WO2016154020A1 - Methods for reducing sebum production and/or excretion - Google Patents

Abstract

Provided herein are methods, compositions and kits for reducing or preventing excessive sebum production and/or excretion by a subject. The method includes administering a composition comprising a peptide that can modulate neurotransmitter release such as acetyl hexapeptide-8 RT001, Vialox^®, Leuphasyl^®, Syn^®-Ake, and any combination thereof. The method can include topical administration of the composition. Also provided herein are methods, compositions and kits for treating or preventing a condition associated with sebum overproduction or excessive excretion, including seborrhea and acne.

Description

METHODS FOR REDUCING SEBUM PRODUCTION AND/OR

EXCRETION

CROSS-REFERENCES TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 62/136,027, filed March 20, 2015, the disclosure of which is hereby incorporated by reference in its entirety for all purposes.

BACKGROUND OF THE INVENTION

[0002] Human skin is composed of three primary layers, the stratum corneum, the epidermis, and the dermis. The outer layer is the stratum corneum. Its primary function is to serve as a barrier to the external environment. Sebum, an oily, waxy substance, is secreted to the surface of the stratum corneum by sebaceous glands. These glands are located over most of the surface of the body with the highest concentration on the scalp, forehead and face. Sebum acts to waterproof and lubricate the skin and hair of mammals. In humans, sebum is primarily composed of triglycerides (about 41%), wax esters (about 26%), squalene (about 12%) free fatty acids (about 16%), cholesterol and cholesterol esters.

[0003] Seborrhea refers to the overproduction of sebum (i.e., sebaceous matter) in a sebaceous gland. Overproduction of sebum causes the sebaceous gland follicles to be partly or completely filled with sebum. Sebum can accumulate to an undesirable level in the sebaceous glands and form an ideal nutrient medium for microorganisms, such as, in particular, Propionibacterium acnes, a microorganism involved decisively in the development of acne. Thus, excessive sebum production is associated with an increased incidence of acne. Areas of skin with increased sebum production are distinguished by an increased number of and/or activity of the sebaceous gland follicles and are preferentially to be found in the area of the face, and more preferentially on the forehead, nose, cheek, chin, hair-covered scalp; front and rear sweat channel; neck; chest and back. Accumulation of sebum on the surface of the skin can also cause the skin to appear shiny or oily and the hair to feel greasy.

[0004] Current treatment for reducing the amount of sebum on the surface of the skin include increasing water consumption, and applying moisturizers to the skin or compositions directed at absorbing the sebum. In cases of severe acne, 13-cis retinoic acid (isotretinoin) is used to treat the skin since it can reduce sebum secretion by up to 90%. However, isotretinoin is associated with a number of serious side effects, including serious birth defects. Thus, it is contraindicated in women of childbearing age and is inappropriate to use as a cosmetic aid.

[0005] There remains a need in the art for a safe and effective method of treating or preventing overproduction of sebum in a subject. The present invention described herein meets this and other needs.

BRIEF SUMMARY OF THE INVENTION

[0006] In one aspect, provided herein is a method for reducing sebum production and/or excretion in the skin of a subject in need thereof. The method comprises administering to the subject an effective amount of a composition comprising a peptide that modulates neurotransmitter release, an equivalent thereof, a variant thereof, or a derivative thereof, and a pharmaceutically acceptable carrier to decrease sebum in the subject's skin. The peptide that modulates neurotransmitter release can be at about 5% to about 20% by weight of the total composition. In some embodiments, the peptide that modulates neurotransmitter release is selected from the group consisting of acetyl hexapeptide-8, RT001, Vial ox^®, Leuphasyl^®, Syn^®-Ake, and any combination thereof.

[0007] The compositions can be administered topically to the skin. In some instances, the composition is a formulation selected from the group consisting of a liquid, aqueous solution, suspension, cream, lotion, ointment, gel, foam and solid. The pharmaceutically acceptable carrier of the composition can be a dermatologically acceptable carrier or a cosmetically acceptable carrier. In some cases, the subject has no symptom of a sebum overproduction condition. The subject in need can have at least one symptom of a sebum overproduction condition, wherein the at least one symptom includes oily skin, combination oily to dry skin, dandruff, acne, greasy hair, or a combination thereof. In some instances, the subject suffers from a sebum overproduction condition selected from the group consisting of acne vulgaris, seborrhea, seborrheic dermatitis, sebopsoriasis, sebaceous hyperplasia, sebaceous cysts, hyperseborrhea, sebaceous carcinoma, acne conglobate, and a combination thereof. [0008] In some embodiments, reducing sebum production and/or excretion includes an at least about 5% reduction in sebum after administration of the composition compared to before administration. In other embodiments, reducing sebum production and/or excretion includes an at least about 10% reduction in sebum after administration of the composition compared to before administration.

[0009] In a second aspect, provided herein is a method for treating a sebum overproduction condition in a subject in need thereof. The method includes administering to the subject an effective amount of a composition comprising a peptide that modulates neurotransmitter release, an equivalent thereof, a variant thereof, or a derivative thereof, and a pharmaceutically acceptable carrier to decrease sebum in the subject's skin. In some embodiments, the peptide that modulates neurotransmitter release can be at about 5% to about 20%) by weight of the total composition. The peptide that modulates neurotransmitter release can be selected from the group consisting of acetyl hexapeptide-8, RT001, Vial ox^®, Leuphasyl^®, Syn^®-Ake, and any combination thereof. In some instances, the composition is administered topically. In some embodiments, the composition is a formulation selected from the group consisting of a liquid, aqueous solution, suspension, cream, lotion, ointment, gel, foam and solid. The pharmaceutically acceptable carrier of the composition can be a dermatologically acceptable carrier or a cosmetically acceptable carrier.

[0010] In some embodiments, the subject suffers from a sebum overproduction condition selected from the group consisting of acne vulgaris, seborrhea, seborrheic dermatitis, sebopsoriasis, sebaceous hyperplasia, sebaceous cysts, hyperseborrhea, sebaceous carcinoma, acne conglobate, and a combination thereof. In some instances, the method further comprises alleviating at least one symptom of the sebum overproduction condition. The at least one symptom can include reducing the appearance of oily skin, combination oily to dry skin, dandruff, acne, greasy hair, or a combination thereof. In some embodiments, the level of sebum in the skin is reduced by at least about 5% or at least about 10%> after administration of the composition. [0011] In a third aspect, provided herein is a method for preventing sebum overproduction and/or excretion in a subject. The prophylactic method comprises administering to the subject an effective amount of a composition comprising a peptide that modulates neurotransmitter release, an equivalent thereof, a variant thereof, or a derivative thereof, and a pharmaceutically acceptable carrier to prevent excessive sebum production and/or excretion in the subject's skin. The peptide that modulates neurotransmitter release can be at about 5% to about 20%) by weight of the total composition. In some embodiments, the peptide that modulates neurotransmitter release can be selected from the group consisting of acetyl hexapeptide-8, RT001, Vial ox^®, Leuphasyl^®, Syn^®-Ake, and any combination thereof.

