WO1996023490A1 - Formulations et procedes permettant de reduire l'irritation cutanee - Google Patents
Formulations et procedes permettant de reduire l'irritation cutanee Download PDFInfo
- Publication number
- WO1996023490A1 WO1996023490A1 PCT/US1996/001289 US9601289W WO9623490A1 WO 1996023490 A1 WO1996023490 A1 WO 1996023490A1 US 9601289 W US9601289 W US 9601289W WO 9623490 A1 WO9623490 A1 WO 9623490A1
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- WIPO (PCT)
- Prior art keywords
- composition
- irritant
- skin
- irritation
- skin irritation
- Prior art date
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Classifications
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Definitions
- skin Many substances are applied topically to the skin or mucous membranes of humans or animals (hereafter “skin”) in order to alter the subject's appearance, to protect the subject from the environment, or to produce a biological change in the skin or other tissue for therapeutic, preventive or cosmetic purposes.
- skin may generically be termed “topical products” and include such substances as cosmetics, over-the-counter and prescription topical drugs, and a variety of other products such as soaps and detergents.
- Topical products occur in a variety of forms, including solids, liquids, suspensions, semisolids (such as creams, gels, pastes or “sticks”), powders or finely dispersed liquids such as sprays or mists.
- topical products commonly classified as “cosmetics” include skin care products such as creams, lotions, moisturizers and “treatment cosmetics” such as exfoliants and/or skin cell renewal agents; fragrances such as perfumes and colognes, and deodorants; shaving-related products such as creams, "bracers” and aftershaves; depilatories and other hair removal products; skin cleansers, toners and astringents; pre- moistened wipes and washcloths; tanning lotions and sunscreens; bath products such as oils; eye care products such as eye lotions and makeup removers; foot care products such as powders and sprays; skin colorant and make-up products such as foundations, blushes, rouges, eye shadows and liners, lip colors and mascaras;
- shampoos, conditioners, colorants, dyes, bleaches, straighteners, and permanent wave products baby products such as baby lotions, oils, shampoos, powders and wet wipes; feminine hygiene products such as deodorants and douches; skin or facial peels applied by dermatologists or cosmeticians; and others.
- topical drugs are many and varied, and include over-the-counter and/or prescription products such as antiperspirants, insect repellents, ocular drugs and eye care products, both therapeutic and non- therapeutic, including eyedrops, rewetting drops, saline solutions and contact lens solutions, sunscreens and sunburn treatments, anti-acne agents, antibiotics, topical respiratory agents, therapeutic retinoids, anti-dandruff agents, external analgesics such as capsaicin products, topical contraceptives, topical drug delivery systems, gastrointestinal agents, suppositories and enemas, hemorrhoid treatments, reproductive tract agents such as vaginal treatments, lozenges, and many other products with therapeutic or other effects, for use on skin or mucous membranes, including ocular, nasal, otic, laryngopharyngeal, and pulmonary membranes.
- over-the-counter and/or prescription products such as antiperspirants, insect repellents, ocular drugs and eye care products, both therapeutic and non
- topical products include hand, facial and body soaps and detergents and other forms of skin cleansers, as well as household detergents and many other household products such as solvents, propellants, polishes, lubricants, adhesives, waxes and others which are either applied topically or are topically exposed to the body during normal use.
- topical products contain chemicals which may produce "irritation,” including various mflammation symptoms, when applied to the skin or mucosa ("skin").
- the present invention is directed in part to compositions and methods for inhibiting the irritation associated with such topical products.
- the occurrence, frequency and nature of topical-product-induced irritation often varies from user to user.
- the severity of irritation to the susceptible user may range from subclinical to mild to severe.
- Typical symptoms of "irritation” include itching (pruritus), stinging, burning, tingling, "tightness,” erythema (redness) or edema (swelling).
- the irritation response may be due to the direct effect on the skin of certain topical product chemicals or to a response by the immune system directed toward the chemicals alone or in combination with skin components (e.g. allergic dermatitis).
- the sensation of itch is one of the most common skin problems experienced by humans and animals. Itch can be defined as a sensation which provokes the desire to scratch the site from which the sensation originates. All skin contains sensory nerves which can transmit itch or other similar sensory impulses in response to chemical irritation, environmental exposure or disease processes. Although the precise population of itch-producing nerves have not been identified, the thinnest unmyelinated nerve population, termed type C nociceptive neurons are thought to be the most important in producing the sensation. Itch: Mechanisms and Management of Pruritus. Jeffrey D. Bernhard, ed. (McGraw-Hill, Inc., San Francisco, 1994), pp. 1-22.
- the itch-producing nerves of the skin can be considered to be a "final common pathway" for the many irritating conditions which are ultimately sensed as itch, including chemical exposure, environmental exposure (such as that which produces dry, itchy skin) and disease processes such as atopic dermatitis. Many chemical substances are able to produce itch when topically applied to the skin. No matter what the ultimate cause of itch, the sensation experienced is the same and provokes the desire to scratch.
