WO2015051260A2

WO2015051260A2 - Skin care composition containing a biologic

Info

Publication number: WO2015051260A2
Application number: PCT/US2014/059067
Authority: WO
Inventors: Keith D. Crawford
Original assignee: Crawford Keith D
Priority date: 2013-10-03
Filing date: 2014-10-03
Publication date: 2015-04-09
Also published as: WO2015051260A3

Abstract

Compositions, methods, and kits are provided for regenerating or treating skin cells using a composition with a biologic such as an antimicrobial peptide (AMP). The composition includes at least one of: a safe and effective amount of a vitamin B₃ molecule; silicone elastomer; antioxidant; and a dermatologically acceptable carrier. The AMP is, for example, H2A, H1, H6, HDL, Sal-2, a defensin, a hepcidin, an apidaecin, a cathelicidin, or a piscidin. The AMP includes, for example, a peptide represented by the formula: APKAMX¹X²X³X⁴X⁵X⁶X⁷X⁸LQKKGI, such that X¹ and X⁸ represent basic amino acid residues; X2 and X3 represent hydrophobic amino acid residues which may be the same or different residues; X⁴ and X⁵represent basic amino acid residues which may be the same or different residues; X⁶ and X⁷ represent hydrophobic amino acid residues which may be the same or different residues.

Description

Skin care composition containing a biologic

Field of the Invention

Compositions, methods and kits for treating skin conditions and disorders.

Background

Skin is subject to damage by many intrinsic and extrinsic factors. Intrinsic factors include chronological aging and other biochemical changes from within the skin. Extrinsic factors include ultraviolet radiation (e.g., from sun exposure), environmental pollution, wind, heat, low humidity, harsh surfactants, abrasives, and the like. One constantly overlooked problem is the exposure of the skin for long periods of time to unclean cosmetics. Both cosmetics and cosmetic applicators serve as a breeding ground for harmful microorganisms.

Whether extrinsic or intrinsic, these factors result in visible signs of skin aging and environmental damage, such as wrinkling and other forms of roughness and other histological changes associated with skin aging or damage. Consumers' desire to age gracefully has created a growing market for people requesting products and treatments that elim inate wrinkles, heal or rej uvenate the skin. These products and treatments can range from chemical cosmetic creams, lotions, to moisturizers, and even cosmetic surgery. However, even the most effective chemical cream begins to deteriorate upon exposure to air and sun, and cosmetic surgery is a costly and intensive treatment process. Clearly as more men and well as women begin to use cosmetics there is also a growing need to develop improved cosmetics that effectively treat skin conditions.

Summary

An aspect of the invention provides a topical skin care composition including: an antimicrobial peptide (AMP); an effective amount of a vitamin B₃ molecule; a silicone elastomer; an antioxidant; and a dermatologicaliy acceptable carrier. In various embodiments, the AM P includes a plurality of AMPs.

In various embodiments of the composition, the AMP comprises about 0.05% to about 10% of the composition. The percentages and ratios used herein are by weight of the total composition and all measurements are made at 25°C, unless otherwise designated. In various embodiments of the composition, the AMP includes from about 2% to about 5% of the composition. In various embodiments of the composition, the AMP includes from about 0.2% to about 0.5% of the composition, about 0.5% to about 1.5% of the composition, about 1.5% to about 3.0% of the composition, or about 3.0% about 5% of the composition.

In various embodiments of the composition, the AMP comprises a concentration of about 0.5 micromolar (μΜ) to about 2 μΜ. For example, the concentration is from about 0.2% to about 0.5%, about 0.5 μΜ to about 0.75 μΜ, about 0.75 μΜ to about 1 μΜ, about 1 μΜ to about 1.5 μΜ , or about 1.5 μΜ to about 2 μΜ.

In various embodiments of the composition, the AMP is a naturally occurring AMP found in living things, for example a plant and an animal. In various embodiments of the composition, the AMP is selected from a group consisting of: H2A, HI, H6, HDL, Sal-2, an apidaecin, a defensin, a hepcidin, a cathelicidin, and a piscidin. In various embodiments, the naturally occurring AMP is isolated from a bacterium, fungus, plant, invertebrate, or vertebrate. For example, the isolated peptide exhibits broad-spectrum activity against Gram-positive bacteria, Gram-negative bacteria, yeasts, fungi, or viruses.

In various embodiments of the composition, the AMP is a synthetically manufactured AMP, having for example a common structure of AMP of a naturally-occurring animal antibiotic, such as a mature peptide comprising for example amphipathic and cationic amino acids.

In various embodiments of the composition, the AMP includes at least one activity selected from: antibacterial, antifungal, and antiviral.

The AMP in various embodiments of the composition includes a peptide sequence represented by general formula of:

N-APKAMX'X²X³X⁴X⁵ X⁶ X⁷ X⁸LQKKGI-C (SEQ ID NO: 1) such that X¹ represents a basic amino acid residue; X² represents a hydrophobic amino acid residue; X³ represents a hydrophobic amino acid residue, which may be the same or different than X²; X⁴ represents a basic amino acid residue; X⁵ represents a basic amino acid residue, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue; X⁷ represents a hydrophobic amino acid residue, which may be the same or different than X⁶; and X^s represents a basic amino acid residue. In various embodiments, the basic amino acid residue is a lysine, an arginine, a histidine, or a derivative or homolog thereof. In various embodiments, the hydrophobic amino acid residue is an alanine, a valine, a leucine, or a derivative or homolog thereof. In various embodiments, the AMP is amidated at the C-terminal end. In various embodiments of the composition, the peptide promotes wound healing and skin rejuvenation and interacts with regenerating cells of the skin. For example, the peptide reduces skin sagging and improves the appearance of the skin by reducing wrinkles and sagging.

In various embodiments of the composition, the antimicrobial activity of the AMP is functional at a salt concentration of about 100 miilimolar (mM) to about 135 mM, about 135 mM to about 155 mM, about 1 55 mM to about 175 mM, or about 175 mM to about 200 mM.

In various embodiments, the composition further includes a particulate material. In various embodiments of the composition, the particulate material is selected from the group consisting of: a bismuth oxychloride; an iron oxide; a mica for example mica treated with a barium sulfate and/or a titanium dioxide (Ti(¾); a silica; a nylon; a polyethylene; a talc; a styrene; a polypropylene; an ethylene/acrylic acid copolymer; a titanium dioxide; an iron oxide; a bismuth oxychloride; a sericite; an aluminum oxide; a silicone resin; a barium sulfate; a calcium carbonate; a cellulose acetate; a polymethyl methacrylate; and mixtures thereof.

In various embodiments, the silicone elastomer includes particles of a silicone material. In various embodiments of the composition, the particles are in the form of spheres, for example hollow spheres. In various embodiments, the silicone elastomer includes a fatty phase component comprising at least one oil, at least one spherical silicone particle, at least one non- spherical silicone particle, at least one concave silicone particles, or at least one non-concave silicon particle.

The composition in various embodiments further includes a sunscreen active ingredient. In various embodiments, the sunscreen active ingredient is selected from the group consisting of 4,4'-t-butylmethoxydibenzoylmethane, 2-ethylhexyl-p-methoxycinnamate, phenyl

benzimidazole sulfonic acid, octocrylene, and mixtures thereof. For example, the sunscreen active ingredient has a specific sunscreen protective factor (SPF) value. In various embodiments, the SPF value is at least about 1 5, 25, 30, 40, or 50.

In various embodiments, the vitamin B₃ molecule is a naturally occurring. Alternatively, the vitamin B₃ molecule is synthetic.

An aspect of the invention provides a composition for regenerating skin cells, the composition including as an active ingredient a peptide having a sequence represented by general formula [ N-APKAMX^!X²X³X⁴X⁵X⁶X⁷X⁸LQKKGI-C] (SEQ ID NO: 1), such that X¹ represents a basic amino acid residue; X² represents a hydrophobic amino acid residue; X³ represents a hydrophobic amino acid residue, which may be the same or different than X²; X⁴ represents a basic amino acid residue; X⁵ represents a basic amino acid residue, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue; X⁷ represents a hydrophobic amino acid residue, which may be the same or different than X⁶; and X⁸ represents a basic amino acid residue. In various embodiments, the composition further includes at least one of: an effective amount of a vitamin B₃ molecule; a silicone elastomer; an antioxidant; and a dermatologically acceptable carrier.

In various embodiments, the basic amino acid residue is a lysine, an arginine, a histidine, or a derivative or a homolog thereof. In a various embodiments, the hydrophobic amino acid residue is an alanine, a valine, a leucine, or a derivative or a homolog thereof. In various the peptide of general formula I is amidated at the C-terminal end.

In various embodiments of the composition, the peptide exhibits antimicrobial activity at a salt concentration of about from 100 mM to about 200 mM. The composition in various embodiments further includes a pharmaceutically acceptable carrier, excipient or diluent. In various embodiments the composition has a pH of about 6 to about 7.4.

