Compositions and methods for skin
By using C-glycosides or derivatives thereof to combine with skin modification irritants, the problem of difficulty in preventing or reducing scars in the prior art is solved, and effective improvements in scar formation and appearance are achieved.
Patent Information
- Application Number
- CN202380071460.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2022-12-14
- Filing Date
- 2023-08-30
- Publication Date
- 2025-05-13
AI Technical Summary
The prior art is difficult to effectively prevent or reduce scar formation and appearance, and traditional scar treatment methods cannot completely eliminate or prevent scars.
Compositions containing C-glycosides or derivatives thereof are used to combine with skin modification stimuli for the treatment of skin and/or scar tissue, prevent or reduce scar formation and improve appearance by reducing the transformation of fibroblasts and modulating TGF-β signaling.
Effectively reduce scar formation and appearance, improve skin appearance and health, and provide a new and different mechanism to handle and prevent scars.
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Figure CN119997929A_ABST
Abstract
Description
[0001] CROSS-REFERENCE TO RELATED APPLICATIONS
[0002] This application claims priority to U.S. application No. 17 / 900,094, filed on August 31, 2022, and French application No. FR2213336, filed on December 14, 2022, the entire contents of both patent documents are incorporated herein by reference. Technical Field
[0003] The present disclosure relates to compositions and methods for use on the skin, for example, for preventing and / or treating scars. The compositions include at least one C-glycoside or a derivative thereof, and the methods include treating the skin and / or scar tissue using at least one C-glycoside or a derivative thereof and at least one skin modification stimulant. Background Art
[0004] Scars may form after the wound has healed as part of the natural healing process of the skin following injuries such as burns, lacerations, abrasions, acne, skin infections, animal bites, punctures, surgery, etc. Types of scars include, for example, atrophic scars (including acne scars), hypertrophic scars (including raised scars and keloid scars), contracture scars, and stretch marks scars.
[0005] Typically, a wound site undergoes stages of inflammation, granulation, and matrix remodeling during the healing process. The inflammatory phase begins shortly after injury and lasts for several days, while the granulation phase begins about 24 hours after injury and lasts for one to two weeks. The remodeling phase lasts up to about a year and includes the cross-linking and replacement of collagen, where a new collagen matrix that fills the scar tissue is formed.
[0006] The signaling pathway of transforming growth factor β-1 (TGF-β1) is particularly important for scar formation. TGF-β1 has been shown to be present at high levels in hypertrophic scars after burns and to be overexpressed in fibroblasts isolated from scar tissue. Therefore, scarring is believed to be caused in part by signaling of TGF-β1, which triggers the transformation of fibroblasts to myofibroblasts, ultimately leading to the formation of thick fibrous scar tissue at the wound site.
[0007] Many people wish to reduce or improve the appearance of scars and therefore seek scar management. For example, retinoids, topical or injectable steroids, and silicone dressings are currently used to reduce or improve the appearance of scars. In addition, surgical or non-surgical procedures that remove part of the epidermis can speed up the renewal of the skin surface, thereby reducing the appearance of scars. For example, clinicians can use scar modification techniques (such as laser treatment and chemical peels) to reduce the appearance of scars and even reduce scar formation after surgical procedures. Although this treatment cannot completely eliminate or prevent scars, it can make scars less noticeable and uncomfortable.
[0008] The development of improved scar management regimens is of great importance in improving the quality of life of patients with undesirable scar appearance. Thus, there is a continuing need for improved skin treatment agents to prevent scar formation or to treat scars that have already formed.
[0009] Surprisingly, it has now been discovered that C-glycosides and their derivatives, such as proxylane (also known as Pro-xylane TM and hydroxypropyltetrahydropyrantriol), have unexpected advantages in the treatment of scars in that these compounds are particularly effective in minimizing the incidence and / or appearance of scars, thereby improving the appearance of the skin. Summary of the invention
[0010] The present disclosure relates to compositions and methods for treating scars, such as reducing scar tissue, improving scar appearance, and / or preventing or reducing scar tissue formation. The compositions of the present disclosure include at least one C-glycoside or a derivative thereof, and the methods of the present disclosure combine the use of at least one C-glycoside or a derivative thereof with the use of a skin modification stimulant to treat skin or scar tissue.
[0011] In various embodiments, the present disclosure relates to the use of at least one C-glycoside or a derivative thereof in combination with various cosmetic procedures for preventing, reducing and / or improving the appearance of scars. In some embodiments, the present disclosure relates to methods comprising applying at least one C-glycoside or a derivative thereof before, during and / or after a skin surface treatment or scar modification treatment.
[0012] In various embodiments, the present disclosure relates to a method for treating scar tissue, such as by reducing the appearance of scar tissue, comprising applying at least one C-glycoside or a derivative thereof to the scar tissue, and combining it with treatment with a skin modification stimulant. For example, in some embodiments, the present disclosure relates to a two-step method for treating scar tissue, comprising:
[0013] (1) treating scar tissue with at least one skin modifying stimulant, and
[0014] (2) applying at least one C-glycoside or a derivative thereof to the scar tissue.
[0015] In other embodiments, the present disclosure relates to a method for preventing or reducing scar tissue formation, comprising applying at least one C-glycoside or a derivative thereof to skin without scar tissue prior to skin injury (e.g., prior to a surgical procedure) and combining it with a skin modification stimulant treatment. For example, in some embodiments, the present disclosure relates to a two-step method for preventing or reducing scar tissue formation, comprising:
[0016] (1) treating intact skin with at least one skin modifying stimulant, and
[0017] (2) applying at least one C-glycoside or a derivative thereof to the skin.
[0018] In another embodiment, the present disclosure is directed to a two-step method for treating skin after surgery to prevent or reduce scar tissue formation, the method comprising:
[0019] (1) causing skin damage, and
[0020] (2) applying at least one C-glycoside or a derivative thereof to the skin.
[0021] In various embodiments, at least one C-glycoside or derivative thereof may be applied to the skin or scar tissue during treatment with a skin modification stimulant. In other embodiments, 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 stimulant, for example, within a few seconds, about 1 minute, or about 1 hour before and / or after treatment of the skin with a skin modification stimulant, up to about 6 hours, about 12 hours, about 18 hours, or about 24 hours before and / or after treatment of the skin with a scar modification procedure. In various embodiments, at least one C-glycoside or derivative thereof may be applied to the skin or scar tissue once or more per day, for example, twice per day, three times per day, or more times per day. In other embodiments, at least one C-glycoside or a derivative thereof can be applied to the skin or scar tissue at least once a day in one day or multiple consecutive days (e.g., at least 2 days, at least 3 days, at least 4 days, at least 5 days or more), or at least once a day in one day or multiple non-consecutive days (e.g., 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 longer). In other embodiments, the methods of the present disclosure can 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 longer.
[0022] In a preferred embodiment, the present disclosure relates to a method for treating scar tissue, the method comprising (1) treating scar tissue with at least one skin modification stimulant, and (2) applying at least one C-glycoside or a derivative thereof to the scar tissue; wherein the skin modification stimulant is selected from laser, plasma, radio frequency, high intensity focused ultrasound, electric field, heat, low intensity light device, needle, microneedle, abrasive element and / or chemical agent (e.g., chemical peel); and wherein the C-glycoside is preferably selected from C-xylopyranoside and / or its derivatives, more preferably C13-D-xylopyranoside-2-hydroxypropane and / or Cα-D-xylopyranoside-2-hydroxypropane; and wherein step (2) occurs before, during and / or after step (1).
[0023] In a preferred embodiment, the present disclosure relates to a method for preventing or reducing scar tissue formation, the method comprising (1) treating intact skin with at least one skin modification stimulant, and (2) applying at least one C-glycoside or a derivative thereof to the skin; wherein the skin modification stimulant is selected from laser, plasma, radio frequency, high intensity focused ultrasound, electric field, heat, low intensity light device, needle, microneedle, abrasive element and / or chemical agent (e.g., chemical peel); wherein the C-glycoside is preferably selected from C-xylopyranoside and / or its derivatives, more preferably C13-D-xylopyranoside-2-hydroxypropane and / or Cα-D-xylopyranoside-2-hydroxypropane; and wherein step (2) occurs before, during and / or after step (1).
[0024] In a preferred embodiment, the present disclosure relates to a method for treating skin after surgical intervention to prevent or reduce scar tissue formation, the method comprising (1) causing skin damage, and (2) applying at least one C-glycoside or its derivative to the skin; wherein the C-glycoside is preferably selected from C-xylopyranoside and / or its derivatives, more preferably C13-D-xylopyranoside-2-hydroxypropane and / or Cα-D-xylopyranoside-2-hydroxypropane; and wherein step (2) occurs before, during and / or after step (1).
[0025] In a preferred embodiment, the present disclosure relates to a method for reducing the transformation of fibroblasts to myofibroblasts, increasing the expression level of DKK-1, increasing the phosphorylation of β-catenin, and / or downregulating the signal transduction of TGF-β in intact skin and / or scar tissue, the method comprising (1) treating intact skin and / or scar tissue with at least one skin modification stimulus, and (2) applying at least one C-glycoside or a derivative thereof to the intact skin and / or scar tissue; wherein the skin modification stimulus is selected from laser, plasma, radiofrequency, high intensity focused ultrasound, electric field, heat, low intensity light device, needle, microneedle, abrasive element and / or chemical agent (e.g., chemical peel); wherein the C-glycoside is preferably selected from C-xylopyranoside and / or its derivatives, more preferably C13-D-xylopyranoside-2-hydroxypropane and / or Cα-D-xylopyranoside-2-hydroxypropane; and wherein step (2) occurs before, during and / or after step (1).