- Topical product active ingredients including chemicals that may also be classified as drugs, produce irritation when applied to the skin or mucous membranes. These include, but are not limited to, such ingredients as exfoliants and skin cell renewal agents, anti-acne drugs, antiperspirant compounds, antihistamines, anti-inflammatory agents, skin protective agents, insect repellent chemicals, sunscreens, nasal and respiratory medications in the form of mists or sprays, and many others. Where more than one chemical irritant is present, their irritating effects may be additive. Furthermore, chemical ingredients may react with one another, or in the environment of the skin, to form new chemicals which are irritating. The vehicles in which the active drug ingredients are formulated may also produce irritation in sensitive people, especially in the case of drugs such as topical corticosteroids.
- retinoids e.g. tretinoin, retinol and retinal
- carboxylic acids including ⁇ -hydroxy acids (e.g. lactic acid, glycolic acid), ⁇ -hydroxy acids (e.g.
- salicylic acid ⁇ -keto acids, acetic acid and trichloroacetic acid, l-pyrrolidone-5-carboxylic acid, capryloyl salicylic acid, ⁇ - hydroxy decanoic acid, ⁇ -hydroxy octanoic acid, gluconolactone, methoxypropyl gluconamide, oxalic acid, malic acid, tartaric acid, mandelic acid, benzylic acid, gluconic acid, benzoyl peroxide and phenol, among others, may cause the skin to become more sensitive to irritation triggered by other topically-applied chemicals such as moisturizers, sunscreens, fragrances, preservatives, surfactants (e.g.
- Exfoliants and other ingredients may also increase the skin's sensitivity to environmental conditions such as sunlight, wind, cold temperature and dry air, or to chemical agents such as allergens, or may exacerbate the irritation attributable to a pre-existing skin disease.
- environmental influences may themselves increase the skin's sensitivity to chemicals in topical products by reducing the epidermal skin's "barrier function.”
- the barrier function acts to minimize absorption or passage of potentially irritating chemicals through the outer "dead" cell layer of epidermal skin into the living skin tissue. Extremes of humidity, for example, can greatly increase irritation from topically-applied products.
- winter itch A very common condition due to low humidity is termed "winter itch" in which the very low humidity characteristics of many cold climates (particularly when accompanied by indoor heating) or long exposure to refrigerated air from air conditioners in the summer produces itchy skin — especially in older people — which can exacerbate the irritating effects of topical products.
- soaps, detergents, cleansing products, shaving creams, alcohol and other products which remove some of the skin's protective lipids and/or secretions may increase the skin's permeability and sensitivity to topically-applied chemicals which would otherwise not produce irritation.
- Normal processes such as sweating may also increase the ability of irritant materials, such as antiperspirants, deodorants or sunscreens, to penetrate the skin through pores or glands, thus exacerbating the potential for irritation.
- Exposure of the skin to high humidity environments or liquids may also increase the ability of potential irritants to penetrate the skin.
- the skin may become sensitized or inflamed due to infection, shaving abrasion, repeated or excessive washing or bathing, sun exposure, or other mechanical abrasion or injury, resulting in sensory irritation responses upon subsequent application of underarm deodorants, after-shaves or other topical products.
- many people have an inherent sensitivity or genetic predisposition to skin irritants. People with respiratory allergies, for example, tend to have excessively dry skin which facilitates increased absorption of potentially irritating chemicals.
- the excessively dry skin which accompanies atopic dermatitis predisposes patients with this condition to irritation from many topically-applied products.
- Other skin diseases and conditions such as allergic or non-allergic contact dermatitis, asthma (including exercise-mduced asthma as may be precipitated by inhalation of cold or dry air), hay fever, allergic rhinitis, inflammatory bowel disease, psoriasis, eczema, candidiasis, post-herpetic neuralgia, infectious diseases manifested by, for example, sore throat or skin lesions, insect bites and the like produce inherent irritation which may be exacerbated by application of topical products or by exposure to chemical or environmental influences such as allergens, cold air, low humidity and the like. Many other individuals exhibit sensitive skin as a condition that is not related to an identifiable skin disease.
- exfoliants include ⁇ - and ⁇ -hydroxy carboxylic acids such as lactic acid, glycolic acid, salicylic acid and the like, ⁇ -keto acids such as pyruvic acid, as well as assorted compounds such as acetic acid and trichloroacetic acid, l-pyrrolidone-5- carboxylic acid, capryloyl salicylic acid, ⁇ -hydroxy decanoic acid, ⁇ -hydroxy octanoic acid, gluconolactone, methoxypropyl gluconamide, oxalic acid, malic acid, tartaric acid, mandelic acid, benzylic acid, gluconic acid, peroxides, phenols, and skin cell renewal agents such as retinoids.
- Such products are used as exfoliants and/or cell renewal agents to reduce the occurrence or severity of skin wrinkles, particularly facial wrinkles, or as anti-acne, anti-"dry skin” or skin whitening agents.
- the present invention involves the surprising discovery that multiply-protonated organic polyamines (i.e., organic molecules containing two or more protonated amino functional groups), are effective in reducing the incidence and severity of irritation associated with topically applied skin irritants.
- a plurality (two or more) of the amino moities (which may be primary, secondary, tertiary, or quarternary amino functions) are protonated at the particular pH of the topically applied composition or product.
- the mutiply-protonated polyamines of the present invention are amino acids containing a positively-charged nitrogen-containing side chain, and derivatives of these amino acids.