The peptide in various embodiments of the composition is present at a concentration of about 0.5 μΜ to about 1 μΜ, about 1 μΜ to about 1.5 μλ ΐ, or about 1.5 μΜ to about 2 μΜ.

An aspect of the invention provides a cosmetic for skin rejuvenation including any of the compositions described herein. For example the composition in the cosmetic is described in claims 19-25 herein.

An aspect of the invention provides a method for regenerating skin cells in a wound of an animal, the method comprising administering to the wound a composition that includes a peptide having a sequence represented by the general formula I:

[N-terminal end- A PKAMX ¹ X²X³X^''x⁵X^;'X⁷X⁸l .QKKG1 -C-terminal end] (SEQ ID NO: 1 ) such that X¹ represents a basic amino acid residue; X² represents a hydrophobic amino acid residue; X³ represents a hydrophobic amino acid residue, which may be the same or different than X²; X⁴ represents a basic amino acid residue; X³ represents a basic amino acid residue, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue; X⁷ represents a hydrophobic amino acid residue, which may be the same or different than X⁶; and X^s represents a basic amino acid residue. In various embodiments, the composition further includes at least one of: an effective amount of a vitamin B3 molecule; a silicone elastomer; an antioxidant; and a dermatologically acceptable carrier.

In various embodiments of the method, the basic amino acid residue is a lysine, an arginine, a histidine, or a derivative or a homolog thereof. In various embodiments of the method the hydrophobic amino acid residue is an alanine, a valine, a leucine, or a derivative or a homolog thereof. In various embodiments of the method, the peptide is amidated at the C- terminal end. Alternatively, in various embodiments of the method the peptide is amidated at the N -terminal end

In various embodiments of the method, the peptide exhibits antimicrobial activity at a salt concentration of about 100 mM to about 200 mM. In various embodiments of the method, the composition further includes a pharmaceutically acceptable carrier, an excipient or a diluent. In various embodiments, the peptide is present at a concentration of about 0.5 μΜ to about 2 μ\1.

In various embodiments, the method further includes observing an increase in an indicium, a parameter, or an indicator of regeneration of the skin cells or healing of the wound. For example the parameter or the indicator is a marker. For example, the marker is a hormone or a growth factor (e.g., an epithelial growth factor) that indicates skin cell growth. In various embodiments of the method, the indicium, the parameter, or the indicator includes a protein, a peptide, a carbohydrate, or a genetic material such as DNA or RNA.

In various embodiments, the method further includes prior to administering, formulating the composition for delivery to the wound. For example, formulating the composition includes preparation into a form selected from the group of: an injection, a cream, a salve, a compress, an eye drop, a patch, an ointment, a gel, or a spray. In various embodiments, the formulating the composition further includes adding at least one of: an effective amount of a vitamin B₃ molecule; a silicone elastomer; an antioxidant; and a dermatologically acceptable carrier.

In various embodiments of the method, administering is performed by a route of selected from: intravenous, intramuscular, intraperitoneal, intradermal, intrapulmonary, intravaginal, oral, buccal, topical, sublingual, intranasal, topical, and intraocular.

An aspect of the invention provides a method for regenerating skin cells comprising: adm in istering to damaged or injured skin a composition that includes a peptide having a sequence represented by general formula: N-terminal end-

APKAMX ' x x 'X^Xlx'x'X'YO KG I -C-terminal end] (SEQ ID NO: 1), such that X¹ represents a basic amino acid residue; X² represents a hydrophobic amino acid residue; X³ represents a hydrophobic amino acid residue, which may be the same or different than X²; X⁴ represents a basic amino acid residue; X³ represents a basic amino acid, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue; X⁷ represents a hydrophobic amino acid residue, which may be the same or different than X⁶; and X⁸ represents a basic amino acid residue.

In various embodiments, the method further includes prior to administering, formulating the composition for del ivery to the skin. For example, formulating the composition includes compounding the composition in at least one form selected from: a cream, a lotion, an injection, an eye drop, a patch, an ointment, a gel, or a spray. In various embodiments, the formulating the composition further includes adding at least one of: an effective amount of a vitamin B₃ molecule; a silicone elastomer; an antioxidant; and a dermatologically acceptable carrier. In various embodiments of the method, formulating the composition further includes adding a pharmaceutically acceptable carrier, an excipient, or a diluent.

In various embodiments of the method, the basic amino acid residue is a lysine, an arginine, a histidine, or a derivative or a homolog thereof. In various embodiments, the hydrophobic amino acid residue is an alanine, a valine, a leucine, or a derivative or a homolog thereof. In various embodiments of the method, at least one of X¹, X², X³, X⁴, X⁵, X⁶, X⁷, and X⁸ is a naturally-occurring amino acid residue. In various embodiments of the method, at least one of X¹, X X\ X X X X', and X° is a synthetic amino acid residue. In various embodiments of the method, peptide is amidated at the C-terminal end.

In various embodiments of the method, the peptide exhibits antimicrobial activity at a salt concentration of about 100 to about 200 mM. In various embodiments of the method, the peptide is present at a concentration of about 0.5 μΜ to about 2 μΜ.

An aspect of the invention provides use of a peptide having a sequence represented by general formula I in preparing a pharmaceutical composition for regenerating skin cells, such that the formula includes [N-terminal end- AP AMX 'X²X³X⁴X⁵X⁶X⁷X⁸LQKKGI -C-terminal end] (SEQ ID NO: 1), such that X¹ represents a basic amino acid residue; X² represents a hydrophobic amino acid residue; X represents a hydrophobic amino acid residue, which may be the same or different than X²; X⁴ represents a basic amino acid residue; X⁵ represents a basic amino acid residue, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue; X⁷ represents a hydrophobic amino acid residue, which may be the same or different than X⁶; and X⁸ represents a basic amino acid residue.

In various embodiments of the use, the basic amino acid residue is a lysine, an arginine, a histidine, or a derivative or a homolog thereof. In various embodiments of the use, the hydrophobic amino acid residue is an alanine, a valine, a leucine, or a derivative or a homolog thereof. In various embodiments of the use, peptide is amidated at the C-terminal end. In various embodiments of the use, the composition effectively regenerates the skin cells at the site of a wound or an injury.

In various embodiments of the use, the peptide exhibits antimicrobial activity at a salt concentration of about 100 mM to 200 mM. In various embodiments of the use, the composition further includes a pharmaceutically acceptable carrier, excipient or diluent. In various embodiments, the composition further includes adding at least one of: an effective amount of a vitamin B₃ molecule; a silicone elastomer; an antioxidant; and a derm ato logically acceptable carrier. In various embodiments of the use, the peptide is present at a concentration of about 0.5 μΜ to about 2 μΜ.

An aspect of the invention provides use of a peptide having a sequence represented by general formula I in preparing a composition for regenerating skin cells, such that the formula includes: [N-terminal end- AP AMX' X²X³X⁴X⁵X⁶X⁷X⁸LQ GI -C-terminal end] (SEQ ID NO: 1 ), such that X¹ represents a basic amino acid residue; X² represents a hydrophobic amino acid residue; X³ represents a hydrophobic amino acid residue, which may be the same or different than X²; X⁴ represents a basic amino acid residue; X^s represents a basic amino acid residue, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue; X⁷ represents a hydrophobic amino acid residue, which may be the same or different than X⁶; and X⁸ represents a basic amino acid residue. In various embodiments, the composition is further formulated to include at least one of: an effective amount of a vitamin B3 molecule; a silicone elastomer; an antioxidant; and a dermatologically acceptable carrier.

In various embodiments of the use, the peptide exhibits antimicrobial activity at a salt concentration of about 100 mM to 200 mM. In various embodiments of the use, the composition further includes a pharmaceutically acceptable carrier, excipient or diluent. In various embodiments of the use, the peptide is present at a concentration of about 0.5 μΜ to about 2 μΜ. In various embodiments of the use, wherein the composition comprises a salt concentration of about 100 mM to about 200 mM.

In various embodiments of the use, the composition further includes a particulate material.

In various embodiments, the particulate material is selected from the group consisting of: a bismuth oxychloride; an iron oxide; a mica; a silica; a nylon; a polyethylene; a talc; a styrene; a polypropylene; an ethylene/acrylic acid copolymer; a titanium dioxide; an iron oxide; a bismuth oxychloride; a sericite; an aluminum oxide; a silicone resin; a barium sulfate; a calcium carbonate; a cellulose acetate; a polymethyl methacrylate; and mixtures thereof. The composition in various embodiments of the use further includes a sunscreen active ingredient. For example, the sunscreen active ingredient is selected from the group consisting of 4 ,4'-t-butylmethoxydibenzoyl methane, 2-ethylhexyl-p-methoxycinnamate, phenyl

benzimidazole sulfonic acid, octocrylene, and mixtures thereof.