[0012] In some embodiments, the composition is a formulation selected from the group consisting of a liquid, aqueous solution, suspension, cream, lotion, ointment, gel, foam and solid. The pharmaceutically acceptable carrier of the composition can be a dermatologically acceptable carrier or a cosmetically acceptable carrier. In some embodiments, preventing excessive sebum production and/or excretion can include an at least about 5% reduction in sebum production and/or excretion after administration of the composition compared to before administration. In other embodiments, preventing excessive sebum production and/or excretion includes an at least about 10% reduction in sebum production and/or excretion after administration of the composition compared to before administration. In some cases, the subject does not suffer from excessive sebum overproduction.

[0013] In a fourth aspect, provided herein is a kit comprising a first composition comprising a peptide that modulates neurotransmitter release, an equivalent thereof, a variant thereof, or a derivative thereof, and a pharmaceutically acceptable carrier; and a second composition comprising a skin care composition or a hair care composition. In some instances, the peptide that modulates neurotransmitter release is at about 5% to about 20% by weight of the total composition. In some embodiments, the peptide that modulates neurotransmitter release is selected from the group consisting of acetyl hexapeptide-8, RT001, Vial ox^®, Leuphasyl^®, Syn^®-Ake, and any combination thereof. The skin care composition can be selected from a skin cleanser, moisturizer, serum, lotion, anti-acne medication, anti-aging cream, sunscreen, and a combination thereof. The hair care composition can be shampoo.

[0014] Other objects, features, and advantages of the present invention will be apparent to one of skill in the art from the following detailed description and figures.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] FIG. 1 illustrates sebocyte lipid production after acetyl hexapeptide-8 treatment.

[0016] FIG. 2 illustrates sebocyte proliferation after acetyl hexapeptide-8 treatment. DETAILED DESCRIPTION OF THE INVENTION

I. INTRODUCTION

[0017] The methods and compositions provided herein may be administered to an individual to decrease the amount of sebum secreted by the individual's sebaceous glands. The compositions containing a peptide that modulates neurotransmitter release such as acetyl hexapeptide-8, RT001, Vial ox^®, Leuphasyl^®, Syn^®-Ake, and any combination can be administered topically to the areas of the body with sebum production, such as the surface of the skin and hair. The methods can be used to alleviate dermatological and cosmetic disorders as well as conditions that are associated with overproduction of sebum, including oily skin, oily hair, acne, seborrhea, and seborrheic dermatitis. The methods and compositions can also be used prophylactically to prevent or reduce excessive sebum production.

II. DEFINITIONS

[0018] As used herein, the following terms have the meanings ascribed to them unless specified otherwise.

[0019] The terms "a," "an," or "the" as used herein not only include aspects with one member, but also include aspects with more than one member. For instance, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a cell" includes a plurality of such cells and reference to "the agent" includes reference to one or more agents known to those skilled in the art, and so forth.

[0020] The terms "about" and "approximately" are defined as being close to as understood by one of ordinary skill in the art, and in one non-limiting embodiment the terms are defined to be within 10%, preferably within 5%, more preferably within 1%, and most preferably within 0.5%.

[0021] The term "treating" or "treatment" refers to the treating or treatment of a disease or medical condition (such as a skin disease) in a patient, such as a mammal (particularly a human or an animal) which includes: ameliorating the disease or medical condition, i.e., eliminating or causing regression of the disease or medical condition in a patient; suppressing the disease or medical condition, i.e., slowing or arresting the development of the disease or medical condition in a patient; or alleviating one or more symptoms of the disease or medical condition in a patient. The term encompasses the prophylactic treatment of a disease as to prevent or reduce the risk of acquiring or developing a specific disease, or to prevent or reduce the risk of disease recurrence.

[0022] The term "administering" or "administration" refers to the process by which compounds, compositions, dosage forms and/or combinations disclosed herein are delivered to a subject for treatment or prophylactic purposes. Compounds, compositions, dosage forms and/or combinations disclosed herein are administered in accordance with good medical practices taking into account the subject's clinical condition, the site and method of administration, dosage, subject age, sex, body weight, and other factors known to the physician. For example, the terms "administering" or "administration" include providing, giving, dosing and/or prescribing compounds, compositions, dosage forms and/or combinations disclosed herein by a clinician or other clinical professional.

[0023] The term "an effective amount" or "a therapeutically effective amount" of a pharmaceutically active agent refers to an amount of the pharmaceutically active agent sufficient enough to have a desired effect on the area of application. Accordingly, these amounts are sufficient to modify the skin disorder, condition, or appearance to be treated but low enough to avoid serious side effects. A therapeutically effective amount of the pharmaceutically active agent can cause relief of one or more symptoms when applied once or repeatedly over time. Effective amounts of the pharmaceutically active agent will vary with the particular condition or conditions being treated, the severity of the condition, the duration of the treatment, the specific components of the composition being used, and other factors that might have an influence on general effectiveness.

[0024] The term "reducing sebum production," "reducing sebum excretion" or "reducing sebum secretion" refers to a reduction of the amount sebum of the skin, including a reduction of the sebum concentration in the skin, in particular in the sebaceous gland follicles, on the skin, on the hair-covered scalp, and/or on the hair, relative to the amount of sebum prior to administration. This reduction of the sebum concentration of the skin can be determined, for example, by means of sebumetry, in particular by means of Sebutape^®-Chromameter (Cuderm), Sebufix (CK Electronic), Skin Analyzer SHP 88 (Concepts Computer), Skin Diagnostic SD 27(CK Electronic), or Sebumeter^® SM815 (CK Electronic). The level of sebum at a specific location of the surface of the skin can be measured before administration of the composition and compared to the level of sebum at the same location after administration.

[0025] The term "sebum overproduction" or "excessive sebum production" refers to the production and/or secretion of sebum such that a subject's skin sebum level is higher than that of a normal, control subject, that of an average of normal, control subjects, that of the subject at an earlier time point. "Sebum overproduction" includes, but is not limited to, increased sebocyte proliferation, increased production/synthesis of sebum, increased lipid production/synthesis by sebocytes, and increased sebum excretion or secretion. Sebum overproduction can be determined by the presence of oily skin, oily and dry combination skin, greasy hair, pimples, skin pustules, papules, nodules and other skin issues due to acne. Levels of sebum on the skin can be measured using standard methods by means of sebumetry, in particular by means of Sebutape^®-Chromameter (Cuderm), Sebufix (CK Electronic), Skin Analyzer SHP 88 (Concepts Computer), Skin Diagnostic SD 27(CK Electronic), or Sebumeter^® SM815 (CK Electronic). See, e.g., Pande and Misrl, Indian J Dermatol Venereol Leprol, 71(6):444-446 (2005). In some instances, a clinician, e.g., dermatologist, can determine whether a subject is experiencing excessive sebum production or has a sebum overproduction condition.

[0026] The term "sebum overproduction condition" refers a condition or physical state of a subject that is caused by or associated with overproduction of sebum. Non-limiting examples of a sebum overproduction condition include acne vulgaris, seborrhea, seborrheic dermatitis, sebopsoriasis, sebaceous hyperplasia, sebaceous cysts, hyperseborrhea, sebaceous carcinoma, acne conglobate, or any combination thereof. The condition can include any disease, disorder or condition that is caused by, associated with, or a side effect of producing, synthesizing, and/or secreting sebum at a level that is higher (e.g., at least 5% higher) than what is considered normal by a clinician, e.g., a dermatologist, or higher than a control value.