- Amino acids are the chemical units from which proteins are made. "Amino acids” as a class are chemically based upon the so-called “natural” 20 amino acids, which are found in nature. They all have a primary amino function (-NH 2 ) and a carboxylic acid function (-COOH) which are joined to the same carbon atom (- ⁇ -amino acids) or to neighboring carbons (e.g., ⁇ -amino acids). Similar structures in this class include alpha-imino acids (e.g., proline). In addition, analogs and homologs of the natural amino acids (commonly referred to as "unnatural" amino acids, isomers and enantiomers) may also be synthesized. Amino acids and their analogs and homologs may be chemically modified to prepare unique amino acid structures. These modifications include those in which a chemical modification or substitution on the amino, carboxyl or side chain structures (derivatives) alters the amino acid.
- the inventors have discovered that the anti- irritant activity of the compounds of the present invention is maintained even where the polyamine compound possesses, in addition to multiple centers of protonation, a negatively-charged functional group (e.g., HEPES, N-[2- hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid], a common biological buffer which contains, at pH's between about 1 and 7, two protonated amino moieties and one negatively-charged sulfonate functional group).
- HEPES N-[2- hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid]
- a common biological buffer which contains, at pH's between about 1 and 7, two protonated amino moieties and one negatively-charged sulfonate functional group.
- various metal cations are effective at reducing irritation caused by topical application of skin irritants.
- the positive charge(s) on these anti-irritant compounds may reduce irritation by interacting with epidermal or mucosal nerve cells to prevent or counteract the sensation of irritation, and/or by interfering with irritation-inducing components of skin cells that are triggered by the application of the skin irritant.
- the positive charge(s) may alter the ability of skin nerve cells to depolarize or repolarize, as for example, by blocking or interfering with ion channel or pump operation or by altering the transmembranal action potential, or the positive charge(s) may interfere with the transmission of nerve impulses from one nerve cell to another.
- the positive charge(s) on the protonated polyamines may non-specifically bind to cell membranes and contribute to a charge shielding effect, which consequently, alters the ion regulatory activity of the cells.
- Amines particularly amino acids, are widely found in a variety of commercial topical products, especially cosmetics such as skin creams or emollients and hair care products. Small amounts of amino acids are added to these products because of their humectant properties, as they are believed to enhance transdermal penetration of water and other compounds.
- specific forms of some amino acids have been used in topical skin preparations for a variety of applications.
- salts of glutamic acid an amino acid containing an acidic negatively-charged side chain
- Sodium dihydroxyethylglycine has been used in formulating cleansing and disinfecting solutions which are also claimed to reduce pain and itching.
- U.S. Patent No. 4,868,213 (Farrish).
- N-acylates of amino acids and their salts, formed by butyric acid have been used to treat wrinkles of the human skin. See U.S. Patent No. 4,859,653 (Morelle et al.).
- the human skin presents a complex sensory and structural environment.
- the skin contains nerves and highly specific sensory organs that are specialized and disposed so as to differentiate the stimuli leading to such distinct sensations as heat, cold, pressure, pain, itch and the like.
- nerves in the skin are also responsive to native or foreign chemicals such as proteases, prostaglandins, complement-system molecules, allergens, mitogens and the like which may be presented due to tissue injury or environmental exposure.
- Agents which are effective to combat one source of sensory stimulus for example, steroidal agents to treat skin inflammation ⁇ are ineffective against other sensory stimuli such as pressure, heat, or the transitory sting or itch caused by an applied skin care product.
- anesthetic agents which are effective to depress all sensory or even motor activity in a treated region are not desirable if only a single sensation ⁇ for example, a transitory sting or itch — is sought to be eliminated.
- the structural matrix of the epidermal skin affords a "barrier function" which tends to exclude or inhibit the entry of foreign material, including potentially therapeutic agents.
- the present invention provides compositions and methods for reducing specific irritant effects from a variety of sources without negative effects such as caused by the use of anesthetics.
- the present invention is directed to the use of multiply-protonated organic polyamines (organic molecules containing two or more protonated amino functions), preferably, amino acids (and their derivatives) that possess a positively charged nitrogen-containing side chain, as ingredients to provide fast- acting, efficient and safe topical skin anti-irritant effects, and to formulations containing such compounds. It is one object of the present invention to provide ingredients, formulations and methods of use which can suppress skin irritation due to chemical or environmental exposure, or due to tissue inflammation, injury or other skin pathology.
- the invention is particularly useful for preventing, reducing or eliminating the potential irritation caused by topical application of products containing other irritating ingredients, including cosmetics such as, especially, hydroxy acid or other exfoliant containing products, facial peels, shaving products, sunscreen products, deodorants and other cosmetics as described above, as well as topical drug products containing irritating active ingredients or vehicles, and other products such as soaps, detergents, solvents and the like which are either applied topically or are topically exposed to the body during use.
- cosmetics such as, especially, hydroxy acid or other exfoliant containing products, facial peels, shaving products, sunscreen products, deodorants and other cosmetics as described above
- topical drug products containing irritating active ingredients or vehicles and other products such as soaps, detergents, solvents and the like which are either applied topically or are topically exposed to the body during use.
- the invention is also useful for preventing, reducing or eliminating the skin irritation caused by skin diseases or other conditions such as environmental exposure to irritating chemicals or influences such as wind, heat, cold and extremes in humidity, including the intrinsic irritation associated with these conditions as well as such irritation as may be exacerbated by the application of a topical product.