An aspect of the invention provides a topical skin care composition including: an AMP; a vitamin B3 molecule; an sunscreen active ingredient; an antioxidant; and a dermatologically acceptable carrier.

In various embodiments, the AMP comprises from about 2% to 5% of the composition. In various embodiments, the vitamin B3 molecule comprises from about 0.2% to about 5% of the composition. In various embodiments, the vitamin B3 molecule is a naturally-occurring compound. Alternatively, the vitamin B3 molecule is a synthetic molecule.

In various embodiments of the composition, the sunscreen active ingredient includes a naturally-occurring molecule or compound. Alternatively, the sunscreen active ingredient is a synthetic compound. In various embodiments, the sunscreen active ingredient is selected from the group consisting of 4,4'-t-butylmethoxydibenzoylmethane, 2-ethylhexyl-p- methoxycinnamate, phenyl benzimidazole sulfonic acid, octocrylene, and mixtures thereof.

In various embodiments the composition further includes a particulate material. In various embodiments of the composition, the particulate material is selected from the group consisting of: bismuth oxychloride, iron oxide, mica, mica treated with barium sulfate and T1O2, silica, nylon, polyethylene, talc, styrene, polypropylene, ethy ene/acrylic acid copolymer, titanium dioxide, iron oxide, bismuth oxychloride, sericite, aluminum oxide, silicone resin, barium sulfate, calcium carbonate, cellulose acetate, polymethyl methacrylate, and mixtures thereof.

An aspect of the invention provides a method for regulating a mammalian skin condition comprising contacting to an area of skin in need of regulation any one of the compositions described herein. For example the composition is any of the compositions described in claims 1 - 25 and 61 -66. In various embod iments of the method, contacting the composition is performed according to a regimen over a period of time, for example the period is at least days, weeks, or months. In various embodiments, contacting the compositions includes administering several times a day, every day, three to four days, every week, or once every two weeks depending on half-life and clearance rate of the particular composition. In various embodiments, the period includes at least about three months. In various embodiments, the AMP includes from about 2% to 5% of the composition.

In various embodiments of the method, contacting comprises administering by a route selected from at least one of the group consisting of : topically (as by powders, ointments, or drops), orally, rectally, mucosally, sublingually, intravaginally, intraperitoneally, bucally, sublingually, ocularly, or intranasal ly,

An aspect of the invention provides a method for regulating a mammalian skin condition comprising the step of applying or administering to an area having the condition any of the composition described herein. For example, the composition is any of the AMP-containing compositions described herein. In various embodiments, the composition is described herein in claims 61 -66. In various embodiments, the composition contains a biologic that promotes skin repair, rejuvenation, regeneration, and overall skin health. The biologic includes for example an AMP, a temperature-dependent self-assembly peptide, a small molecule, an aptimer, a microRNA/iRNA, and a cell specific peptide. The biologic for example is compounded into a cosmetic formulation for use in a skin-care cream, a lotion, a powder, a perfume, a lipstick, a nail polish, a hair treatment (e.g., a hair color treatment), a hair spray, a gel, a deodorant, a hand sanitizer, a towelette, a bath oil, a bubble bath, a bath salt, a skin butter, and any beauty and a cosmetic product. In various embodiments, the composition further includes at least one of: an effective amount of a vitamin B₃ molecule; a silicone elastomer; an antioxidant; and a dermatologically acceptable carrier.

Detailed description

The phrases "amino acid" and "amino acid sequence" can include one or more components which are amino acid derivatives and/or amino acid analogs comprising part or the entirety of the residues for any one or more of the 20 naturally occurring amino acids indicated by that sequence. For example in an amino acid sequence having one or more tyrosine residues, a portion of one or more of those residues can be substituted with homotyrosine. Further, an amino acid sequence having one or more non-peptide or peptidomimetic bonds between two adjacent residues, is included within this definition.

The term "hydrophobic" amino acid means aliphatic amino acids alanine (A or ala), glycine (G or gly), isoleucine (1 or ile), leucine (L or leu), methionine (M or Met), proline (P or pro), and valine (V or val), the terms in parentheses being the one letter and three letter standard code abbreviations for each amino acid, and aromatic amino acids tryptophan (W or trp), phenylalanine (F or phe), and tyrosine (Y or tyr). These amino acids confer hydrophobic ity as a function of the length of aliphatic and size of aromatic side chains, when found as residues within a protein.

The term "hydrophilic" amino acid means water soluble amino acids serine (S or ser), threonine (T or thr), cysteine (C or cys), asparagine (N or asn), glutamine (Q or gin), aspartate (D or asp), glutamate (E or glu), histidine (H or his), lysine (K or lys), and arginine (R or arg), the terms in parentheses being the one letter and three letter standard code abbreviations for each amino acid. These amino acids are hydrophilic as a function of the polarity of the side chains.

The term "amphiphilic" and the term " amphipathic" are used interchangeably herein and each refers to a molecule that possess both a polar and a non-polar region, such that the molecule has hydrophilic and hydrophobic properties. Examples of amphipathic molecules are certain phospholipids and detergents.

The phrase "an effective amount" as used herein means an amount of a compound or composition sufficient to significantly induce a positive benefit in the cells or tissue being treated. A positive benefit includes for example the regenerations of skin cells, growth of tissue (e.g., keratinous tissue), improved skin characteristics (e.g., reduction in sagging and increased smoothing).

The phrase "antimicrobial peptide" as used herein refers to a small peptide or small- molecular weight protein having antimicrobial activity. In various embodiments, the

antimicrobial peptide has a length of about 5-50 amino acid residues. In various embodiments, the peptide plays an important role as an immunomodulator in innate host defense.

Antimicrobial peptides are found among all classes of life and are responsible for defense against local infections by penetrating into and disturbing the membranes of microbes such as bacteria, fungi and viruses. In various embodiments, the antimicrobial peptide is observed to have broad antimicrobial activity against Gram-positive bacteria and/or Gram-negative bacteria. In various embodiments, the antimicrobial peptide is amphipathic, such that the peptide effectively passes through the membrane lipid bi layer of microbes, e.g., bacteria. The cationic charge of the antimicrobial peptide in various embodiments is caused by the anionic charges of the phospholipids in the membrane. The antimicrobial peptide in various embodiments herein is resistant to acid, alkali and heat.

The term "antioxidant" as used herein refers broadly to the class of compounds and substances which prevent the formation of compounds such as peroxides, ketones, aldehydes and acids from materials. In various embodiments, the antioxidant is a naturally-occurring molecule, compound, or material. Alternatively, the antioxidant in various embodiments is synthetic. In various embodiments, the antioxidant is soluble in water (hydrophilic) or is soluble in a lipid (hydrophobic).

The term "cosmeceutical" as used herein refers to a formulation or composition comprising at least one biologically active ingredient that has an effect on the user of the product and at least one cosmeceutically-acceptable carrier. Cosmeceuticals provide improvements in appearance and also medicinal or drug-like benefits. In certain applications, for example, cosmeceuticals may affect the underlying structure of the skin, decrease wrinkle depth, or reverse or ameliorate the effect of photooxidation or aging on the skin. Cosmeceuticals may be particularly useful as skin care products, hair care products, and sun care products.

The phrase "dermatologically-acceptable" as used herein, means that the compositions or components thereof so described are suitable for use in contact with mammalian keratinous tissue without undue toxicity, incompatibility, instability, allergic response, and the like.

The phrase "keratinous tissue" as used herein refers to keratin-containing layers disposed as the outermost protective covering of mammals (e.g., humans, dogs, and cats). The keratinous tissue for example is skin, mucosa, lips, hair, a toenail, a fingernail, a cuticle, a hoof, etc.

Topical administering the compositions described herein include contacting any of these keratinous tissue to improve the condition and appearance of the tissue.

The phrase "particulate material" as used herein refers to solid or liquid particles that can be emitted for example in a liquid or air. These particles may in various embodiments be large enough to be seen, and others are so small that the particles can only be detected with an electron microscope.

The phrase "prophylactically regulating a skin condition" as used herein refers to delaying, minimizing and/or preventing visible and/or tactile discontinuities in skin (e.g., texture irregularities in the skin which may be detected visually or by feel).

The term "sagging" as used herein means the laxity, slackness, or the like condition of skin that occurs as a result of loss of, damage to, alterations to, and/or abnormalities in dermal elastin, muscle and/or subcutaneous fat.

The phrase "silicone elastomer" as here used refers to a polymer composed of silicone. The polymer in various embodiments is a material including silicon in addition

to carbon, hydrogen, and oxygen. The silicone elastomer in various embodiments is a rubberlike material that is synthetically produced to have characteristic viscoelasticity. The silicone elastomer described herein includes in various embodiments one polymer or two or more part polymers, and may contain fillers to improve properties or reduce cost. The silicone elastomer in various embodiments is a thermoset (requiring vulcanization) or a thermoplastic.

