WO2010105634A1

WO2010105634A1 - Use of interleukin-1 beta in cosmetic compositions and methods thereof

Info

Publication number: WO2010105634A1
Application number: PCT/EP2009/001947
Authority: WO
Inventors: Igor Anatolievich Pomytkin
Original assignee: United Technologies Ut Ag
Priority date: 2009-03-17
Filing date: 2009-03-17
Publication date: 2010-09-23
Also published as: EA201100392A1; EA023680B1; UA99990C2

Abstract

The present invention relates to the use of interleukin-1 beta in cosmetic methods and compositions for skin conditioning, reducing cellulite severity, improving skin elasticity and firmness, reducing wrinkles, enhancing collagen and elastin production in skin, reducing stretch marks, and/or reducing or preventing scars.

Description

USE OF INTERLEUKIN-1 BETA IN COSMETIC COMPOSITIONS AND

METHODS THEREOF

Field of the Invention [0001] The present invention relates to the use of interleukin-1 beta in cosmetic compositions and methods thereof.

Background of the invention

[0002] Interleukin-1 beta (IL- lβ), which is also named IL- 1F2, is a naturally occurring polypeptide with the sequence well-known from the art. Interleukin-1 beta is synthesized in a skin keratinocytes as a 269 amino acid length non-active precursor, which is not processed in skin keratinocytes to the active form. Mizutani H et al.. J Clin Invest. 1991, 87OU066-71. Interleukin-1 beta has no capacity to be transported throughout the skin, being a big hydrophilic polypeptide of mass about 30 kDa. Thus, skin can not been regulated by interleukin-1 beta in norm, distinctive of interleukin-1 alpha that is produced by skin keratinocytes in active form playing a role of a primary inductor of the skin renewal program. Interleukin-1 alpha is produced in skin on a constitutive basis and is involved in proliferation and differentiation of epidermal cells and in production of major components of dermis such as procollagen, hyaluronic acid, and elastin. The interleukin-1 alpha production in skin is decreased with age. Maas-Szabowski N et al.. J Invest Dermatol. 2000. 114(6U 075-84. Duncan MR et al.. J Invest Dermatol. 1989. 92(5):699-706. Postlethwaite AE et al.. J Cell Biol. 1988. 106(2):311-8. Interleukin-1 alpha, while can not penetrate through a skin, has a specific mechanism of spreading throughout the skin by initiating a process of expression of new molecules of interleukin-1 alpha by keratinocytes. Lee S, et al., J Invest Dermatol 97: 106-110. 1991. [0003] The use of interleukin-1 beta as an active component of topical cosmetic compositions is restricted completely by a very low transport capacity of the big molecule through the skin barrier.

[0004] Surprisingly, we found that interlekin-1 beta can induce biological response in skin under topical application, through the activation of production of interleukin-1 alpha in epidermis. So, interleukin-1 beta effects in a skin are mediated through interleukin-1 alpha. It provides a molecular basis for the use of interleukin-1 alpha in topical cosmetic applications useful for maintaining skin in normal condition. [0005] The use of interleukin-1 beta in medicinal applications is known from the art. For example, EP0569042 discloses medical uses of interleukin-1 beta. U.S. patent 5,723,117 discloses the use of interleukin-1 beta in inhibiting development of hepatitis. U.S. patent 5,342,614 discloses the method for the treatment of arthritis and inflammation with interleukin-1 beta or derivatives thereof. However, no published or disclosed in the art related to the use of interleukin-1 beta for skin conditioning, reducing cellulite severity, improving skin elasticity and firmness, reducing wrinkles, enhancing collagen and elastin production in skin, reducing stretch marks, and/or reducing or preventing scars.

[0006] It is an object of the present invention to provide the use of interleukin-1 beta in cosmetic methods and compositions for skin conditioning, reducing cellulite severity, improving skin elasticity and firmness, reducing wrinkles, enhancing collagen and elastin production in skin, reducing stretch marks, and/or reducing or preventing scars.