- the polyamine anti-irritants of the invention are included in a suitable topical vehicle at a concentration of about 10 to about 3000 mM, more preferably about 50 to about 2000 rnM, and most preferably about 100 to about 1000 mM.
- one or more of the polyamines of the invention are combined in a topical product formulation further comprising a potentially irritating ingredient, the polyamine(s) being present in a total amount effective to reduce or eliminate irritation due to the irritant ingredient.
- a polyamine anti-irritant component of the present invention is combined in a hydroxy acid or other exfoliant preparation such that the pH of the hydroxy acid preparation is maintained in the range of pH 1-6, and more preferably, in the range of pH 2-4. It will be understood that, where the formulation employs an anhydrous vehicle, the acidity of the formulation may not be expressible in typical pH terms, but that such acidity will manifest itself upon exposure of the formulation to the skin where water is present both intracellularly and extracellularly.
- the compounds of the present invention may be combined in a formulation with other anti-irritants, such as steroidal or non- steroidal anti-inflammatory agents or other materials such as aloe vera, chamomile, ⁇ -bisabolol, Cola nitida extract, green tea extract, tea tree oil, licorice extract, allantoin, urea, caffeine or other xanthines, glycyrrhizic acid and its derivatives, or with other anti-irritant species such as those identified in co- pending U.S. Patent Application Serial Nos.
- steroidal or non- steroidal anti-inflammatory agents such as aloe vera, chamomile, ⁇ -bisabolol, Cola nitida extract, green tea extract, tea tree oil, licorice extract, allantoin, urea, caffeine or other xanthines, glycyrrhizic acid and its derivatives, or with other anti-irritant species such as those identified in
- the invention further provides methods of treating, reducing or eliminating skin irritation comprising the topical application of a formulation comprising an anti-irritant effective amount of one or more polyamines of the invention.
- the formulation may further include one or more potentially irritating components.
- the formulation may be applied separately and prior to application of another product containing a potentially irritating component, or the formulation may be applied alone in order to prevent the development of irritation or to treat a pre-existing irritation attributable to conditions such as skin disease, chemical irritant exposure or environmental exposure.
- aqueous-soluble multiply-protonated polyamines including amino acids (and derivatives thereof) having a positively-charged nitrogen- containing side chain
- Formulations containing such anti-irritant compounds are useful in suppressing a wide range of topical-product-induced irritation responses attributable to exfoliants, sunscreens, retinoids, anti-perspirants, deodorants, anti- acne and other products which contain components potentially capable of causing sensory irritation.
- the compounds of the present invention are useful for preventing or reducing the skin irritation caused by ⁇ - or ⁇ -hydroxy acids, ⁇ -keto acids and other carboxylic acids, as well as retinoids, phenols, peroxides and similar irritants found in over-the-counter topical products for home or cosmetologist use (such as l-pyrrolidone-5-carboxylic acid, capryloyl salicylic acid, ⁇ -hydroxy decanoic acid, ⁇ -hydroxy octanoic acid, gluconolactone, methoxypropyl gluconamide, oxalic acid, malic acid, tartaric acid, mandelic acid, benzylic acid, and gluconic acid), as well as in certain prescription topical drugs containing high (for example, 12% w/w or even higher) dosage forms of such irritants.
- formulations of the invention can also be inhibited by the formulations of the invention.
- formulations containing such compounds are useful in ameliorating irritation in conditions where the skin is inherently hypersensitive to topical products (e.g. dry skin, "winter itch,” and other inflammation or injury conditions) and in ameliorating the irritation due to such conditions even in the absence of other applied topical products.
- the formulations are also useful in treating non-human animal skin irritation, as for example dog or cat irritation and resultant scratching due to fleas or other skin disease or condition.
- An additional benefit of the present anti-irritant compounds and formulations is that they do not have the undesirable anesthetic side-effects exhibited by lidocaine and other similar skin local anesthetics.
- subjects Upon application of a solution of the compound used in the clinical trials described here, subjects typically reported no sensations other than those sensations caused by the vehicle alone, and no lack of normal sensation(s).
- the protonated polyamines of the present invention include straight-chain and branched-chain polyamines, as well as heterocyclic amines.
- the protonated amino moieties of these polyamine molecules may be primary, secondary, tertiary, or quarternary amino functions.
- the polyamine anti-irritant compounds are preferably selected from the group consisting of spermine, spermidine, putrescine, protamine, HEPES, imidazole, and piperazine, since these polyamines possess two or more protonated amino groups under acidic conditions (low pH).
- polyamines of the present invention are amino acids
- they are preferably selected from the group consisting of arginine, lysine, histidine, and ornithine, since these amino acids have, in addition to a positively-charged N- ⁇ amino moiety, a positively-charged side chain amino function at physiological pH and below.
- Arginine, lysine, histidine, and ornithine possess predominantly two positive charges at low pH (pH ⁇ 5), one positive charge on the side chain amine group and another positive charge on the N- ⁇ terminus of the amino acid backbone. It is believed that the multiply-protonated state of these amino acids at low pH contributes to these compounds' anti-irritant properties.
- substituted or otherwise derivatized forms of such amino acids are also within the scope of the present invention.
- derivatized amino acids also include analog forms of the amino acids.