The phrase "skin aging" as used here refers to the outward visibly and tactilely perceptible manifestations as well as any other macro or micro effects due to exposure or time. 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 and coarse deep wrinkles, fine lines, skin lines, crevices, bumps, large pores (e.g., associated with adnexal structures such as sweat gland ducts, sebaceous glands, or hair follicles), or 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 under eye 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 (e.g., fat and/or muscle), especially those proximate to the skin.

The terms "smoothing" and "softening" as used herein refers alterations of the surface of the keratinous tissue such that its tactile feel of the tissue is improved.

The phrase "sunscreen active ingredient" as used herein refers to a molecule, material or compound that absorbs or reflects and protects against ultraviolet (UV) radiation. For example the sunscreen active ingredient protects skin exposed to sunlight and thus helps protect against sunburn. For example, the sunscreen active ingredient is in the form of or is formulated as a powder, a lotion, a spray, a gel or other product.

The phrase "therapeutically regulating a skin condition^"' as used herein refers to ameliorating, diminishing, minimizing and/or effacing discontinuities in skin.

The phrase "vitamin B₃ molecule" as used herein refers to any or all of molecules containing vitamin B3, niacin, or nicotinic acid. These include the amide form, nicotinamide or niacinamide. Vitamin B3 molecules are water-soluble vitamins whose derivatives such as NADH, NAD, NAD^", and NADP play important roles in energy metabolism in the living cell and DNA repair. These molecules also assist the body make various sex and stress-related hormones in the adrenal glands and other parts of the body. A vitamin B3 molecule is effective in improving circulation and reducing cholesterol levels in the blood. The vitamin B3 molecule described herein includes a naturally-occurring molecule or a synthetic molecule. Methods of producing a vitamin B₃ molecules and formulating a. composition containing the vitamin B3 molecule are shown in Jacobsen et al., U.S. patent number 6,337,065 issued January 8, 2002; U.S. patent number 6,464,992 issued October 15, 2002; and U.S. patent number 6,552,050 April 22, 2003, each of which is incorporated by reference herein in its entirety. The vitamin B₃ molecule may be fonnulated as a compound having vitamin B₃, which is referred to as a vitamin B₃ compound.

Extrinsic or intrinsic factors may result in the thinning, general degradation of the skin, and loss of the antimicrobial peptides. As skin naturally ages blood vessels decrease causing reduction in cell count and flattening of the dermal-epidermal junction. This flattening of the dermal-epidermal junction results in weaker mechanical resistance at this site (Oikarinen, A. et al. 1990 Photodermatol. Photoimmunol. Photomed., vol. 7, pp. 3-4). Examples of skin defects include an ulcer, acne vulgaris, actinic keratosis, and a sarcoma. Acne vulgaris, referred to commonly as acne, is characterized by inflammation and infection of a sebaceous gland of the skin.

Methods of treating acne include applying chemical creams, lotions, masks, or washes to the affected skin to clean clogged pores or glands, inhibit growth of bacteria, moisturize, and to reduce inflammation and irritation (Bernstein U.S. patent number 7,371 ,367 issued May 13, 2008). Acne treatments include microdermabrasion and exfoliation procedures (e.g., peels) using an alpha-hydroxy acid such as glycolic acid to remove surface layers of skin (Sefton U.S. patent number 6,262, 1 ] 7 issued July 1 , 2001 : Perricone U.S. patent number 6,743,433 issued June 1, 2004; Ashely U.S. patent number 7,014,858 issued March 21 , 2006; and Voorhees et al. U.S. patent number 7,268, 148 issued September 1 1 , 2007, each of which is incorporated herein by reference in its entirety).

Salicylic acid and benzoyl peroxide are generally accepted chemicals that are used to treat skin conditions. These compositions inhibit growth of microorganisms on the face, exfoliate the skin as well as decrease inflammation. Problems can arise when high

concentrations of salicylic acid are applied to skin for a long period of time, leading to a salicylate toxicity. Benzyl peroxide treatment in some case may make patients more sensitive to the sun. Retinoid-containing products also are commonly used to reduce signs of aging. Retinoid is a vitamin A derivative that rapidly breaks down upon exposure to the sunlight and air. Users of benzyl peroxide and retinoid-containing products often experience skin discoloration, burning and redness. Clearly there is a need for skin care formulations that produce healthy skin and are free from pathogens that promote skin damage.

Antimicrobial peptides are widely distributed in nature amino acid residues in length. They are almost free of influence by acid, alkali and heat, and can be readily degraded after performing their antimicrobial activity. Among them, cathelicidin LL-37 and magainin 2, a magainin derivative, function as potent antibiotics as well as having the ability to regenerate cells. The ability of these antibiotics to regenerate cells starts with the association of the peptides with EGFR (epidermal growth factor receptor) to which EGF (epidermal growth factor), responsible for cell regeneration, binds. It is also found that antimicrobial peptides having alpha- helix structures, like LL-37, can regenerate cells (TokuMaru, S. et al. 2005

JImmunol.Japan, 175(7): pages 4662-4668).

The use of the peptides in wound healing is being studied by various research groups. For example, human cathelicidin LL-37, ceragenin, cecropin, bacteriocin, fungal defensin, and plectasin are in pre-clinical trials for use as wound healing agents, while pexiganan (MSI-78), a derivative of frog magainin, and iseganan (IB-367), a derivative of pig protegrin, are in phase 3 clinical trials for treatment of diabetic foot ulcer and oral mucositis. However, these peptides are often instable in in vivo conditions, which results in a decrease in wound healing potential. Thus, these peptides have not been formulated in acceptable dermatological agents for effective wound healing or skin regeneration. See Archour et al., U.S. patent publication number 20030087255 published May 8, 2003 (showing heparin affin regulatory peptide, HARP, that induces cytokine production); and Blick et al., U.S. patent number 5183805 issued February 2, 1993 (showing a synthetic peptide analog of epidermal growth factor for promoting wound healing).

Without being limited by any particular theory or mechanism of action, it is here envisioned that biologies should be formulated into cosmeticeutical compositions using acceptable dermatological carriers and ingredients to effective treat skin conditions. The biologies (e.g., antimicrobial peptides, temperature-dependent self-assembly peptides, small molecules, aptimers, microRNA/iRNA, and cell specific peptides) have the ability to

treat/prevent the underlying cause of the condition and if used with the appropriate carrier should have no side effects in vivo.

Methods are shown herein for compounding biologies in cosmetic formulations or cosmeceuticals to promote skin repair, rejuvenation, regeneration, and overall skin health. The biologies (AMPs, temperature-dependent self-assembly peptides, small molecules, aptimers, microRNA/iRNA, and cell specific peptides) are compounded into cosmetic formulations for use in skin-care creams, lotions, powders, perfumes, lipsticks, nail polishes, permanent waves (perms), hair color treatment, hair sprays, gels, deodorants, towelettes, hand sanitizer, baby products, bath oils, bubble baths, bath salts, skin butters, and other beauty and cosmetic products.

Examples herein show that AMP-containing compositions of the present invention exhibit inhibitory activity against microbes (e.g., antibiotic-resistant bacterial strains), and that the antimicrobial activity of the AMP is maintained without loss of structural stability even under a high salt conditions found in cosmeceutical and pharmaceutical formulations.

Furthermore, the AMP-containing compositions and formulations described herein are stable on skin and in the body and promote migration of cells to skin cells. The antimicrobial peptides preserve the integrity of the cosmetic by preventing microbial grow and promote skin regeneration. Compositions containing at least one AMP and acceptable carrier described herein are useful in various fields including the medical industry and the cosmetic industry. Examples herein show that methods using AMP-containing formulations having acceptable carriers (e.g., dermatological) are effective for regenerating skin cells. In various embodiments, the composition further includes a carrier having at least one of: an effective amount of a vitamin B3 compound; a silicone elastomer; an antioxidant; and a dermatologically acceptable carrier. The antimicrobial peptides are effective treatment agents for antibiotic treatment, wound healing, and cosmetics.

