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WO2024049923A1 - Compositions et méthodes pour la peau - Google Patents

Compositions et méthodes pour la peau Download PDF

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Publication number
WO2024049923A1
WO2024049923A1 PCT/US2023/031570 US2023031570W WO2024049923A1 WO 2024049923 A1 WO2024049923 A1 WO 2024049923A1 US 2023031570 W US2023031570 W US 2023031570W WO 2024049923 A1 WO2024049923 A1 WO 2024049923A1
Authority
WO
WIPO (PCT)
Prior art keywords
skin
scar tissue
glycoside
derivative
hydroxypropane
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/US2023/031570
Other languages
English (en)
Inventor
I-Chien Liao
Charbel Bouez
Chunmei DING
Chunyan He
Qian Zheng
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.)
LOreal SA
Original Assignee
LOreal SA
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
Priority claimed from US17/900,094 external-priority patent/US20240082279A1/en
Priority claimed from FR2213336A external-priority patent/FR3143355A1/fr
Application filed by LOreal SA filed Critical LOreal SA
Priority to EP23773067.6A priority Critical patent/EP4580595A1/fr
Priority to CN202380071460.0A priority patent/CN119997929A/zh
Publication of WO2024049923A1 publication Critical patent/WO2024049923A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/602—Glycosides, e.g. rutin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14—Probes or electrodes therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/328—Applying electric currents by contact electrodes alternating or intermittent currents for improving the appearance of the skin, e.g. facial toning or wrinkle treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/0616—Skin treatment other than tanning
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/067—Radiation therapy using light using laser light
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B18/203—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser applying laser energy to the outside of the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00571—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for achieving a particular surgical effect
    • A61B2018/00577—Ablation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00571—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for achieving a particular surgical effect
    • A61B2018/00589—Coagulation
    • 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
    • A61K2800/81—Preparation or application process involves irradiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0635—Radiation therapy using light characterised by the body area to be irradiated
    • A61N2005/0643—Applicators, probes irradiating specific body areas in close proximity
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy

Definitions

  • compositions and methods for skin for example for preventing and/or treating scars.
  • the compositions comprise at least one C- glycoside or derivative thereof, and the methods comprise treating skin and/or scar tissue with at least one C-glycoside or derivative thereof and at least one skin modification stimulus.
  • Scars which may occur as part of the skin’s natural healing process following injury from burns, lacerations, abrasion, acne, skin infection, animal bites, piercings, surgery, etc., form after the wound is healed.
  • Types of scars include, for example, atrophic scars (including acne scars), hypertrophic scars (including raised scars and keloid scars), contractive scars, and stretch mark scars.
  • a wound site goes through stages of inflammation, granulation, and matrix remodeling during the healing process.
  • the inflammation stage begins shortly after the injury and lasts for several days, and the granulation stage begins about 24 hours after the injury and lasts for one to two weeks.
  • the remodeling stage lasts up to about a year and involves collagen cross-linking and replacement, wherein a new collagen matrix making up the scar tissue forms.
  • TGF-pi transforming growth factor beta-1
  • retinoids for example, retinoids, topical or injectable steroids, and silicone dressings are currently used to reduce or improve the appearance of scars.
  • surgical or non-surgical procedures that remove parts of the epidermis can accelerate the renewal of the skin’s surface, and thus reduce the appearance of scars.
  • clinicians may use scar modification techniques such as laser treatments and chemical peels to reduce a scar’s appearance, and to even reduce the formation of scars after surgery. Although such treatments cannot completely remove or prevent scars, it can make them less noticeable and uncomfortable.
  • C-glycosides and derivatives thereof such as proxylane (also known as Pro-xylaneTM and hydroxypropyl tetrahydropyrantriol) have an unexpected advantage in treating scars in that these compounds are particularly effective at minimizing the occurrence and/or appearance of scars, thereby improving the appearance of the skin.
  • proxylane also known as Pro-xylaneTM and hydroxypropyl tetrahydropyrantriol
  • compositions and methods for treating scars for example reducing scar tissue, improving the appearance of a scar, and/or preventing or reducing the formation of scar tissue.
  • Compositions according to the disclosure comprise at least one C-glycoside or derivative thereof, and methods according to the disclosure combine the use of at least one C-glycoside or derivative thereof with treatment of skin or scar tissue using a skin modification stimulus.
  • the disclosure relates to the use of at least one C- glycoside or derivative thereof in conjunction with various aesthetic procedures for preventing, reducing, and/or improving the appearance of scars.
  • the disclosure relates to methods comprising applying at least one C- glycoside or derivative thereof before, during, and/or after a skin surfacing or scar modification treatment.
  • the disclosure relates to methods for treating scar tissue, for example by reducing the appearance of the scar, comprising applying at least one C-glycoside or derivative thereof to the scar tissue in combination with treatment with a skin modification stimulus.
  • the disclosure relates to two-step methods for treating scar tissue, the methods comprising:
  • the disclosure relates to methods for preventing or reducing the formation of scar tissue, comprising applying at least one C-glycoside or derivative thereof to skin that does not have scar tissue prior to a skin injury, e.g. prior to a surgical procedure, in combination with a skin modification stimulus treatment.
  • the disclosure relates to two-step methods for preventing or reducing the formation of scar tissue, the methods comprising:
  • the disclosure relates to two-step methods of treating skin to prevent or reduce the formation of scar tissue after surgery, the methods comprising:
  • the at least one C-glycoside or derivative thereof may be applied to skin or scar tissue during treatment with a skin modification stimulus.
  • the at least one C-glycoside or derivative thereof may be applied to the skin or scar tissue before and/or after treatment with a skin modification stimulus, for example within a few seconds, about 1 minute, or about 1 hour before and/or after treating the skin with a skin modification stimulus treatment, to within about 6 hours, about 12 hours, about 18 hours, or about 24 hours before and/or after treating the skin with a scar modification procedure.
  • the at least one C-glycoside or derivative thereof may be applied to the skin or scar tissue one or more times per day, for example 2 times per day, 3 times per day, or more.
  • the at least one C-glycoside or derivative thereof can be applied to the skin or scar tissue at least once a day over a period of one or more consecutive days, for example at least 2 days, at least 3 days, at least 4 days, at least 5 days, or more, or at least once a day over a period of one or more non-consecutive days, for example every other day, about three times a week, about twice a week, about once a week, about once every 2 weeks, about once every 3 weeks, about once every 4 weeks, or more.
  • methods according to the disclosure may be repeated one or more times, for example every day, every other day, about three times a week, about twice a week, about once a week, about once every 2 weeks, about once every 3 weeks, about once every 4 weeks, or more.
  • the disclosure relates to methods for treating scar tissue, comprising (1 ) treating scar tissue with at least one skin modification stimulus, and (2) applying at least one C-glycoside or derivative thereof to the scar tissue; wherein the skin modification stimulus is chosen from a laser, plasma, radiofrequency, a high-intensity focused ultrasound, an electrical field, heat, a low- level light device, a needle, a microneedle, an abrasive element, and/or a chemical agent such as a chemical exfoliating agent; and wherein the C-glycoside is preferably chosen from C-xylopyranosides and/or derivatives thereof, more preferably C13-D- xylopyranoside-2-hydroxypropane and/or Co-D-xylopyranoside-2-hydroxypropane; and wherein step (2) occurs before, during, and/or after step (1 ).