- Preferred substituents include substituents (at either or both of the N- ⁇ - terminus and the C-terminus ends of the amino acid) at the N- ⁇ -terminus of the amino acid of the form RCO- or R-, carboxyl (C)-terminal substituents of the form -NH 2 , -NHNHj , and -NHR, where each R is independently an unsubstituted or substituted alkyl, alkenyl or alkynyl (either unbranched or branched, and preferably from 1 to about 10 carbons), or aryl, alkaryl, aralkyl or cycloalkyl (preferably of from about 3 to 20 carbons), or, in the case of -NR 2 , the R- groups are together a cyclized group forming (in attachment with the
- An amino-terminal acetyl substituent is a particularly preferred substituent for the derivatized amino acid compounds.
- Amidating or esterifying carboxyl- terminal substituents formed from unsubstituted or lower alkyl-substituted amino, or from lower alkoxy or single-ring aryloxy, groups are preferred, and groups of the form -NH 2 , -OCH 3 , -OCH 2 CH 3 are especially preferred.
- Amidating substituents are particularly preferred. Where an amidating group of the structure -NR 2 is to be cyclic in form, the N-morpholino heterocyclic structure is preferred.
- both D- and L- forms of the amino acid anti- irritant compounds of the present invention exhibit irritant reducing activity. It is expected that guanidinium, a triamine side chain constituent of arginine, may also be effective at reducing irritation. Similarly, other isomeric forms, homologs and suitable salts of the amino acid compounds are predicted to be active.
- the anti-irritant topical formulations of the invention comprise a topical vehicle suitable for administration to the animal (particularly human) skin, and an amount of one or more polyamine anti-irritant compounds of the invention effective /23490 PCI7US96/01289
- the anti-irritant topical formulations additionally contain an irritant ingredient(s) that is itself capable of inducing skin irritation, such as symptoms associated with inflammation, as, for example, a cosmetic or skin care product ingredient, or a pharmaceutically active ingredient or drug ingredient.
- the polyamine anti-irritant compounds for use in the anti-irritant formulations of the invention are contained in a topical formulation in a concentration effective to prevent or reduce (hereafter, "inhibit") the skin irritation and/or inflammation (such as inflammation) symptoms that are sought to be eliminated.
- the formulation preferably contains the selected compound in a suitable topical vehicle at a total concentration of about 10 to about 3000 mM, more preferably about 50 to about 2000 mM, and most preferably about 100 to about 1000 mM.
- the appropriate concentration can be achieved using a single polyamine anti- irritant component of the invention, or multiple different such compounds may be combined to yield the total desired concentration. If other anti-irritant components are included in the formulation, then lower concentrations of the compounds of the invention may be utilized.
- Preferred concentrations can also be expressed in weight volume or weight/weight percentage terms which will vary somewhat depending on the density of the vehicle and other components in the formulation.
- the vehicle has a density of 0.93 g/ml (as in a 50:50 [by volume] mixture of 95% ethyl alcohol and water) and the nitrogenous compound is incorporated in the form of histidine (formula weight 155)
- representative molarity concentration values correspond approximately to 100 mM: 0.78% (w/v) 0.83% (w/w)
- compositions are readily formulated and do not leave any significant visible residue when applied to the skin.
- Higher concentration formulations such as saturated pastes or other forms, may also be successfully used, particularly where visible appearance is not a limiting consideration (as in therapeutic applications).
- concentration of the polyamine anti-irritant compound(s) of the invention can readily be employed to optimize the concentration of the polyamine anti-irritant compound(s) of the invention and to ascertain if lower, or higher, concentrations are appropriate for a given formulation or irritation indication.
- concentration may be adjusted to account for the amount of formulation that is typically applied to a given skin area by the user, which will depend to an extent on the physical nature of the topical vehicle (e.g., lotion as compared to liquid spray vehicles).
- the amount of the compound required may be reduced in such cases where the formulation contains a skin penetration-enhancing ingredient or other agent which increases the ability of the compounds to permeate the stratum corneum to their site of anti-irritant activity.
- the formulations of the invention include an amount of polyamine anti-irritant compound (or compounds) capable of inhibiting irritation in susceptible individuals by at least about 20% or more, as measured by a mean reduction in cumulative irritation across a susceptible test population as exemplified in the clinical protocols described below.
- the formulations of the invention include an amount of anti-irritant compound capable of inhibiting irritation by at least about 40% or more in at least about 10% of the susceptible population, as measured by a reduction in cumulative irritation on an individual-by-individual basis (treated vs. control areas). This latter measure of efficacy reflects the fact that the present formulations, similar to many therapeutic products, may in some cases be effective in delivering a significant benefit to some, but not all, of the susceptible population.
- optimum concentration of a compound of the invention may be reduced below (or within) the preferred ranges set forth above if some other anti-irritant component is included in the formulation along with the polyamine anti-irritant compound of the invention.
- lower (e.g. halved) amounts of the anti-irritant species may be used, while still maintaining comparable levels of anti-irritant activity, by further including an approximately equal concentration of, for example, a calcium-channel blocking or regulatory agent, or other anti-irritant agent such as a steroid or non-steroidal anti-inflammatory agent.
- suitable additional anti-irritant ingredients are described in applicants' U.S.
- Patent Application Serial Nos.08/362,100, 08/362,101, 08/362,097, 08/362,055 and 08/362,058 (entitled “Formulations and Methods for Reducing Skin Irritation"), filed December 21, 1994 and incorporated by reference in their entirety.
