MXPA97005954A - Formulations and methods to reduce irritation of the p - Google Patents

Abstract

Compositions and formulations containing organic polyamines protonated several times (such as amino acids with amine containing side groups), and methods for using same, to inhibit skin irritation in animal

Description

FORMULATIONS AND METHODS TO REDUCE SKIN IRRITATION RELATED REQUESTS I have a part in the patent application of E.U.A. do not. of sene 00/18, 263, filed on February 3, 1995 by the inventors of the present, of which the complete content is incorporated herein by roi ci ncia, BACKGROUND Many substances are applied topically to the skin or mucous membranes of humans or animals (hereinafter "the skin") in order to alter the appearance of the subject,? pfOteger the subject of the environment, or to produce a biological change in the tissue or tissue for therapeutic, preventive or cosmetic purposes. These substances can generally be referred to as "topical products" and include substances such as cosmetics, drugs-sideboard and proscription drugs, and a variety of other products such as soaps and ergents. Topical products occur in a variety of forms, including solids, liquids, suspensions, sernisolides (such as creams, gels, pastes or "bars"), powders or finely dispersed liquids such as sprays or mists.

Examples of typical products commonly referred to as "cosmetics" include skin care products such as chromas, lotions, humectants and "cosmetic cosmetics" such as exfoliators and / or skin-renewing agents.; petals fragrances as perfumes and colognes, and deodorants; products related to afei-t da such as creams, "tonics" and after-shave products; epilators and other elo removers; cleaners of the p, toni f i cadores and ast ingentes; prehumedeei towels and towels for washing; acetaminophen lotions and sunscreens; bath products such as oil; products for the care of children such as eye lotions and make-up refiners; foot care products such as powders and sprays; dye and make-up products for the skin such as foundations, blushes, lipsticks, shadows and eye peels, colors for the lips and prnel; balm and ba ras for the lips; products for the care and treatment of hair such as shampoos, conditioners, dyes, reds, bleach-is, malaxers, and permanent corrugator products; baby products such as lotions, oils, shampoos, powders and wet towels; feminine hygiene products such as deodorants and vaginal washes; skin and facial peelers applied by dermatologists or cosmetics; and others. Examples of topical products commonly classified as "Typical products" are many and varied, and include prescription and / or prescription products such as antitranspi. antos, insect repellents, ocular drugs and eye care products, both therapeutic and non-therapeutic, including eye drops, rewetting drops, saline solutions and solutions for contact lenses, sunscreens and sunscreens. sunburn treatments, anti-acne agents, antibiotics, topical respi- rators, therapeutic agents, anti-dandruff agents, external analgesics such as capsac products, topical iconceptives, topical product assortment systems, gastrointestinal agents, suppositories, enemas and hemorrhoids treatments, reproductive system agents such as vagina treatments, oral treatments such as troches, and many other products with therapeutic or other effects, for use on the skin and on mucous membranes, including ocular, nasal membranes , otic, laringofari gea and pulmonary. Other topical products include soaps for the hands, face and body as well as detergents and many other household products such as solvents, propellants, polishers, lubpcan + es, adhesives, waxes and others that are applied topically or are topically exposed to body during normal use. In a large number of cases, topical products contain chemical compounds that can produce "irritation", including various symptoms of inflammation, 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 said topical products. The occurrence, frequency and nature of irritation induced by topical products often varies from user to user. The severity of irritation to the susceptible user can range from your clinic to moderate and severe. Typical symptoms of "irritation" include itching (pruritus), itching, burning, tingling, "stinging," redness (swelling), or edema (swelling). The irritation response may be due to the direct effect on the skin of certain chemical compounds of topical products or to an immune response directed towards the chemical compounds alone or in combination with skin components (eg, allergic dermatitis) . The itching sensation is one of the most common skin problems experienced by humans and animals. Coming can be defined as a sensation that provokes the desire to scratch the place in which the sensation originates. All skin contains sensory nerves that can transmit itching impulses or other similar sensory impulses in response to chemical irritation, exposure to the environment or disease processes. Although the population needs of producing nerves has not been identified, the population of thinner non-honey nerves called neurons nociocepti vas of type C is thought to be the most important in terms of producing the sensation. Itch: Mecha isrns and Management of Pruptus. 