[0026] In a preferred embodiment, the present disclosure relates to a method for treating scar tissue, the method comprising (1) treating the scar tissue with at least one skin modification stimulant, and (2) applying to the scar tissue a composition as described herein comprising at least one C-glycoside or a derivative thereof, at least one solvent or carrier, and optionally at least one additional active ingredient and / or additive; wherein the skin modification stimulant is selected from laser, plasma, radiofrequency, high intensity focused ultrasound, electric field, heat, low intensity light device, needle, microneedle, abrasive element and / or chemical agent (e.g., chemical peel); wherein the C-glycoside is preferably selected from C-xylopyranoside and / or its derivatives, more preferably C13-D-xylopyranoside-2-hydroxypropane and / or Cα-D-xylopyranoside-2-hydroxypropane. -hydroxypropane, and the total amount of C-glycosides is from about 0.01% to about 30% by weight of the composition, preferably from about 0.1% to about 20% by weight, more preferably from about 0.3% to about 12% by weight, more preferably from about 0.5% to about 10% by weight, still more preferably from about 1% to about 5% by weight, from about 1.5% to about 4.5% by weight, or from about 2% to about 4% by weight, and most preferably from about 2.5% to about 3.5% by weight, or about 3% by weight of the composition; wherein the composition is applied to the skin at least once a day, for example once, twice, three times or four times a day, at least one day a week, for example 2, 3, 4, 5, 6 or 7 days a week; and wherein step (2) occurs before, during and / or after step (1).
[0027] In a preferred embodiment, the present disclosure relates to a method for preventing or reducing scar tissue formation, the method comprising (1) treating intact skin with at least one skin modification stimulant, and (2) applying to the skin a composition as described herein comprising at least one C-glycoside or a derivative thereof, at least one solvent or carrier, and optionally at least one additional active ingredient and / or additive; wherein the skin modification stimulant is selected from laser, plasma, radiofrequency, high intensity focused ultrasound, electric field, heat, low intensity light device, needle, microneedle, abrasive element and / or chemical agent (e.g., chemical peel); wherein the C-glycoside is preferably selected from C-xylopyranoside and / or its derivatives, more preferably C13-D-xylopyranoside-2-hydroxypropane and / or Cα-D-xylopyranoside. -2-hydroxypropane, and the total amount of C-glycosides is from about 0.01% to about 30% by weight of the composition, preferably from about 0.1% to about 20% by weight, more preferably from about 0.3% to about 12% by weight, more preferably from about 0.5% to about 10% by weight, still more preferably from about 1% to about 5% by weight, from about 1.5% to about 4.5% by weight, or from about 2% to about 4% by weight, and most preferably from about 2.5% to about 3.5% by weight, or about 3% by weight of the composition; wherein the composition is applied to the skin at least once a day, for example once, twice, three times or four times a day, at least one day a week, for example 2, 3, 4, 5, 6 or 7 days a week; and wherein step (2) occurs before, during and / or after step (1).
[0028] In a preferred embodiment, the present disclosure relates to a method for treating skin after surgical intervention to prevent or reduce scar tissue formation, the method comprising (1) causing skin injury, and (2) applying to the skin a composition as described herein comprising at least one C-glycoside or a derivative thereof, at least one solvent or carrier, and optionally at least one additional active ingredient and / or additive; wherein the C-glycoside is preferably selected from C-xylopyranoside and / or a derivative thereof, more preferably C13-D-xylopyranoside-2-hydroxypropane and / or Cα-D-xylopyranoside-2-hydroxypropane, and the total amount of C-glycoside is from about 0.01% to about 30% by weight of the composition, preferably about 0.01% by weight. .1 wt % to about 20 wt %, more preferably about 0.3 wt % to about 12 wt %, more preferably about 0.5 wt % to about 10 wt %, still more preferably about 1 wt % to about 5 wt %, about 1.5 wt % to about 4.5 wt %, or about 2 wt % to about 4 wt %, and most preferably about 2.5 wt % to about 3.5 wt %, or about 3 wt % of the composition; wherein the composition is applied to the skin at least once a day, for example once, twice, three times or four times a day, at least one day a week, for example two, three, four, five, six or seven days a week, before and / or after surgery; and wherein step (2) occurs before, during and / or after step (1).
[0029] In a preferred embodiment, the present disclosure relates to a method for reducing the transformation of fibroblasts to myofibroblasts, increasing the expression level of DKK-1, increasing the phosphorylation of β-catenin, and / or downregulating the signal transduction of TGF-β in intact skin and / or scar tissue, the method comprising (1) treating the intact skin and / or scar tissue with at least one skin modification stimulus, and (2) applying to the intact skin and / or scar tissue a composition as described herein comprising at least one C-glycoside or a derivative thereof, at least one solvent or carrier, and optionally at least one additional active ingredient and / or additive; wherein the skin modification stimulus is selected from the group consisting of lasers, plasma, radiofrequency, high intensity focused ultrasound, electric fields, heat, low intensity light devices, needles, microneedles, abrasive elements and / or chemicals (e.g., chemical peels); wherein the C-glycoside is preferably selected from the group consisting of C-xylopyranosides and / or its derivatives, more preferably C13-D-xylopyranoside-2-hydroxypropane and / or Cα-D-xylopyranoside-2-hydroxypropane, and the total amount of C-glycosides is from about 0.01% to about 30% by weight of the composition, preferably from about 0.1% to about 20% by weight, more preferably from about 0.3% to about 12% by weight, more preferably from about 0.5% to about 10% by weight, still more preferably from about 1% to about 5% by weight, from about 1.5% to about 4.5% by weight, or from about 2% to about 4% by weight, and most preferably from about 2.5% to about 3.5% by weight, or about 3% by weight of the composition; wherein the composition is applied to the skin at least once a day, for example once, twice, three times or four times a day, at least one day a week, for example 2, 3, 4, 5, 6 or 7 days a week; and wherein step (2) occurs before, during and / or after step (1).
[0030] In other embodiments, the method comprises:
[0031] (1) treating the skin or scar tissue using at least one type of skin-modifying stimulus, such as laser, radiofrequency, electricity, heat, low-intensity light, needles, or abrasive devices; and
[0032] (2) After treating skin or scar tissue, it will contain about 0.01% to about 50%, about 0.025%
[0033] From about 40%, from about 0.05% to about 30%, 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%, or from about 2% to about 4% of at least one C-glycoside or derivative thereof is applied to a subject who has undergone The treated skin or scar tissue is applied at least once, preferably at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 times, wherein the at least one C-glycoside or derivative thereof is applied at least 12 hours apart, wherein all amounts are by weight relative to the total weight of the composition in which they are present. BRIEF DESCRIPTION OF THE DRAWINGS
[0036] The accompanying drawings, which are incorporated herein and constitute a part of this specification, illustrate exemplary embodiments of the present disclosure and, together with the general description given above and the description provided herein, serve to explain the features of the present disclosure.
[0037] Figure 1 A schematic diagram of an exemplary scar repair surgical procedure of the present disclosure comprising the use of at least one C-glycoside or a derivative thereof is shown. Scars are formed after tissue injury. Scar tissue is first treated with a cosmetic laser and then with hydroxypropyl tetrahydropyrantriol.
[0038] Figure 2 Softskin that had undergone laser ablation ("laser group") or had not undergone laser ablation ("control group") are shown. TM Hematoxylin and eosin (H&E) stained cross sections of model epidermal tissue. Parts of the tissue were treated once a day for 3 days using a solution of 3% hydroxypropyl tetrahydropyrantriol in 3% propylene glycol ("laser / 3% hyaluronic acid group") or 2% hyaluronic acid ("laser / 2% hyaluronic acid group"). Cross sections were obtained and stained on days 0, 2, and 4.
[0039] Figure 3 Showing Day 2 Softskin TM Cross-sections of model epidermal tissue immunostained with Filaggrin antibodies, a) untreated (control), b) laser treated, c) laser treated followed by 3% hydroxypropyl tetrahydropyrantriol in 3% propylene glycol, and d) laser treated followed by 3% propylene glycol control vehicle. Green: Filaggrin, blue: DAPI (nuclei).
[0040] Figure 4Softskin at day 2 measured using Image J software TM Relative filaggrin expression in model epidermal tissue before and after laser ablation and in tissue further treated with either 3% propylene glycol vehicle (negative control / placebo group) or 3% hydroxypropyltetrahydropyrantriol in 3% propylene glycol.
[0041] Figure 5 Showing Day 2 Softskin TM Cross sections of model epidermal tissue immunostained with Ki-67 antibody, where a) no treatment (control), b) laser treatment, c) laser treatment followed by treatment with 3% hydroxypropyl tetrahydropyrantriol in 3% propylene glycol, and d) laser treatment followed by treatment with 3% propylene glycol control vehicle. Red: KI67, blue: DAPI (nuclei).
[0042] Figure 6 Shows day 2 softskin measured using the 3D HISTECH PANNORAMIC MIDI II fluorescence scanner TM Ratio of Ki67 (antigen Ki-67 or MKI67) expression to DAPI expression in model epidermal tissue before and after laser ablation, and in tissue further treated with 3% propylene glycol vehicle (negative control / placebo group) or 3% hydroxypropyltetrahydropyrantriol in 3% propylene glycol.
[0043] Figure 7 Showing Day 1 Softskin TM Relative α-Dickkopf WNT signaling pathway inhibitor 1 (DKK-1) expression in model epidermal tissue before and after laser ablation and in tissue further treated with 3% propylene glycol vehicle (negative control / placebo group) or 3% hydroxypropyltetrahydropyrantriol in 3% propylene glycol.
[0044] Figure 8 Showing Day 2 Softskin TM Relative α-smooth muscle actin (α-SMA) expression in model epidermal tissue before and after laser ablation and in tissue further treated with 3% propylene glycol vehicle (negative control / placebo group) or 3% hydroxypropyltetrahydropyrantriol in 3% propylene glycol. DETAILED DESCRIPTION
[0045] The present disclosure relates to compositions and methods for treating scar tissue, for example, by increasing, promoting and / or improving healthy skin renewal instead of scar tissue, and / or by improving the appearance of scarred skin. The types of scars that can be treated are not limited, and include, for example, keloid scars, flat scars, raised scars, contracture scars, atrophic scars, stretch marks, etc. The present disclosure also relates to compositions and methods for preventing or minimizing scar tissue formation before skin injury (e.g., before surgical procedures).