The AMP for example is H2A, H I , H6, HDL, Sal-2, an apidaecin, a defensin, a hepcidin, a cathelicidin, a piscidin, or a peptide having a sequence represented by the general formula [N- terminal end- APKAMX VxVx⁵X⁶X⁷X⁸LQKKGI -C-terminal end] (SEQ ID NO: 1 ). In various embodiments, the X represents a basic amino acid residue; X represents a

hydrophobic amino acid residue; X³ represents a hydrophobic amino acid residue, which may be the same or different than X²; X⁴ represents a basic amino acid residue; X³ represents a basic amino acid residue, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue; X⁷ represents a hydrophobic amino acid residue, which may be the same or different than X⁶; and X⁸ represents a basic amino acid residue. Methods for producing a peptide having antimicrobial activity are shown in Kim et al, international patent publication WO/2012/046922 published April 12, 2012. In addition reference Samian (international publication WO2011073440A3 published Jun 23, 201 1) shows a phylloseptin peptide of formula:

S-L-I-P-H-A-I-N-A-V-S-X 1-X2-X3-X4-H-X5 (SEQ ID NO: 2) such that: XI and X5 each correspond to a hydrophobic or neutral hydrophilic amino acid; X2 and X3 each correspond to a hydrophobic amino acid residue; X4 corresponds to an alkaline or neutral hydrophilic amino acid residue. In addition, Keefer (international patent publication WO2005019241 published March 3, 2005 shows antimicrobial peptide having formula (B)-(U)- (Z-B-B-Z-Z-B-Z)n-(U), in which B, U and Z represent natural or synthetic amino acid residues. See also Sayed et al., international patent publication number WO2013050590 published April 11, 2013 (showing SprAl antimicrobial peptides); Yang et al., U.S. patent publication number 2013/0225481 published August 29, 2013 (showing antimicrobial peptides composed of hydrophobic amino acid residues, cationic amino acid residues, and an amino acid residue having a free thiol or thioether group); and Hancock et al, international patent publication number WO2002000687 published Sep 6, 2002 (showing polyphemusin-like peptides having antimicrobial activity), each of which is incorporated by reference herein in its entirety.

Peptides H2A, HI, H6, HDL, and Sal-2 are antimicrobial peptides obtained from the epidermis of fish. Rakers, S. et al., 2013 Journal of Investigative Dermatology 133: 1 140-1 149. These peptides function as a part of a protective shield for the fish. The peptides are

evolutionarily well preserved and also found in higher vertebrate skin including human epidermis. Apidaecins (apidaecin-type peptides) refer to a series of small, proline-rich (Pro-rich), 18- to 20-residue peptides produced by insects. These peptides are a large group of Pro-rich AMPs. Casteels, P. 1994 The Journal of Biological Chemistry 269: 26107-261 15; and Li, W.F. et al. 2006 Peptides. 27(9): 2350-2359.

Defensins are small cysteine-rich cationic proteins found in plants, vertebrates and invertebrates. Defensins function as host defense peptides that actively combat against bacteria, fungi and many enveloped and non-enveloped viruses. They consist of 18-45 amino acid residues having six to eight conserved cysteine residues. Cells of the immune

system contain and use these peptides to assist in killing phagocytosed bacteria (Selsted et al., U.S. patent number 7,462,598 issued December 9, 2008; and Moss et al., U.S. patent number 7,51 1,015 issued March 31 , 2009).

Cathelicidins are a family of structurally diverse antimicrobial peptides that are located at the carboxyl terminus of a 15-1 8 kilodalton (kDa or kD) highly conserved cathepsin- L-inhibitor (cathelin)-like domain. Thennarasu, S. et al. 2010 A. Biophys. J. 98: 248-257;

Melgarejo et al., U.S. patent number 7,985,832 issued July 26, 201 1 ; and Gallo et al., U.S.

patent number 7,777,000 issued August 17, 2010, each of which is incorporated by reference in its entirety. Members of the cathelicidin family have been isolated and synthesized.

Hepcidin is a peptide hormone produced by the liver. The peptide is antimicrobial and is a master regulator of iron homeostasis in humans and other mammals. Krause, A. et al 2010 FEBS Letters, Volume 480, Issue 2, Pages 147-150; Leung et al, U.S. patent number 8,329, 174 issued December 1 1, 2012; and Vaulont et al, U.S. patent number 8,487,081 issued July 16, 2013.

Piscidin, an antibacterial peptide isolated from the mast cells of striped bass, has potent antimicrobial activity against a broad spectrum of pathogens in vitro. Campagna, S. et al., 2007 Biochemistry. 46(7): 1 771 -8; Lee, S.A. 2007 Biochemistry 46: 3653-3663; and Noga, E.J. 2009 Comp Biochem Physiol B Biochem Mol Biol. 152(4): 299-305.

Examples herein show that compositions and formulation containing an AMP and an acceptable carrier are useful for regulating visible and/or tactile discontinuities in mammalian skin, including discontinuities in skin texture and color. In various embodiments, contacting skin with the AMP-containing composition or formulation decreases the diameter of skin pores, increases the height of tissue immediately proximate to pore openings such that the tissue approaches that of the interadnexal skin making the skin appear uniform, and decreases wrinkles.

The compositions containing AMP are useful for regulating the condition of skin and especially for regulating a keratinous tissue condition. The AMP in the compositions act as an active agent that regenerates skin cells and reduces the negative skin conditions induced or caused by factors internal and/or external to the body. The composition containing the AMP and the acceptable carrier and materials (e.g., an effective amount of a vitamin B3 molecule; a silicone elastomer; an antioxidant; and a dermatologically acceptable carrier) improves the appearance of skin affected by environmental damage, radiation exposure (including ultraviolet radiation), aging, menopausal status (e.g., post-menopausal changes in skin), stress, diseases, and other disorders in skin. For instance, the AMP-containing compositions used in methods herein treat skin conditions by prophylactically and/or therapeutically regulating skin conditions, in addition to providing the following benefits: thickening of skin (e.g., building the epidermis, dermis, or sub-dermal tissue such as the subcutaneous fat or muscle); counteracting skin atrophy; increasing the convolution of the dermal-epidermal border (also known as the rete ridges);

preventing loss of skin elasticity by preventing the loss, damage and/or inactivation of functional skin elastin; reducing elastosis, sagging, loss of skin recoil from deformation; reducing non- melanin skin discoloration such as under eye circles; reducing blotching (e.g., uneven red coloration due to, e.g., rosacea), sallowness, and discoloration caused by telangiectasia or spider vessels. The compositions, methods and kits described herein containing an AMP are also useful for improving skin appearance and/or feel. For example, AMP-containing compositions improve the elasticity of the contacted skin. The compositions provide additional benefits, including stability, absence of significant (consumer-unacceptable) skin irritation and good aesthetics.

The AMP of the present invention exhibits inhibitory activity against antibiotic-resistant strains, and the antimicrobial activity is maintained without loss of structural stability even under high salt conditions found in cosmeceutical and pharmaceutical formulations. Furthermore, the AMPs formulations are capable of promoting the migration of regenerative cells to a site of a wound and promoting regeneration skin cells at the wound. The antimicrobial peptides of the present invention may be widely used to preserve the integrity of the cosmetic by preventing microbial grow, in addition to, promoting skin regeneration.

An aspect of the invention provides use of topical compositions including at least one AMP and optionally containing a combination of skin care actives, for example a terpene alcohol, a retinoid, a non-AMP peptide, a tocopherol sorbate, and a vitamin B₃ molecule. Such compositions are useful for regulating the condition of skin, especially for regulating visible and/or tactile discontinuities in skin associated, e.g., age spots. In various embodiments the composition contains the biologic active agent (e.g., an AMP) in combination with: a glucosamine, a farnesol, a retinyl propionate, a tocopherol sorbate; or a niacinamide.

The composition containing at least one biologic optionally further includes another selected skin care ingredient that further improves the aesthetics of the skin. Examples of ingredients that improve aesthetics are fillers, oils, waxes, creams, and lotions. The cream or lotion for example is light and nongreasy to the touch, and has a smooth, silky feel upon the skin, spreading easily, or being absorb edquickly. Other examples of an ingredient included in a composition to improve skin aesthetics is a molecule or material that has a consumer acceptable appearance, provides good skin feel, has no unpleasant odor, or does not produce discoloration in the skin.

The composition containing at least one AMP described herein further contains in various embodiments another skin care active ingredient. For example the skin composition includes the AMP in combination with at least one of: glucosamine; farnesol; retinyl propionate; tocopherol sorbate; or and niacinamide. The compositions herein may include a wide variety of other ingredients used in cosmetic formulations. The compositions described herein are formulated in various embodiments as cosmetic formulations, which could be used in as a sunscreen, a lotion, a makeup, a mascara, a shampoo, an injectable filler (e,g., having hyaluronic acid), towelettes, or a deodorant.

For example, topical formulations are formulated in various embodiments with a biologic in combination with a tocopherol sorbate, which may synergistically improve the appearance of irregularities of the mammalian skin, which includes fine lines, wrinkles, enlarged pores, roughness, dryness, and other skin texture discontinuities. Another example involves the use of another antimicrobial peptide, a terpene alcohol, or a retinoid formulation that is formulated into the composition to improve the effect of the AMP. The ingredients in various embodiments may synergistically improve the effect of the AMP and the composition by treating (prophylactically and/or therapeutically) visible and/or tactile discontinuities.

In various embodiments, the composition including an AMP as an active ingredient effectively regenerates skin cells. In various embodiments, the composition containing the AMP as an active ingredient is formulated with an acceptable carrier into a cosmetic composition for skin rejuvenation.