  • the skin modification stimulus is chosen from a laser, plasma, radiofrequency, a high-intensity focused ultrasound, an electrical field, heat,
  • the disclosure relates to methods for preventing or reducing the formation of scar tissue, comprising (1 ) treating uninjured skin with at least one skin modification stimulus, and (2) applying at least one C-glycoside or derivative thereof to the skin; wherein the skin modification stimulus is chosen from a laser, plasma, radiofrequency, a high-intensity focused ultrasound, an electrical field, heat, a low-level light device, a needle, a microneedle, an abrasive element, and/or a chemical agent such as a chemical exfoliating agent; wherein the C-glycoside is preferably chosen from C-xylopyranosides and/or derivatives thereof, more preferably C13-D-xylopyranoside-2-hydroxypropane and/or Ca-D-xylopyranoside-2- hydroxypropane; and wherein step (2) occurs before, during, and/or after step (1 ).
  • the skin modification stimulus is chosen from a laser, plasma, radiofrequency, a high-intensity focused
  • the disclosure relates to methods of treating skin to prevent or reduce the formation of scar tissue after surgery, comprising (1 ) injuring skin, and (2) applying at least one C-glycoside or derivative thereof to the skin; wherein the C-glycoside is preferably chosen from C-xylopyranosides and/or derivatives thereof, more preferably C13-D-xylopyranoside-2-hydroxypropane and/or Ca-D- xylopyranoside-2-hydroxypropane; and wherein step (2) occurs before, during, and/or after step (1 ).
  • the disclosure relates to methods for reducing the conversion of fibroblasts to myofibroblasts, increasing the expression level of DKK- 1 , increasing the phosphorylation of -catenin, and/or downregulating the signal transduction of TGF-p in uninjured skin and/or scar tissue, comprising (1 ) treating the uninjured skin and/or scar tissue with at least one skin modification stimulus, and (2) applying at least one C-glycoside or derivative thereof to the uninjured skin and/or scar tissue; wherein the skin modification stimulus is chosen from a laser, plasma, radiofrequency, a high-intensity focused ultrasound, an electrical field, heat, a low- level light device, a needle, a microneedle, an abrasive element, and/or a chemical agent such as a chemical exfoliating agent; wherein the C-glycoside is preferably chosen from C-xylopyranosides and/or derivatives thereof, more preferably C13-D- x
  • the disclosure relates to methods for treating scar tissue, comprising (1 ) treating scar tissue with at least one skin modification stimulus, and (2) applying a composition comprising at least one C-glycoside or derivative thereof, at least one solvent or carrier, and optionally at least one additional active ingredient and/or additive described herein, to the scar tissue;
  • the skin modification stimulus is chosen from a laser, plasma, radiofrequency, a high-intensity focused ultrasound, an electrical field, heat, a low-level light device, a needle, a microneedle, an abrasive element, and/or a chemical agent such as a chemical exfoliating agent;
  • the C-glycoside is preferably chosen from C- xylopyranosides and/or derivatives thereof, more preferably C13-D-xylopyranoside-2- hydroxypropane and/or Ca-D-xylopyranoside-2-hydroxypropane, and the total amount of C-glycoside(s) range
  • the disclosure relates to methods for preventing or reducing the formation of scar tissue, comprising (1 ) treating uninjured skin with at least one skin modification stimulus, and (2) applying a composition comprising at least one C-glycoside or derivative thereof, at least one solvent or carrier, and optionally at least one additional active ingredient and/or additive described herein, to the skin;
  • the skin modification stimulus is chosen from a laser, plasma, radiofrequency, a high-intensity focused ultrasound, an electrical field, heat, a low- level light device, a needle, a microneedle, an abrasive element, and/or a chemical agent such as a chemical exfoliating agent;
  • the C-glycoside is preferably chosen from C-xylopyranosides and/or derivatives thereof, more preferably C13-D- xylopyranoside-2-hydroxypropane and/or Co-D-xylopyranoside-2-hydroxypropane, and the total amount of C-
  • the disclosure relates to methods of treating skin to prevent or reduce the formation of scar tissue after surgery, comprising (1 ) injuring skin, and (2) applying a composition comprising at least one C-glycoside or derivative thereof, at least one solvent or carrier, and optionally at least one additional active ingredient and/or additive described herein, to the skin; wherein the C-glycoside is preferably chosen from C-xylopyranosides and/or derivatives thereof, more preferably C13-D-xylopyranoside-2-hydroxypropane and/or Ca-D-xylopyranoside-2- hydroxypropane, and the total amount of C-glycoside(s) ranges from about 0.01% to about 30%, preferably from about 0.1% to about 20%, more preferably from about 0.3% to about 12%, more preferably from about 0.5% to about 10%, still more preferably from about 1 % to about 5%, from about 1 .5% to about 4.5%, or from about 2% to about 4%
  • the disclosure relates to methods for reducing the conversion of fibroblasts to myofibroblasts, increasing the expression level of DKK- 1 , increasing the phosphorylation of p-catenin, and/or downregulating the signal transduction of TGF- in uninjured skin and/or scar tissue, comprising (1 ) treating the uninjured skin and/or scar tissue with at least one skin modification stimulus, and (2) applying a composition comprising at least one C-glycoside or derivative thereof, at least one solvent or carrier, and optionally at least one additional active ingredient and/or additive described herein, to the uninjured skin and/or scar tissue; wherein the skin modification stimulus is chosen from a laser, plasma, radiofrequency, a high- intensity focused ultrasound, an electrical field, heat, a low-level light device, a needle, a microneedle, an abrasive element, and/or a chemical agent such as a chemical exfoliating agent; wherein the C-glycoside is preferably chosen from
  • the methods comprise:
  • FIG. 1 discloses a diagram of an exemplary scar revision surgery according to the disclosure which involves the use of at least one C-glycoside or derivative thereof.
  • a scar is formed after tissue injury.
  • the scar tissue is treated with an aesthetic laser, followed by hydroxypropyl tetrahydropyrantriol.
  • FIG. 2 discloses hematoxylin and eosin (H&E) stained cross-sections of SoftskinTM model epidermal tissues that have (“Laser”) or have not (“Control”) been subjected to laser ablation. Some tissues were treated once a day for 3 days with 3% hydro xypropyl tetrahydropyrantriol in 3% propylene glycol (“Laser/3% Proxylane”), or 2% hyaluronic acid (“Laser/2% Hyaluronic Acid”). Cross-sections were obtained and stained on days 0, 2, and 4.
  • H&E hematoxylin and eosin
  • FIG. 3 discloses filament aggregating protein (Filaggrin) antibody immunostained cross-sections of Day 2 SoftskinTM model epidermal tissues that a) have not been treated (control), b) were laser-treated, c) were laser treated, then treated with 3% hydroxypropyl tetrahydropyrantriol in 3% propylene glycol, and d) were laser treated, then treated with 3% propylene glycol control vehicle.
  • Blue DARI (nucleus).