[0046] According to various aspects of the present disclosure, the composition comprises at least one C-glycoside or a derivative thereof, such as at least one C-xylopyranoside or a derivative thereof, and, in at least some embodiments, hydroxypropyltetrahydropyrantriol.
[0047] According to various embodiments, the method comprises treating scar tissue with at least one skin modification stimulant and applying at least one C-glycoside or derivative thereof, e.g., C-xylopyranoside or derivative thereof, e.g., hydroxypropyltetrahydropyrantriol, to the scar tissue. In other embodiments, the method comprises treating intact skin with at least one skin modification stimulant and applying at least one C-glycoside or derivative thereof, e.g., C-xylopyranoside or derivative thereof, e.g., hydroxypropyltetrahydropyrantriol, to the skin to prevent or reduce scarring.
[0048] Without being bound by theory, it is understood that C-glycosides and their derivatives may advantageously prevent or reduce scarring by reducing the transformation of fibroblasts to myofibroblasts and / or by targeting TGF-β1 signaling (which is reduced by regulating β-catenin via Dickkopf WNT signaling pathway inhibitor 1 (DKK-1) expression), and / or may improve scar appearance, and / or enhance scar reduction kinetics. Thus, in some embodiments, the at least one C-glycoside or its derivative increases the expression level of DKK-1 in scar tissue (which targets the Wnt / LRP6 association), increases the phosphorylation of β-catenin, and ultimately downregulates TGF-β signaling in scar tissue.
[0049] Thus, the compositions and methods of the present disclosure address the problem of scar prevention and management in a new and previously unknown manner through a mechanism that is different from known methods (e.g., retinoids, topical or injectable steroids, silicone dressings, and surgical and non-surgical medical procedures. By treating the skin and / or scar tissue with a skin modifying stimulus and applying at least one C-glycoside or a derivative thereof to the targeted area, this promotes new growth of normal skin tissue rather than new growth of scar tissue.
[0050] Surprisingly, it has been discovered that, in some embodiments, the scar management and prevention methods and compositions of the present disclosure impart more extensive and / or stronger scar management and prevention benefits to the skin, with or without enhanced kinetics, compared to known scar treatments.
[0051] A more detailed description of compositions, methods, and kits for treating skin and scar tissue is provided below.
[0052] I. Composition
[0053] The composition of the present disclosure comprises at least one C-glycoside or a derivative thereof. The composition may further comprise additional components, such as a carrier, an active ingredient other than the C-glycoside or a derivative thereof, and additives generally present in skin care compositions.
[0054] C-glycosides are sugar groups linked to a non-sugar moiety (aglycone) via a carbon-carbon (CC) bond. In various embodiments, the C-glycoside may be selected from C13-D-xylopyranosyl-n-propane-2-one; Cα-D-xylopyranosyl-n-propane-2-one; C13-D-xylopyranosyl-2-hydroxypropane; Cα-D-xylopyranosyl-2-hydroxypropane; 1-(C13-D-fucopyranosyl)-propane-2-one; 1-(Cα-D-fucopyranosyl)-propane-2-one; 1 -(C13-L-fucopyranoside)-propane-2-one; 1-(Cα-L-fucopyranoside)-propane-2-one; 2-one, 1-(C13-D-fucopyranoside)-2-hydroxypropane, 1-(Cα-D-fucopyranoside)-2-hydroxypropane; 1-(C13-L-fucopyranoside)-2-hydroxypropane; 1-(Cα-L-fucopyranoside)-2-hydroxypropane Propane; 1-(C13-D-glucopyranosyl)-2-hydroxypropane; 1-(Cα-D-glucopyranosyl)-2-hydroxypropane; 1-(C13-D-galactopyranosyl)-2-hydroxypropane; 1-(Cα-D-galactopyranosyl)-2-hydroxypropane-1-(C13-D-fucofuranosyl)propane-2-one; 1-(Cα-D-fucofuranosyl)-propane-2-one Ketone; 1-(C13-L-fucofuranosyl)-propane-2-one; 1-(Cα-L-fucofuranosyl)-propane-2-one; C13-D-maltopyranosyl-n-propane-2-one-Cα-D-maltopyranosyl-n-propane-2-one-C13-D-maltopyranosyl-2-hydroxypropane; Cα-D-maltopyranosyl-2-hydroxypropane; and derivatives thereof or mixtures thereof.
[0055] In various embodiments, the at least one C-glycoside is a C-xylopyranoside. In at least some embodiments, the C-glycoside comprises, consists essentially of, or consists of C13-D-xylopyranoside-2-hydroxypropane, Cα-D-xylopyranoside-2-hydroxypropane, or a mixture thereof. In other embodiments, the C-glycoside comprises, consists essentially of, or consists of C13-D-xylopyranosyl-2-hydroxypropane (also known as Cβ-D-xylopyranosyl-2-hydroxypropane, hydroxypropyl tetrahydropyrantriol, or bosaiin). Hydroxypropyl tetrahydropyrantriol has the structure of Formula (I):
[0056]
[0057] According to various embodiments, the compositions of the present disclosure may include a total amount of C-glycosides and derivatives thereof of from about 0.01 wt % to about 30 wt %, from about 0.05 wt % to about 25 wt %, from about 0.1 wt % to about 20 wt %, from about 0.2 wt % to about 15 wt %, from about 0.3 wt % to about 12 wt %, from about 0.4 wt % to about 11 wt %, from about 0.5 wt % to about 10 wt %, from about 0.6 wt % to about 9 wt %, from about 0.7 wt % to about 8 wt %, from about 0.8 wt % to about 7 wt %, from about 0.9 wt % to about 6 wt %, from about 1 wt % to about 5 wt %, from about 1.5 wt % to about 4.5 wt %, from about 2 wt % to about 4 wt %, from about 2.5 wt % to about 3.5 wt %, or about 3 wt %, including all ranges and subranges between using any disclosed lower limit as the lower limit and any disclosed upper limit as the upper limit, relative to the total weight of the composition in which they are located. For example, the total amount of C-glycoside and its derivatives in the composition of the present disclosure can be about 0.01 wt%, about 0.05 wt%, about 0.1 wt%, about 0.25 wt%, about 0.5 wt%, about 0.75 wt%, about 1 wt%, about 1.25 wt%, about 1.5 wt%, about 1.75 wt%, about 2 wt%, about 2.25 wt%, about 2.5 wt%, about 2.75 wt%, about 3 wt%, about 3.25 wt%, about 3.5 wt%, about 3.75 wt%, about 3.5 wt%, about 3.25 wt%, about 3. ...25 wt%, about 3.5 wt%, about 3.25 wt%, about 3.5 wt%, about 3.25 wt%, about 3.5 wt%, about %, about 3.5 wt %, about 3.75 wt %, about 5 wt %, about 5.25 wt %, about 5.5 wt %, about 5.75 wt %, about 6 wt %, about 6.25 wt %, about 6.5 wt %, about 6.75 wt %, about 7 wt %, about 7.25 wt %, about 7.5 wt %, about 7.75 wt %, about 8 wt %, about 8.25 wt %, about 8.5 wt %, about 8.75 wt %, about 9 wt %, about %, about 9.25 wt%, about 9.5 wt%, about 9.75 wt%, about 10 wt%, about 10.5 wt%, about 11 wt%, about 11.5 wt%, about 12 wt%, about 12.5 wt%, about 13 wt%, about 13.5 wt%, about 14 wt%, about 14.5 wt%, about 15 wt%, about 15.5 wt%, about 16 wt%, about 16.5 wt%, about 17 wt%, about 17.5 wt%, about 18 wt%, about 19 wt%, about 20 wt%, about 21 wt%, about 22 wt%, about 23 wt%, about 24 wt%, about 25 wt%, about 26 wt%, about 27 wt%, about 28 wt%, about 29 wt%, about 30 wt%, about 31 wt%, about 32 wt%, about 33 wt%, about 34 wt%, about 35 wt%, about 36 wt%, about 37 %, about 8 wt %, about 18.5 wt %, about 19 wt %, about 19.5 wt %, about 20 wt %, about 21 wt %, about 22 wt %, about 23 wt %, about 24 wt %, about 25 wt %, about 26 wt %, about 27 wt %, about 28 wt %, about 29 wt %, or about 30 wt %, including all ranges and subranges between using any disclosed amount as the lower or upper limit, relative to the total weight of the composition in which it is located.
[0058] The composition generally comprises one or more cosmetically acceptable carriers, including but not limited to water and / or non-aqueous solvents. Exemplary non-aqueous solvents include glycerol; glycols such as ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, pentaethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, polyethylene glycol, octanediol, 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 monoisopropyl ether, diethylene glycol monoisopropyl ether, ethylene glycol mono-n-butyl ether, ethylene glycol mono-tert-butyl ether, diethylene glycol mono-tert-butyl ether, propylene glycol monoisopropyl ether, ethylene ... The invention relates to a kind of non-aqueous solvents, for example, glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol mono-tert-butyl ether, propylene glycol mono-n-propyl ether, propylene glycol mono-isopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, dipropylene glycol mono-n-propyl ether and dipropylene glycol mono-isopropyl ether; and alcohols, for example, ethanol, propanol, isopropanol, butanol, amyl alcohol, hexanol, heptanol, octanol, decanol, dodecanol, hexadecanol, octadecyl alcohol, eicosanol, 2-propanol, 2-methyl-1-propanol, 2-methyl-2-butanol, cetyl alcohol, stearyl alcohol, arachidyl alcohol, behenyl alcohol and cyclohexanol. A mixture of two or more non-aqueous solvents can also be selected, and it is envisioned that in various embodiments, the carrier comprises water and at least one non-aqueous solvent.