Examples herein show that use topical skin care composition containing a safe and effective amount of AMPs. The compositions containing at least one AMP and an acceptable carrier are shown to possess rejuvenative, regenerative and antimicrobial properties. In various embodiments the composition includes an amount of a: terpene alcohol; a retinoid; and a dermatologically acceptable carrier. For example, the dermatologically acceptable carrier includes terpene alcohol or a retinoid. In various embodiments, the AMPs is compounded in combination with: 95% ethyl alcohol or one or more conditioners selected from the group consisting of isopropyl palmitate, caprylic triglyceride, capric triglyceride, isopropyl myristate and alkylbenzoate. In various embodiments, the composition including the AMP further contains: ethyl alcohol, isopropyl palmitate, caprylic triglyceride, isopropyl myristate, and alkylbenzoate. For example, the composition contains (by weight) at least about: about 5% to about 95% ethyl alcohol, about 0.01 % to about 1 % isopropyl palmitate, about 0.01% to about 1 % caprylic triglyceride, about 0.01% to about 1 % isopropyl myristate, and about 0.01% to about 1 %, alkylbenzoate.

The compositions of the present invention can comprise, consist essentially of, or consist of, the biologies of the present invention as well as other ingredients described herein. As used herein, "consisting essentially of means that the composition or component may include additional ingredients, but only if the additional ingredients do not materially alter the basic and novel characteristics of the claimed compositions or methods.

The present invention provides pharmaceutical compositions containing an AMP and a cosmetically or dermatogically acceptable carrier, diluents or ingredient, the composition being suitable for administration to a subject, for example, a human, for the treatment, prevention or amelioration of a skin condition by regenerating skin cells .

The pharmaceutical compositions generally include an effective dose of each of the biologic, e.g., an AMP. The effective dose is an amount of biologic that is different from an optimal amount of that component if administered in a therapeutic regiment absent the other active biologic. An effective dose of the composition when administered to a subject, prevents or ameliorates a disease symptom of condition of the skin, e.g., reduces and/or ameliorates skin discoloration. One of ordinary skill in the art of treatment of skin diseases can readily determine an effective amount of the AMP.

Cosmeceutical or pharmaceutical compositions

In one aspect of the present invention, cosmeceutical or pharmaceutical compositions are provided, such that these compositions comprise at least one biologic (e.g, an AMP), and optionally comprises an acceptable carrier. In certain embodiments, these compositions optionally further comprise one or more additional therapeutic agents. In certain embodiments, the additional therapeutic agent or agents are selected from the group consisting of growth factors, anti-inflammatory agents, vasopressor agents, collagenase inhibitors, topical steroids, matrix metal!oproteinase inhibitors, ascorbates, angiotensin Π, angiotensin III, calreticulin, tetracyclines, fibronectin, collagen, thrombospondin, transforming growth factors (TGF), keratinocyte growth factor (KGF), fibroblast growth factor (FGF), insulin-like growth factors (IGF), epidermal growth factor (EGF), platelet derived growth factor (PDGF), neu

differentiation factor (NDF), hepatocyte growth factor (HGF), B vitamins such as biotin, and hyaluronic acid.

The phrases " acceptable carrier" and " suitable carrier" are used interchangeably herein and include any and all solvents, diluents, or other liquid vehicle, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, solid binders, lubricants and the like, as suited to the particular dosage form desired. See Robinson et al. U.S. patent number 6444647 issued September 3, 2002; and Kim et al, international patent publication WO/2012/046922 published April 12, 2012. Remington's Pharmaceutical Sciences Ed. by Gennaro, Mack Publishing, Easton, PA, 1995 discloses various carriers used in formulating pharmaceutical compositions and known techniques for the preparation thereof. Some examples of materials which can serve as pharmaceutically acceptable carriers include, but are not limited to, sugars such as glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethy! cellulose, ethyl cellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols; such a propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator.

Therapeutically effective dose

In yet another aspect, according to the methods of treatment of the present invention, the treatment of skin conditions (e.g., discoloration and sagging) by contacting the eye with a composition containing a biologic (e.g., an AMP) as described herein. Thus, the invention provides methods for the treatment of skin conditions or skin disorders comprising

administering a therapeutically effective amount of a composition comprising active agents including at least one biologic for treating a subject in need thereof, in such amounts and for such time as is necessary to achieve the desired result. It will be appreciated that this encompasses administering an inventive pharmaceutical as a therapeutic measure to regenerate skin cells, or as a prophylactic measure to minimize complications associated with a skin conditions or disorders such as increased pore size, skin flaking, sun spots, redness, and skin lines, and inflammation. In certain embodiments a "therapeutically effective amount" of the composition is that amount effective for modulating the skin condition for example improving elasticity of the skin. The compositions, according to the method of the present invention, may be administered using any amount and any route of administration effective for treating the eye or other tissue. Thus, the expression "amount effective for promoting the treating the skin condition", as used herein, refers to a sufficient amount of composition to regenerate skin cells and/or improve the appearance of the skin. The exact dosage is chosen by the individual physician in view of the patient to be treated. Dosage and administration are adjusted to provide sufficient levels of the active agent(s) or to maintain the desired effect. Additional factors which may be taken into account include the severity of the disease or condition, e.g. , extent of skin damage, history of the condition; age, weight and gender of the patient; diet, time and frequency of administration; drug interactions; reaction sensitivities; and tolerance/response to therapy. Long acting pharmaceutical compositions might be administered several times a day, every day, 3 to 4 days, every week, or once every two weeks depending on half-life and clearance rate of the particular composition.

The active agents of the invention are preferably formulated in dosage unit form for ease of administration and uniformity of dosage. The expression "dosage unit form" as used herein refers to a physically discrete unit of active agent appropriate for the patient to be treated, it will be understood, however, that the total daily usage of the compositions will be decided by the attending physician within the scope of sound medical judgment. For any active agent, the therapeutically effective dose can be estimated initially either in animal models, usually mice, rabbits, dogs, or pigs. The animal model is also used to achieve a desirable concentration range and route of administration. While direct application to the skin is envisioned as the route of administration, such information can then be used to determine useful doses and additional routes for administration in humans. A therapeutically effective dose refers to that amount of active agent that ameliorates the symptoms or condition. Therapeutic efficacy and toxicity of active agents can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., ED50 (the dose is therapeutically effective in 50% of the population) and LD50 (the dose is lethal to 50% of the population). The dose ratio of toxic to therapeutic effects is the therapeutic index, and it can be expressed as the ratio, LD50/ED50.

Pharmaceutical compositions that exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies is used in formulating a range of dosage for human use.

Administration of pharmaceutical compositions

After formulation with an appropriate pharmaceutically acceptable carrier in a desired dosage, the pharmaceutical compositions of this invention can be administered to humans and other mammals topically such as topically (as by gels, ointments, or drops), i.e., as applied directly to external tissues of the skin or dermis. Alternative and additional routes such as injection into the eye including invitreally, subcutaneous, intramuscarly, subtenonally, and subretinally, or orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneal ly, bucally, or nasally, depending on the severity of the condition being treated, are envisioned. Liquid dosage forms for topical or parenteral administration include buffers and solubilizing agents, preferred diluents such as water, preservatives such as thymosoL and one or more biopolymers or polymers for conditioning the solution, such as polyethylene glycol, hydroxypropylmethylcellulose, sodium hyaluronate, sodium polyacrylate or tamarind gum.

Liquid dosage forms for administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active agent(s), the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.

Dosage forms for topical or transdermal administration of an inventive pharmaceutical composition include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants, or patches. The active agent is admixed under sterile conditions with a

pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. For example, ocular or cutaneous conditions may be treated with aqueous drops, a mist, an emulsion, or a cream. Administration may be therapeutic or it may be prophylactic.

Prophylactic formulations may be present or applied to the site of potential wounds, or to sources of wounds, such as contact lenses, contact lens cleaning and rinsing solutions, containers for contact lens storage or transport, devices for contact lens handling, eye drops, surgical irrigation solutions, ear drops, eye patches, and cosmetics for the eye area, including creams, lotions, mascara, eyeliner, and eyeshadow. The invention includes ophthalmo logical devices, surgical devices, audiological devices or products which contain disclosed compositions {e.g., gauze bandages or strips), and methods of making or using such devices or products. These devices may be coated with, impregnated with, bonded to or otherwise treated with a disclosed composition.

The ointments, pastes, creams, and gels may contain, in addition to an active agent of this invention, excipients such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc, zinc oxide, or mixtures thereof.

Powders and sprays can contain, in addition to the agents of this invention, excipients such as talc, silicic acid, aluminum hydroxide, calcium silicates, polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants such as

chlorofluorohydrocarbons.

Transdermal patches have the added advantage of providing controlled delivery of the active ingredients to the body. Such dosage forms can be made by dissolving or dispensing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate can be controlled by either providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel.

Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a steri le injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1 ,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, U.S. P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables. The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. In order to prolong the effect of an active agent, it is often desirable to slow the absorption of the agent from subcutaneous or intramuscular injection. Delayed absorption of a parenterally

administered active agent may be accomplished by dissolving or suspending the agent in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the agent in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of active agent to polymer and the nature of the particular polymer employed, the rate of active agent release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the agent in liposomes or microemulsions which are compatible with body tissues.

Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the active agent(s) of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active agent(s).

Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active agent is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, poly vinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium laury! sulfate, and mixtures thereof.

Solid compositions of a similar type may also be employed as fillers in soft and hard- filled gelatin capsules using such excipients as milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active agent(s) may be admixed with at least one inert diluent such as sucrose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition that they release the active agent(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes.

Uses of cosmeceutical and pharmaceutical compositions

As discussed above and described in greater detail in the Examples, administeration of compositions containing at least one AMP and an acceptable carrier are useful to treat or modulate skin conditions by promoting the migration of regenerative cells, and restoring restoring nutrients to the skin. In general, it is believed that these compositions containing at least one AMP will be useful in inhibiting microbial growth in the compositions and one the treated skin.

Each publication and application cited herein is hereby incorporated by reference herein in its entirety.

Examples

Example 1 . Formulating biologic formulations The compositions containing at least one biologic, and an acceptable dermatological carrier are prepared. The compositions are formulated to include one of: a temperature- dependent self-assembly peptide, a small molecule, an aptimers, a microRNA/iR A, a cel l specific peptide, H2A, HI , H6, HDL, Sal-2, a defensin, a hepcidin, a cathelicidin, a piscidin, or a peptide having a sequence represented by the general formula [N-terminal end- APK.A MX ' X ^: X ³ X X ⁵ X ⁶ X X ^s L Q K G I -C-terminal end] (SEQ ID NO: 1), such that such that X¹ represents a basic amino acid residue; X² represents a hydrophobic amino acid residue; X³ represents a hydrophobic amino acid residue, which may be the same or different than X"; X⁴ represents a basic amino acid residue; X^s represents a basic amino acid residue, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue; X⁷ represents a hydrophobic amino acid residue, which may be the same or different than X⁶; and X^s represents a basic amino acid residue. The acceptable carriers used include each of: a vitamin B3 molecule, an elastomer, an antioxidant, an oil, a wax, an emulsifying agent, a stabilizer, a diluent, a moisturizer, and combinations thereof.

Example 2. Biologic compositions inhibit microbial growth on epithelial tissue

Subjects are chosen and an area of skin is administered a skin composition described herein containing at least one biologic, and an acceptable carrier. Control subjects were administered a composition absent the biologic. The epithelial tissues administered the compositions are wiped to remove excess composition, and the tissues are analyzed for microbial growth of strains including Staphylococcus epidermidis, a common strain found on skin.

Data show that the biologic compositions increased inhibition of microbial growth compared to the control composition. Inhibition of microbial growth on the epithelial tissue by the AMP compositions are observed to be multiple-fold greater than results for the tissues contacted with the control compositions. Further, the biologic compositions do not discolor or damaged the epithelial tissues

The biologic compositions are not toxic and effectively inhibit microbial growth for bacterial and fungal strains found on human skin.

Example 3: Delivery of biologies formulations to improve skin conditions

Routes of administering the biologic-containing compounds are investigated for effectiveness in treating skin conditions. The subjects are adminstered the biologic compositions by a route of adminsteration selected from: intradermal, intravaginal, oral, buccal, topical, and intraocular. Control subjects are adminstered phosphate buffered saline or formulations not containing the biologcs. Animals are induced to have skin damage using UV exposure. Animals are sacrificed and tissue samples are removed and analyzed for indicia of skin conditions or disorders. Tissue are analyzed for areas of inflammation, redness, scarring and irritation.

Administering the biologic compositions are observed to result in prevention or modulation of skin disorders in the subjects compared to results for control subjects. Tissues from the biologies foiTnulation treated subjects show reduced level of inflammation and redness compared to tissues from control subjects with each type of biologic used (i.e., antimicrobial peptides, temperature-dependent self-assembly peptides, small molecules, aptimers, microRNA/iRNA, and cell specific peptides), and route of adminstration.

Claims

What is claimed is:

1 . A topical skin care composition comprising: an antimicrobial peptide (AMP); an effective amount of a vitamin B₃ molecule; a silicone elastomer; an antioxidant; and a dermatologically acceptable carrier.

2. The composition according to claim 1, wherein the AMP comprises from about 0.05% to about 10% of the composition.

3. The composition according to claim 2, wherein the AMP comprises from about 2% to about 5% of the composition.

4. The composition according to claim 2, wherein the AMP comprises a concentration of about 0.5 μΜ to about 2 μΜ.

5. The composition according to any of claims 1 to 4, wherein the AMP is a naturally occurring AMP found in living things, for example a plant and an animal.

6. The composition according to claim 5, wherein the AMP is selected from a group consisting of: H2A, HI, H6, HDL, Sal-2, a defensin, a hepcidin, an apidaecin, a cathelicidin, and a piscidin.

7. The composition according to any of claims 2-4, wherein the AMP is a synthetically manufactured AMP, having for example a common structure of AMP of a naturally-occurring animal antibiotic, such as a mature peptide comprising for example amphipathic and cationic amino acid residues.

8. The composition according to any of claims 1-7, wherein the AMP comprises at least one activity selected from: antibacterial, antifungal, and antiviral.

9. The composition according to claim 7, wherein the AMP is selected from a group consisting of a peptide sequence represented by general formula of:

N- APKAMX ^! X²X X X⁵X'^:X⁷X^SI .QKKGI -C (SEQ ID NO: 1) wherein X¹ represents a basic amino acid residue; X² represents a hydrophobic amino acid residue; X³ represents a hydrophobic amino acid residue, which may be the same or different than X²; X⁴ represents a basic amino acid residue; X^s represents a basic amino acid residue, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue; X⁷ represents a hydrophobic amino acid residue, which may be the same or different than X⁶; and X^s represents a basic amino acid residue.

10. The composition according to claim 9, wherein the basic amino acid residue is lysine, arginine or histidine.

1 1 . The composition according to claim 9, wherein the hydrophobic amino acid residue is alanine, valine or leucine.

12. The composition according to claim 9, wherein the AMP is amidated at the C-terminal end.

13. The composition according to claim 9, wherein the peptide promotes wound healing and skin rejuvenation and interacts with regenerating cells of the skin.

14. The composition according to claim 9 wherein the antimicrobial activity is functional at a salt concentration of about 100 mM to about 200 mM.

1 5. The composition according to any of claims 1 to 14, further comprising a particulate material.

16. The composition according to claim 15, wherein the particulate material is selected from the group consisting of: a bismuth oxychloride; an iron oxide; a mica for example mica treated with barium sulfate and titanium dioxide; a silica; a nylon; a polyethylene; a talc; a styrene; a polypropylene; an ethylene/acrylic acid copolymer; a titanium dioxide; an iron oxide; a bismuth oxychloride; a sericite; an aluminum oxide; a silicone resin; a barium sulfate; a calcium carbonate; a cellulose acetate; a polymethyl methacrylate; and mixtures thereof.

17. The composition according to any of claims 1 to 16 further comprising a sunscreen active ingredient.

18. The composition according to claim 17, wherein the sunscreen active ingredient is selected from the group consisting of 4,4' -butylmethoxydibenzoylmethane, 2-ethylhexyl-p- methoxycinnamate, phenyl benzimidazole sulfonic acid, octocrylene, and mixtures thereof.

19. A composition for regenerating skin cells comprising: as an active ingredient a peptide

1 ^ 3 4 5 6 7 8 having a sequence represented by general formula [N- APKAMX X X X X X X X LQ KGI - C] (SEQ ID NO: 1), wherein X¹ represents a basic amino acid residue; X² represents a hydrophobic amino acid residue; X³ represents a hydrophobic amino acid residue, which may be the same or different than X²; X⁴ represents a basic amino acid residue; X⁵ represents a basic amino acid residue, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue; X⁷ represents a hydrophobic amino acid residue, which may be the same or different than X⁶; and X⁸ represents a basic amino acid residue.

20. The composition according to claim 19, wherein the basic amino acid residue is lysine, arginine or histidine.

21. The composition according to claim 19, wherein the hydrophobic amino acid residue is alanine, valine or leucine.

22. The composition according to claim 19, wherein the peptide of general formula 1 is amidated at the C-terminal end.

23. The composition according to claim 19 further exhibiting antimicrobial activity at a salt concentration of about from 100 mM to about 200 niM.

24. The composition according to one of claims 19 to 23, further comprising a

pharmaceutically acceptable carrier, excipient or diluent.