- Other anti- irritant ingredients such as aloe vera, chamomile, ⁇ -bisabolol, Cola nitida extract, green tea extract, tea tree oil, licorice extract, allantoin, urea, caffeine or other xanthines, and glycyrrhizic acid and its derivatives, may also be beneficially incorporated into the formulations of the invention in order further to inhibit irritation effects or symptoms.
- the compounds of the invention are typically incorporated into the present formulations by mixing an appropriate amount of a sufficiently soluble form of the selected compound into the chosen formulation vehicle at an appropriate pH such that the polyamine is multiply protonated (e.g., where the side chains of the amino acid compounds are positively charged), along with such other skin care components as are desired.
- the selected compound be sufficiently soluble in the formulation vehicle as to allow a consistent formulation having the desired physical and topical application characteristics.
- the compound (or compounds) chosen be sufficiently aqueous-soluble such that, upon application to the skin, the component compounds are taken up into the water-containing milieu of the skin.
- the anti-irritants chosen should be topically acceptable and preferably will not themselves be irritating, toxic or otherwise deleterious to the user.
- Suitable topical vehicles for use with the formulations of the invention are well known in the cosmetic and pharmaceutical arts, and include such vehicles (or vehicle components) as water; organic solvents such as alcohols (particularly lower alcohols readily capable of evaporating from the skin such as ethanol), glycols (such as glycerin), aliphatic alcohols (such as lanolin); mixtures of water and organic solvents (such as water and alcohol), and mixtures of organic solvents such as alcohol and glycerin (optionally also with water); lipid-based materials such as fatty acids, acylglycerols (including oils, such as mineral oil, and fats of natural or synthetic origin), phosphoglycerides, sphingolipids and waxes; protein-based materials such as collagen and gelatin; silicone-based materials (both non-volatile and volatile) such as cyclomethicone, demethiconol and dimethicone copolyol (Dow Corning); hydrocarbon-based materials such as petrolatum and squalene
- the vehicle may further include components adapted to improve the stability or effectiveness of the applied formulation, such as preservatives, antioxidants, skin penetration enhancers, sustained release materials, and the like.
- components adapted to improve the stability or effectiveness of the applied formulation such as preservatives, antioxidants, skin penetration enhancers, sustained release materials, and the like. Examples of such vehicles and vehicle components are well known in the art and are described in such reference works as Martindale - The Extra Pharmacopoeia (Pharmaceutical Press, London 1993) and Martin (ed.). Remington's Pharmaceutical Sciences.
- a suitable vehicle will depend on the particular physical form and mode of delivery that the formulation is to achieve.
- suitable forms include liquids (including dissolved forms of the compounds of the invention, as well as suspensions, emulsions and the like); solids and semisolids such as gels, foams, pastes, creams, ointments, "sticks” (as in lipsticks or underarm deodorant sticks), powders and the like; formulations containing liposomes or other delivery vesicles; rectal or vaginal suppositories, creams, foams, gels, ointments, enemas, douches and other forms.
- Typical modes of delivery include application using the fingers; application using a physical applicator such as a cloth, tissue, swab, stick or brush (as achieved, for example, by soaking the applicator with the formulation just prior to application, or by applying or adhering a prepared applicator already containing the formulation ⁇ such as a treated or premoistened bandage, wipe, washcloth or stick - to the skin); spraying (including mist, aerosol or foam spraying, such as nasal sprays); dropper application (as, for example, with ear or eye drops); sprinkling (as with a suitable powder form of the formulation); soaking; and injection (particularly intradermal or subcutaneous injection). Iontophoresis or other electromagnetic-enhanced delivery systems may also be usefully employed, as for example to increase delivery to the dermis.
- a physical applicator such as a cloth, tissue, swab, stick or brush
- the formulations of the invention are most preferably prepared such that the formulation (as occurring with any accompanying components) is substantially invisible upon application to the skin. This is particularly true in the case of many cosmetic formulations that are applied to the face or other exposed parts of the body, although it is also generally desirable that the formulation not be visible even if applied to non-exposed portions of the body. It will be recognized that in some cases, particularly with colored facial skin care products such as blushes, blemish covers, lipsticks and the like, the formulation will be designed to be visible on the skin; in such cases, it is desirable that the polyamine anti-irritant component itself be "invisible,” that is, that it not adversely change the appearance of the overall formulation as applied to the skin.
- the present anti-irritant species can be formulated in a form for topical oral administration to treat pain or irritation in the mouth, throat or other portions of the upper gastrointestinal tract such as that due to sore throats, canker sores, gum irritation or inflammation or the like, including such irritation as may be exacerbated by spicy or acidic foods as, for example, in the case of ulcers or heartburn.
- suitable forms for such oral administration include liquids (e.g. mouthwash or gargle solutions), lozenges, tablets, pills and capsules.
- the components used in such oral formulations should be chosen to be non-toxic. Methods for preparing oral formulations suitable for use in the present invention are well known in the art.
- formulations suitable for rectal, vaginal, nasal, pulmonary, respiratory, laryngopharyngeal, otic and ocular uses are contemplated and may be readily prepared.
- the objective of the clinical trials was to dete ⁇ riine whether and to what extent the compounds of the present invention reduced or prevented skin irritation caused by lactic acid, an ⁇ -hydroxy carboxylic acid known for its skin irritating potential.