[0059] The composition may optionally include one or more active ingredients other than C-glycosides or derivatives thereof, such as active substances that can modulate inflammation (including but not limited to carotenoids, curcumin, steroids, cannabinoids, glycoproteins, essential oils, flavonoids and flavonoid derivatives, phenolic acids, ascorbic acid, polyphenols and seaweed extracts), active substances that can enhance the skin barrier (including but not limited to pantothenic acid, ceramides, pseudoceramides (such as 2-oleyl (Oleyl)-1,3-octadecanediol), niacinamide, niacinamide derivatives, carob seed extract, oligogalactomannan, colloidal oatmeal, hyaluronic acid, probiotics and β-glucan), and / or active substances that can modulate skin fibrosis (including but not limited to TNF inhibitors, TGF-β inhibitors, mTOR pathway inhibitors and kynurenic acid and its derivatives).
[0060] The composition may optionally include one or more additives, such as those commonly found in skin care compositions, including but not limited to oils, waxes or other fatty substances; gelling agents and / or thickeners; emulsifiers; moisturizers; emollients; sunscreens; hydrophilic or lipophilic active agents, such as ceramides; anti-free radical agents; bactericides; chelating agents; preservatives; pH regulators; skin penetration enhancers; fragrances; surfactants; fillers; natural products or extracts thereof, such as aloe vera or green tea extracts; vitamins; and / or colorants. If present, the amount of the additives will vary depending on the intended use and / or characteristics of the composition and the desired effect, but the amount alone or in combination is generally about 0.0001% to about 20% by weight, such as about 0.001% to about 15% by weight, about 0.01% to about 10% by weight, about 0.1% to about 7.5% by weight, about 0.5% to about 5% by weight, or about 1% to about 3% by weight, relative to the total weight of the composition.
[0061] The form of the compositions of the present disclosure is not limited, and may include, for example, liquids, emulsions, suspensions, lotions, creams, gels (including hydrogels), balms, pastes, serums, ointments, foams, and the like.
[0062] The compositions are typically applied topically, and in various embodiments, may be applied by the consumer in an at-home formulation, or by a professional, such as in a clinical setting as part of a cosmetic procedure.
[0063] A non-limiting example of a composition of the present disclosure includes a carrier (e.g., water and / or at least one non-aqueous solvent), optionally at least one active ingredient other than C-glycoside or a derivative thereof, and / or at least one additive, and the total amount of C-glycoside and its derivatives is from about 0.01 wt % to about 30 wt %, from about 0.05 wt % to about 25 wt %, from about 0.1 wt % to about 20 wt %, from about 0.2 wt % to about 15 wt %, from about 0.3 wt % to about 12 wt %, from about 0.4 wt % to about 15 wt %, from about 0.5 wt % to about 10 wt %, from about 0.6 wt % to about 15 wt %, from about 0.8 wt % to about 10 wt %, from about 0.9 wt % to about 15 wt %, from about 0.10 wt % to about 10 wt %, from about 0.20 wt % to about 15 wt %, from about 0.30 wt % to about 10 wt %, from about 0.40 wt % to about 10 wt %. From about 11 wt %, from about 0.5 wt % to about 10 wt %, from about 0.6 wt % to about 9 wt %, from about 0.7 wt % to about 8 wt %, from about 0.8 wt % to about 7 wt %, from about 0.9 wt % to about 6 wt %, from about 1 wt % to about 5 wt %, from about 1.5 wt % to about 4.5 wt %, from about 2 wt % to about 4 wt %, from about 2.5 wt % to about 3.5 wt %, or about 3 wt %, including all ranges and subranges therebetween, relative to the total weight of the composition in which it is located. Another non-limiting example of a composition of the present disclosure includes a carrier comprising water and optionally at least one non-aqueous solvent, optionally at least one active ingredient other than C-glycoside or a derivative thereof and / or at least one additive, and hydroxypropyl tetrahydropyrantriol is present in an amount of about 0.01 wt % to about 30 wt %, about 0.05 wt % to about 25 wt %, about 0.1 wt % to about 20 wt %, about 0.2 wt % to about 15 wt %, about 0.3 wt % to about 12 wt %, about 0.4 wt % to about 15 wt %, about 0.5 wt % to about 10 wt %, about 0.6 wt % to about 15 wt %, about 0.7 wt % to about 10 wt %, about 0.8 wt % to about 15 wt %, about 0.9 wt % to about 10 wt %, about 0.10 wt % to about 15 wt %, about 0.8 wt % to about 10 wt %, about 0.9 ...8 wt % to about 15 wt %, about 0. From about 1 1 wt %, from about 0.5 wt % to about 10 wt %, from about 0.6 wt % to about 9 wt %, from about 0.7 wt % to about 8 wt %, from about 0.8 wt % to about 7 wt %, from about 0.9 wt % to about 6 wt %, from about 1 wt % to about 5 wt %, from about 1.5 wt % to about 4.5 wt %, from about 2 wt % to about 4 wt %, from about 2.5 wt % to about 3.5 wt %, or about 3 wt %, including all ranges and subranges therebetween, relative to the total weight of the composition in which it is located.
[0064] II. method
[0065] In various embodiments, the present disclosure relates to methods for treating scar tissue to reduce or improve the appearance of scars. In other embodiments, the present disclosure relates to methods for treating skin (e.g., skin without visible scar tissue, e.g., undamaged skin) to prevent and / or reduce scar tissue formation. In other embodiments, the present disclosure relates to methods for reducing the transformation of fibroblasts to myofibroblasts, targeting transforming growth factor β1 (TGF-β1) signaling, reducing regulation of β-catenin, increasing the expression level of DKK-1, interrupting Wnt / LRP6 association, increasing phosphorylation of β-catenin and / or downregulating TGF-β signaling.
[0066] Typically, the method comprises applying at least one C-glycoside or derivative thereof, e.g., C-xylopyranoside or derivative thereof, e.g., hydroxypropyltetrahydropyrantriol, to a desired area to be treated, e.g., to intact skin or scar tissue (collectively referred to herein as the "target area" in some instances) before, during, and / or after treatment of intact skin or scar tissue with a stimulant for modifying skin or scar tissue (interchangeably referred to herein as a "skin modifying stimulant"). In various methods, the C-glycoside or derivative thereof comprises, consists essentially of, or consists of C-xylopyranoside or derivative thereof, and in other methods, the C-glycoside or derivative thereof comprises, consists essentially of, or consists of hydroxypropyltetrahydropyrantriol.
[0067] In the methods of the present disclosure, useful skin modification stimulants include those used in the field of skin care to modify or destroy skin or scar tissue, thereby promoting new growth in a controlled manner. These treatments usually cause relatively mild damage to the outermost layer of skin or scar tissue, thereby starting the body's natural healing process. The treatment can also stimulate the production of collagen. Therefore, any known method or device for modifying or destroying skin or scar tissue can be used in the methods of the present disclosure. For example, in various embodiments, the skin modification stimulant can modify or destroy skin or scar tissue by cutting, burning, chemically destroying, ablating, micro-ablating, coagulating or otherwise affecting the corneal layer and subcutaneous tissue of the target area. Therefore, as used herein, "modified scar tissue" refers to scar tissue that has been modified or destroyed using one or more skin modification stimulants and is healing from the skin modification stimulant treatment. Similarly, "modified skin tissue" refers to skin tissue (usually undamaged and / or scar-free tissue) that has been modified or destroyed using one or more skin modification stimulants and is healing from the skin modification stimulant treatment.
[0068] In various embodiments, the skin modification stimuli used in the methods of the present disclosure may be invasive or non-invasive. By way of non-limiting example, the skin modification stimuli may be laser, plasma, radiofrequency, high intensity focused ultrasound, electric field, heat, low intensity light device, needle, microneedle, abrasive element, chemical agent (e.g., chemical peel), etc., and the skin modification stimulant treatment may be laser operation, microneedle operation, high intensity focused ultrasound operation, electroporation operation, dermabrasion operation, microdermabrasion operation, plasma skin rejuvenation operation, chemical peel operation, etc.
[0069] Any type of cosmetic laser can be used, varying in wavelength and the manner in which the laser is delivered. In various embodiments, the target area can be treated with an ablative or non-ablative laser. Ablative lasers can include, for example, carbon dioxide or erbium lasers. Non-ablative lasers can include, for example, pulsed light, pulsed dye, and fractional lasers. Lasers can also be modified when combined with other elements, such as gases, gemstones, and metals. Non-limiting examples include Clear+ Laser, fractional photothermolysis laser, alexandrite laser, carbon dioxide (CO2) laser, erbium (Er:YAG) laser, intense pulsed light (IPL) laser, Nd:YAG laser, pulsed dye laser, Q-switched laser, picosecond laser, etc.
[0070] In various embodiments, the target area can be treated with mechanical microneedles, which use an electric pen with tiny elongated needles to create thousands of channels up to 2.5 mm deep. These channels disturb intact skin or scar tissue, allowing new skin to grow. Non-limiting examples of mechanical microneedle devices that can be used include SkinPenPrecision, MDpen, Skin Stylus, etc.
[0071] In some embodiments, the target area can be treated with fractional radio frequency (RF) microneedles, which is a heat-based therapy that uses thicker needles to transmit heat deep into the skin. RF microneedles thermally coagulate tissue to stimulate collagen denaturation and renewal. Radio frequency (RF) microneedles create fewer microchannels than mechanical needles. In one embodiment, the target area can be treated with standard or short-pulse RF microneedles. Non-limiting examples of RF devices that can be used include Scarlet SRF, AgnesRF, Endymed Intensif, Secret RF, Vivace, Virtue RF, Morpheus8, etc.
[0072] The target area can also be treated with ultrasound, such as by ultrasound therapy. Ultrasound can cause thermal relaxation, stretching and reorientation of collagen tissue. Ultrasound waves mechanically act on the skin and scar tissue in the form of micro-massage and create tiny oxygen droplets in the vibrations (cavitation).
[0073] Electroporation mesotherapy can also be used with the disclosed methods. Electroporation uses electrical energy to increase the permeability of the skin or scar tissue membrane by creating microscopic channels that open pathways deep into the skin, thereby disrupting the scar tissue.