3effrey D. flernhard. McGraw-Hi 11, Inc. Cía Francisco, 1994), pp. 1-22. The itching nerves of the skin can be considered "a final runway" for the many irritating conditions that are finally detected as itching including chemical response, exposure to the environment (in such a way that it produces dry and itchy skin) and disease processes such as erm titis atopica. Many chemicals can cause itching when they are applied to the skin only. No matter what the itching eventually causes, the sensation experienced is the same and provokes a desire to scratch. LO Many ingredients used in topical products are known irritants or are potentially irritant, especially for people with "sensitive skin". These irritating ingredients include fragrances, preservatives, solvents, propellants, and many other ingredients that can '5 in other ways be considered inert components of the products. In addition, many active ingredients of topical products, including chemical compounds that can 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 exfoliators and skin cell renewing agents, anti-acne drugs, anti-transgenic compounds, anti-ishtanarins, an-inflammatory agents, skin-protecting agents, chemical insect repellents, sunscreens, nasal medications and respiratory 5 in steam or spray, and many others. Where more than one chemical irritant is present, its irritant effects may be additive. Also, the chemical ingredients can react one < = with others, in the environment of the skin, to form new chemical compounds that are irritating. The vehicles in which the active drug ingredients are formulated can also cause irritation in sensory people, especially in the case of drugs as a co-operative agent. In addition to the chemical compounds that directly act to irritate the skin, these chemical compounds If) they indirectly cause the p to become more sensitive to other chemical compounds and other environmental conditions that would not normally produce irritation. Many chemical compounds that act as "e foliators" of the skin such as retinoids (eg, nipple, retinal and retinal), acids carboxylic acids including α-hydroxyl acids (e.g., lactic acid, glycolic acid), R-hydroxyloxy acids (e.g., acidic salt), cr-cotoarj dos, acetic acid and acid t nc .Loraacetic acid, 1-pyrrolidone, 5-carboxylic acid, citric acid, citric acid, decanoic acid, 20-hydroxyoctanoic acid, gluconolactone, oxopropylgluconate, oxalic acid. , alic acid, tartaric acid, 1-maleate acid, benzyl acid, glucocortico acid, benzoyl peroxide and phenol, in others, can make the skin more sensitive to irritation activated by other chemical compounds typically applied such as wetting agents, sunscreens, fragrances, preservatives, surfactants (eg, soaps, shaving creams) and other topical products. Exfoliators and other ingredients may also increase the sensitivity of the skin to environmental conditions such as sunlight, wind, cold temperature and dry air, or to chemical agents such as antigens, or may exacerbate the irritation that can be trapped by a disease. the pre-existing skin On the contrary, environmental influences by themselves can increase the skin's sensitivity to chemical compounds in topical products by reducing the "bar-rera function" of the epidermal skin. The barrier function to reduce to a minimum the absorption or passage of chemical compounds irritates irritantly through the layer of external "dead" cells of the epidermal skin towards the living tissue of the p. Moisture extremes, for example, can greatly increase the irritation of topically applied products. A very common condition due to low humidity is called "winter weather" in which the characteristics of very low humidity or many cold climates (parcularly when accompanied by indoor heating) or long exposure to re-refrigeration of the Air conditioners in the summer produce itchy skin - especially in the elderly - that can exacerbate the irritant effects of topical products. In addition, soaps, detergents, cleaning products, shaving creams, alcohol, and other products that remove some of the protective lipids of the skin and / or secretions may increase the permeability and sensitivity of the skin, topically applied chemical compounds. that otherwise would not produce irritation. Normal processes such as sweating can also increase the capacity of irritating materials, such as ant transpirants, deodorants or sunscreens, to penetrate the skin through pores or glands, thus exacerbating the potential for irritation. Exposing the skin to high humidity or liquid environments can also increase the potential irritants' ability to penetrate the skin. In similar fashion, the skin may be sensitized or inflamed due to infection, abrasion by shaving, repeated or excessive washing or bathing, sun exposure or other mechanical abrasion or mechanical damage, resulting in sensory irritation responses. The subsequent application of deodorants to the arm, after-shave products or other COS products. Because of the chemical and environmental causes of skin irritation, many people have an inherent sensitivity or genetic predisposition to skin irritants. People who have respiratory allergies, for example, tend to have excessively dry skin that facilitates the increased absorption of chemical compounds that are extremely irritating. The excessively dry skin that accompanies atopic dermatitis, for example, predisposes patients with this condition to irritation of many topically applied products. Other diseases and conditions of the skin such as dermatitis due to allergic or non-allergic contact, asthma (including exercise-induced asthma such as can be precipitated by