Detailed Description of the Invention [0007] The present invention provides a cosmetic method of improving the appearance of wrinkled, lined, dry, aged, photodamaged, cellulite-affected, scar- affected, stretch mark-affected, and/or acne-affected skin, the method comprising the step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle. [0008] As used herein, the term "interleukin-1 beta" refers to a protein having the amino acid sequence and structure of naturally occurring human interleukin-1 beta, and biologically active analogues and derivatives thereof. The interleukin-1 beta structure is well-known from the art, for example, Uniprot/Swiss-Prot database (#P01584) contains the structure of human interleukin-1 beta as 269 amino acid sequence of the protein, wherein the sequence 117-269 represents the active form of the interleukin-1 beta. The term thus includes interleukin-1 beta which is chemically synthesized or expressed using recombinant protein expression systems that use, for example, E-coli or yeast as the host. A preferred interleukin-1 beta is a human interleukin-1 beta expressed using a protein expression system.

[0009] As used herein, the term "analogue of interleukin-1 beta" refers to an interleukin-1 beta that contains one or more amino acid substitutions, deletions, additions, or rearrangements compared with human interleukin-1 beta at sites such that the interleukin-1 beta analogue still retains the in vivo biological activity of interleukin-1 beta. Examples of interleukin-1 beta analogues include OCT-43 (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan), Gly4-interleukin-l beta, and Ser8-interleukin-l beta.

[0010] As used herein, the term "derivative of interleukin-1 beta" refers to naturally occurring interleukin-1 beta and interleukin-1 beta analogues that are chemically or enzymatically derivatized at one or more constituent amino acids, including side chain modifications, backbone modifications, and N-and C- terminal modifications, by for example acetylation, acylation, hydroxylation, methylation, amidation, phosphorylation, pegylation, or glycosylation, and that retain the in vivo biological activity of interleukin-1 beta. An example of an interleukin-1 beta derivative is myristoyl-Lysl6-interleukin-l beta and HisTag- interleukin-1 beta.

[0011] In preferred embodiments of the present invention, the content of interleukin-1 beta in said compositions is in the range from 10^"7 to 10^"4 wt. %. [0012] As used herein, the term "dermatologically acceptable vehicle" refers to one or more liquid, semi-solid, or solid diluents, which are compatible with interleukin-1 beta, and are suitable for administration to any portion of the human skin without undue/unacceptable aesthetic effects, e.g., greasiness, color, odor, etc.. Examples of such carriers include, but are not limited to, distilled or deionized water, propyleneglycol, glycerol, and oil.

[0013] In preferred embodiments of the present invention, said compositions further comprise a buffer at a concentration effective to maintain the pH of the composition at between about 4.0 to about 7.5. Examples of dermatologically or cosmetically acceptable buffers include, but are not limited to, phosphate buffer, acetate, citrate buffer, succinate buffer, and glycine buffer.

[0014] The compositions of the present invention can comprise optional ingredients. Such optional ingredients generally are used individually at levels from about 0.0005% to about 10.0%, preferably from about 0.005% to about 1.0% by weight of the composition.

[0015] Examples of suitable optional ingredients include, but are not limited to, depigmentation agents; reflectants; humectants; antimicrobial (e.g., antibacterial) agents; UV absorbers; anti-acne agents; anti-aging agents; anti- wrinkling agents, antiseptics; local anesthetics; wound healing promoters; deodorants and antiperspirants; skin emollients and skin moisturizers; tanning agents; skin lightening agents; antifungals; depilating agents; external analgesics; counterirritants; anti-diaper rash agents; make-up preparations; vitamins and nutrients such as thiamin, riboflavin, niacin, pantothenates, pyridoxine, folic acid, cobalamin, biotin, choline, inositol, ascorbic acid, lipoic acid, carnitine, and etc.; amino acids and their derivatives such as alanine, arginine, asparagine, aspartic acid, carnitine, citrulline, cysteine, dimethylglycine, gamma-aminobutyric acid, glutamic acid, glutamine, glutathione, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, praline, serine, taurine, threonine, tryptophan, tyrosine, valine; minerals such as boron, calcium, chromium, cobalt, copper, fluoride, germanium, iodine, iron, lithium, magnesium, manganese, molybdenum, phosphorus, potassium, selenium, silicon, sodium, sulfur, vanadium, zinc; herbal extracts; retinoids; bioflavonoids; anti-oxidants; skin conditioners; hair lighteners; chelating agents; cell turnover enhancers; coloring agents; sunscreens and the like, and mixtures thereof. [0016] Examples of suitable reflectants include, but not limited to, mica, alumina, calcium silicate, glycol dioleate, glycol distearate, silica, sodium magnesium fluorosilicate, and mixtures thereof.