[0027] The term "inhibiting" or "reducing" refers to a measurable decrease or complete reduction to an achieve an expected, forecasted or intended result.

[0028] The term "preventing" refers to prophylactically averting or hindering an expected, forecasted or intended result. [0029] The term "pharmaceutically acceptable carrier" includes any and all additives which are acceptable in the pharmaceutical sciences, and can include, for example, high molecular weight polymeric agents such as a cellulosic polymer, hydroxyethylcellulose, hydroxypropylcellulose, methylcellulose, a vinylic polymer, polyvinylpyrolidone, polyvinyl alcohol, polyethylene glycol, petrolatum, talcum or other additives or binders. In some embodiments, a pharmaceutically acceptable carrier is pharmaceutically acceptable for use in humans. The term "dermatologically acceptable carrier" or "cosmetically acceptable carrier" can include, but is not limited to, water, salicylic acid, benzoyl peroxide, phenoxyethanol, butylene glycol, citric acid, propylene glycol, methylparaben, propylparaben, glycerin, chlorphenesin, sodium metabisulfite, and the like.

[0030] The terms "subject," "patient," and "individual" are used interchangeably to refer to any mammalian subject, particularly humans. The subject can be a human of any age including those who are undergoing or have undergone puberty. In some cases, the human subject is an adult or at least 12 years old.

III. DETAILED DESCRIPTION OF THE EMBODIMENTS A. Peptides that modulate neurotransmitter release

[0031] Peptides described herein include naturally occurring peptides and synthetic peptides that can serve as peptide mimetics of botulinum neurotoxins. These bioactive peptides can affect neurotransmitter release, for example, at neuromuscular junctions. In some cases, the peptide can inhibit acetylcholine release or binding. In some embodiments, the peptides include acetyl hexapeptide-8, RT001, Vial ox^®, Leuphasyl^®, Syn^®-Ake, and any combination thereof. [0032] The present invention is based, in part, on the surprising discovery that acetyl- hexapeptide-8 can decrease lipid production by sebocytes. Acetyl hexapeptide-8, which is also referred to as AH8, acetyl hexapeptide-3 (AH3), and Argireline^®, is a synthetic cosmetics ingredient. It is a peptide fragment of SNAP-25, a substrate of botulinum toxin (Botox). Acetyl-hexapeptide-8 has the amino acid sequence of SEQ ID NO: l (Ac-Glu-Glu- Met-Gln-Arg-Arg- H₂). Acetyl hexapeptide-8, having the chemical name acetyl glutamyl- glutamyl-methyonyl-glutamyl-arginyl-arginylamide (Argireline^®), may be purchased from Lipotec S.A. in either a powder or solution form. The powder form appears as a white to off- white powder comprising about 2.7 to 3.3% glutamic acid, about 0.6 to 1.0% methionine, and about 1.8 to 2.2%) arginine. The solution form is a transparent solution containing about 0.05%) powder in water and about 0.5% preservative. [0033] Extensive in vitro studies have been performed to elucidate its mechanism of action (J. Biol. Chem., 272(5):2634-39, 1997). One such study demonstrated that the peptide acts by preventing formation of the soluble N-ethylmaleimide-sensitive fusion attachment protein (SNAP) receptor complex, and thus inhibiting vesicle docking. Catecholamine release, including epinephrine and norepinephrine, was inhibited by acetyl-hexapeptide-8 in vitro.

[0034] In some embodiments, the composition described herein includes about 5% to about 20%, e.g., about 5-20%, about 5-15%, about 5-10%, about 10%-20%, about 10%- 15%, or about 15%-20% by weight of acetyl-hexapeptide-8. In other embodiments, the composition described herein includes about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%), about 19%), or about 20% by weight of acetyl-hexapeptide-8.

[0035] At concentrations such as at about 5% or more by weight of the total composition, acetyl-hexapeptide-8 has been shown to decrease sebocyte proliferation in the skin. At a range of from about 5% to about 20% by weight of the total weight to the total composition, acetyl-hexapeptide-8 can reduce lipid production by the sebaceous glands by at least about 5% or more, e.g., about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% or more, compared to not applying acetyl- hexapeptide-8 to the subject's skin.

[0036] In some instances, administration of acetyl-hexapeptide-8 can decrease sebum production, sebum excretion, or both in the skin by at least about 5% or more, e.g., about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%), 70%) or more, compared to not applying acetyl-hexapeptide-8 to the skin. In other instances, the decrease in sebum production, sebum excretion, or both is by at least about 10% or more, e.g., 10%, 11%, 12%, 13%, 14%, 15%, 16%. 17%. 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% or more, compared to not applying acetyl-hexapeptide-8 to the skin. In some embodiments, lipid production is reduced by administration of acetyl-hexapeptide-8 such that the subject's skin is no longer oily to the touch or the subject's hair is no longer greasy after the treatment.

[0037] In other embodiments, the oiliness of the subject's skin is reduced by at least about 5% or more, e.g., about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% or more, after administering the acetyl- hexapeptide-8-containing composition to, e.g., the surface of the skin. In yet other embodiments, the greasiness of the subject's hair is reduced by at least 5% or more, e.g., about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%. 17%. 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% or more, after administering the acetyl-hexapeptide-8-containing composition to, e.g., the hair and/or scalp. The amount of sebum or lipid production and/or excretion by the sebaceous glands directly corresponds to the level of sebum on the surface of a subject's skin. Described below are methods for measuring the sebum level of a subject's skin. In some instances, acetyl-hexapeptide-8- containing composition can diminish the appearance of oily skin, combination oily to dry skin, dandruff, acne, greasy hair, or a combination thereof. [0038] In some aspects, the peptide that modulates neurotransmitter release can be a peptide mimetic of the botulinum neurotoxins (BoNT). In some embodiments, the peptide can be RT001 or RTT150 from Revance Therapeutics (Newark, California) or other peptide mimetics of BoNT -A or the other BoNT serotypes. In other embodiments, the peptide can be synthetic pentapeptide-3 such as Vialox^® (Pentapharma; Basel, Switzerland). The pentapeptide-3 or equivalent thereof can antagonize the acetylcholine postsynaptic membrane receptor. In yet other embodiments, the peptide can be pentapeptide with an encephalin-like structure such as Leuphasyl^® (Lipotec S.A.; Barcelona, Spain). In some embodiments, the peptide can be tripeptide-3 (beta-Ala-Pro-Dab-NH-benzyl x 2 AcOH) that functions similarly to walglerin-1 such as Syn^®-Ake (Pentapharma). The tripeptide-3 or equivalent thereof can antagonize the muscular nicotinic acetylcholine receptor at the postsynaptic membrane. Detailed descriptions of these peptides are found, e.g., in Reddy et al., Exp Dermatol, 2012, 21(8): 569-75. Additional useful peptides can include bioactive peptides that can be used to reduce the depth of wrinkles and/or number of wrinkles of the skin.