  • FIG. 4 discloses relative Filaggrin expression in day 2 SoftskinTM model epidermal tissues before and after laser ablation, and in tissues further treated with 3% propylene glycol (negative control/placebo) vehicle or 3% hydroxypropyl tetrahydropyrantriol in 3% propylene glycol as measured using Image J software.
  • FIG. 5 discloses Ki-67 antibody immunostained cross-sections of Day 2 SoftskinTM model epidermal tissues that a) have not been treated (control), b) were laser-treated, c) were laser treated, then treated with 3% hydroxypropyl tetrahydropyrantriol in 3% propylene glycol, and d) were laser treated, then treated with 3% propylene glycol control vehicle.
  • FIG. 6 discloses the ratio of Ki67 (Antigen KI-67, or MKI67) expression to DAPI expression in day 2 SoftskinTM model epidermal tissues before and after laser ablation, and in tissues further treated with 3% propylene glycol (negative control/placebo) vehicle or 3% hydroxypropyl tetrahydropyrantriol in 3% propylene glycol as measured using a 3D HISTECH PANNORAMIC MIDI II fluorescence scanner.
  • Ki67 Antigen KI-67, or MKI67
  • FIG. 7 discloses relative alpha Dickkopf WNT signaling pathway inhibitor 1 (DKK-1 ) expression in day 1 SoftskinTM model epidermal tissues before and after laser ablation, and in tissues further treated with 3% propylene glycol (negative control/placebo) vehicle or 3% hydroxypropyl tetrahydropyrantriol in 3% propylene glycol.
  • DKK-1 Dickkopf WNT signaling pathway inhibitor 1
  • FIG. 8 discloses relative alpha-smooth muscle actin (a-SMA) expression in day 2 SoftskinTM model epidermal tissues before and after laser ablation, and in tissues further treated with 3% propylene glycol (negative control/placebo) vehicle or 3% hydroxypropyl tetrahydropyrantriol in 3% propylene glycol.
  • a-SMA alpha-smooth muscle actin
  • the disclosure relates to compositions and methods for treating scar tissue, such as by increasing, accelerating, and/or improving healthy skin renewal instead of scar tissue, and/or improving the appearance of scarred skin.
  • the type of scars that can be treated is not limited, and includes, for example, keloid scars, flat scars, raised scars, contracture scars, atrophic scars, stretch marks, etc.
  • the disclosure also relates to compositions and methods for preventing or minimizing the formation of scar tissue prior to a skin injury, for example prior to a surgical procedure.
  • compositions according to various aspects of the disclosure comprise at least one C-glycoside or derivative, for example at least one C-xylopyranoside or derivative, and in at least certain embodiments comprise hydroxypropyl tetrahydropyrantriol.
  • the methods comprise treating scar tissue with at least one skin modification stimulus and applying at least one C- glycoside or derivative thereof, for example a C-xylopyranoside or derivative thereof, e.g. hydroxypropyl tetrahydropyrantriol, to the scar tissue.
  • the methods comprise treating uninjured skin with at least one skin modification stimulus and applying at least one C-glycoside or derivative thereof, for example a C- xylopyranoside or derivative thereof, e.g. hydroxypropyl tetrahydropyrantriol, to the skin, in order to prevent or reduce the formation of scars.
  • C-glycosides and derivatives thereof may advantageously prevent or reduce the formation of scars, and/or may improve the appearance of scars, by reducing the conversion of fibroblasts to myofibroblasts and/or by targeting TGF-pi signaling, which is reduced by modulating beta catenin (P-catenin) via Dickkopf WNT signaling pathway inhibitor 1 (DKK-1 ) expression, and/or enhances scar reduction kinetics.
  • P-catenin beta catenin
  • DKK-1 Dickkopf WNT signaling pathway inhibitor 1
  • the at least one C-glycoside or derivative thereof increases the expression level of DKK-1 in scar tissue, which targets Wnt/LRP6 association, increases the phosphorylation of p-catenin, and ultimately downregulates the signal transduction of TGF-p in scar tissue.
  • compositions and methods according to the disclosure address the problem of scar prevention and treatment in a new and previously unknown manner, via a mechanism that is different from that of known methods such as retinoids, topical or injectable steroids, silicone dressings, and surgical and non-surgical medical procedures.
  • retinoids topical or injectable steroids
  • silicone dressings silicone dressings
  • surgical and non-surgical medical procedures By treating skin and/or scar tissue with a skin modification stimulus and applying at least one C-glycoside or derivative thereof to the targeted area, it encourages new growth of normal skin tissue, rather than new growth of scar tissue.
  • the scar treatment and prevention methods and compositions according to the disclosure impart broader and/or stronger scar treatment and prevention benefits to skin, with or without enhanced kinetics, as compared to known scar treatments.
  • compositions, methods, and kits for treating skin and scar tissue are provided below.
  • compositions according to the disclosure comprise at least one C-glycoside or derivative thereof.
  • the compositions may further comprise additional components such carriers, active ingredients other than C-glycosides or derivatives thereof, and additives typically found in skin care compositions.
  • a C-glycoside is a sugar moiety linked via a carbon-carbon (C-C) bond to a non-sugar moiety (aglycone).
  • the C-glycoside may be chosen from C13-D-xylopyranoside-n-propan-2-one; Ca-D-xylopyranoside n-propan- 2-one; C13-D-xylopyranoside-2-hydroxypropane; Ca-D-xylopyranoside-2- hydroxypropane; 1 -(C13-D-fucopyranoside)-propane-2-one; 1 -(Ca-D- fucopyranoside)-propan-2-one; 1 -(C13-L-fucopyranoside)-propan-2-one; 1 -(Ca-L- fucopyranoside)-propane-2-one; 2-one, 1 -(C13-D-fucopyranoside)-2-
  • the at least one C-glycoside is a C-xylopyranoside.
  • the C-glycoside comprises, consists essentially of, or consists of C13-D-xylopyranoside-2-hydroxypropane, Ca-D-xylopyranoside-2- hydroxypropane, or mixtures thereof.
  • the C-glycoside comprises, consists essentially of, or consists of C13-D-xylopyranoside-2- hydroxypropane (also known as Cp-D-xylopyranoside-2-hydroxypropane, hydroxypropyl tetrahydropyrantriol, or Proxylane). Hydroxypropyl tetrahydropyrantriol has the structure of Formula (I) below:
  • compositions according to the disclosure may comprise a total amount of C-glycoside and derivatives thereof from about 0.01 % to about 30%, from about 0.05% to about 25%, from about 0.1 % to about 20%, from about 0.2% to about 15%, from about 0.3% to about 12%, from about 0.4% to about 11 %, from about 0.5% to about 10%, from about 0.6% to about 9%, from about 0.7% to about 8%, from about 0.8% to about 7%, from about 0.9% to about 6%, from about 1 % to about 5%, from about 1 .5% to about 4.5%, from about 2% to about 4%, from about 2.5% to about 3.5%, or about 3% by weight, including all ranges and subranges therebetween using any of the disclosed lower limits as a lower limit and disclosed upper limits as an upper limit, relative to the total weight of the composition in which it is present.