cold or dry air), hay fever, allergic rhinitis, intestinal disease Flammatory, sopasis, eczema, candidiasis, post-herpetic neuralgia, infectious diseases manifested, for example, by sore throat or skin lesions, insect bites and the like produce inherent irritation that can be exacerbated by the application of products topical or by exposure to chemical or environmental influences such as allergens, cold air, low humidity and the like. Many other individuals show sensitive skin as a condition that is not related to a skin disease dent i i ca 1 o. Whatever the exact cause of irritation, many attempts have been made to reduce the potential for irritation of topical products by-) identifying chemical compounds that tend to cause irritation and reducing their concentration or eliminating them from the products. Many of these products are advertised to consumers as "hypoallergenic" or similar to designate a reduced tendency of the product to produce irritation to consumers with sensitive skin. Many irritation responses of the skin (including mucosa), however, are not allergic at source. In any case, it is often not feasible or practical to identify or eliminate all irritating chemical compounds, par- ticularly when irritant chemical compounds are the active ingredients of the product or are required for formulation, preservation or for other func- tional reasons. As an example, there is a substantial practical and commercial need in the field of exfoliators and related skin care products for a composition or method that reduces or prevents irritation caused by such products. Common exfoliators include acids and hydroxy carboxylic acids such as lactic acid, glycolic acid, cylindrical salt acid and the like, -acid acids such as pyruvic acid, as well as various compounds such as acetic acid and trichloroacetic acid, acid. l-pi rrolidon-5-carboxylic acid, capploilsalicylic acid 11, v-hydroxydecanoic acid, or-hydroxyoctanoic acid, gluconolacone, rnetoxiprop lgl ucolami da, oxalic acid, malic acid, tartaric acid, andelic acid, benzyl acid, gluconic acid, peroxides, phenols and renewing agents of skin cells such as re moids. Said products are used co or exfoliators and / or cell renewing agents to reduce the occurrence or severity of wrinkles in the skin, particularly wrinkles on the face., or as antiacne, ant? - "the dry" or skin whitening agents. See Patents of E.U.A. Nos. 4,105,702, 4,105,783, 4,246,251, and 5,091, 171 (Yu et al.) And 5,262,153 (Mi hima et al.); U.P. Srnith, "Hydroxy Acids and Sk n Ag ny", Soap / Cosmet Les / Chemical pecialt es for Septernber 1993, p. 54 1 L (1993). Hydroxy acids, in sufficiently high concentrations to exfoliate, are often well known to cause skin irritation and edema. The danger of irritation is even greater for people who have sensitive skin. The currently available methods reported by Yu and others to reduce the irritation caused by hydroxy and keto acids in topical products include adding a strong alkali metal base such as sodium hydroxide or potassium hydroxide, thereby raising the pH of the preparation and reducing the acidity of hydroxy acid. Such methods have the reported disadvantage of reducing the ability of the resulting lamellar salt to penetrate the skin and thereby compromise the beneficial effects (particularly anti-acne or anti-"dry skin") effects of the hydroxyacid. Al ernatively, Yu and ot have proposed to make you react with hydroxy acid with a > non-alkaline metal base such as ammonium hydroxide or an organic base such as a primary, secondary or tertiary organic amine, thus forming an amide or ammonium salt of the hydroxy acid (or keto-acid) active ingredient. See the patents of E.U.A. Nos. 4,105,782 and 4,105,783 (Yu et al.). The effect of such formulations again is to raise the pH of the preparation to a non-irritating level. However, the increased pH (reduced acidity) of the r-esultant.es preparations makes them less effective as exfoliators or anti-wrinkle agents, which desirably has an acid equivalent at a pH of 1-6 and very preferably a pH from 2-4. See r, rn? < h, formerly, in Table 1. Other approaches to reduce irritation associated with exfoliating products include the use of slow release topical formulations such as polymer-based vehicles (see, e.g., Chess et al. US No. 4,971,800) or rn-sponges, and the inclusion e.g., of plant-derived anthrunit components (see, v. Gr-., S th et al., U.S. Patent No. 5,028,428). There is a clear need, therefore, for a composition or method that prevents or reduces skin irritation caused by organic or inorganic acid (high acidity) products of low pH, but does not reduce the effectiveness of acids as exfoliating / cell renewing agents. Very generally, it would be highly desirable to identify compounds with anti-curing activities that reduce irritation caused by a wide range of otherwise safe and effective topical products, or that reduce the intrinsic irritation associated with various skin diseases and conditions (such as dermatitis). atopic, allergic dermatitis, asthma (including exercise-induced asthma), hay fever, allergic rhinitis, inflammatory bowel disease or other respiratory allergy, eczema or psoriasis) or caused by exposure to chemical compounds or environmental conditions such as allergens, sun , wind, cold or extreme humidity. As is explained with reference to the legends in The Detailed Description, the present invention involves the surprising discovery