[0039] In some embodiments, the composition described herein includes about 5% to about 20%, e.g., about 5-20%, about 5-15%, about 5-10%, about 10%-20%, about 10%- 15%, or about 15%-20% by weight of any of the peptides described herein. In other embodiments, the composition described herein includes about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%), about 18%, about 19%, or about 20% by weight of any of the peptides described herein.

[0040] At concentrations such as at about 5% or more by weight of the total weight of the composition, one or more of the peptides described herein has been shown to decrease sebocyte proliferation. At a range of from about 5% to about 20% by weight of the total composition, one or more of the peptides can reduce lipid production by the sebaceous glands by at least about 5% or more, e.g., about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% or more, compared to not applying the peptide(s) to the subject's skin. In some instances, administration of one or more of the peptides can decrease sebum production and/or secretion by at least about 5% or more, e.g., about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% or more, compared to not applying the peptide(s) to the skin. In other instances, the decrease in sebum production, sebum excretion or both is by at least about 10% or more, e.g., 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%), 60%), 65%), 70%) or more, compared to not applying the peptide(s) to the skin. In some embodiments, one or more, e.g., 1, 2, 3, 4 or more peptides are formulated together in the composition. [0041] In some embodiments, lipid production is reduced by administration of one or more of the peptides such that the subject's skin is no longer oily to the touch or the subject's hair is no longer greasy after the treatment. In other embodiments, the oiliness of the subject's skin is reduced by at least about 5% or more, e.g., about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%), 65%), 70%) or more, after administering the peptide-containing composition to, e.g., the surface of the skin. The oiliness of the subject's skin is reduced by at least about 10% or more, e.g., about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% or more, after administering the peptide- containing composition to, e.g., the surface of the skin. [0042] In yet other embodiments, the greasiness of the subject's hair is reduced by at least 5% or more, e.g., about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% or more, after administering the peptide-containing composition to, e.g., the hair and/or scalp. The greasiness of the subject's hair is reduced by at least 10% or more, e.g., about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%), 65%), 70%) or more, after administering the peptide-containing composition to, e.g., the hair and/or scalp. The amount of sebum production or excretion by the sebaceous glands directly corresponds to the level of sebum on the surface of a subject's skin. [0043] The peptide-containing composition can be administered to a subject as a prophylactic treatment for sebum overproduction. In some embodiments, the composition described herein can prevent an increase in sebum production in a subject. For example, upon treatment with the composition, the sebum level of the subject's skin can decrease, remain substantially unchanged, remain unchanged, or increase by no more than about 3%, e.g., about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%), 2.9%), 3%), compared to the sebum level prior to treatment. In some embodiments, the level of sebum in skin decreases by at least about 5%, e.g., 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, more after administration of the composition. In other embodiments, the level of sebum in skin decreases by at least about 10%, e.g., 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, or more after administration of the composition.

B. Administration of peptide-containing compositions [0044] The peptide composition can be administered in a quantity sufficient to reduce, inhibit or prevent the production or secretion of sebum by sebaceous glands. In some embodiments, acetyl hexapeptide-8, RT001, Vial ox^®, Leuphasyl^®, Syn^®-Ake, or any combination thereof can reduce the level of sebum on the skin of a subject following administration. In other embodiments, administration of acetyl hexapeptide-8, RT001, Vialox^®, Leuphasyl^®, Syn^®-Ake, or any combination thereof can prevent an increase in the level of sebum on the skin of a subject who oily skin, combination oily to dry skin, dandruff, acne, greasy hair, or a combination thereof. Alternatively, the peptide composition can be administered to a subject who does not have oily skin, combination oily to dry skin, dandruff, acne, greasy hair, or a combination thereof. The subject may have normal skin. For instance, upon applying the composition to the skin to this subject, the level of sebum will remain substantially unchanged.

[0045] The peptide composition can be used to decrease sebum production and/or sebum excretion in a subject that exhibits one or more symptoms of a sebum over production condition. Similarly, the dermatological composition can be used to treat a sebum overproduction condition including any condition that is characterized by an increased sebum level as determined by, for example, a sebumeter. [0046] The amount required can vary depending upon the particular disorder or condition being treated, the severity of the patient's disorder or condition, the route of administration, the presence of other underlying disorders or conditions, and the like. The peptide containing composition can be administered systemically or locally at a dosage range sufficient to alleviate at least one symptom of any of the diseases or conditions described herein.

[0047] The peptide-containing composition can be applied at intervals to achieve effective results. For example, the peptide-containing composition can be topically applied once a day. In certain embodiments, application can be at least once a day, twice a day, or more frequently. Repetitive daily administration, e.g., administration 2 times, 3 times, 4 times, 5 times or more per day, may be desirable and will vary according to the conditions set forth herein. In alternative embodiments, application that occurs less frequently, e.g., administration once, twice, three, or four times a week or month, may be desirable and will vary according to the conditions set forth herein. Treatment periods will depend on the severity of the condition and also whether the peptide compound is being applied as a preventative measure for the development of oily skin or after oily skin has emerged or the more serious acne or seborrhea manifestation exists. The treatment period can be 1 week or more, e.g., 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or more. The frequency and duration of application, e.g., topical administration, may vary from person to person. A significant reduction in the oily appearance of skin or hair can occur after 1 or more weeks, e.g., after 1, 2, 3, 4, 5, 6, 7, 8 or more weeks, of administration. In some embodiments, the method includes administering the composition containing acetyl hexapeptide-8, RT001, Vial ox^®, Leuphasyl^®, Syn^®-Ake, or any combination thereof for a length of time such that the appearance of sebum production is reduced, decreased or minimized compared to before the initial administration.

[0048] The compound of the present invention may be administered by a variety of routes. It has been shown to be effective if administered topically. The compounds may also be administered parenterally (i.e., subcutaneously, intravenously, intramuscularly, intraperitoneally, or intrathecally), rectally, or orally. [0049] In some embodiments, the peptide, such as acetyl hexapeptide-8, RT001, Vial ox^®, Leuphasyl^®, Syn^®-Ake, or any combination thereof is administered topically. Topical administration is especially appropriate for acne, seborrhea, and for dermatological and cosmetic indications. The compound can be applied to those areas of the skin afflicted with excess sebum production, such as the face, neck, hair and scalp. For prophylactic treatment, the peptide-containing composition can be administered to one or more sites on the skin that may exhibit increased sebum levels. The topical formulation, dependent on its nature, can be simply applied with a finger or through incorporation in a suitable substrate such as a suitable fabric. In some embodiments, the composition can be used for localized topical application. The composition can be applied to a specific localized area of the skin to target a specific skin condition. The composition can be administered to the skin surface of any part of the body including, but not limited to, the face, neck, scalp, arms, chest, buttocks, abdomen, and legs.

[0050] The dose will vary, but as a general guideline, the compound can be present in a dermatologically or cosmetically acceptable carrier in an amount of from about 5% to about 20% by weight of the total composition, e.g., about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%), about 17%, about 18%>, about 19%, about 20% by weight. In some embodiments, the dermatological or cosmetic preparation can be applied to the affected area when needed, such as upon the appearance of oily skin, greasy hair, or acne associated blackheads, whiteheads, pimples, microcomedones, comedones, papules, pustules, nodules, large papules, or scarring.