[0074] In some embodiments, dermabrasion (including microdermabrasion) can also be used to treat the target area. Dermabrasion involves controlled deeper abrasion of the surface to the middle layers of intact skin or scar tissue using any type of strong abrasive device (e.g., a wire brush, diamond wheel (or milling cutter), or sawtooth). Exemplary embodiments may include crystal microdermabrasion or diamond microdermabrasion.
[0075] In other embodiments, plasma skin rejuvenation can be used in the disclosed methods. Plasma skin regeneration can be used to deliver energy in the form of plasma to a target area, similar to thermal devices and dry exfoliation. This method is particularly useful for destroying scar tissue.
[0076] In certain embodiments, chemical exfoliants (also referred to as chemical peels or dermal exfoliants) can be used as skin modification stimulants. Exemplary and non-limiting chemical agents that can be used to treat the target area include those that can directly affect exfoliation by promoting epidermal exfoliation, such as beta-hydroxy acids (BHAs), such as salicylic acid and its derivatives (including n-octanoyl 5-salicylic acid, also known as octanoyl salicylic acid (INCI name)); alpha-hydroxy acids (AHAs), such as glycolic acid, lactic acid, tartaric acid, malic acid, or mandelic acid; 8-hexadecene-1,16-dicarboxylic acid or 9-octadecenedioic acid; urea and its derivatives; trichloroacetic acid; gentisic acid and its derivatives; oligofuctose; cinnamic acid; Saphora japonica extract; resveratrol; resorcinol; carbolic acid (phenol); or mixtures thereof.
[0077] Other exemplary and non-limiting chemical exfoliants that can be used include compounds involved in exfoliating or breaking down corneous desmosomes, such as aminosulfonic acid compounds, such as 4-(2-hydroxyethyl)piperazine-1-propanesulfonic acid (HEPES); 2-oxothiazolidine-4-carboxylic acid (propylcysteine) and its derivatives; derivatives of glycine-type α-amino acids (as described in EP-0 852 949) and sodium methylglycine diacetate sold by BASF under the trade name Trilon M; honey; sugar derivatives, such as O-octanoyl-6-D-maltose and N-acetylglucosamine; or mixtures thereof.
[0078] As other exemplary and non-limiting chemical exfoliants suitable for the compositions of the present disclosure, mention is made of EDTA and its derivatives, kelp extract, O-linoleyl-6-D-glucose; (3-hydroxy-2-pentylcyclopentyl)acetic acid, trilactin, S-carboxymethylcysteine, silicon-containing derivatives of salicylic acid (such as those described in patent EP 0 796 861), oligofuctase (such as those described in patent EP 0 218 200), agents affecting glutamine aminotransferase in patent EP 0899330; extract of ficus opuntia indica flowers (such as those purchased from Silab ); 8-hexadecene 1,16-dicarboxylic acid; esters of glucose and esters of vitamin F; or mixtures thereof.
[0079] In certain embodiments, the chemical exfoliant can be selected from an alpha-hydroxy acid, such as citric acid, lactic acid, glycolic acid, malic acid, tartaric acid, or mandelic acid; a beta-hydroxy acid, such as salicylic acid or a derivative thereof, such as n-octanoyl-5-salicylic acid; trichloroacetic acid; phenol; croton oil peel; or a mixture thereof.
[0080] The C-glycoside or its derivative will usually remain on the skin (e.g., intact skin or scar tissue, which may or may not be modified skin tissue or modified scar tissue) for a sufficient time to obtain the desired beneficial effect. Therefore, it may be preferred to leave the C-glycoside or its derivative on the skin until it penetrates the skin or is removed during normal personal hygiene (e.g., when the skin is next washed). For example, in some embodiments, the at least one C-glycoside or derivative thereof is left on the skin for a desired period of time, e.g., 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, and then removed, e.g., by, for example, wiping or rinsing the skin. For example, the at least one C-glycoside or derivative thereof can be left on the skin for a period of 5 to 60 minutes, such as 5 to 50 minutes, 5 to 40 minutes, 5 to 35 minutes, 5 to 30 minutes, 5 to 25 minutes, 5 to 20 minutes, 5 to 15 minutes, or 5 to 10 minutes. As other examples, the at least one C-glycoside or derivative thereof can be left on the skin for a period of 10 to 60 minutes, such as 10 to 50 minutes, 10 to 40 minutes, 10 to 35 minutes, 10 to 30 minutes, 10 to 25 minutes, 10 to 20 minutes, or 10 to 15 minutes.
[0081] The step of applying a C-glycoside or a derivative thereof may include applying to the target area one or more times, such as two or more applications, three or more applications, etc. Thus, in various embodiments, the method includes applying to the target area at least one C-glycoside or a derivative thereof at least once before treatment with a skin modification stimulant, at least once during treatment with a skin modification stimulant, and / or at least once after treatment with a skin modification stimulant. For example, the at least one C-glycoside or a derivative thereof may be applied to the target area at least once before treatment with a skin modification stimulant, at least once during treatment with a skin modification stimulant, and at least once after treatment with a skin modification stimulant. As another example, the method includes applying to the target area at least two times before treatment with a skin modification stimulant, at least two times during treatment with a skin modification stimulant, and / or at least two times after treatment with a skin modification stimulant. As yet another example, the method includes applying to the target area at least one C-glycoside or a derivative thereof at least once (e.g., at least twice) before treatment with a skin modification stimulant and at least once (e.g., at least twice) after treatment with a skin modification stimulant. As yet another example, the method includes applying at least one C-glycoside or a derivative thereof to the target area at least once (eg, at least twice) after treatment with the skin modifying stimulant.
[0082] In various embodiments, the at least one C-glycoside or derivative thereof can be applied to the target area at least once a day, at least twice a day, or at least three times a day, for example, one to five times a day, one to four times a day, one to three times a day, or one to two times a day, for example, once a day, before and / or after treatment with the skin modification stimulant.
[0083] The at least one C-glycoside or derivative thereof may be applied to the skin before and / or after treatment with the skin modifying irritant at least once a day for at least about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 7 days, about 8 days, about 9 days, about 10 days, about 11 days, about 12 days, about 13 days, about 14 days, about 15 days, about 16 days, about 17 days, about 18 days, about 19 days, about 20 days, about 21 days, about 22 days, about 23 days, about 24 days, about 25 days, about 26 days, about 27 days, about 28 days, about 29 days, about 30 days, about 31 days, about 32 days, about 33 days, about 34 days, about 35 days, about 36 days, about 37 days, about 38 days, about 39 days, about 40 days, about 41 days, about 42 days, about 43 days, about 44 days, about 45 days, about 46 days, about 47 days, about 48 days, about 49 days, about 50 days, about 51 days, about 52 days, about 53 days, about 54 days, about 55 days, about 56 days, about 57 days, about 58 days The at least one C-glycoside or derivative thereof can be applied to the target area at least once a day, at least about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 7 days, about 8 days, about 9 days, about 10 days, about 11 days, about 12 days, about 13 days, about 14 days, about 15 days, about 16 days, about 17 days, about 18 days, about 19 days, about 20 days, about 21 days, about 22 days, about 23 days, about 24 days, about 25 days, about 26 days, about 27 days, about 28 days, about 29 days, about 30 days, about 31 days, about 32 days, about 33 days, about 34 days, about 35 days, about 36 days, about 37 days, about 38 days, about 39 days, about 40 days, about 41 days, about 42 days, about 43 days, about 44 days, about 45 days, about 46 days, about 47 days, about 48 days, about 49 days, about 50 days, about 51 days, about 52 days, about 53 days, about 54 days, about 55 days, about 56 days, about 57 days, about 58 days, about 59 days, or about 60 days. The at least one C-glycoside or derivative thereof can be applied to the target area at least once a day, at least about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, or about 7 days a week. For example, the at least one C-glycoside or derivative thereof can be applied to the target area at least twice a day, wherein the second or subsequent application is performed at least about 6 hours, e.g., at least about 8 hours, at least about 10 hours, at least about 12 hours, or at least about 15 hours after the previous application.
[0084] In various embodiments, the methods of the present disclosure may be performed at least once a month for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 months, either continuously or non-continuously.
[0085] In various embodiments, the at least one C-glycoside or derivative thereof can be applied to the target area within about 1 minute, e.g., 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 treatment of the skin or scar tissue with the skin modification stimulant.
[0086] In various methods of the present disclosure, administering at least one C-glycoside or derivative thereof is accomplished by applying a composition comprising at least one C-glycoside or derivative thereof, such as a composition comprising at least one C-xylopyranoside or derivative thereof, such as hydroxypropyltetrahydropyrantriol, to the target area before, during, and / or after treatment of the skin or scar tissue with a skin modification stimulant. Any composition described herein can be used in the methods of the present disclosure.
[0087] In at least some embodiments, treatment with a skin-modifying stimulant is performed by an at-home device. As a non-limiting example, microneedling and microdermabrasion can be accomplished by an at-home device. The at-home device can be sold in the form of a kit containing a composition comprising at least one C-glycoside or a derivative thereof, such as a composition comprising at least one C-xylopyranoside or a derivative thereof, such as hydroxypropyltetrahydropyrantriol.
[0088] The methods of the present disclosure treat skin or scar tissue using a skin modifying stimulant in accordance with known conventional procedures. Thus, while it may be done, it is not necessary to change the duration, intensity, or other parameters of the treatment currently being performed using a skin modifying stimulant in order to obtain the unexpected and unexpected scar prevention benefits and / or improvement or reduction in scar appearance of the present disclosure. For example, in a conventional microdermabrasion procedure, a device with exfoliating crystals is moved over the skin with light pressure for about 30 minutes. In the methods of the present disclosure, the same microdermabrasion procedure may be performed with the abrasive element selected as the skin modifying stimulant, and the at least one C-glycoside or derivative thereof may be applied to the target area before, during, and / or after the procedure.
[0089] The disclosed methods are not directed to enhancing or improving wound healing, but rather to different and unique biological processes associated with scarring as described herein. Thus, in at least some embodiments, the methods of the present disclosure do not include applying C-glycoside or a derivative thereof to injured skin that does not have scar tissue.