25. The composition according to claim 19, wherein the peptide is present at a concentration of about 0.5 μΜ to about 2 μΜ.

26. A cosmetic for skin rejuvenation comprising the composition of any of claims 19-25.

27. A method for regenerating skin cells in a wound of an animal, the method comprising administering to the wound a composition that comprises a peptide having a sequence represented by the general formula I:

[N-terminal end- APKAMX^X^X XVLQKKGI -C-terminal end] (SEQ I D NO: 1) wherein X¹ represents a basic amino acid residue; X² represents a hydrophobic amino acid residue; X³ represents a hydrophobic amino acid residue, which may be the same or different than X²; X⁴ represents a basic amino acid residue; X³ represents a basic amino acid residue, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue;

7 6

X represents a hydrophobic amino acid residue, which may be the same or different than X ; and X^s represents a basic amino acid residue.

28. The method according to claim 27, wherein the basic amino acid residue is lysine, arginine or histidine.

29. The method according to claim 27, wherein the hydrophobic amino acid residue is alanine, valine or leucine.

30. The method according to claim 27, wherein the peptide is amidated at the C-terminal end.

3 1. The method according to claim 23, wherein the peptide exhibits antimicrobial activity at a salt concentration of about 100 mM to about 200 mM.

32. The method according to one of claims 27 to 31 , wherein the composition further comprises a pharmaceutically acceptable carrier, excipient or diluent.

33. The method according to any of claims 27-32, wherein the peptide is present at a concentration of about 0.5 μΜ to about 2 μΜ.

34. A method for regenerating skin cells comprising: administering to damaged or injured skin a composition that comprises a peptide having a sequence represented by general formula: N-terminal end- ΛΡΚΛΜΧ ' X ² X X ⁴ X X X ⁷ X ^s I . O K G I -C-terminal end] (SEQ ID NO:

1 ), wherein x ' represents a basic amino acid residue; X² represents a hydrophobic amino acid residue; X³ represents a hydrophobic amino acid residue, which may be the same or different than X²; X⁴ represents a basic am ino acid residue; X³ represents a basic amino acid residue, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue; X⁷ represents a hydrophobic amino acid residue, which may be the same or different than X⁶; and X^s represents a basic amino acid residue.

35. The method according to claim 34, wherein the basic amino acid residue is lysine, arginine or histidine.

36. The method according to claim 34, wherein the hydrophobic amino acid residue is alanine, valine or leucine.

37. The method according to claim 34, wherein the peptide is amidated at the C-terminal end.

38. The method according to claim 34, wherein the peptide exhibits antimicrobial activity at a salt concentration of about 100 to about 200 mM.

39. The method according to one of claims 34 to 38, wherein the composition further comprises a pharmaceutically acceptable carrier, excipient or diluent.

40. The method according to one of claims 34 to 39, wherein the peptide is present at a concentration of about 0.5 μΜ to about 2 μΜ.

41. Use of a peptide having a sequence represented by general formula I in preparing a pharmaceutical composition for regenerating skin cells: [N-terminal end- AP AMX'X²X³X⁴X⁵X⁶X⁷X⁸LQ KGI -C-terminal end] (SEQ ID NO: 1 ), wherein X¹ represents a basic amino acid residue; X² represents a hydrophobic amino acid residue; X³ represents a hydrophobic amino acid residue, which may be the same or different than X²; X⁴ represents a basic amino acid residue; X^s represents a basic amino acid residue, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue; X⁷ represents a hydrophobic amino acid residue, which may be the same or different than X⁶; and X⁸ represents a basic amino acid residue.

42. The use according to claim 41 , wherein the basic amino acid residue is lysine, arginine or histidine.

43. The use according to claim 41, wherein the hydrophobic amino acid residue is alanine, valine or leucine.

44. The use according to claim 44, wherein the peptide is amidated at the C-terminal end.

45. The use according to any of claims 41 to 44, wherein the composition effectively regenerates the skin cells at the site of a wound or an injury.

46. The use according to any of claims 41 to 44, wherein the peptide exhibits antimicrobial activity at a salt concentration of about 100 mM to 200 mM.

47. The use according to any of claims 41 to 46, wherein the composition further comprises a pharmaceutically acceptable carrier, excipient or diluent.

48. The use according to claim 41, wherein the peptide is present at a concentration of about 0.5 μΜ to about 2 μΜ.

49. Use of a peptide having a sequence represented by general formula I in preparing a composition for regenerating skin cells, wherein the formula comprises: [N-terminal end- AP \MX' X^:X^;iX⁴X⁵X^t,X⁷X^sLO KGl -C-terminal end] (SEQ ID NO: 1 ), wherein X¹ represents a basic amino acid residue; X² represents a hydrophobic amino acid residue; X³ represents a hydrophobic amino acid residue, which may be the same or different than X²; X⁴ represents a basic amino acid residue; X^s represents a basic amino acid residue, which may be the same or different than X⁴; X⁶ represents a hydrophobic amino acid residue; X⁷ represents a hydrophobic amino acid residue, which may be the same or different than X⁶; and X^s represents a basic amino acid residue.

50. The use according to claim 49, wherein the basic amino acid residue is lysine, arginine or histidine.

5 1. The use according to claim 49 or 50, wherein the hydrophobic amino acid residue is alanine, valine or leucine.

52. The use according to any of claims 49-51 , wherein the peptide is amidated at the C-terminal end.

53. The use according to any of claims 49-52, wherein the peptide comprises antimicrobial activity that is functional at a salt concentration of about 100 mM to about 200 mM.

54. The use according to one of claims 49 to 53, wherein the composition further comprises a pharmaceutically acceptable carrier, cxcipient or diluent.

55. The use according to any of claims 49-54, wherein the peptide is present at a concentration of about 0.5 μΜ to about 2 μΜ.

56. The use according to claim 49, wherein the composition comprises a salt concentration of about 100 mM to about 200 mM.

57. The use according to any of claims 49-56, wherein the composition further comprises a particulate material.

58. The use according to claim 57, wherein the particulate material is selected from the group consisting of: a bismuth oxychloride; an iron oxide; a mica; a silica; a nylon; a polyethylene; a talc; a styrene; a polypropylene; an ethylene/acrylic acid copolymer; a titanium dioxide; an iron oxide; a bismuth oxychloride; a sericite; an aluminum oxide; a silicone resin; a barium sulfate; a calcium carbonate; a cellulose acetate; a polymethyl methacrylate; and mixtures thereof.

59. The use according to any of claims 49-58, wherein the composition further comprises a sunscreen active ingredient.

60. The use according to claim 51 , wherein the sunscreen active ingredient is selected from the group consisting of 4,4'-t-butylmethoxydibenzoylmethane, 2-ethylhexyl-p- methoxycinnamate, phenyl benzimidazole sulfonic acid, octocrylene, and mixtures thereof.

61. A topical skin care composition comprising: an antimicrobial peptide (AMP); a vitamin B3 molecule; a sunscreen active ingredient; an antioxidant; and a dermatologically acceptable carrier.

62. The composition according to claim 61 , wherein the AMP comprises from about 2% to 5% of the composition.

63. The composition according to claim 61 or 62, wherein the vitamin B₃ molecule comprises from about 0.2% to about 5% of the composition.

64. The composition according to any of claims 61-63, wherein the organic sunscreen is selected from the group consisting of 4,4'-t-butylmethoxydibenzoylmethane, 2-ethylhexyl-p- methoxycinnamate, phenyl benzimidazole sulfonic acid, octocrylene, and mixtures thereof.

65. The composition according to any of claims 61-64, further comprising a particulate material.

66. The composition according to claim 65, wherein the particulate material is selected from the group consisting of bismuth oxychloride, iron oxide, mica, mica treated with barium sulfate and T1O2, silica, nylon, polyethylene, talc, styrene, polypropylene, ethylene/acrylic acid copolymer, titanium dioxide, iron oxide, bismuth oxychloride, scricite, aluminum oxide, silicone resin, barium sulfate, calcium carbonate, cellulose acetate, polymethyl methacrylate, and mixtures thereof.

67. A method for regulating a mammalian skin condition comprising administering to an area of skin having the condition the composition according to any of claims 1 -25 and 61 -66.

68. The method according to claim 67, wherein contacting the composition is performed according to a regimen over a period of time, for example the period is at least days, weeks, or months.

69. The method according to claim 68, wherein the period comprises at least about three months.

70. The method according to any of claims 67 to 69, wherein the AMP comprises from about 2% to 5% of the composition.

71. The method according to any of claims 67-71 , wherein contacting comprises administering by a route selected from at least one of the group consisting of : topically (as by powders, ointments, or drops), orally, rectally, mucosally, sublingually, intravaginally, intraperitoneally, bucally, subl ingually, ocularly, or intranasally,

71. A method for regulating a mammalian skin condition comprising the step of applying to an area having the condition the composition according to any of claims 61-66.