  • the total amount of C-glycoside and derivatives thereof in compositions according to the disclosure may be about 0.01 %, about 0.05%, about 0.1 %, about 0.25%, about 0.5%, about 0.75%, about 1 %, about 1 .25%, about 1.5%, about 1.75%, about 2%, about 2.25%, about 2.5%, about 2.75%, about 3%, about 3.25%, about 3.5%, about 3.75%, about 5%, about 5.25%, about 5.5%, about 5.75%, about 6%, about 6.25%, about 6.5%, about 6.75%, about 7%, about 7.25%, about 7.5%, about 7.75%, about 8%, about 8.25%, about 8.5%, about 8.5%, about 8.75%, about 9%, about 9.25%, about 9.5%, about 9.75%, about 10%, about 10.5%, about 1 1%, about 1 1.5%, about 12%, about 12.5%, about 13%, about 13.5%, about 14%, about 14.5%, about 15%, about 15.5%, about
  • compositions will generally comprise one or more cosmetically- acceptable carriers, including but not limited to water and/or non-aqueous solvents.
  • non-aqueous solvents include glycerin; glycols, such as ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, pentaethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, polyethylene glycol, caprylyl glycol, and hexylene glycol; glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol mono-n-propyl ether, ethylene glycol mono-iso-propyl ether, diethylene glycol mono-iso-propyl ether, ethylene glycol mono-n-butyl ether, ethylene glycol mono-t-
  • compositions may optionally comprise one or more active ingredients other than C-glycosides or derivatives thereof, such as, for example, actives that can modulate inflammation (including but not limited to carotenoids, curcumin, steroids, cannabinoids, glycoproteins, essential oils, flavonoids & flavonoid derivatives, phenolic acids, ascorbic acid, polyphenols, marine and algal extracts), actives that can enhance skin barrier (including but not limited to pantothenic acid, ceramides, pseudo ceramides such as 2-Oleyl-1 ,3-octadecanediol, niacinamides, niacinamide derivatives, carob seed extracts, oligo-galactomannan, colloidal oatmeal, hyaluronic acids, probiotics and p-glucan), and/or actives that can modulate skin fibrosis (including but not limited to inhibitors of TNF, inhibitors of TGF-p, inhibitors of mTOR pathway and
  • compositions may optionally contain one or more additives such as those typically found in the skin care compositions, including but not limited to oils, waxes, or other fatty substances; gelling agents and/or thickeners; emulsifiers; moisturizing agents; emollients; sunscreens; hydrophilic or lipophilic active agents, such as ceramides; agents for combatting free radicals; bactericides; sequestering agents; preservatives; pH adjusters; skin penetration enhancers; fragrances; surfactants; fillers; natural products or extracts thereof, such as aloe or green tea extract; vitamins; and/or coloring materials.
  • additives such as those typically found in the skin care compositions, including but not limited to oils, waxes, or other fatty substances; gelling agents and/or thickeners; emulsifiers; moisturizing agents; emollients; sunscreens; hydrophilic or lipophilic active agents, such as ceramides; agents for combatting free radicals; bactericides; se
  • the amount of such additives, if present, will vary depending on the intended use and/or properties of the composition and the effect desired, but will, in individual or combined amount, typically range from about 0.0001% to about 20%, such as from about 0.001 % to about 15%, from about 0.01 % to about 10%, from about 0.1 % to about 7.5%, from about 0.5% to about 5%, or from about 1 % to about 3% by weight, relative to the total weight of the composition.
  • compositions according to the disclosure is not limited, and may include, for example, liquids, emulsions, suspensions, lotions, creams, gels (including hydrogels), balms, pastes, serums, salves, foams, or the like.
  • compositions are typically applied topically and can, in various embodiments, be applied by the consumer as an at-home formulation, or by a professional, e.g. in a clinical setting as part of an aesthetic procedure.
  • a non-limiting example of a composition according to the disclosure includes a carrier, for example water and/or at least one non-aqueous solvent, optionally at least one active ingredient other than C-glycosides or derivatives thereof and/or at least one additive, and a total amount of C-glycoside and derivatives thereof ranging from about 0.01 % to about 30%, from about 0.05% to about 25%, from about 0.1% to about 20%, from about 0.2% to about 15%, from about 0.3% to about 12%, from about 0.4% to about 11 %, from about 0.5% to about 10%, from about 0.6% to about 9%, from about 0.7% to about 8%, from about 0.8% to about 7%, from about 0.9% to about 6%, from about 1% to about 5%, from about 1.5% to about 4.5%, from about 2% to about 4%, from about 2.5% to about 3.5%, or about 3% by weight, including all ranges and subranges therebetween, relative to the total weight of the composition in which it is present.
  • a carrier for example water
  • a further non-limiting example of a composition according to the disclosure includes a carrier comprising water and optionally at least one non-aqueous solvent, optionally at least one active ingredient other than C-glycosides or derivatives thereof and/or at least one additive, and hydroxypropyl tetrahydropyrantriol present in an amount ranging from about 0.01 % to about 30%, from about 0.05% to about 25%, from about 0.1 % to about 20%, from about 0.2% to about 15%, from about 0.3% to about 12%, from about 0.4% to about 11 %, from about 0.5% to about 10%, from about 0.6% to about 9%, from about 0.7% to about 8%, from about 0.8% to about 7%, from about 0.9% to about 6%, from about 1 % to about 5%, from about 1 .5% to about 4.5%, from about 2% to about 4%, from about 2.5% to about 3.5%, or about 3% by weight, including all ranges and subranges therebetween, relative to the total weight of the composition in which it is present.
  • the disclosure relates to methods of treating scar tissue to reduce or improve the appearance of the scar.
  • the disclosure relates to methods of treating skin, such as skin that does not have visible scar tissue, to prevent and/or reduce the formation of scar tissue, for example uninjured skin.
  • the disclosure relates to methods of reducing the conversion of fibroblasts to myofibroblasts, targeting transforming growth factor beta 1 (TGF-pi ) signaling, reducing modulating beta catenin (P-catenin), increasing the expression level of DKK-1 , disrupting Wnt/LRP6 association, increasing the phosphorylation of p-catenin, and/or downregulating the signal transduction of TGF-p.
  • TGF-pi transforming growth factor beta 1
  • P-catenin modulating beta catenin
  • the methods comprise applying at least one C-glycoside or derivative thereof, for example a C-xylopyranoside or derivative thereof, e.g. hydroxypropyl tetrahydropyrantriol, to a desired area to be treated, for example to uninjured skin or to scar tissue (referred to collectively in some instances herein as a “target area”), before, during, and/or after treating the uninjured skin or scar tissue with a stimulus for modifying skin or scar tissue (referred to interchangeably herein as a “skin modification stimulus”).
  • a desired area to be treated for example to uninjured skin or to scar tissue
  • a stimulus for modifying skin or scar tissue referred to interchangeably herein as a “skin modification stimulus”.
  • the C-glycoside or derivative thereof comprises, consists essentially of, or consists of C-xylopyranosides and/or derivatives thereof, and in further methods, the C-glycoside or derivative thereof comprises, consists essentially of, or consists of hydroxy propyl tetrahydropyrantriol.