- the trials were conducted in a double blind, randomized, vehicle- controlled manner.
- Various formulations of the invention were tested in over 250 people.
- the subjects were women who had been screened and shown to exhibit normal to above normal susceptibility to irritation by the tested irritant. Tests were conducted in multiple panels of from 7 to 12 subjects each. Subjects were instructed not to wear any makeup or facial lotions to the clinic the day of testing. The subjects were instructed to wash their face with Ivory bar soap in the clinic prior to application of test solutions. Lactic acid skin-irritant compositions were formulated in an appropriate vehicle prior to application to the skin of the subjects. In the majority of the tests, the irritant composition was 7.5% lactic acid dissolved in a 10% ethanol-in-water solution. Other skin tests, such as those using capsaicin or benzoyl peroxide, are also suitable for evaluating the anti-irritant activity of the compounds.
- Test anti-irritant formulations were prepared by combining measured amounts of polyamine anti-irritants (Sigma or Aldrich) of the present invention (concentration 250 mM) in the lactic acid irritant composition.
- the test formulation was applied to a defined portion of the subject's skin, typically the face. Controls were performed by applying a corresponding formulation without any added polyamine anti-irritant to a contralateral portion of the subject's skin.
- test solutions were applied in a double blind, randomized fashion using the prepared solutions as previously placed in coded vials designated for use on either the right or left side of the face (or other test area). Solutions were typically applied using a cotton swab (six strokes) or sponge applicator to the face and cheek area extending from the midline of the nose over to the center of the cheek and from the cheek bone down to the jaw line. Application was made first to the right side and then to the left.
- Symptom scores were cumulated, separately for the anti-irritant-treated and control-treated areas, for each individual and also for the panel as a whole. Individuals not reporting a cumulative score of at least "7" on at least one treatment area were excluded (in a blinded fashion) from further analysis in order to ascertain anti-irritant efficacy with respect to the more severely-susceptible test subjects. From a practical standpoint, scores of "0" and "1" on the above scale would be considered highly desirable for a commercial product because such a response would likely not result in a consumer ceasing to use a product.
- Tables 1 and 2 A representative set of test results, performed using acid anti-irritant concentrations of 250 mM, is set forth in Tables 1 and 2 below.
- Table 1 reports representative test results using various straight-chain, branched-chain and heterocyclic polyamines.
- Table 2 lists representative test results for amino acid compounds of the lysine, arginine, histidine and ornithine families, including various derivatized amino acids. Where multiple panels were studied (n > 1), the percent inhibition is reported as the average of observed values and represents the cumulative irritation inhibition value.
- Ornithine L-Ornithine-HCl 43 (n 2)
- FIGURES 1 through 8 show more detailed experimental data for two panel tests conducted using L-arginine (FIGS. 1-4) and L-lysine (FIGS. 5-8) (250 mM each) as anti-irritant components of the subject formulations.
- FIGS. 1 and 5 show the time course of irritation responses for both anti-irritant-treated and non-treated (control) skin portions for the panels.
- FIGS. 2 and 6 show the cumulative irritation over time for the same panels, while FIGS. 3-4 and 7-8 show cumulative irritation suppression and treated/untreated irritation responses on a subject-by-subject basis. While individual responses vary somewhat, the overall efficacy of the subject formulations is evident.
- the anti-irritant compounds of the invention are preferably chosen from compounds that are not themselves irritating to the user.
- Ethylenediamine a small straight-chain polyamine, is an example of a compound reported to have irritant properties (Merck Index, Eleventh edition).
- Preliminary clinical tests of emylenediamine using the protocol described above yielded variable results and suggested that the compound has relatively low anti-irritant properties ( ⁇ 20% inhibition) for some subjects and in fact may increase irritation somewhat (less than 20%) in some users.