[0051] The term "dermatologically acceptable carrier" refers to a carrier which may be applied to the skin, hair or scalp, and which will allow the drug to diffuse to the site of action (e.g., the sebaceous glands, the sebocytes and/or the acinar cells). The term "cosmetically acceptable carrier" refers to a carrier that provides a composition with particular tactile properties which feel pleasant on the skin or hair (e.g., compositions that are not too watery or greasy, compositions that have a silky texture, compositions that are non-tacky or sticky, etc.). A cosmetically acceptable carrier can be suitable for the application or spreading of a composition onto the surface of skin or hair.

[0052] The compositions can include a cosmetically acceptable carrier to act as a diluent, dispersant or carrier for the active ingredients, so as to facilitate its distribution and uptake when the composition is applied to the skin. Vehicles can include water, liquid or solid emollients, solvents, humectants, thickeners, powders, and perfumes, some of which have been described above. For instance, a suitable carrier may include, for example, glycerin, butylene glycol, propylene glycol, water, various oils (e.g., jojoba, sweet almond, soybean, sunflower, apricot, etc.), and the like.

[0053] Alternatively, the compositions can be applied on skin directly without any other preparation. In some embodiments, the compositions can be applied to the skin after the skin is thoroughly cleaned and dried prior to application of the peptide containing composition.

[0054] In some embodiments, the methods of the present invention can also include applying an additional sebum control agent, such as but not limited to, capryloyl glycine, cinnamomum zeylanicum bark extract and/or sarcosine.

C. Conditions associated with sebum overproduction [0055] Provided herein are methods for preventing, arresting, reversing, decreasing, reducing, diminishing, or inhibiting sebum production (e.g., abnormal sebum production or excessive sebum production) in a subject in need thereof. In some embodiments, the method can be used to reduce the amount of sebum on oily skin or on skin having a shiny appearance. In other embodiments, the method can be used to reduce the amount of sebum on oily (greasy) hair or on hair having a shiny (greasy) appearance.

[0056] In some embodiments, the subject has a baseline sebum excretion rate (SER) of 40 μg/cm²/min or higher, as determined using a Sebumeter^® (Courage and Khazaka, Cologne, Germany) or an equivalent device or method. The baseline facial SER can be obtained by measuring the SER for at least two facial zones, such as the right and left forehead, and/or right and left cheek, and averaged over the measured areas. Alternatively, the baseline facial SER can be determined for one facial zone, such as the left forehead, right forehead, left cheek, right cheek, nose, chin, scalp and the like. In some cases, the subject's facial SER is at least 40 μg/cm 2 /min, 50 μg/cm 2 /min, 60 μg/cm 2 /min, 70 μg/cm 2 /min, 80 μg/cm 2 /min, 90 μg/cm 2 /min, 100 μg/cm 2 /min, 110 μg/cm 2 /min, 120 μg/cm 2 /min, 130 μg/cm 2 /min, 140 μg/cm 2 /min, 150 μg/cm 2 /min, 160 μg/cm 2 /min, 170 μg/cm 2 /min, 180 μg/cm 2 /min, or higher. In other cases, the subject's baseline SER is 40 μg/cm²/min or less, e.g., 40 μg/cm²/min, 30 μg/cm²/min, 20 μg/cm²/min, 10 μg/cm²/min_J or less. The sebum excretion rate can be measured at the skin surface of any part of the body including, but not limited to, the face, neck, scalp, arms, chest, buttocks, abdomen, and legs. [0057] In some embodiments, a subject with a baseline SER of 40 μg/cm²/min or higher, e.g., 40 μg/cm 2 /min, 50 μg/cm 2 /min, 60 μg/cm 2 /min, 70 μg/cm 2 /min, 80 μg/cm 2 /min, 90 μg/cm 2 /min, 100 μg/cm 2 /min, 110 μg/cm 2 /min, 120 μ /οηι 2 /min, 130 μg/cm 2 /min, 140 μ /οηι 2 /min, 150 μ§/αη 2 /min, 160 μg/cm 2 /min, 170 μ /^ 2 /min, 180 μg/cm 2 /min, or higher is selected to be administered the composition comprising one or more peptides that modulate neurotransmitter release. For instance, a subject with a facial baseline SER of 40 μg/cm 2 /min, 50 μg/cm 2 /min, 60 μg/cm 2 /min, 70 μg/cm 2 /min, 80 μg/cm 2 /min, 90 μg/cm 2 /min, 100 μg/cm 2 /min, 110 μg/cm 2 /min, 120 μg/cm 2 /min, 130 μg/cm 2 /min, 140 μg/cm 2 /min, 150 μg/cm 2 /min, 160 μg/cm 2 /min, 170 μg/cm 2 /min, 180 μg/cm 2 /min, or higher can apply any of the compositions disclosed herein to the face to reduce sebum levels in the skin. The subject may have normal skin, normal to oily skin, oily skin, or a combination thereof. The subject may also have a disorder or condition characterized by higher than normal sebum levels.

[0058] Disorders or conditions associated with overproduction of sebum by sebaceous glands can be treated with the methods and compositions provided herein. Non-limiting examples of such disorders or conditions include acne vulgaris, inflammatory acne, comedonal acne, papulopustular acne, nodular acne, acne conglobate, exogenous acne, seborrhea, seborrheic dermatitis, sebopsoriasis, sebaceous hyperplasia, sebaceous cysts, hyperseborrhea, sebaceous carcinoma, acne conglobate, or any combination thereof. Disorders that can be treated using the composition described herein can be directly or indirectly due to sebum production, sebum secretion, sebocyte proliferation, sebocyte growth, sebocyte maturation, sebum synthesis, sebum turnover, abnormal sebum composition, and the like. The peptide-containing composition pf the present disclosure can be used to prevent or treat one or more of the conditions described above.

[0059] In some embodiments, the subject has acne. In some cases, the subject has mild acne vulgaris or moderate to severe acne vulgaris. In other cases, the subject has grade 1 (almost clear acne), grade 2 (mild acne), grade 3 (moderate acne), or grade 4 (severe acne) acne on the Investigator's Global Assessment (IGA).

D. Pharmaceutical compositions

[0060] If desired, the peptide compounds can be administered directly without any carrier. However, to ease administration, they will typically be formulated into pharmaceutical carriers. [0061] The peptide compound can be incorporated into formulations suitable for topical administration. Any of the topical formulations known in the art may be used. Examples of such topical formulations include lotions, sprays, creams, ointments, salves, gels, etc. Actual methods for preparing topical formulations are known or apparent to those skilled in the art, and are described in detail in Remington's Pharmaceutical Sciences, 1990 (supra); and Pharmaceutical Dosage Forms and Drug Delivery Systems, 6th ed., Williams & Wilkins (1995).

