treatment of scalp tissue can include the use of a biocompatible or biodegradable implant.
  • Biodegradable implants can contain a biodegradable delivery system, or carrier, as well as angiogenic factors; said angiogenic factors could be capable of stimulating sufficient neovascularization to overcome local hypoxia.
  • One preferred angiogenic factor FGF- 1, mutant FGF-1, truncated FGF-1, or both mutant and truncated FGF-1 is preferred.
  • FGF- 1 angiogenic factor
  • truncated FGF-1 truncated FGF-1
  • other recombinant naturally derived, in vitro derived, and in vivo derived angiogenic factors may also be used.
  • the biodegradable implant that contains the angiogenic factors contains a carrier.
  • the carrier is preferably chosen so as to remain within the implanted site for a prolonged period and slowly release the angiogenic factors contained therein to the surrounding environment. This mode of delivery allows said angiogenic factors to remain in therapeutically effective amounts within the site for a prolonged period.
  • the implant's carrier is provided in an injectable form. Injectability allows the carrier to be delivered in a minimally invasive and preferably percutaneous method.
  • the injectable carrier is a gel.
  • the injectable carrier comprises hyaluronic acid (HA).
  • angiogenic treatments can be used in conjunction with other treatments, such as introduction and/or injection of stem cells, which may be embryonic stem cells or adult stem cells. Such angiogenic treatments could be used to prepare tissues for subsequent injection of stem cells, or angiogenic compounds could be injected concurrently with and/or after introduction of such cells.
  • stem cells growth factors, synthetic or treated allograft or xenograft tissue for scaffold (or extra-cellular matrix) and stem cells (each of which could be used separately or in varying levels of in combination with each other) could be utilized to “engineer” or otherwise modify the scalp tissue with the goal of regenerating living tissue within the scalp.
  • stem cells engineered tissue, scaffold, growth factors, or combinations thereof, would be enhanced by combining angiogenic factors such as FGF-1 in its native state or through an FGF-1 mutant (through protein engineering technology) or any other appropriate angiogenic factor to decrease intestinal tissue damage.
  • angiogenic factors such as FGF-1 in its native state or through an FGF-1 mutant (through protein engineering technology) or any other appropriate angiogenic factor to decrease intestinal tissue damage.
  • Example 1 Treatment of Hair Loss with FGF-1.
  • the subject was treated by subcutaneous administration as follows. FGF-1 via ⁇ 50 injections over the affected area using an insulin syringe. It was injected by a physician skilled in the field. No side effects reported other than standard pain associated with subcutaneous injections of the scalp, which are consistent with the procedure. There were 5 rows of 10 injections each of 0. Iml/inj ection for a total of 5 ml total. The concentration of FGF-1 used was Img/mL in phosphate buffered saline (PBS).
  • PBS phosphate buffered saline
  • FIG. 1 is a photograph that shows the scalp of a subject on Day 0.
  • FIG. 2 is a photograph that shows the scalp of the same subject 3 months later, which shows significant new hair growth.
  • FIG. 3 is a photograph that shows the scalp of same subject after over one year, showing that hair continued to remain and grow after at least one year. While the single treatment did not fully restore the hairline, the treatment halted the receding hair line and led to new growth and regrowth, which was maintained over time.
  • the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited features, elements, components, groups, integers, and/or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and/or steps.
  • compositions and methods may be replaced with “consisting essentially of’ or “consisting of’.
  • the term “consisting” is used to indicate the presence of the recited integer (e.g., a feature, an element, a characteristic, a property, a method/process step or a limitation) or group of integers (e.g., feature(s), element(s), characteristic(s), property(ies), method/process steps or limitation(s)) only.
  • the phrase “consisting essentially of’ requires the specified features, elements, components, groups, integers, and/or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and/or steps as well as those that do not materially affect the basic and novel characteristic(s) and/or function of the claimed invention.
  • A, B, C, or combinations thereof refers to all permutations and combinations of the listed items preceding the term.
  • “A, B, C, or combinations thereof’ is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB.
  • expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, AB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth.
  • the skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context.
  • words of approximation such as, without limitation, “about”, “substantial” or “substantially” refers to a condition that when so modified is understood to not necessarily be absolute or perfect but would be considered close enough to those of ordinary skill in the art to warrant designating the condition as being present.
  • the extent to which the description may vary will depend on how great a change can be instituted and still have one of ordinary skill in the art recognize the modified feature as still having the required characteristics and capabilities of the unmodified feature.
  • a numerical value herein that is modified by a word of approximation such as “about” may vary from the stated value by at least ⁇ 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 12 or 15%, or as understood to be within a normal tolerance in the art, for example, within 2 standard deviations of the mean. Unless otherwise clear from the context, all numerical values provided herein are modified by the term about.
  • compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.
  • each dependent claim can depend both from the independent claim and from each of the prior dependent claims for each and every claim so long as the prior claim provides a proper antecedent basis for a claim term or element.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Birds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne une méthode de traitement de l'amincissement des cheveux et/ou de la chute des cheveux chez un patient, comprenant l'administration au niveau d'un site ayant besoin d'une croissance capillaire d'un facteur de croissance de fibroblastes-1 (FGF-1), de mutants et de versions tronquées de celui-ci, en une quantité efficace pour traiter l'amincissement des cheveux ou la chute des cheveux.
PCT/US2021/045377 2020-08-10 2021-08-10 Méthodes permettant de réduire la chute des cheveux et/ou d'augmenter la repousse des cheveux Ceased WO2022035849A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202063063599P 2020-08-10 2020-08-10
US63/063,599 2020-08-10