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Abstract
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
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AU48611/96A AU4861196A (en) | 1995-02-03 | 1996-02-02 | Formulations and methods for reducing skin irritation |
MX9705954A MX9705954A (es) | 1995-02-03 | 1996-02-02 | Formulaciones y metodos para reducir irritacion de la piel. |
JP8523692A JPH10513452A (ja) | 1995-02-03 | 1996-02-02 | 皮膚刺激を軽減するための製剤及び方法 |
EP96904530A EP0806947A4 (fr) | 1995-02-03 | 1996-02-02 | Formulations et procedes permettant de reduire l'irritation cutanee |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US38426395A | 1995-02-03 | 1995-02-03 | |
US08/384,263 | 1995-02-03 |
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WO1996023490A1 true WO1996023490A1 (fr) | 1996-08-08 |
WO1996023490A9 WO1996023490A9 (fr) | 1996-12-27 |
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PCT/US1996/001289 WO1996023490A1 (fr) | 1995-02-03 | 1996-02-02 | Formulations et procedes permettant de reduire l'irritation cutanee |
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Country | Link |
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EP (1) | EP0806947A4 (fr) |
JP (1) | JPH10513452A (fr) |
AU (1) | AU4861196A (fr) |
CA (1) | CA2212127A1 (fr) |
MX (1) | MX9705954A (fr) |
WO (1) | WO1996023490A1 (fr) |
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---|---|---|---|---|
US20040067212A1 (en) | 1998-03-11 | 2004-04-08 | Kabushiki Kaisha Soken | Skin conditioner |
JP2008156330A (ja) * | 2006-04-26 | 2008-07-10 | Toyobo Co Ltd | 賦活化剤及び抗老化剤 |
DE102006035252A1 (de) * | 2006-07-26 | 2008-01-31 | Henkel Kgaa | Haarfärbemittel mit Shea Butter |
JP5966231B1 (ja) * | 2015-12-14 | 2016-08-10 | 有限会社アント | アミノ酸配合顔用皮膚外用剤 |
US20210212964A1 (en) * | 2018-06-08 | 2021-07-15 | Vivier Canada Inc. | Sterile topical saline putrescine formulation and uses thereof |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3861868A (en) * | 1971-03-30 | 1975-01-21 | Procter & Gamble | Dyeing human hair with oxidation dyes and arginine or a protamine protein |
US4076799A (en) * | 1972-12-27 | 1978-02-28 | Cincinnati Milacron, Inc. | Method of inhibiting skin irritation |
JPS6025479B2 (ja) * | 1977-03-31 | 1985-06-18 | 三洋化成工業株式会社 | 香粧品・洗浄剤用界面活性剤組成物 |
JPS54163819A (en) * | 1978-06-14 | 1979-12-26 | Meito Sangyo Kk | Digestive tract ulcer and injury treating agent |
US4507321A (en) * | 1982-02-17 | 1985-03-26 | The Research Foundation Of State University Of New York | Epithelial cell growth regulating composition containing polyamines and a method of using same |
EP0100827B1 (fr) * | 1982-08-17 | 1986-09-03 | Rosical Limited | Composition pharmaceutique contenant un acide aminosulfonique aliphatique |
US4704234A (en) * | 1983-01-17 | 1987-11-03 | American Cyanamid Company | Compositions comprising imidazole, pyrazole or derivatives thereof for removing undesirable organic matter from a surface |
IT1190348B (it) * | 1986-06-16 | 1988-02-16 | Lisapharma Spa | Impiego topico vaginale del p-isobutilfenilpropionato di lisina nel trattamento antiinfiammatorio |
US5091171B2 (en) * | 1986-12-23 | 1997-07-15 | Tristrata Inc | Amphoteric compositions and polymeric forms of alpha hydroxyacids and their therapeutic use |
US5252322A (en) * | 1989-09-22 | 1993-10-12 | The Gillette Company | Skin tanning compositions containing imidazoles |
AU641529B2 (en) * | 1990-07-30 | 1993-09-23 | Bloomfield D.A. | Zwitterionic compounds and their N-halo derivatives for use in the treatment of clinical conditions |
JP3575084B2 (ja) * | 1994-11-29 | 2004-10-06 | 味の素株式会社 | 殺菌消毒剤配合組成物 |
-
1996
- 1996-02-02 EP EP96904530A patent/EP0806947A4/fr not_active Withdrawn
- 1996-02-02 WO PCT/US1996/001289 patent/WO1996023490A1/fr not_active Application Discontinuation
- 1996-02-02 JP JP8523692A patent/JPH10513452A/ja active Pending
- 1996-02-02 CA CA002212127A patent/CA2212127A1/fr not_active Abandoned
- 1996-02-02 AU AU48611/96A patent/AU4861196A/en not_active Abandoned
- 1996-02-02 MX MX9705954A patent/MX9705954A/es unknown
Non-Patent Citations (6)
Title |
---|
MEDLINE ABSTRACT, No. 87021350, VON DEN DRIESCH et al., "Zeitschrift fuer Hautkrankheiten", 61(16), 15 August 1986. * |
MEDLINE ABSTRACT, No. 88153675, PIACENTINI et al., "Free and Protein-Conjugated Polyamines in Mouse Epidermal Cells. Effect of High Calcium and Retinoic Acid"; & JOURNAL OF BIOLOGICAL CHEMISTRY, 263(8), 15 March 1988. * |
MEDLINE ABSTRACT, No. 90268590, SASAKI et al., "Enhancing Effect of Pyrrolidone Derivatives on Transdermal Penetration of Phenolsulfonphthalein and Indomethacin from Aqueous Vehicle"; & CHEMICAL AND PHARMACEUTICAL BULLETIN, 38(3), March 1990. * |
MEDLINE ABSTRACT, No. 92013249, WILHELM et al., "Effect of Sodium Lauryl Sulfate-Induced Skin Irritation on in Vivo Percutaneous Penetration of Four Drugs"; & JOURNAL OF INVESTIGATIVE DERMATOLOGY, 97(5), November 1991. * |
MEDLINE ABSTRACT, No. 92027940, VILUKSELA, "Characteristics and Modulation of Dithranol (Anthralin)-Induced Skin Irritation in the Mouse Ear Model"; & ARCHIVES OF DERMATOLOGICAL RESEARCH, 283(4), 1991. * |
See also references of EP0806947A4 * |
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Also Published As
Publication number | Publication date |
---|---|
JPH10513452A (ja) | 1998-12-22 |
MX9705954A (es) | 1998-02-28 |
CA2212127A1 (fr) | 1996-08-08 |
AU4861196A (en) | 1996-08-21 |
EP0806947A1 (fr) | 1997-11-19 |
EP0806947A4 (fr) | 1998-10-14 |
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