  • useful skin modification stimuli include those used in the skin care field to modify or damage skin or scar tissue in order to encourage new growth, generally in a controlled manner. These treatments typically damage the outermost layers of the skin or scar tissue to a relatively mild degree, which sets into motion the body’s natural healing process. Such treatments may also stimulate the production of collagen.
  • any known method or device for modifying or damaging the skin or scar tissue can be used in the methods according to the disclosure.
  • the skin modification stimulus may modify or damage the skin or scar tissue by cutting, burning, chemically damaging, ablating, micro-ablating, coagulating, or otherwise affecting the corneal layer and subcutaneous tissue of the target area.
  • modified scar tissue is scar tissue that has been modified or damaged with one or more skin modification stimuli, and is healing from treatment with the skin modification stimulus.
  • modified skin tissue is skin tissue, typically uninjured and/or without scar tissue, that has been modified or damaged with one or more skin modification stimuli, and is healing from treatment with the skin modification stimulus.
  • the skin modification stimulus used in the methods according to the disclosure may, in various embodiments, be invasive or non-invasive.
  • the skin modification stimulus can be a laser, plasma, radiofrequency, a high-intensity focused ultrasound, an electrical field, heat, a low- level light device, a needle, a microneedle, an abrasive element, a chemical agent such as a chemical exfoliating agent, or the like
  • the skin modification stimulus treatment may be a laser procedure, a microneedling procedure, a high-intensity focused ultrasound procedure, an electroporation procedure, a dermabrasion procedure, a microdermabrasion procedure, a plasma skin rejuvenation procedure, a chemical exfoliation procedure, or the like.
  • any variety of cosmetic lasers distinguished by their wavelength and their mode of delivering the laser, can be used.
  • the target area may be treated with ablative or non-ablative lasers.
  • Ablative lasers may include, e.g., carbon dioxide or Erbium lasers.
  • Non-ablative lasers may include, e.g., pulsed light, pulsed-dye, and fractional lasers. Lasers can also be modified when combined with other elements, such as gases, precious stones, and metals.
  • Nonlimiting examples include Clear+Bril liant® lasers, fractional photothermolysis lasers, alexandrite lasers, carbon dioxide (CO2) lasers, erbium (Er:YAG) lasers, intense pulsed light (I PL) lasers, Nd:YAG lasers, pulse dye lasers, Q-switched lasers, picosecond lasers, etc.
  • the target area may be treated with mechanical microneedling, which uses a motorized pen with tiny slender needles to create thousands of channels that are up to 2.5 millimeters deep. These channels disrupt the uninjured skin or scar tissue to allow for growth of new skin.
  • mechanical microneedling devices that can be used include SkinPen Precision, MDpen, Skin Stylus, etc.
  • the target area may be treated with fractional radiofrequency (RF) microneedling, which is a heat-based therapy that uses thicker needles to transmit heat deep into the skin.
  • RF microneedling thermally coagulates tissue to stimulate collagen denaturation and renewal.
  • Radiofrequency (RF) microneedling generates less microchannels than mechanical needling.
  • the target area may be treated with standard or short-pulse RF microneedling.
  • Non-limiting examples of RF devices include Scarlet SRF, Agnes RF, Endymed Intensif, Secret RF, Vivace, Virtue RF, Morpheus8, etc.
  • the target area can also be treated with ultrasound, such as through ultratherapy.
  • Ultrasound can thermally loosen, stretch, and re-orient collagen tissue.
  • Ultrasound mechanically acts on skin and scar tissue as a micro-massage and produces microscopic droplets of oxygen (calvitation) from the vibration.
  • Electroporation mesotherapy can also be utilized with the disclosed methods. Electroporation uses electricity to boost the permeability of the skin or scar tissue membrane by creating microscopic channels that open up pathways deep into the skin, thus disrupting scar tissue.
  • Dermabrasion including microdermabrasion, may also be used to treat the target area in some embodiments. Dermabrasion involves the controlled deeper abrasion of the upper to mid layers of the uninjured skin or scar tissue with any variety of strong abrasive devices such as a wire brush, diamond wheel (or fraise), or serrated wheel. Exemplary embodiments may include crystal microdermabrasion or diamond microdermabrasion.
  • plasma skin rejuvenation may be used in the disclosed methods.
  • Plasma skin regeneration can be used to deliver energy in the form of plasma to the target area, resembling a thermal device and a dry peel. This process is useful in particular for breaking up scar tissue.
  • chemical peels also known as chemexfoliation or derma-peeling
  • exemplary and nonlimiting chemical agents that may be used to treat the target area include chemical agents capable of acting either directly on peeling by encouraging exfoliation, such as p-hydroxyacids (BHAs), for example salicylic acid and derivatives thereof (including n- octanoyl 5-salicylic acid, otherwise known as capryloyl salicylic acid (INCI name)); a- hydroxyacids (AHAs), such as glycolic, lactic, tartric, malic, or mandelic acids; 8- hexadecene-1 ,16-dicarboxylic acid, or 9-octadecene dioic acid; urea and derivatives thereof; trichloroacetic acid; gentisic acid and derivatives thereof; oligofuctoses; cinnamic acid; extract of Saphora japon
  • chemical peeling agents that may be used include compounds involved in peeling or degrading corneodesmosomes, such as aminosulfonic compounds, e.g. 4-(2-hydroxyethyl)piperazine-1 -propanesulfonic acid (HEPES); 2-oxothiazolidine-4-carboxylic acid (procysteine) and derivatives thereof; the derivatives of a-amino acids of the glycine type (as described in EP-0 852 949) and also sodium methyl glycine diacetate sold by BASF under the trade name Trilon M; honey; derivatives of sugar such as O-octanoyl-6-D-maltose and N-acetyl glucosamine; or mixtures thereof.
  • aminosulfonic compounds e.g. 4-(2-hydroxyethyl)piperazine-1 -propanesulfonic acid (HEPES); 2-oxothiazolidine-4-carboxylic acid (procysteine
  • the chemical peeling agent(s) may, in certain embodiments, be chosen from a-hydroxy acids such as citric, lactic, glycolic, malic, tartric, or mandelic acids; 0- hydroxy acids such as salicylic acid or derivatives thereof, e.g. n-octanoyl-5-salicylic acid; tricholoacetic acid; phenols; croton oil peels; or mixtures thereof.
  • a-hydroxy acids such as citric, lactic, glycolic, malic, tartric, or mandelic acids
  • 0- hydroxy acids such as salicylic acid or derivatives thereof, e.g. n-octanoyl-5-salicylic acid
  • tricholoacetic acid phenols
  • croton oil peels or mixtures thereof.
  • the C-glycoside or derivative thereof will typically remain on the skin (e.g. uninjured skin or scar tissue, which may or may not be modified skin tissue or modified scar tissue) for a time sufficient to achieve the desired benefits.
  • the at least one C- glycoside or derivative thereof is left on the skin for a desired period of time, for example at least 10 seconds, at least 20 seconds, at least 30 seconds, at least 40 seconds, at least 50 seconds, at least 1 minute, at least 2 minutes, at least 3 minutes, at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 20 minutes, at least 25 minutes, at least 30 minutes, at least 35 minutes, at least 40 minutes, at least 45 minutes, at least 1 hour, at least 2 hours, at least 5 hours, at least 8 hours, at least 10 hours, at least 15 hours, at least 20 hours, at least 24 hours, at least 36 hours, or at least 48 hours before it is removed, such as by, for example, wiping or rinsing the skin.