that organic polynomials, protons to multiples (for example, organic molecules containing two or more functional groups). arnino protonados), are effective in reducing the incidence and severity of irritation associated with skin irritants applied topically. In these compounds ant ii rp before poiiarnin, a plurality (two or more) of moieties (which may be primary, secondary, tertiary or quaternary functions) are protonated at the particular pH of the posi ciori or product applied Typically. It is particularly preferred that the multiple protonated polylamines of the present invention are amino acids containing a positively charged nitrogen containing side chain and derivatives of these amides or acids. Amino acids are the chemical units from which proteins are made. "Ami octos" as a class are chemically based on the so-called amino acids 20"natural", which are found in nature. These have a primary amino function (-NH2) and a carboxylic acid function (-C00H) which bind to the same carbon atom (ir amino acids) or approach the carbons (eg, amino acids ß). Similar in this class include alpha-irnmo acids (eg, proline). In addition, the analogues and homologues of natural amino acids (usually referred to as "artificial" amino acids, isomers, and J) can also be felt. enant i omeros). the amino acids and their analogs and homologs can be chemically modified to prepare unique amino acid structures. These modifications include those in which a chemical modification or substitution in the anino, carboxyl or side chain (derivatives) structures alters the amino acid. The exact mechanism (or mechanisms) of the activity of such polyarnins is unknown and the invention is not limited to any particular mechanism. However, it is currently believed that what contributes to the antiperspirant properties of these polyes is the presence of positive change (s) in the compounds of the present invention, especially where the compound possesses multiple sites of protonation. Surprisingly, the inventors have discovered that the anti-urinary activity of the compounds of the present invention remains the same where the polyamine compound possesses, in addition to multiple nuclei of protonation, a negatively charged functional group (cf. HEPFS, N-C2-HJ ro? et? l] peratin-N '. r? -ac? ethane sulphonic acid], a regulator of biological pH common that with a), a pH of ent e about 1 to 7, two portions of protonated arnin and a functional group of negatively charged sulonate). In a related context, applicants have discovered that several metal cations are effective in reducing irritation caused by the topical application of skin irritants. In this regard, reference is made to the antimatter agents described in the patent application nos. of serious 08 / 362,100, 08 / 362,101, 08 / 362,097, 08 / 362,055 and 08 / 362,058 (entitled "Formula + ons and Methods for Reducing Sl'in Irptation"), filed on December 21, 1994 by the present inventors, of which the complete content is incorporated by reference. While the applicants do not wish to be bound by any particular mechanism, it is currently proposed that the positive charge (s) in these antirust compounds (e.g., the amino acids of the present invention may have one or two protonated places (and positively charged) depending on the particular pH typically used in typical products), can reduce irritation by interacting with the epidermal or mucous nerve cells to prevent or counteract the irritation sensation, and / or Interfere with the irritant components of the skin cells that are altered by the application of the skin irritant. Thus, the positive charge (s) can alter the ability of the nerve cells in the skin to depolarize or repolarize, such as blocking or interfering with a pump channel or altering the Transrnernal action potential, or the charge (s) may interfere with the transmission of nerve impulses from one nerve cell to another. The load (s)? Os? T? Va (s) in the most pronated polia can bind non-specifically to the cell membranes and contribute to a charge protection effect. which consequently alters the regulatory activity of the cells. amines, particularly amino acids, are widely found in a variety of commercially available products, especially cosmetics such as creams for p or emollients and hair care products. Small amounts of amino acids are added to these products due to their moisturizing properties, since it is believed that they increase the transdermal penetration of water and other compounds. A Consumers Dictionary of "Cosrnet c Tngredients, 3 <" -? edition, Ruth A. Umter, ed. (Crown Publishers, Ne? York, "1989), p. 33; patent of E.U.A. do not. 4,732,892 (Sarpotdar et al.). In addition, the specific forms of some amino acids have been used in topical preparations for a variety of applications. For example, salts of glutaric acid, an amino acid containing a negatively charged side chain acid, have been found to be useful with topical agents to alleviate the discomfort associated with insect stings. See - the patent of E.U.A. do not. 4, 062,937 (Rea) .. Di hi droxietii gl icma has been used to formulate cleansing and disinfecting solutions that are also used to reduce pain and itching. See patent of E.U.A. do not. 4,868,213 (Farpsh). In addition, the N-acylates of the amino acids and their salts, formed by butyric acid, have been used to treat wrinkles of human skin. See patent of E.U. Year. 4,859,653 (Morelle et al.).