[0062] In some embodiments, the topical formulations may be in the form of a homogeneous phase formulation or in the form of an emulsion or microemulsion including, but not limited to, oil-in-water, water-in-oil and multiple including triple, phase emulsions. These emulsions can cover a broad range of consistencies including thin lotions (which can also be suitable for spray or aerosol delivery), creamy lotions, light creams and heavy creams. Other suitable topical carriers include anhydrous liquid solvents such as oil and alcohol; aqueous-based single phase liquid solvent {e.g., hydro-alcoholic solvent system); anhydrous solid and semisolid (such as gel and stick); and aqueous based gel and mousse system.

[0063] Optionally, the composition may additionally include one or more anesthetics, anti- allergenics, anti-irritants, antifungal agents, anti-microbial agents, anti-inflammatory agents, antiseptics, chelating agents, colorants, whitening or depigmenting agents, exfoliating agents, emollients, emulsifiers, film formers, fragrances, humectants, insect repellents, lubricants, moisturizers, pharmaceutical agents, photostabilizing agents, vitamins, preservatives, perfumes, plant extracts, essential oils, mineral salts, cell extracts, marine extracts, skin protectants, skin penetration enhancers, skin conditioners, sunscreens, stabilizers, surfactants, thickeners, viscosity modifiers, pigments or dyes, anti-wrinkle agents, anti-aging agents, anti- free radical agents, cleansers, or any combinations thereof. In some embodiments, a pharmaceutically or cosmetically acceptable vehicle may also be included in the composition. Non-limiting examples of cosmetically acceptable vehicles include water, C₁-C₄ alcohols, fatty alcohols, fatty ethers, fatty esters, glycerin, glycols, vegetable oils, mineral oils, lecithin, hydrogenated lecithin, liposomes, laminar lipid materials, phospholipids, polyglycols, polyols, propyl alcohol, silicone oils, vegetable oil, or any combinations thereof. [0064] Peptide compounds of the present invention can be added to dermatological or cosmetic compositions. Non-limiting examples of cosmetic compositions include sunscreen products, sunless skin tanning products, hair products, e.g., shampoos and conditioners, moisturizing creams, serums, skin benefit creams and lotions, softeners, day lotions, gels, ointments, foundations, night creams, eyeshadows, eyeliners, cheek colors, cleansers, toners, masks, or other known cosmetic products or applications. In some embodiments, the compositions of the present invention include additional cosmetic ingredients. The CTFA International Cosmetic Ingredient Dictionary and Handbook (2004 and 2008 versions) describes a wide variety of non-limiting cosmetic ingredients that can be used. Examples of these ingredient classes include: fragrances (artificial and natural), dyes and color ingredients (e.g., Blue 1, Blue 1 Lake, Red 40, titanium dioxide, D&C blue no. 4, D&C green no. 5, D&C orange no. 4, D&C red no. 17, D&C red no. 33, D&C violet no. 2, D&C yellow no. 10, and D&C yellow no. 1 1), adsorbents, emulsifiers, stabilizers, lubricants, solvents, moisturizers (including, e.g., emollients, humectants, film formers, occlusive agents, and agents that affect the natural moisturization mechanisms of the skin), water-repellants, UV absorbers (physical and chemical absorbers such as paraminobenzoic acid ("PABA") and corresponding PABA derivatives, titanium dioxide, zinc oxide, avobenzone, octocrylene, oxybenzone, homosalate, octinocate, octisalate, etc.), essential oils, vitamins (e.g., A, B, C, D, E, and K), trace metals (e.g., zinc, calcium and selenium), anti-irritants (e.g., steroids and non-steroidal anti -inflammatories), botanical extracts (e.g., aloe vera, chamomile, cucumber extract, ginkgo biloba, ginseng, and rosemary), anti-mi crobial agents, antioxidants (e.g., BHT and tocopherol), chelating agents (e.g., disodium EDTA and tetrasodium EDTA), preservatives (e.g., methylparaben and propylparaben), pH adjusters (e.g., sodium hydroxide and citric acid), absorbents (e.g., aluminum starch octenyl succinate, kaolin, corn starch, oat starch, cyclodextrin, talc, and zeolite), skin bleaching and lightening agents (e.g., hydroquinone and niacinamide lactate), humectants (e.g., glycerin, propylene glycol, butylene glycol, pentylene glycol, sorbitol, urea, and mannitol), exfoliants (e.g., alpha- hydroxyacids, and beta-hydroxyacids such as lactic acid, glycolic acid, and salicylic acid; and salts thereof) waterproofing agents (e.g., magnesium/aluminum hydroxide stearate), skin conditioning agents (e.g., aloe extracts, allantoin, bisabolol, ceramides, dimethicone, hyaluronic acid, and dipotassium glycyrrhizate), and thickening agents (e.g., substances which that can increase the viscosity of a composition such as carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers, polysaccharides, and gums).

[0065] For oral administration, the peptide compounds can be formulated into solid or liquid preparations such as capsules, pills, tablets, lozenges, melts, powders, suspensions, or emulsions. Solid unit dosage forms can be capsules of the ordinary gelatin type containing, for example, surfactants, lubricants and inert fillers such as lactose, sucrose, and cornstarch or they can be sustained release preparations.

[0066] In some embodiments, the compounds can be tableted with conventional tablet bases such as lactose, sucrose, and cornstarch in combination with binders, such as acacia, cornstarch, or gelatin, disintegrating agents such as potato starch or alginic acid, and a lubricant such as stearic acid or magnesium stearate. Liquid preparations are prepared by dissolving the active ingredient in an aqueous or non-aqueous pharmaceutically acceptable solvent, which may also contain suspending agents, sweetening agents, flavoring agents, and preservative agents as are known in the art. [0067] For parenteral administration the peptide compounds may be dissolved in a physiologically acceptable pharmaceutical carrier and administered as either a solution or a suspension. Exemplary suitable pharmaceutical carriers are water, saline, dextrose solutions, fructose solutions, ethanol, or oils of animal, vegetative, or synthetic origin. The pharmaceutical carrier may also contain preservatives, buffers, etc., as are known in the art. E. Assaying sebum production

[0068] In particular embodiments, the level of sebum production by an individual can be measured using commercially available sebutape or by means of a sebumeter.

[0069] Sebutape is a microporous patch available from CeDerm Corporation. Sebutape detects sebum production without the use of any solvents, powders, or chemicals. The microporous patch acts as a passive collector of sebum. Gradual displacement of air in the pores of the patch changes the patches appearance. The sebum filled pores in the patch do not scatter light and thus appear transparent. The size of the transparent area is a measure of the amount of sebum collected. Patches can be placed on a dark background storage card for evaluation by eye or by computer imaging (Eisner (1995) in "BIOENGINEERING OF THE SKIN: METHODS AND INSTRUMENTATION," Berardesca et al, eds., 81-89, CRC Press, Boca Raton, Fla.).

[0070] Sebum production can also be measured by means of a device referred to in the art as a sebumeter, for example, a model SM810 PC sebumeter, available from Courage & Khazaka (Koln, Germany). A sebumeter measures the content of sebum in the stratum comeum of skin, the values of which are expressed in micrograms/cm² or micrograms/cm²/minute. The sebumeter can be fitted with a manual data collector which has a band designed to absorb skin sebum. The band is 0.1 mm thick and has a 64 mm² contact surface. The higher the amount of lipids present in the band, the higher the film transparency. The numeric values shown on the display are directly proportional to the band transparency and thereby to the amount of lipids present in the band itself (Eisner (1995), supra, and Clarys and Barel (1995) Quantitative Evaluation of Skin Surface Lipids, CLINICS IN DERMATOLOGY 13 : 307-321).