  • a desired period of time for example at least 10 seconds, at least 20 seconds, at least 30 seconds, at least 40 seconds, at least 50 seconds, at least 1 minute, at least 2 minutes, at least 3 minutes, at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 20 minutes,
  • the at least one C-glycoside or derivative thereof may be left on the skin for a period of time ranging from 5 minutes to 60 minutes, such as from 5 minutes to 50 minutes, from 5 minutes to 40 minutes, from 5 minutes to 35 minutes, from 5 minutes to 30 minutes, from 5 minutes to 25 minutes, from 5 minutes to 20 minutes, from 5 minutes to 15 minutes, or from 5 minutes to 10 minutes.
  • the at least one C-glycoside or derivative thereof may be left on the skin for a period of time ranging from 10 minutes to 60 minutes, such as from 10 minutes to 50 minutes, from 10 minutes to 40 minutes, from 10 minutes to 35 minutes, from 10 minutes to 30 minutes, from 10 minutes to 25 minutes, from 10 minutes to 20 minutes, or from 10 minutes to 15 minutes.
  • the step of applying a C-glycoside or derivative thereof may comprise one or more applications, such as two or more applications, three or more applications, etc., to the target area.
  • the methods comprise applying at least one C-glycoside or derivative thereof to the target area at least one time before, at least one time during, and/or at least one time after treatment with the skin modification stimulus.
  • the at least one C-glycoside or derivative thereof may be applied to the target area at least one time before, at least one time during, and at least one time after treatment with the skin modification stimulus treatment.
  • the methods comprise applying at least one C-glycoside or derivative thereof to the target area at least two times before, at least two times during, and/or at least two times after treatment with the skin modification stimulus.
  • the methods comprise applying at least one C-glycoside or derivative thereof to the target area at least one time, such as at least two times, before treatment with the skin modification stimulus, and at least one time, such as at least two times, after treatment with the skin modification stimulus.
  • the methods comprise applying at least one C-glycoside or derivative thereof to the target area at least one time, such as at least two times, after treatment with the skin modification stimulus.
  • the at least one C-glycoside or derivative thereof can be applied to the target area at least one time per day, at least two times per day, or at least three times per day, such as from one to five times a day, from one to four times a day, from one to three times a day, or from one to two times a day, for example once per day, before and/or after treatment with the skin modification stimulus.
  • the at least one C-glycoside or derivative thereof can be applied to the target area at least one time per day for at least about 1 , about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 1 1 , about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21 , about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, about 30, about 31 , about 32, about 33, about 34, about 35, about 36, about 37, about 38, about 39, about 40, about 41 , about 42, about 43, about 44, about 45, about 46, about 47, about 48, about 49, about 50, about 51 , about 52, about 53, about 54, about 55, about 56, about 57, about 58, about 59, or about 60 consecutive or non-consecutive days, before and/or after treatment with the skin modification stimulus.
  • the at least one C- glycoside or derivative thereof may be applied to the target area at least one time per day, for at least about 1 , about 2, about 3, about 4, about 5, about 6, about 7 days per week.
  • the at least one C-glycoside or derivative thereof may be applied to the target area at least two times per day, wherein the second or subsequent application is at least about 6 hours, for example at least about 8 hours, at least about 10 hours, at least about 12 hours, or at least about 15 hours after the prior application.
  • the methods according to the disclosure may be performed at least one time per month for at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, or 28 consecutive or non- consecutive months.
  • the at least one C-glycoside or derivative thereof is applied to the target area within about 1 minute, such as within about 5 minutes, within about 10 minutes, within about 15 minutes, within about 20 minutes, within about 30 minutes, within about 45 minutes, within about 60 minutes, within about 90 minutes, within about 2 hours, within about 3 hours, within about 4 hours, within about 5 hours, within about 6 hours, within about 8 hours, within about 10 hours, within about 12 hours, within about 18 hours, within about 24 hours, within about 36 hours, or within about 48 hours before and/or after treating the skin or scar tissue with a skin modification stimulus treatment.
  • applying at least one C- glycoside or derivative thereof is accomplished by applying a composition comprising at least one C-glycoside or derivative thereof, for example a composition comprising at least one C-xylopyranoside or derivative thereof, e.g. hydroxypropyl tetrahydropyrantriol, to the target area before, during, and/or after the skin or scar tissue is treated with a skin modification stimulus.
  • a composition comprising at least one C-glycoside or derivative thereof for example a composition comprising at least one C-xylopyranoside or derivative thereof, e.g. hydroxypropyl tetrahydropyrantriol
  • treatments with the skin modification stimulus are carried out with at-home devices.
  • microneedling and microdermabrasion can be accomplished with at-home devices.
  • Such at-home devices can be sold in kits with compositions comprising at least one C-glycoside or derivative thereof, for example a composition comprising at least one C-xylopyranoside or derivative thereof, e.g. hydroxypropyl tetrahydropyrantriol.
  • the methods according to the disclosure treat skin or scar tissue using the skin modification stimuli according to known, typical procedures.
  • skin modification stimuli for example, in a typical microdermabrasion procedure, a device having exfoliating crystals is moved across the skin with light pressure for a period of about 30 minutes.
  • the same microdermabrasion procedure can be performed and the at least one C-glycoside or derivative thereof can be applied to the target area before, during, and/or after the procedure.
  • the disclosed methods do not relate to enhancing or improving wound healing, but rather to the separate and distinct biological processes related to scar formation discussed herein.
  • the methods according to the disclosure do not include applying a C-glycoside or derivative thereof to wounded skin that does not have scar tissue.
  • the methods comprise treating scar tissue by applying at least one C-glycoside or derivative thereof to the scar tissue in connection with treating the scar tissue with a skin modification stimulus.
  • the methods comprise:
  • the step of (1 ) treating scar tissue with at least one skin modification stimulus occurs before the step of (2) applying at least one C- glycoside or derivative thereof to the scar tissue, such that the at least one C-glycoside or derivative thereof is applied to modified scar tissue.
  • the step of (2) applying at least one C-glycoside or derivative thereof to the scar tissue comprises applying a composition comprising at least one C-glycoside or derivative thereof and at least one carrier to the scar tissue before and/or after step (1 ), wherein the total amount of C-glycosides and derivatives thereof present in the composition ranges from about 0.1 % to about 30%, for example about 0.5% to about 10% by weight, relative to the total weight of the composition.
  • the methods comprise applying at least one C-glycoside or derivative thereof to skin prior to a skin injury, e.g. prior to a surgical procedure in connection with treating the skin with a skin modification stimulus.
  • the methods comprise:
  • the step of (1 ) treating uninjured skin with at least one skin modification stimulus occurs before the step of (2) applying at least one C- glycoside or derivative thereof to the uninjured skin, such that the at least one C- glycoside or derivative thereof is applied to modified skin tissue.