[0017] Examples of suitable UV absorbers include, but not limited to, benzophenone, bomelone, butyl paba, cinnamidopropyl trimethyl ammonium chloride, disodium distyrylbiphenyl disulfonate, paba, potassium methoxycinnamate, and mixtures thereof.

[0018] Examples of suitable humectants include, but not limited to, water soluble liquid polyols selected from the group comprising glycerine, propylene glycol, hexylene glycol, butylene glycol, pentylene glycol, dipropylene glycol, and mixtures thereof. The humectant is preferably present in an amount of from about 0 percent to about percent, more preferably from about 0.5 percent to about 5 percent, based on the overall weight of the composition.

[0019] Suitable amino acid agents include amino acids derived from the hydrolysis of various proteins as well as the salts, esters, and acyl derivatives thereof. Examples of such amino acid agents nonexclusively include amphoteric amino acids such as alkylamido alkylamines, i.e. stearyl acetyl glutamate, capryloyl silk amino acid, caprylol collagen amino acids; capryloyl kertain amino acids; capryloyl pea amino acids; cocodimonium hydroxypropyl silk amino acids; corn gluten amino acids; cysteine; glutamic acid; glycine; hair keratin amino acids; hair amino acids such as aspartic acid, threonine, serine, glutamic acid, glycine, alanine, half-cystine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, cysteic acid, lysine, histidine, arginine, cysteine, tryptophan, citrulline; lysine; silk amino acids, wheat amino acids; and mixtures thereof [0020] Examples of suitable proteins include, but not limited to, collagen, deoxyribonuclease, iodized corn protein; keratin; milk protein; protease; serum protein; silk; sweet almond protein; wheat germ protein; wheat protein; wheat protein, alpha and beta helix of keratin proteins; hair proteins, such as intermediate filament proteins, high-sulfur proteins, ultrahigh-sulfur proteins, intermediate filament-associated proteins, high-tyrosine proteins, high-glycine tyrosine proteins, tricohyalin, arginine-rich peptides like as oligoarginines (Arg)₈, and mixtures thereof. [0021] Examples of suitable antiperspirants and deodorants include, but not limited to, aluminium chlorohydrates, aluminium zirconium chlorohydrates, and mixtures thereof.

[0022] Examples of sunscreen agents include, but not limited to, titanium dioxide and zinc oxide.

[0023] Examples of suitable counterirritants include, but not limited to, camphor, menthol, methyl salicylate, peppermint and clove oils, ichtammol, and mixtures thereof.