Publications (1)

Publication Number Publication Date
WO2022035849A1 true WO2022035849A1 (fr) 2022-02-17

Family

ID=80247296

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2021/045377 Ceased WO2022035849A1 (fr) 2020-08-10 2021-08-10 Méthodes permettant de réduire la chute des cheveux et/ou d'augmenter la repousse des cheveux

Country Status (1)

Country Link
WO (1) WO2022035849A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0455422A2 (fr) * 1990-04-27 1991-11-06 Merck & Co. Inc. Méthode pour traiter ou empêcher la calvitie utilisant une composition comprenant du facteur de croissance de fibroblastes
WO2014027363A1 (fr) * 2012-08-17 2014-02-20 Kasiak Research Pvt. Ltd. Concentré de facteurs de croissance pour traiter la perte de cheveux
WO2018018010A1 (fr) * 2016-07-21 2018-01-25 Metacrine, Inc. Mutants de fgf et leurs utilisations
US20180230192A1 (en) * 2009-05-20 2018-08-16 Florida State University Research Foundation, Inc. Fibroblast growth factor mutants having improved functional half-life and methods of their use

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0455422A2 (fr) * 1990-04-27 1991-11-06 Merck & Co. Inc. Méthode pour traiter ou empêcher la calvitie utilisant une composition comprenant du facteur de croissance de fibroblastes
US20180230192A1 (en) * 2009-05-20 2018-08-16 Florida State University Research Foundation, Inc. Fibroblast growth factor mutants having improved functional half-life and methods of their use
WO2014027363A1 (fr) * 2012-08-17 2014-02-20 Kasiak Research Pvt. Ltd. Concentré de facteurs de croissance pour traiter la perte de cheveux
WO2018018010A1 (fr) * 2016-07-21 2018-01-25 Metacrine, Inc. Mutants de fgf et leurs utilisations

Similar Documents

Publication Publication Date Title
AU2015388056B2 (en) Method for promoting hair growth and preventing hair loss of patient, composition therefor, and method for preparing composition
TWI397411B (zh) 光動力美容步驟及癒合方法
AU2010303414B2 (en) Methods and compositions for skin regeneration
US9700504B2 (en) Composition and method for an intradermal hair growth solution
AU2010200621A1 (en) Use of low-dose erythropoietin for stimulation of endothelial progenitor cells, for organ regeneration and for slowing the progression of end-organ damage
EP1270013A1 (fr) Compositions topiques pour le traitement des plaies contenant de l'acide hyaluronique et un inhibiteur de sérine protéase
US20070154532A1 (en) Compositions comprising vitamins and/or derivatives thereof stablished with olea europea extract and/or ionene polymers
KR102324076B1 (ko) 엘라스틴 및 콜라겐 유도를 이용한 피부 주름 및 탄력 개선 효과 조성물
US8518878B2 (en) Method for treating skin aging by administration of bFGF
ES2864328T3 (es) Utilización de fibroblastos gingivales en el tratamiento de la alopecia
WO2022035849A1 (fr) Méthodes permettant de réduire la chute des cheveux et/ou d'augmenter la repousse des cheveux
US20150037382A1 (en) Microsphere skin treatment
US20200009226A1 (en) Compositions and Methods for Treating Stroke
WO2025032597A1 (fr) Composition de croissance des cheveux
AU1318597A (en) Skin treatment formulation and uses thereof
KR102238748B1 (ko) 섬유아세포 배양액을 포함하는 발모 촉진 또는 탈모 치료용 조성물
Fedorchenko PLATELET-RICH PLASMA IN ANTI-AGING AND AESTHETIC MEDICINE
JP4790195B2 (ja) 組織再生剤
Lima et al. Microneedle for skin bioengineering: concepts and approaches
HK1121043A (en) Epidermal growth factor composition, a process therefor and its application
HK1151968A (en) Agent for treating skin aging and scars
HK1151968B (en) Agent for treating skin aging and scars

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: 21856566

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21856566

Country of ref document: EP

Kind code of ref document: A1