  • the step of (2) applying at least one C-glycoside or derivative thereof to the uninjured skin comprises applying a composition comprising at least one C- glycoside or derivative thereof and at least one carrier to the uninjured skin before and/or after step (1 ), wherein the total amount of C-glycosides and derivatives thereof present in the composition ranges from about 0.1 % to about 30%, for example about 0.5% to about 10% by weight, relative to the total weight of the composition.
  • one or more additional active agents other than C-glycosides or derivatives thereof can be applied to the skin either as part of a composition comprising the at least one C-glycoside or derivative thereof or separately, including by way of example actives that can modulate inflammation (including but not limited to carotenoids, curcumin, steroids, cannabinoids, glycoproteins, essential oils, flavonoids & flavonoid derivatives, phenolic acids, ascorbic acid, polyphenols, marine and algal extracts) actives that can enhance skin barrier (including but not limited to pantothenic acid, ceramides, pseudo ceramides such as 2-Oley I- 1 ,3-octadecanediol niacinamides, colloidal oatmeal, probiotics and - glucan), and/or actives that can modulate skin fibrosis (including but not limited to inhibitors of TNF, inhibitors of TGF-p, inhibitors of mTOR pathway and ky
  • the additional active agent(s) may be applied to the target area before, during, and/or after the uninjured skin or scar tissue is treated with a skin modification stimulus, and/or before, during, and/or after the at least one C-glycoside or derivative thereof is applied to the target area.
  • At least one additional composition such as, for example, moisturizer, sunscreen, and/or anti-aging compositions, may be applied to the target area before and/or after application of the at least one C-glycoside or derivative thereof.
  • the at least one C-glycoside or derivative thereof is applied to the target area first, and is not removed prior to application of at the least one additional skin composition.
  • the at least one additional skin composition applied to the target area first, and is not removed prior to application of the at least one C-glycoside or derivative thereof.
  • any of the disclosed steps or methods may be repeated one or more times, using the same or a different skin modification stimulus, and/or the same or a different C-glycoside or derivative.
  • treatment with a skin modification stimulus may be different in any manner, for example may use different skin modification stimuli, may use the same stimulus but for a different length of time, etc.
  • application of a C-glycoside or derivative may be different in any manner, for example may be different C-glycosides, may be the same C-glycoside but at different concentrations, etc.
  • one method may comprise repeating treatment with the skin modification stimulus one or more times before and/or after the at least one C- glycoside or derivative thereof is applied to the target area, where the treatments with the skin modification stimulus may be the same or different.
  • Another exemplary method may comprise repeating application of at least one C-glycoside or derivative thereof to the target area one or more times before and/or after treatment with the skin modification stimulus, where the C-glycoside or derivative may be the same or different.
  • a first skin modification stimulus may be a laser, where the first treatment is a Clear+Brilliant® laser procedure, and a second skin modification stimulus may be an abrasive element, where the second treatment is a microdermabrasion procedure.
  • a first skin modification stimulus may be a laser, where the first treatment is a Clear+Brilliant® laser procedure, and a second treatment may be a second Clear+Brilliant® laser procedure.
  • a method may be a method of treating scar tissue in order to reduce or improve the appearance thereof, where a first skin modification stimulus is a laser and the first treatment is a Clear+Brilliant® laser procedure, and a second skin modification stimulus is an abrasive element where the second treatment is a microdermabrasion procedure, with application of at least one C-glycoside or derivative thereof to the target area before, between, during, and/or after the first and second treatments, where the C-glycoside or derivative in each application is the same or different.
  • applying a C- glycoside or derivative to a target area “before and/or after” treatment with a skin modification stimulus includes applying a C-glycoside or derivative to a target area before treatment with a skin modification stimulus and after treatment with a skin modification stimulus, as well as applying a C-glycoside or derivative to a target area before treatment with a skin modification stimulus or after treatment with a skin modification stimulus.
  • the expression “at least one” means one or more and thus includes individual components as well as mixtures/combinations.
  • a range of “1 % to 10%, such as 2% to 8%, such as 3% to 5%,” is intended to encompass ranges of “1 % to 8%,” “1 % to 5%,” “2% to 10%,” and so on. All numbers, amounts, ranges, etc., are intended to be modified by the term “about,” whether or not so expressly stated. Similarly, a range given of “about 1% to 10%” is intended to have the term “about” modifying both the 1 % and the 10% endpoints.
  • ranges provided are meant to include every specific range within, and combination of sub ranges between, the given ranges.
  • a range from 1 -5 includes specifically 1 , 2, 3, 4, and 5, as well as sub ranges such as 2- 5, 3-5, 2-3, 2-4, 1 -4, etc.
  • All ranges and values disclosed herein are inclusive and combinable. For example, any value or point described herein that falls within a range described herein can serve as a minimum or maximum value to derive a sub-range, etc.
  • uninjured skin means skin that has not been injured in a manner that could lead to a visible scar, such as, for example, a burn, a laceration, an abrasion, acne, a skin infection, an animal bite, a piercing, surgery, etc., but does not include skin that is damaged by treatment with a skin modification stimulus as described herein.
  • Uninjured skin is intended to be distinct from skin that was previously injured, such as, for example, by a burn, a laceration, an abrasion, acne, a skin infection, an animal bite, a piercing, surgery, etc., and which, when treated according to methods of the disclosure, has visible scar tissue from such injury.
  • cosmetically treated means treated to improve or restore appearance.
  • biomarker As used herein, “medically treated” (and its grammatical variations) refers to the improvement of at least one biomarker for good health.
  • topical application refers to the application of the compositions of the disclosure onto keratinous substrates such as skin.
  • reducing” or “improving” the appearance of a scar or scar tissue means that the scar or scar tissue is less visible or noticeable than it would have been in the absence of treatment according to methods disclosed herein.
  • preventing the formation of a scar or scar tissue means preventing the appearance of scar tissue that is visible to the naked eye.
  • reducing the formation of a scar or scar tissue means that although a scar or scar tissue may form, its appearance to the naked eye is less visible or noticeable than it would have been in the absence of treatment according to methods disclosed herein.
  • compositions and methods of the present disclosure can comprise, consist of, or consist essentially of the essential elements and limitations of the disclosure described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise useful.
  • Surgical skin samples were taken from adults and subjected to the 0.25% trypsin dermis/epidermis separation method described in Rheinwald to obtain suspensions of normal human keratinocytes (NHK) and dermal fibroblasts.
  • NHS normal human keratinocytes
  • dermal fibroblasts See Rheinwald J.G., Green H.: Serial cultivation of strains of human epidermal keratinocytes: The formation of keratinizing colonies from single cells. Cell. 6(3):331 - 43. 1975.
  • the separated normal human dermal fibroblasts were cultured in DMEM +10% fetal calf serum.
  • the fibroblasts were cast onto a lower layer of proto-SoftSkinTM gel.
  • a full-thickness dermal layer equivalent was obtained after contraction of a mixture of Collagen Type I and human normal fibroblasts.
  • the separated normal human keratinocyte cell cultures were initiated using the 3T3 feeder-layer technique described in Rheinwald J.G., Green H.: Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes. Nature 265:421 -424 (1977).