[0090] According to various embodiments of the present disclosure, the method comprises treating scar tissue by applying at least one C-glycoside or a derivative thereof to the scar tissue, and combining the scar tissue with a skin modification stimulant. In various embodiments, the method comprises:
[0091] (1) treating scar tissue with at least one skin modifying stimulant,
[0092] (2) applying at least one C-glycoside or a derivative thereof to the scar tissue.
[0093] In some embodiments, the step of (1) treating the scar tissue with at least one skin modification stimulant occurs before the step of (2) applying at least one C-glycoside or a derivative thereof to the scar tissue, such that the at least one C-glycoside or a derivative thereof is applied to the modified scar tissue. In some embodiments, the step of (2) applying at least one C-glycoside or a derivative thereof to the scar tissue comprises applying a composition comprising at least one C-glycoside or a derivative thereof and at least one carrier to the scar tissue before and / or after step (1), wherein the total amount of C-glycoside and its derivatives present in the composition is from about 0.1 wt % to about 30 wt %, such as from about 0.5 wt % to about 10 wt %, relative to the total weight of the composition.
[0094] According to other embodiments of the present disclosure, the method comprises applying at least one C-glycoside or a derivative thereof to the skin before skin damage (e.g., before a surgical procedure), and treating the skin with a skin modification stimulant. In various embodiments, the method comprises:
[0095] (1) treating intact skin with at least one skin modifying stimulant, and
[0096] (2) applying at least one C-glycoside or a derivative thereof to the skin.
[0097] In some embodiments, the step of (1) treating the intact skin with at least one skin modification stimulant occurs before the step of (2) applying at least one C-glycoside or a derivative thereof to the intact skin, such that the at least one C-glycoside or a derivative thereof is applied to the modified skin tissue. In some embodiments, the step of (2) applying at least one C-glycoside or a derivative thereof to the intact skin comprises applying a composition comprising at least one C-glycoside or a derivative thereof and at least one carrier to the intact skin before and / or after step (1), wherein the total amount of C-glycoside and its derivatives present in the composition is from about 0.1 wt % to about 30 wt %, such as from about 0.5 wt % to about 10 wt %, relative to the total weight of the composition.
[0098] Optionally, in some embodiments, one or more additional active agents other than C-glycosides or derivatives thereof may be applied to the skin either as part of a composition comprising at least one C-glycoside or derivative thereof or separately, including, for example, actives that modulate inflammation (including, but not limited to, carotenoids, curcumin, steroids, cannabinoids, glycoproteins, essential oils, flavonoids and flavonoid derivatives, phenolic acids, ascorbic acid, polyphenols, and seaweed extracts), actives that enhance the skin barrier (including, but not limited to, pantothenic acid, ceramides, pseudoceramides (e.g., 2-oleyl-1,3-octadecanediol), niacinamide, colloidal oatmeal, probiotics, and β-glucans), and / or actives that modulate skin fibrosis (including, but not limited to, TNF inhibitors, TGF-β inhibitors, mTOR pathway inhibitors, and kynurenic acid and its derivatives). One or more additional active agents may be applied to the target area before, during, and / or after treatment of intact skin or scar tissue with a skin modifying stimulant, and / or before, during, and / or after application of at least one C-glycoside or derivative thereof to the target area.
[0099] In some embodiments, at least one additional composition, such as a moisturizer, sunscreen, and / or anti-aging composition, may be applied to the target area before and / or after the application of the at least one C-glycoside or derivative thereof. In various embodiments, the at least one C-glycoside or derivative thereof is first applied to the target area and is not removed prior to the application of the at least one additional skin composition. In another embodiment, the at least one additional skin composition is first applied to the target area and is not removed prior to the application of the at least one C-glycoside or derivative thereof.
[0100] If desired, any disclosed step or method can be repeated one or more times using the same or different skin-modifying stimulants, and / or the same or different C-glycosides or derivatives thereof. If different, the treatment with the skin-modifying stimulants can be different in any way, such as using different skin-modifying stimulants, using the same stimulant but for different lengths of time, etc. Likewise, if different, the application of the C-glycoside or derivatives thereof can be different in any way, such as using different C-glycosides, using the same C-glycoside but at different concentrations, etc.
[0101] For example, one method may include repeating treatment with a skin-modifying stimulant one or more times before and / or after applying the at least one C-glycoside or derivative thereof to the target area, wherein the treatment with the skin-modifying stimulant may be the same or different. Another exemplary method may include repeating application of at least one C-glycoside or derivative thereof to the target area one or more times before and / or after treating with the skin-modifying stimulant, wherein the C-glycoside or derivative thereof may be the same or different.
[0102] As another non-limiting example, the first skin modification stimulus may be a laser, wherein the first treatment is Clear+ The first skin modification stimulus may be a laser, and the second skin modification stimulus may be an abrasive element, wherein the second treatment is a microdermabrasion operation. As yet another non-limiting example, the first skin modification stimulus may be a laser, wherein the first treatment is a Clear+ Laser operation, and the second treatment can be a second Clear+ Laser operation.
[0103] In yet another example, the first step is applying at least one C-glycoside or a derivative thereof to the skin of an individual before surgery, before, during and / or after treating the skin with at least one skin-modifying stimulant; then, 7 days after the individual's surgical wound has healed, the second step is applying at least one C-glycoside or a derivative thereof to scar tissue formed at the wound site, before, during and / or after treating the scar tissue with at least one skin-modifying stimulant, wherein one or both of the C-glycoside or a derivative thereof and the skin-modifying stimulant are the same or different in the first step and the second step.
[0104] As another non-limiting example, the method may be a method of treating a scar to reduce or improve its appearance, wherein the first skin irritant is a laser and the first treatment is a Clear+ The method comprises the steps of: applying a laser to a target area, wherein the second treatment is a microdermabrasion treatment, and applying the second skin irritant is an abrasive element, wherein the second treatment is a microdermabrasion treatment, and applying at least one C-glycoside or a derivative thereof to the target area before, between, during and / or after the first treatment and the second treatment, wherein the C-glycoside or derivative thereof applied each time is the same or different.
[0105] Based on the foregoing, it will be appreciated by those skilled in the art that many additional variations of the processing scheme according to the present disclosure are considered to fall within the scope of the present disclosure.
[0106] In this application, unless otherwise expressly stated, the use of the singular includes the plural. Thus, the terms "a," "an," and "the" are to be understood to include the plural as well as the singular; thus, "skin-modifying irritant" is to be understood to mean "at least one skin-modifying irritant," unless otherwise expressly stated. In this application, the use of "or" means "and / or," unless otherwise expressly stated. Furthermore, the use of the term "including," as well as other forms such as "include" and "included," is non-limiting. In addition, unless otherwise expressly stated, terms such as "element" or "component" include both elements and components comprising one unit and elements and components comprising more than one unit.
[0107] The term "and / or" is to be understood to include conjunctions and transitional terms, and specifically encompasses instances of either conjunctions and transitional terms. For example, applying C-glycoside or its derivative to the target area "before and / or after" treatment with a skin-modifying irritant includes applying C-glycoside or its derivative to the target area before treatment with the skin-modifying irritant and after treatment with the skin-modifying irritant, as well as applying C-glycoside or its derivative to the target area before treatment with the skin-modifying irritant or after treatment with the skin-modifying irritant.
[0108] As used herein, the expression "at least one" means one or more and thus includes single components as well as mixtures / combinations.
[0109] Except in the operating examples, or where otherwise indicated, according to various embodiments, all numerical values indicating the amounts of ingredients and / or reaction conditions are to be understood as modified in all cases by the term "about", meaning within 10% of the indicated numerical value (e.g., "about 10%" means 9%-11%, "about 2%" means 1.8%-2.2%), such as within 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or 1%. All numerical values disclosed herein (including ratios, concentrations, etc.) are to be understood to include the term "about", whether or not it exists.
[0110] For the purpose of this disclosure, it should be noted that in order to provide a more concise description, some quantitative expressions given herein are not limited by the term "about". It should be understood that, whether or not the term "about" is explicitly used, each amount given herein is intended to refer to the actual given value, and also to the approximate value of the given value reasonably inferred by a person of ordinary skill in the art, including the approximate value resulting from the experimental and / or measurement conditions of the given value. All ranges and amounts given herein are intended to include sub-ranges and amounts using any disclosed point as endpoints. Therefore, the range "1% to 10%, such as 2% to 8%, such as 3% to 5%" is intended to include the range "1% to 8%, "1% to 5%, "2% to 10%", etc. All numerical values, amounts, ranges, etc. are intended to be modified by the term "about", whether or not so explicitly stated. Similarly, the given range "about 1% to 10%" is intended to use the term "about" to modify the two endpoints of 1% and 10%. The term "about" is used herein to indicate a difference of up to + / - 10% from a stated value, for example + / - 9%, + / - 8%, + / - 7%, + / - 6%, + / - 5%, + / - 4%, + / - 3%, + / - 2%, + / - 1%, + / - 0.5%, + / - 0.1% or + / - 0.01%.
[0111] As used herein, the expressions "ranging from to" and "between" include the endpoints of the range.
[0112] As used herein, all ranges provided are intended to include each specific range within a given range and combinations of subranges between given ranges. Thus, ranges 1-5 specifically include 1, 2, 3, 4, and 5, as well as subranges 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 the range described herein can be used as a minimum or maximum value from which a subrange, etc., is derived.
[0113] As used herein, the term "comprising" (and its grammatical variations) is used in the inclusive sense of "having" or "including," and not in the exclusive sense of "consisting only of."
[0114] As used herein, "uninjured skin" means skin that has not been damaged in a manner that would produce a visible scar (e.g., burns, lacerations, abrasions, acne, skin infections, animal bites, punctures, surgery, etc.), but does not include skin that has been disrupted by treatment with the skin-modifying stimulants described herein. Uninjured skin is intended to be distinguished from skin that has been previously damaged, such as by burns, lacerations, abrasions, acne, skin infections, animal bites, punctures, surgery, etc., and which, when treated according to the methods of the present disclosure, has visible scar tissue resulting from such damage.