[0024] Examples of suitable anti-aging agents include, but are not limited to, inorganic sunscreens such as zinc oxide; organic sunscreens such as octyl-methyl cinnamates and derivatives thereof; retinoids; vitamins such as vitamin C, vitamin B, and derivatives thereof; antioxidants including acid such as glycolic acid, citric acid, lactic acid, malic acid, mandelic acid, ascorbic acid, alpha-hydroxybutyric acid, alpha-hydroxyisobutyric acid, alpha-hydroxyisocaproic acid, atrrolactic acid, alpha-hydroxyiso valeric acid, ethyl pyruvate, galacturonic acid, glucopehtonic acid, glucopheptono 1,4-lactone, gluconic acid, gluconolactone, glucuronic acid, glucurronolactone, glycolic acid, isopropyl pyruvate, methyl pyruvate, mucic acid, pyruvia acid, saccharic acid, saccaric acid 1,4-lactone, tartaric acid, and tartronic acid; succinic acid or salts thereof; acids such as beta-hydroxybutyric acid, beta- phenyl-lactic acid, beta-phenylpyruvic acid; botanical extracts such as green tea, soy, milk thistle, algae, aloe, angelica, bitter orange, coffee, goldthread, grapefruit, hoellen, honeysuckle, Job's tears, lithospermum, mulberry, peony, puerarua, rice, safflower, and mixtures thereof. Suitable amounts of anti-aging agents include, based upon the total weight of the composition, from about 0.01 percent to about 10 percent, and preferably from about 0.04 percent to about 5 percent.

[0025] Examples of suitable depigmentation agents include, but are not limited to, hydroquinone and it derivatives; vitamins such as niacin, vitamin C and its derivatives; extracts such as chamomile and green tea, and mixtures thereof.

[0026] Examples of skin lightening agents include, but not limited to, hydroquinone, catechol and its derivatives, ascorbic acid and its derivatives, and mixtures thereof. [0027] The compositions of the invention are prepared by well-known procedures.

Such procedures include, but are not limited to, mixing the interleukin-1 beta with other ingredients of the composition in conventional manner. Guidance for the preparation of cosmetic or dermatological compositions of the invention can be found in " Remington: The science and practice of pharmacy" 20th ed. Mack Publishing, Easton PA, 2000 ISBN 0-912734-04-3 and " Encyclopaedia of Pharmaceutical Technology", edited by Swarbrick, J. & J. C. Boylan, Marcel Dekker, Inc., New York, 1988 ISBN 0-8247-2800-9 or a newer edition. As well known to the skilled person, illustrative additives to dermatological compositions include, but is not limited to: ointment bases, solvents, buffering agents, pH- adjusting agents, preservatives, humectants, chelating agents, antioxidants, stabilizers, emulsifying agents, suspending agents, gel-forming agents, perfumes, and skin protective agents.

[0028] The compositions of the present invention can be formulated in a variety of forms including, but are not limited to, lotions, gels, creams, sprays, and solutions. The compositions of the invention are prepared by methods well-known from the art in accordance with accepted procedures in a variety of forms. Such forms include, but are not limited to, solution, lotion, gel, emulsion, spray, and cream.

[0029] Further, the present invention provides a cosmetic method for skin conditioning, the method comprising a step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

[0030] The term "skin conditioning" refers to the maintaining the human skin in a good condition, including regulating the skin condition, preventing or reducing visible and/or tactile discontinuities in skin, and/or protecting the skin as it is indicated in European cosmetic legislation. The visible and/or tactile discontinuities in skin, especially at the skin surface wherein such discontinuities are generally undesirable, may be induced or caused by internal and/or external factors, and include the signs of skin aging described herein. The term "regulating skin condition" includes delaying, minimizing and/or preventing visible and/or tactile discontinuities in skin; ameliorating, e.g., diminishing, minimizing and/or effacing, discontinuities in skin; as well as improving skin appearance and/or feel. [0031] The methods of the present invention are particularly advantageous for maintenance of aged skin in good condition, including regulating signs of skin aging, more especially visible and/or tactile discontinuities in skin texture associated with aging. "Regulating the signs of skin aging" includes regulating one or more of such signs, e.g., lines, wrinkles or pores. As used herein, regulating such signs includes delaying, minimizing and/or preventing signs of skin aging; as well as ameliorating, e.g., diminishing, minimizing and/or effacing signs of skin aging.