The human skin presents a sensory and structural environment. For example, the skin contains highly specialized nerves and organs, which are specialized and are arranged to differentiate the stimuli that lead to such distinct sensations as heat, cold, pressure, pain, itching and the like. In addition to normal sensory stimuli, nerves in the skin also contribute to foreign or native chemicals such as proteases, prostaglandins, complement system molecules, allergens, myons, and the like that may be present due to tissue damage. or environmental exposure. Agents that are effective will combat-a source of sensory stimulation-for example, steroid agents to treat inflammation of the skin-are ineffective with other sensory stimuli such as pressure, heat or the itching or transient itching caused by a product for care. of the applied p. On the contrary, local anesthetic agents that are effective in depressing all sensory or even motor activity in a trialated form are not suitable if only one sensation is to be eliminated - for example, itching or transient eating. To complicate the situation, the structural matrix of the epidermal skin gives rise to a "barr-era function" that tends to exclude or inhibit the entry of foreign material, including potentially therapeutic agents. Therefore, it would be convenient to identify agents that are effective on the skin to inhibit certain sensory and related responses (such as pain or coma), although it does not adversely affect other nerve responses in the same tissue (such as sensations of touch). . The present invention provides compositions and methods to reduce specific antitumor effects from a variety of sources without negative effects such as those caused by the use of anesthetics. All publications, patents and other reference materials mentioned in the present specification are hereby incorporated by reference.

BRIEF DESCRIPTION OF THE INVENTION The present invention is directed to the use of proton organic polymines several times (organic molecules containing two or more protonated arnin functions), preferably, arnioacids (and their derivatives) possessing a positively charged nitrogen containing side chain. , as ingredients to provide topical effects against skin aging, fast acting, efficient and safe. An object of the present invention is to provide ingredients, formulations and methods of use that can suppress skin irritation due to exposure to chemical compounds or the environment, or due to tissue inflammation, damage or other skin pathology. The invention is particularly useful for preventing, reducing or eliminating potential irradiation caused by the mild application of products containing other irritant ingredients, including cosmetics such as, in particular, hydroxyacid or other products containing exfoliators, facial peelers, shaving products, sunscreen products, deodorants and other cosmetics as described above, as well as topical drug products containing irritant active ingredients or vehicles thereof, and other products such as soaps, detergents, solvents and the like which are either They are typically applied or exposed topically to the body during use. For the time being, the present invention satisfies a clear need for formulations and ingredients that will prevent or reduce potential skin irritation caused by topical products. The invention is also useful for preventing, reducing or eliminating skin irritation caused by skin diseases or other conditions such as environmental exposure to irritating chemical compounds or such influences as wind, heat, cold and extremes in humidity, including the intrinsic irritation associated with these conditions as well as the irritation that can be exacerbated by the application of a topical product. In a preferred embodiment, the polyacid irritants of the invention are included in a suitable topical carrier at a concentration of about 10 to about 3000 mM, more preferably * of about 50 to about 2000 mM, and even more preferably about 100 to about 1000 nm.