  • the separated normal human keratinocytes were seeded on a lattice on the top layer of a proto-SoftSkinTM gel and the culture was left for 7 days in submerged conditions at 37°C in the presence of 5% carbon dioxide in MEM containing 10% fetal calf serum, allowing the cells to proliferate and form an epidermal layer. Then, the culture was raised upwards to airliquid interface for an additional 7 days to grow reconstructed skin models (SoftSkinTM).
  • Example 2 CO2 Laser Skin modification stimulus
  • Fig. 1 illustrates the experimental setup, where the reconstructed skin is subjected to laser wounds which leave behind a series of well-defined circular wounds. The healing process is tracked by studying the healing of the circular wound over time.
  • Fig. 2 discloses the wound recovery kinetics of SoftskinTM model epidermal cells after laser ablation through hematoxylin and eosin (H&E) stained cross-sections. The “Control” and “Laser” cross-sections of Fig. 2 demonstrate that the laser wounded skin model is an acceptable model for simulating the process of wound healing, which includes inflammation, proliferation and remodeling.
  • Proxylane (C-glycoside) in 35% propylene glycol(vehicle) was diluted with water to prepare a working solution as 3% Proxylane in 3% propylene glycol.
  • 100% of the propylene vehicle was diluted with water as a working solution of 3% propylene glycol vehicle as placebo treatment (negative control).
  • a working solution of 3% hyaluronic acid (HA) in water was also prepared as a control to determine whether alternative actives can induce the same repair/scarring prevention effect as Proxylane.
  • OCT Optimal Cutting Temperature
  • H&E haematoxylin and eosin
  • Filaggrin MA5-13440, Thermo Fisher Scientific, Waltham, MA, USA, mouse, 1 M OO
  • KI67 M7240, Dako, Glostrup, Denmark, mouse 1 M OO
  • C-glycoside treated wounded skin showed significantly higher level of KI67 and filaggrin compared to wounded skin alone and placebo treated wounded skin (Figs. 4 and 6).
  • Hydroxypropyl tetrahydropyrantriol (3%) increased Filaggrin expression, which assists in skin barrier function and water retention, in a statistically significant manner compared to laser treatment alone, laser + vehicle treatment and the untreated control.
  • Hydroxypropyl tetrahydropyrantriol (3%) increased Ki67 expression, a marker for keratinocyte proliferation, in a statistically significant manner compared to laser treatment alone, laser + vehicle treatment and the untreated control.
  • Proxylane appears to modulate the development of acne scars by targeting TGF-B1 the signaling pathways by enhancing the expression of DKK-1 (a key Wnt antagonist molecule that prevents skin fibrosis through TGF beta pathway). This illustrates the ability of C-glycoside to alter the wound environment by increasing the level of DKK-1 and reducing the possibility of developing fibrosis and scarring.
  • DKK-1 a key Wnt antagonist molecule that prevents skin fibrosis through TGF beta pathway
  • Hydroxypropyl tetrahydropyrantriol (3%) reduced a-SMA expression in a statistically significant manner compared to laser treated tissues that were not further treated. Tissues treated with 3% negative control did not demonstrate such statistically significant improvements.
  • the application of C-glycoside reduced the level of a-smooth muscle actin in laser wounded skin in a statistically significant manner as opposed to laser alone. Such reductions in a-smooth muscle actin were not observed when the placebo was used.
  • the results demonstrate that C-glycoside is beneficial for post procedure wound healing and also for providing a specific mode of action which reduces the potential of scar development by targeting the TGF-p pathway.
  • the ELISA analysis from the wounded skin model further elucidate the benefits of C-glycosides for wound healing and scar management applications.

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Abstract

La divulgation concerne des compositions et des méthodes pour prévenir, réduire et/ou traiter des cicatrices. Les compositions comprennent au moins un C-glycoside ou un dérivé de celui-ci, et les méthodes consistent à traiter la peau et/ou le tissu cicatriciel avec au moins un C-glycoside ou un dérivé de celui-ci et au moins un stimulus de modification de la peau.
PCT/US2023/031570 2022-08-31 2023-08-30 Compositions et méthodes pour la peau Ceased WO2024049923A1 (fr)

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EP23773067.6A EP4580595A1 (fr) 2022-08-31 2023-08-30 Compositions et méthodes pour la peau
CN202380071460.0A CN119997929A (zh) 2022-08-31 2023-08-30 用于皮肤的组合物和方法

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US17/900,094 US20240082279A1 (en) 2022-08-31 2022-08-31 Compositions and methods for preventing and/or treating scars
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FR2213336A FR3143355A1 (fr) 2022-12-14 2022-12-14 Compositions et procédés de prévention et/ou de traitement des cicatrices
FRFR2213336 2022-12-14

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EP0796861A1 (fr) 1996-03-22 1997-09-24 L'oreal Nouveaux dérivés siliciés de l'acide salicilique à propriétés desquamantes
EP0852949A2 (fr) 1997-03-31 1998-07-15 Shiseido Company Limited Utilisation des alpha-aminoacides pour favoriser la dégradation des desmosomes ou la desquamation du stratum corneum
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CN114642606A (zh) * 2022-04-18 2022-06-21 山东禾三千医疗科技有限公司 一种具有皮肤屏障修复功能的组合物及其制备方法和应用

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EP0218200A2 (fr) 1985-10-11 1987-04-15 D. Swarovski & Co. Objet décoratif en verre
EP0796861A1 (fr) 1996-03-22 1997-09-24 L'oreal Nouveaux dérivés siliciés de l'acide salicilique à propriétés desquamantes
EP0852949A2 (fr) 1997-03-31 1998-07-15 Shiseido Company Limited Utilisation des alpha-aminoacides pour favoriser la dégradation des desmosomes ou la desquamation du stratum corneum
EP0899330A1 (fr) 1997-08-29 1999-03-03 L'oreal Polypeptide isolé de l'épiderme et son utilisation
US20170106206A1 (en) * 2005-10-12 2017-04-20 Brooke R. Seckel Method for non-surgical facial rejuvenation
WO2008004164A2 (fr) * 2006-07-03 2008-01-10 L'oreal Composition cosmétique et/ou dermatologique combinant un dérivé de c-glycoside et un agent desquamant
FR2932679A1 (fr) * 2008-06-24 2009-12-25 Oreal Utilisation de l'acide ferulique ou ses derives pour ameliorer l'etat de surface d'une peau alteree.
FR2942962A1 (fr) * 2009-03-11 2010-09-17 Oreal Utilisation d'une dihydrochalcone ou l'un de ses derives pour ameliorer l'etat de surface d'une peau fragilisee et/ou alteree
FR2946254A1 (fr) * 2009-06-08 2010-12-10 Oreal Composition cosmetique associant un derive c-glycoside a un extrait de graines de vigna aconitifolia
FR2973237A1 (fr) * 2011-03-31 2012-10-05 Oreal Procede de traitement cosmetique fractionne utilisant un laser ou des micro-aiguilles
CN114642606A (zh) * 2022-04-18 2022-06-21 山东禾三千医疗科技有限公司 一种具有皮肤屏障修复功能的组合物及其制备方法和应用

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