[0071] Any method known to one of ordinary skill in the art can be used to measure or determine whether the compositions provided herein can modulate sebum production or secretion. For instance, Luderschmidt et al. {Arch Derm Res, 258: 185-191 (1977)) describes an animal model for testing dermatological compounds on the lipid production of sebaceous glands. The method includes treating the ear of Syrian hamster with a test compound and measuring the lipid content of the treated tissue using HPLC analysis. Detailed descriptions of this assay method are found in, e.g. , U. S. Patent Application Publication No. 2013/0178446. [0072] In some embodiments, administration of the peptide containing composition reduces a subject's SER by at least 5%, e.g. , 5%, 6%, 7%, 8%, 9%, 10%, 1 1%, 12%, 13%, 14%, 15%, 16%), 17%), 18%), 19%), 20%) or more from baseline after at least two weeks, e.g. , 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 1 1 months, 1 year or more of treatment. In some cases, an at least 20% reduction of SER is achieved over at least two weeks, e.g., 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 1 1 months, 1 year or more of treatment.

F. Kits

[0073] Kits are also contemplated as being used in certain aspects of the present invention. For instance, a composition of the present invention can be included in a kit. The composition can include a peptide disclosed herein formulated as a liquid, solution, suspension, cream, lotion, moisturizer, ointment, gel, foam or solid. In some embodiments, the kit includes the peptide and a cosmetic or dermatological agent such as a lotion, cream, ointment, serum, sunscreen, anti-acne medication, shampoo, conditioner, cleanser, toner, mask, skin softener, foundation, night cream, sunless tanning product, hair product, skin benefit product, skin protectant, or other cosmetic or dermatological agent. In some cases, the peptide is present in an amount that is about 5% to about 20% by weight of the total weight of the composition or formulation of the kit.

[0074] A kit can include a container. Containers can include a bottle, a metal tube, a laminate tube, a plastic tube, a dispenser, a pressurized container, a barrier container, a package, a compartment, a compact container, or other types of containers such as injection or blow-molded plastic containers into which the dispersions or compositions or desired bottles, dispensers, or packages are retained.

[0075] The containers can dispense a pre-determined amount of a composition. In other embodiments, the container can be squeezed (e.g., metal, laminate, or plastic tube) to dispense a desired amount of the composition. The composition can be dispensed as a spray, an aerosol, a liquid, a fluid, or a semi-solid. The containers can have spray, pump, or squeeze mechanisms. A kit can also include instructions for using the kit and/or compositions. Instructions can include an explanation of how to apply, use, and maintain the compositions.

IV. EXAMPLES [0076] The following examples are offered to illustrate, but not to limit, the claimed invention.

Example 1: Reduction of lipid production by sebocytes after treatment with acetyl hexapeptide-8 (Argireline^®).

Background

[0077] Human sebaceous glands express nicotinic acetylcholine (Ach) receptors, and Ach can increase sebaceous lipid synthesis in vivo. Argireline^® (acetyl hexapeptide-8; AH8) is a synthetic peptide with botulinum-like properties. It is structurally patterned from the N- terminal end of the SNAP-25 proteins and inhibits Ach docking by preventing the formation of the SNARE complex in nerve terminals. Intradermal botulinum injection has shown promising results for the treatment of acne vulgaris, a condition with excessive sebum production. However, it is not known if Argireline^® has a direct effect on sebocytes. The aim of this study is to examine whether Argireline^® can directly alter sebocytes lipid synthesis and cell proliferation, and attempt to examine the mechanism at which it regulates sterol biosynthesis. Materials and Methods [0078] SEB-1 human sebocytes were treated with increasing concentrations of Argireline peptide solution (0.00005% or 1 : 1000, 0.0005% or 1 : 100, 0.005% or 1 : 10, and 0.025% or 1 :2) and incubated for 48 hours. PBS was used as negative control treatments. Nile red was used for lipid content measurement and normalized to cell count using DAPI. [0079] Sebocytes treated with 0.0005%> Argireline^® solution were lysed for protein collection and western blot analysis for expression of sterol regulatory element binding protein-1 (SREBP-1), a key regulator of sterol biosynthesis. GAPDH expression was used as an internal reference.

[0080] Cell proliferation was measured using the MTT colorimetric assay. SEB-1 cells were passed into wells of a 96-well plate at 5,000 cells per well and incubated for 24 hours. Cells were then exposed to treatments in sebocyte cell culture media with (0.00005%), 0.0005%, 0.005% and 0.025%) Argireline^® peptide solution (Lipotec, Spain) and incubated for 48 hours. The MTT assay was conducted per manufacturer's protocol (Sigma- Aldrich, St. Louis, MO). Results

[0081] Sebocyte lipid production was significantly decreased after Argireline^® treatment in a dose-dependent manner, when compared to control treatment (FIG. 1, p<0.05 at 0.00005%), p = 0.09 at 0.0005%, p<0.05 at 0.005% and p<0.001 at 0.025% Argireline^®). Sebocyte proliferation was unchanged at the Argireline^® concentrations of 0.00005%), 0.0005%) and 0.005% (FIG. 2). At an Argireline^® concentration of 0.025% (1 :2), sebocyte proliferation was markedly decreased compared to untreated control sebocytes (FIG. 2). Sebocytes exhibited no significant difference in the expression of SREBP-1 (a lipid synthesis transcription factor) after 0.0005% Argireline^® treatment.

Conclusion

[0082] Argireline^® inhibits sebaceous production and/or accumulation of lipid in vitro. Sebocyte proliferation was unchanged at the lower concentrations of Argireline^® tested. SREBP-1 expression was also unchanged following 0.0005%> Argireline^® treatment. The data in this example clearly demonstrate that Argireline^® can be used as an agent to reduce or inhibit sebocyte lipid production and/or accumulation. As such, Argireline^® can be used to treat or prevent conditions associated with sebum overproduction, such as acne and seborrhea.

Example 2: Reduction of sebum excretion rate in patients treated with Argireline^®. [0083] The study described herein examined the effects of Argireline on 12 healthy adult volunteers. Subjects had a range of baseline sebum excretion rates, ranging from low to high rates. None of the subjects were taking a medication that affects sebum levels, and none exhibited a facial skin condition such as acne, dermatitis, psoriasis, rosacea, and the like. [0084] Each subject was given blindly labeled tubes containing either an Argireline^® treatment (10% (by weight) solution of Argireline^® in facial moisturizing lotion (Cetaphil^®)) or a vehicle treatment (facial moisturizing lotion (Cetaphil^®) alone). They were instructed to apply either treatment to the right or left side once a day. In other words, for each subject one side of the face was treated with Argireline^® and the other side was treated with vehicle. The subjects were assessed 2 weeks after the initial application (week 2 follow-up). The facial sebum excretion rate (SER) was evaluated using a Sebumeter^® (Courage-Khazaka, Koln, Germany). Topical administration of Argireline^® reduced the average SER by 9% compared to vehicle in subjects with a baseline SER of greater than or equal to 40 μg/cm²/minute (n=7, p-value=0.016). The results of the study demonstrate that application of Argireline^® can decrease sebum production, sebum excretion (sebum secretion) and/or the amount of sebum on the skin.