[0032] "Signs of skin aging" include, but are not limited to, all outward visibly and tactilely perceptible manifestations as well as any other macro or micro effects due to skin aging. Such signs may be induced or caused by intrinsic factors or extrinsic factors, e.g., chronological aging and/or environmental damage. These signs may result from processes which include, but are not limited to, the development of textural discontinuities such as wrinkles, including both fine superficial wrinkles and coarse deep wrinkles, skin lines, crevices, bumps, large pores (e.g., associated with adnexal structures such as sweat gland ducts, sebaceous glands, or hair follicles), scaliness, flakiness and/or other forms of skin unevenness or roughness, loss of skin elasticity (loss and/or inactivation of functional skin elastin), sagging (including puffiness in the eye area and jowls), loss of skin firmness, loss of skin tightness, loss of skin recoil from deformation, discoloration (including undereye circles), blotching, sallowness, hyperpigmented skin regions such as age spots and freckles, keratoses, abnormal differentiation, hyperkeratinization, elastosis, collagen breakdown, and other histological changes in the stratum corneum, dermis, epidermis, the skin vascular system (e.g., telangiectasia or spider vessels), and underlying tissues, especially those proximate to the skin.

[0033] Further, the present invention provides a cosmetic method for reducing cellulite severity, the method comprising a step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

[0034] The term "cellulite" refers to visible and tactile irregularities of skin caused by irregularities of subcutaneous tissue, also is named as orange peel, gynoid lipodystrophy, and etc. Cellulite is frequently accompanied with an increase in regional fat at the cellulite-affected area and is caused by irregularity of dermis- hypodermis junction and fat protrusions to the lower dermis giving rise to visible irregularity at skin surface. The term "cellulite severity" refers to the extent of skin irregularity and can be estimated by a skilled artisan or instrumental methods as it described in public domain, for example, by Smalls LK et al., J Cosmet Sci, 2005, 56(2): 105. The term "reducing cellulite severity" means reducing visible or tactile irregularity of skin surface at cellulite-affected skin area.

[0035] Further, the present invention provides a cosmetic method for improving skin elasticity and firmness, the method comprising a step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

[0036] Further, the present invention provides a cosmetic method of reducing wrinkles, the method comprising the step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

[0037] Further, the present invention provides a cosmetic method of enhancing collagen and elastin production in skin, the method comprising the step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

[0038] Further, the present invention provides a cosmetic method of reducing stretch marks, the method comprising the step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

[0039] Further, the present invention provides the use of interleukin-1 beta for manufacturing a cosmetic composition for skin conditioning, reducing cellulite severity, improving skin elasticity and firmness, reducing wrinkles, enhancing collagen and elastin production in skin, reducing stretch marks, and/or reducing or preventing scars. [0040] In practicing the methods of the invention, an effective amount of the composition of the invention is topically applied to the skin, and is preferably left on the skin for a period of at least about 15 minutes, more preferably at least about 30 minutes, even more preferably at least about 1 hour, most preferably for at least several hours, e.g., up to about 12 hours. This method can be reapplied from 1 to about 5, preferably from 1 to 3 times per day. Typically, the effective amount of the composition is from about 1 gram to about 100 grams, preferably from about 1 gram to about 20 grams.

[0041] The following examples are presented to demonstrate the invention. The examples are illustrative only and are not intended to limit the scope of the invention in any way.

Example 1

[0042] This example demonstrates that interleukin-1 beta induces production of interleukin-1 alpha by keratinocytes. A431 keratinocytes were incubated with or without 100 ng/ml of the commercially available recombinant human interleukin-1 beta for 48 hours. The level of interleukin-1 alpha in incubation medium was assessed by ELISA. Data are presented as mean ± SEM (n=10) of interleukin-1 alpha in the incubation medium. The level of interleukin-1 alpha in control was accepted for 100%.

Treatment IL-I alpha, %

Control 100 ± 17 Interleukin-1 beta 373 ± 48* *Differs significantly of the control (p<0.05).

Example 2

[0043] This example demonstrates the cosmetic composition comprising interleukin-1 beta.

Ingredient Content, wt.%

Interleukin-1 beta 0.00001 Tris buffer qs to pH 7.0

Carbopol Ultrez 10 0.1

Distilled water to 100

The composition preparation: ingredients are mixed in the conventional manner to prepare the aqueous gel. In the cosmetic method, the composition (1.5 ml) is topically applied to the skin, and is preferably left on the skin for a period of at least about 15 minutes.