[0115] As used herein, "cosmetic treatment" (and grammatical variations thereof) means a treatment intended to improve or restore physical appearance.
[0116] As used herein, "medical treatment" (and grammatical variations thereof) refers to the improvement of at least one biomarker for good health.
[0117] As used herein, "topical administration" (and grammatical variations thereof) refers to applying a composition of the present disclosure to a keratinous substrate, such as the skin.
[0118] As used herein, "reducing" or "improving" the appearance of a scar or scar tissue means that the scar or scar tissue is less visible or less noticeable than when not treated according to the methods disclosed herein.
[0119] As used herein, "preventing" the formation of scars or scar tissue means preventing the appearance of scar tissue visible to the naked eye.
[0120] As used herein, "reducing" the formation of scars or scar tissue means that although scars or scar tissue may form, their appearance observed by the naked eye is less visible or less obvious than when not treated according to the methods disclosed herein.
[0121] Unless otherwise expressly stated, it is not intended that any method described herein be construed as requiring that its steps be performed in a specific order. Therefore, if a method claim does not explicitly list the order in which its steps should be followed, or if it is not otherwise expressly stated in the claims or description that the steps should be limited to a specific order, it is not intended to imply any specific order.
[0122] The compositions and methods of the present disclosure may comprise, consist of, or consist essentially of the basic elements and limitations of the present disclosure described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise useful.
[0123] Various embodiments have been described herein, and the disclosure may be better understood by reference to the examples. The following examples are for illustrative purposes only and should not be construed as limiting in any way.
[0124] Example
[0125] The following examples are intended to be non-limiting and illustrative only.
[0126] Example 1: Cell culture
[0127] Surgical skin samples were obtained from adults and subjected to the 0.25% trypsin dermal / epidermal separation method described in Rheinwald to obtain a suspension of normal human keratinocytes (NHK) and dermal fibroblasts. See Rheinwald JG, Green H.: Serial cultivation of strains of human epidermalkeratinocytes: The formation of keratinizing colonies from single cells. Cell. 6(3): 331-43. 1975. The isolated normal human dermal fibroblasts were cultured in DMEM + 10% fetal bovine serum. The fibroblasts were cast onto original SoftSkin TM The lower layer of the gel. After the mixture of type I collagen and normal human fibroblasts contracted, a full-thickness dermis equivalent was obtained. The culture of isolated normal human keratinocytes was initiated using the 3T3 feeder layer technology (described in Rheinwald JG, Green H.: Epidermal growth factor and the multiplication of cultured human epidermalkeratinocytes. Nature 265: 421-424 (1977)). The isolated normal human keratinocytes were inoculated on the original Soft SkinTM The cells were placed on the top layer of the gel and kept in MEM containing 10% fetal bovine serum at 37°C and 5% carbon dioxide for 7 days to allow the cells to proliferate and form an epidermal layer. The culture was then raised to the air-liquid interface and cultured for another 7 days to generate a reconstructed skin model (SoftSkin TM ).
[0128] Example 2: CO2 Laser Skin Modification Stimulants
[0129] Reconstructed skin samples derived from normal human dermal fibroblasts and normal human keratinocytes were treated with CO2 laser. Laser treatment was performed using a Syneron (Candela, Israel) system. The energy level was set to Deep mode (5% dot coverage, 30 mJ core energy, and 170 J / cm core energy density). 2 ). Each wound tissue was treated with laser for 0.5 seconds to form a 9 mm wound pattern with 56 micro wounds, and each micro wound had a single diameter of 200 μm and a depth of 700 μm. After laser treatment (day 0), the skin model was transferred to a 6-well plate. The medium was changed on day 0, day 2, and day 4.
[0130] Figure 1 The experimental setup is shown, where reconstructed skin is subjected to laser injury, leaving a series of well-defined circular wounds. The healing process is followed by studying the healing of the circular wounds over time. Figure 2 Shows Softskin TM Wound recovery kinetics of model epidermal cells after laser ablation via hematoxylin and eosin (H&E) stained cross sections. Figure 2 The cross-sections of the “control group” and “laser group” indicated that the laser-injured skin model is an acceptable model to simulate the wound healing process including inflammation, proliferation, and remodeling.
[0131] Skin samples were collected on days 0, 2, and 4 for histological staining experiments, and ELISA assays were performed on day 2.
[0132] Example 3: Topical administration of Bossain
[0133] A solution of 35% Bossain (C-glycoside) in 35% propylene glycol (vehicle) was diluted with water to prepare a working solution of 3% Bossain in 3% propylene glycol. A working solution of 3% propylene glycol vehicle was diluted with water to prepare a placebo treatment (negative control group). In addition, a working solution of 3% hyaluronic acid (HA) in water was prepared as a control group to determine whether alternative active substances can produce the same repair / scar prevention effect as Bossain.
[0134] Starting from 2 hours (day 0), 24 hours (day 1) and 48 hours (day 2) after laser treatment, 10 μL of the prepared working solution was applied to the laser wound surface of a separate skin model every 24 hours. The effect of C-glycoside on the skin was observed by studying the effect of bosine on laser-induced wounds using reconstructed skin. The following examples show that C-glycoside can be used to improve the appearance of scars and reduce scar formation.
[0135] Example 4: Histology and immunofluorescence staining
[0136] 10 mm diameter reconstructed skin tissue pieces were pressed out for histological staining. Skin samples were embedded in optimal cutting temperature (OCT) compound for cryosectioning. 7 μm sections were cut and dried at room temperature for 1 hour, then fixed in cold acetone for 5 minutes, washed twice with DPBS, and blocked with 0.2% BSA in DPBS for another 10 minutes.
[0137] Some fixed sections were stained with hematoxylin and eosin (H&E). Figure 2 As shown. In hydroxypropyltetrahydropyrantriol treated tissues, keratinocytes invaded into the laser dermal injury site, whereas there was no invasion in hyaluronic acid or negative control treated tissues. These immunostaining analyses from the injured skin model further support the beneficial effects of C-glycoside in wound healing and scar management applications.
[0138] Some fixed sections were stained to evaluate the presence of filaggrin or Ki67. Primary antibodies for filaggrin (MA5-13440, Thermo Fisher Scientific, Waltham, MA, USA, mouse, 1:100) and Ki67 (M7240, Dako, Glostrup, Denmark, mouse 1:100) were diluted in DPBS containing 1% donkey serum, and sections were incubated with filaggrin or Ki67 antibodies for 2 hours at room temperature in a humidity chamber and then washed three times with DPBS. Secondary antibodies (donkey anti-mouse Alexa Fluor 488, Invitrogen A21202, 1:300) were diluted in DPBS containing 1% donkey serum, and sections stained with filaggrin or Ki67 antibodies were incubated with secondary antibodies for 1 hour at room temperature and washed three times with DPBS. Secondary antibody-stained sections were then stained with DAPI (Invitrogen D1306, 1:10000) and washed with DPBS. The stained sections were imaged using a 3DHISTECH PANNORAMIC MIDI II fluorescence scanner. Figure 3 and Figure 5 As shown. The ratio of Ki67-positive cells in the basal layer to the total number of cells in each scanned image of the Ki67 antibody-stained sections was analyzed. The relative fluorescence intensity of filaggrin in the filaggrin antibody-stained sections was measured using Image J software. The results are shown in Figure 4 and Figure 6 shown.
[0139] Compared with wounded skin alone and wounded skin treated with placebo, wounded skin treated with C-glycoside had significantly higher levels of KI67 and filaggrin ( Figure 4 and Figure 6 ). Hydroxypropyl tetrahydropyrantriol (3%) increased filaggrin expression in a statistically significant sense compared to laser treatment alone, laser + vehicle treatment, and untreated control groups, which promotes skin barrier function and moisture retention. Hydroxypropyl tetrahydropyrantriol (3%) increased Ki67 expression (a marker for keratinocyte proliferation) in a statistically significant sense compared to laser treatment alone, laser + vehicle treatment, and untreated control groups. This suggests that C-glycosides can be used to aid barrier repair in injured skin. Therefore, these additional immunostaining analyses from the injured skin model further illustrate the beneficial effects of C-glycosides in wound healing and scar management applications.
[0140] Example 5: Protein determination
[0141] Culture supernatants were collected from reconstructed skin samples. DKK-1 secretion was measured using Luminex Assay (R&D Systems) on a panel following the manufacturer's guidelines. Figure 7 As shown. Both laser-injured and placebo-treated tissues showed reduced levels of DKK-1 compared to the control group. In contrast, C-glycoside treatment restored DKK-1 secretion to levels similar to the control group. Hydroxypropyl tetrahydropyrantriol enhanced the expression of DKR-1 compared to laser treatment alone, laser + vehicle treatment, and untreated control groups. Bosine has been shown to regulate the progression of acne scars by targeting the TGF-β1 signaling pathway by enhancing the expression of DKK-1, a key Wnt antagonist molecule that prevents skin fibrosis through the TGFβ pathway. This suggests that C-glycoside has the ability to modify the wound environment by increasing DKK-1 levels and reducing the likelihood of fibrosis and scarring.
[0142] The extruded day 2 normal human tissue culture tissue was soaked in tissue lysis buffer (R&D systems), cryogenically ground three times, and lysed on ice for another 30 minutes. Cell debris was removed by centrifugation at 10,000 × g for 10 minutes at 4°C. Aliquots of the supernatant were removed and stored at -80°C until assayed. The concentration of α-SMA in the ECM was determined using a BCA protein array kit (Absin, abs9232-500) and normalized before ELISA assay (αSMA human ELISA kit #Abcam, ab240678). The results are shown in Figure 8 As shown. α-smooth muscle actin levels were increased in laser-injured reconstructed skin compared to the control group. Hydroxypropyl tetrahydropyrantriol (3%) reduced α-SMA expression in a statistically significant sense compared to laser-treated tissue without further treatment. Tissue treated with the 3% negative control did not show the statistically significant improvement. Administration of C-glycoside reduced α-smooth muscle actin levels in laser-injured skin in a statistically significant sense compared to the laser group alone. This reduction in α-smooth muscle actin was not observed when a placebo was used. The results suggest that C-glycoside is beneficial for postoperative wound healing and also provides a specific mode of action to reduce the likelihood of scar progression by targeting the TGF-β pathway.