[0085] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, one of skill in the art will appreciate that certain changes and modifications may be practiced within the scope of the appended claims. In addition, each reference provided herein is incorporated by reference in its entirety to the same extent as if each reference was individually incorporated by reference.

INFORMAL SEQUENCE LISTING

SEQIDNO:l

Argireline^®

Ac-Glu-Glu-Met-Gln-Arg-Arg-NFL

Claims

WHAT IS CLAIMED IS: 1. A method for reducing sebum production and/or excretion in the skin of a subject in need thereof, the method comprising administering to the subject an effective amount of a composition comprising a peptide that modulates neurotransmitter release, an equivalent thereof, a variant thereof, or a derivative thereof, and a pharmaceutically acceptable carrier to decrease sebum in the subject's skin.

2. The method of claim 1, wherein the peptide that modulates neurotransmitter release is at about 5% to about 20% by weight of the total composition.

3. The method of claim 1 or 2, wherein the peptide that modulates neurotransmitter release is selected from the group consisting of acetyl hexapeptide-8, RT001, Vial ox^®, Leuphasyl^®, Syn^®-Ake, and any combination thereof.

4. The method of any one of claims 1 to 3, wherein the composition is administered topically.

5. The method of any one of claims 1 to 4, wherein the composition is a formulation selected from the group consisting of a liquid, aqueous solution, suspension, cream, lotion, ointment, gel, foam and solid.

6. The method of any one of claims 1 to 5, wherein the pharmaceutically acceptable carrier is a dermatological acceptable carrier or a cosmetically acceptable carrier.

7. The method of any one of claims 1 to 6, wherein the subject has no symptoms of a sebum overproduction condition.

8. The method of any one of claims 1 to 6, wherein the subject has at least one symptom of a sebum overproduction condition.

9. The method of claim 8, wherein the at least one symptom is selected from the group consisting of oily skin, combination oily to dry skin, dandruff, acne, greasy hair, and a combination thereof.

10. The method of any one of claims 7 to 9, wherein the sebum overproduction condition is selected from the group consisting of acne vulgaris, seborrhea, seborrheic dermatitis, sebopsoriasis, sebaceous hyperplasia, sebaceous cysts, hyperseborrhea, sebaceous carcinoma, acne conglobate, and a combination thereof.

11. The method of any one of claims 1 to 10, wherein reducing sebum production and/or excretion comprises an at least about 5% reduction in sebum after administration of the composition compared to before administration.

12. The method of any one of claims 1 to 10, wherein reducing sebum production and/or excretion comprises an at least about 10% reduction in sebum after administration the composition compared to before administration.

13. A method for treating a sebum overproduction condition in a subject in need thereof, the method comprising administering to the subject an effective amount of a composition comprising a peptide that modulates neurotransmitter release, an equivalent thereof, a variant thereof, or a derivative thereof, and a pharmaceutically acceptable carrier to decrease sebum in the subject's skin.

14. The method of claim 13, wherein the peptide that modulates neurotransmitter release is at about 5% to about 20% by weight of the total composition.

15. The method of claim 13 or 14, wherein the peptide that modulates neurotransmitter release is selected from the group consisting of acetyl hexapeptide-8, RT001, Vial ox^®, Leuphasyl^®, Syn^®-Ake, and any combination thereof.

16. The method of any one of claims 13 to 15, wherein the composition is administered topically.

17. The method of any one of claims 13 to 16, wherein the composition is a formulation selected from the group consisting of a liquid, aqueous solution, suspension, cream, lotion, ointment, gel, foam and solid.

18. The method of any one of claims 13 to 17, wherein the pharmaceutically acceptable carrier is a dermatological acceptable carrier or a cosmetically acceptable carrier.

19. The method of any one of claims 13 to 18, wherein the sebum overproduction condition is selected from the group consisting of acne vulgaris, seborrhea, seborrheic dermatitis, sebopsoriasis, sebaceous hyperplasia, sebaceous cysts, hyperseborrhea, sebaceous carcinoma, acne conglobate, and a combination thereof.

20. The method of any one of claims 13 to 19, wherein the method alleviates at least one symptom of the sebum overproduction condition.

21. The method of claim 20, wherein alleviating the at least one symptom of the sebum overproduction condition comprises reducing the appearance of oily skin, combination oily to dry skin, dandruff, acne, greasy hair, or a combination thereof.

22. A method for preventing excessive sebum production and/or excretion in a subject, the method comprising administering to the subject an effective amount of a composition comprising a peptide that modulates neurotransmitter release, an equivalent thereof, a variant thereof, or a derivative thereof, and a pharmaceutically acceptable carrier to prevent excessive sebum production and/or excretion in the subject's skin.

23. The method of claim 22, wherein the peptide that modulates neurotransmitter release is at about 5% to about 20% by weight of the total composition.

24. The method of claim 22 or 23, wherein the peptide that modulates neurotransmitter release is selected from the group consisting of acetyl hexapeptide-8, RT001, Vial ox^®, Leuphasyl^®, Syn^®-Ake, and any combination thereof.

25. The method of any one of claims 22 to 24, wherein the composition is administered topically.

26. The method of any one of claims 22 to 25, wherein the composition is a formulation selected from the group consisting of a liquid, aqueous solution, suspension, cream, lotion, ointment, gel, foam and solid.

27. The method of any one of claims 22 to 26, wherein preventing excessive sebum production and/or excretion comprises an at least about 5% reduction in sebum production and/or excretion after administration of the composition compared to before administration.

28. The method of any one of claims 22 to 26, wherein preventing excessive sebum production and/or excretion comprises an at least about 10% reduction in sebum production and/or excretion after administration of the composition compared to before administration.

29. The method of any one of claims 22 to 28, wherein the subject does not suffer from excessive sebum overproduction.

30. A kit comprising a first composition comprising a peptide that modulates neurotransmitter release, an equivalent thereof, a variant thereof, or a derivative thereof, and a pharmaceutically acceptable carrier; and a second composition comprising a skin care composition or a hair care composition.

31. The kit of claim 30, wherein the peptide that modulates neurotransmitter release is at about 5% to about 20% by weight of the total composition.

32. The kit of claim 30 or 31, wherein the peptide that modulates neurotransmitter release is selected from the group consisting of acetyl hexapeptide-8, RT001, Vial ox^®, Leuphasyl^®, Syn^®-Ake, and any combination thereof.

33. The kit of any one of claims 30 to 32, wherein the skin care composition is selected from the group consisting of a skin cleanser, moisturizer, serum, lotion, anti-acne medication, anti-aging cream, sunscreen, and a combination thereof.

34. The kit of any one of claims 30 to 32, wherein the hair care composition is a shampoo.