Example 3 [0044] This example demonstrates the cosmetic methods of the present invention.

The composition of example 2 was applied once-a-day for eight weeks to the aging sign-affected skin regions of faces of ten women aged > 45 years. The efficacy of the composition for the reducing signs of aging skin was assessed by a battery of tests. Skin substructure was assessed by ultrasonography. Wrinkles deepness and orientation were assessed by profilometry. Skin elasticity and firmness was assessed by a suction method. Skin conditioning efficacy was assessed by transepidermal water loss (TEWL). Results obtained at eight week of the treatment are presented in the Table below in percent of changes of mean to basal level (just before the treatment).

Thus, the example shows that topical applying the composition comprising interleukin-1 beta is effective for reducing wrinkles, enhancing collagen and elastin production in skin, improving skin elasticity and firmness, and keeping the skin in a good condition. Example 4

[0045] This example demonstrates the cosmetic methods of the present invention.

Three women having the symmetric scars after the plastic surgery treated scars with micro-needle roller with or without (control) the step of applying the composition of the example 2 onto the scars. It was found that the applying the composition decreases the time for the scar reducing as compared to the only roller use. Thus, the example shows that topical applying the composition of present invention is effective for reducing scars.

Example 5 [0046] This example demonstrates the cosmetic methods of the present invention.

The composition of example 2 was applied twice-a-day for eight weeks to the cellulite-affected skin region of thighs of fifteen women aged > 35 years with body fat index (BFI) > 25.

Cellulite is significantly related to irregularity of dermis and dermis-hypodermis junction surface caused by fat deposition in dermis and fat protrusions to the lower dermis, the irregularities giving rise to visible irregularity of skin surface. Smalls

LK et al.. Quantitative model of cellulite: three-dimensional skin surface topography, biophysical characterization, and relationship to human perception. J

Cosmet Sci. 2005. 56(2): 105-20. The efficacy of the method for the reducing cellulite severity was assessed by ultrasonography. Results obtained at eight week of the treatment are presented in the Table below in percent of changes of mean to basal level (just before the treatment).

Thus, the example shows that topical applying the composition of present invention is effective for reducing cellulite severity. Example 6

[0047] This example demonstrates the cosmetic methods of the present invention.

Three women having the stretch marks after the pregnancy applied the composition of example 2 onto the stretch marks for eight weeks. It was found that the applying the composition reduced stretch marks as compared to baseline. Thus, the example shows that topical applying the composition of present invention is effective for reducing stretch marks.

Claims

Patent Claims

1. A cosmetic method of improving the appearance of wrinkled, lined, dry, aged, photodamaged, cellulite-affected, scar-affected, stretch mark-affected, and/or acne-affected skin, the method comprising the step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

2. A cosmetic method for skin conditioning, the method comprising a step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

3. A cosmetic method for reducing cellulite severity, the method comprising a step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

4. A cosmetic method for improving skin elasticity and firmness, the method comprising a step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

5. A cosmetic method of reducing wrinkles, the method comprising the step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

6. A cosmetic method of enhancing collagen and elastin production in skin, the method comprising the step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

7. A cosmetic method of reducing stretch marks, the method comprising the step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

8. A cosmetic method of reducing and/or preventing scars, the method comprising the step of applying to the skin of a subject in need thereof an effective amount of a composition comprising interleukin-1 beta and a dermatologically acceptable vehicle.

9. The method of any one of preceding claims 1 through 8, wherein the content of interleukin-1 beta in said composition is in the range from 10^"7 to 10^"4 wt. %.

10. Use of interleukin-1 beta for manufacturing a cosmetic composition for skin conditioning, reducing cellulite severity, improving skin elasticity and firmness, reducing wrinkles, enhancing collagen and elastin production in skin, reducing stretch marks, and/or reducing or preventing scars.