[0143] Therefore, ELISA analysis from the wounded skin model further illustrates the beneficial effects of C-glycoside in wound healing and scar management applications.
[0144] Example 6: Data Analysis
[0145] Each experiment in Examples 2-5 was repeated three times. For immunostaining studies, one cryosection was taken for each replicate, and 4 fluorescent images / section were taken for data analysis. Unless otherwise stated, all data were statistically analyzed using GraphPadPrism and are presented as mean ± standard deviation. One-sided Student's t-test was used for statistical analysis. Figure 4 , Figure 6 , Figure 7 and Figure 8 In the table, *, **, and *** indicate significant differences with p values less than 0.01, 0.005, and 0.001, respectively.
[0146] The above examples illustrate the unexpected and beneficial effects obtained by the methods of the present disclosure, which include treating skin and / or scar tissue with the compounds and compositions described herein, and subjecting the skin and / or scar tissue to injury and / or treatment with various skin modifying stimuli.
Claims
1. A method for improving the appearance of scar tissue, the method comprising: (a) treating scar tissue with at least one skin modifying stimulant, and (b) applying at least one C-glycoside or a derivative thereof to the scar tissue, wherein Step (b) occurs before, during and / or after step (a).
2. A method for reducing scar tissue formation, the method comprising: (a) treating intact skin with at least one skin modifying stimulant, and (b) applying at least one C-glycoside or a derivative thereof to said intact skin, wherein (b) occurs before, during and / or after step (a).
3. A method of treating the skin after a surgical procedure to prevent or reduce scar tissue formation, the method comprising: (a) causing skin damage, and (b) applying at least one C-glycoside or a derivative thereof to the damaged skin, wherein step (b) occurs before, during and / or after step (a).
4. The method of any one of claims 1-3, wherein step (b) of applying at least one C-glycoside or derivative thereof to the scar tissue occurs within about 24 hours before and / or after step (a) of treating the scar tissue with at least one skin modifying stimulant.
5. The method according to any one of claims 1 to 4, wherein the at least one C-glycoside comprises at least one C-xylopyranoside or a derivative thereof.
6. The method according to any one of claims 1 to 5, wherein the at least one C-glycoside is selected from C13-D-xylopyranosyl-n-propane-2-one; Cα-D-xylopyranosyl-n-propane-2-one; C13-D-xylopyranosyl-2-hydroxypropane; Cα-D-xylopyranosyl-2-hydroxypropane; 1-(C13-D-fucopyranosyl)-propane-2-one; 1-(Cα-D-pyranosyl)- Fucoside)-propane-2-one; 1-(C13-L-fucopyranoside)-propane-2-one; 1-(Cα-L-fucopyranoside)-propane-2-one; 2-one, 1-(C13-D-fucopyranoside)-2-hydroxypropane, 1-(Cα-D-fucopyranoside)-2-hydroxypropane; 1-(C13-L-fucopyranoside)-2-hydroxypropane; 1-(Cα-L-pyranoside)-2-hydroxypropane; Fucoside)-2-hydroxypropane; 1-(C13-D-pyranosyl-glucopyranosyl)-2-hydroxypropane; 1-(Cα-D-pyranosyl-glucopyranosyl)-2-hydroxypropane; 1-(C13-D-galactopyranosyl)-2-hydroxypropane; 1-(Cα-D-galactopyranosyl)-2-hydroxypropane-1-(C13-D-fucofuranosyl)propane-2-one; 1-(Cα-D-fucofuranosyl) )-propan-2-one; 1-(C13-L-fucofuranosyl)-propan-2-one; 1-(Cα-L-fucofuranosyl)-propan-2-one; C13-D-maltopyranosyl-n-propane-2-one-Cα-D-maltopyranosyl-n-propane-2-one-C13-D-maltopyranosyl-2-hydroxypropane; Cα-D-maltopyranosyl-2-hydroxypropane; derivatives thereof or combinations thereof.
7. The method according to any one of claims 1 to 6, wherein the at least one C-glycoside is selected from C13-D-xylopyranosyl-2-hydroxypropane, Ca-D-xylopyranosyl-2-hydroxypropane, or a combination thereof.
8. The method of any one of claims 1-2 or 4-7, wherein the at least one skin modification stimulus is selected from one or more of a laser, plasma, radiofrequency, high intensity focused ultrasound, an electric field, heat, a low intensity light device, a needle, a microneedle, an abrasive element, or a chemical agent.
9. The method of any one of claims 1 or 4-8, wherein the step of treating the scar tissue with at least one skin modification stimulant comprises treating the scar tissue with one or more of the following procedures: ablative laser procedures, non-ablative laser procedures, microneedle procedures, high-intensity focused ultrasound procedures, electroporation procedures, dermabrasion procedures, microdermabrasion procedures, plasma rejuvenation procedures, and / or chemical peel procedures.
10. The method of any one of claims 1 to 9, wherein the step of applying at least one C-glycoside or a derivative thereof to scar tissue, intact skin or damaged skin comprises applying a composition comprising at least one C-glycoside or a derivative thereof and at least one carrier to the scar tissue, intact skin or damaged skin, The total amount of C-glycoside and its derivatives present in the composition is from about 0.1 wt % to about 30 wt %, preferably from about 0.1 wt % to about 20 wt %, more preferably from about 0.5 wt % to about 10 wt %, still more preferably from about 1 wt % to about 5 wt %, most preferably from about 2 wt % to about 4 wt %, relative to the total weight of the composition.
11. The method of any one of claims 1-10, wherein step (b) is repeated at least once at least about 12 hours after the first administration.
12. The method of any one of claims 1-10, wherein step (b) is repeated at least once at least about 24 hours after the first administration.
13. The method of any one of claims 1-10, wherein step (b) is repeated at least once at least about 36 hours after the first administration.
14. The method according to any one of claims 1 to 10, wherein step (b) occurs after step (a), and is optionally repeated one or more times.
15. The method according to any one of claims 1 to 10, wherein step (b) occurs before step (a), and is optionally repeated one or more times before and / or after step (a).
16. The method according to any one of claims 1 or 4-10, comprising: (a) treating scar tissue with at least one skin modifying stimulus to produce modified scar tissue, and (b) applying at least one C-glycoside or a derivative thereof to the modified scar tissue within about 6 hours of step (a).
17. The method of claim 16, wherein step (b) is repeated at least once at least about 12 hours after the first administration.
18. The method of claim 16, wherein step (b) is repeated at least once at least about 36 hours after the first administration.
19. The method of claim 16, wherein step (b) comprises: A composition comprising at least one C-xylopyranoside and / or its derivative, preferably selected from the group consisting of: Cα-D-xylopyranoside-2-hydroxypropane and / or C13-D-xylopyranoside-2-hydroxypropane, more preferably C13-D-xylopyranoside-2-hydroxypropane, The total amount of C-xylopyranosides and their derivatives present in the composition is About 3% by weight, relative to the total weight of the composition.
20. A method for improving the appearance of scar tissue, the method comprising: (a) treating scar tissue with at least one skin modifying stimulus to produce modified scar tissue, and (b) within about 24 hours after step (a), adding at least one C-xylopyranoside and / or its derivatives, preferably C13-D-xylopyranoside 2-hydroxypropane and / or applying a composition of Cα-D-xylopyranoside-2-hydroxypropane to the modified scar tissue, wherein the total amount of C-xylopyranosides and their derivatives present in the composition is from about 1 wt % to about 5 wt %, relative to the total weight of the composition, wherein step (b) occurs before, during and / or after step (a).
21. The method of claim 20, wherein step (b) occurs after step (a), and is optionally repeated one or more times.
22. The method of claim 20 or claim 21, wherein step (b) is repeated at least once at least about 12 hours after the first administration following step (a).
23. The method of any one of claims 20-22, wherein step (b) is repeated at least once at least about 36 hours after the first administration following step (a).
24. A method for improving the appearance of modified skin and / or modified scar tissue comprising applying at least one C-glycoside or a derivative thereof to said modified skin and / or modified scar tissue.
25. A kit, comprising: (a) at least one skin modification irritant, and (b) at least one composition comprising at least one C-glycoside or a derivative thereof and at least one carrier, The total amount of C-glycoside and its derivatives present in the composition is from about 0.1 wt % to about 30 wt %, preferably from about 0.1 wt % to about 20 wt %, more preferably from about 0.5 wt % to about 10 wt %, still more preferably from about 1 wt % to about 5 wt %, Most preferably, from about 2% to about 4% by weight, relative to the total weight of the composition.
26. A method for reducing the transformation of fibroblasts to myofibroblasts in intact skin and / or scar tissue, the method comprising: (a) treating intact skin and / or scar tissue with at least one skin modifying stimulant, and (b) applying at least one C-glycoside or a derivative thereof to said intact skin and / or scar tissue, wherein step (b) occurs before, during and / or after step (a).
27. A method for increasing the expression level of DKK-1 in intact skin and / or scar tissue, the method comprising: (a) treating intact skin and / or scar tissue with at least one skin modifying stimulant, and (b) applying at least one C-glycoside or a derivative thereof to said intact skin and / or scar tissue, wherein step (b) occurs before, during and / or after step (a).
28. A method for increasing phosphorylation of β-catenin in intact skin and / or scar tissue, the method comprising: (a) treating intact skin and / or scar tissue with at least one skin modifying stimulant, and (b) applying at least one C-glycoside or a derivative thereof to said intact skin and / or scar tissue, wherein step (b) occurs before, during and / or after step (a).
29. A method for downregulating TGF-β signaling in intact skin and / or scar tissue, the method comprising: (a) treating intact skin and / or scar tissue with at least one skin modifying stimulant, and (b) applying at least one C-glycoside or a derivative thereof to said intact skin and / or scar tissue, wherein step (b) occurs before, during and / or after step (a).
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