In another preferred embodiment, one or more of the compound polylamines are combined in a formulation that further comprises a potentially irritating ingredient, the polyrnene (s) present in a total amount effective to reduce or eliminate irritation due to the anti-irritant ingredient. In a particularly preferred embodiment, an anti-irritant polyarynin component of the present invention is combined in an acidic hydroxy or other exfoliating preparation such that the pH of the hydroxylase preparation is maintained in the pH scale 1-6, and preferably on the pH 2-4 scale. It will be understood that, where the formulation employs an anhydrous vehicle, the acidity of the formulation may not be expressible in terms of typical pH, but that said acidity will manifest itself upon exposure of the formulation to the skin where the water is present so much to trace as ext. In another preferred embodiment, the compounds of the present invention can be combined in a formulation with other anthrrugs such as steroidal or nonsteroidal anti-inflammatory agents or other materials such as aloe ver-a, chamomile, or-bisabobol, clear Cola extract, extract of tea see-ie, tea tree oil, licorice extract, allanto, urea, caffeine or others, glycemic acid and its derivatives, or other anti- irritant species? such as those identified in the U.S. Patent Application. Copendent Serie Nos ,. 08/362/100 08/362/101, 08/362/097, 08 / 362,055 and 08 / 362,058 (entitled "Forms and Methods for Reducing Sl -? N Tritration"), presented on December 21 of 1 4 by the inventors of the present, to achieve a multiple anti-irritant effect. In addition, it is currently believed that the properties for reducing irritation of the polyainin antipoptants of the present invention can be added if portions fail. C o nals of different polya species combine to create a combined total concentration within the scales referred to above. Therefore, it is contemplated that the mixtures or combinations of the claimed anti-amino acid anti-irritants can be used in the appropriate total concentration to be effective in the irritant reducing properties, despite the concentration of any other anti-irritant component. The invention further provides methods of treatment, reduction or elimination of skin irritation comprising the topical application of a formulation comprising an antitumor effective amount of one or more pol arnines of the present invention. The formulation may also include one or more potentially irritant components. Alternatively, the formulation can be applied separately and before the application of another product that has a potentially irritating component or the formulation can be applied alone to prevent the development of irritation or to treat preexisting irritation attributable to such conditions. c rno skin disease, exposure to chemical irritants or exposure to the environment.

DETAILED DESCRIPTION Clinical tests with human beings performed in connection with the present invention have established that the water-soluble multiple protonated polyamines, including amino acids (and derivatives thereof) have a positively charged nitrogen which contains a side chain, are effective, when topical meat is applied > Appropriate care and appropriate vehicles for suppressing severe itching, burning, tingling, itching and / or erythema induced by the topical application of skin irritant to lactic acid droxiazid as well as skin irritants. . Formulations containing these anti-rritant compounds are useful in the suppression of a wide variety of irritation responses induced by topical products atphobic to exfoliators, sunscreens, retina? des, ant 1 t ransp, deodorants, anti-acne and other products that contain potonially components capable of producing sensory irritation. For example, the compounds of the present invention are useful for preventing or reducing skin irritation caused by "or β-hydroxy acids, ot-ketoations and other carbohydrate acids, as well as re-molds, phenols, peroxides and Similar irritants found in topical products of sideboard for home or cosmetological use (such as 1-γ-rrro-5-carboxylic acid in, capriloyl-allylic acid, acid or-hi drox idecanoic, acid <* - hydroxioctanoic acid, gluconolactone, methoxypropyl glycogen, oxic acid, rhenic acid, tar + apco acid, andelic acid, benzyl acid, and gluconic acid), as well as certain topical prescription drugs containing high dose forms (eg, example, 12% p / po even higher) of said irritants. Atptable irritation to combinations of such irritant ingredients, such as lactic acid / salicylic acid combinations and hydroxyacid / nitric acid combinations, as well as irritating to purified isomeric forms of said ingredients, may also be inhibited by the formulations. of the invention. In addition, formulations containing such compounds are useful in reducing irritation in conditions where the skin is inherently persistent to topical products (eg, dry skin, "winter itch"), and other inflammatory conditions. or of injury) and to reduce the irritation due to such conditions even in the absence of other topical products applied. The formulations are also useful for binding skin irritation on animals other than humans, for example irritation in dogs or cats and the resulting itching due to fleas or other skin disease or condition. An additional benefit of the antimicrobial compounds and formulations herein is that they do not have the undesirable anesthetic side effects shown by lidocna and other similar local anesthetics of the skin. When a solution of the compound used in clinical trials described above was applied, the subjects typically did not report sensations other than the sensations caused, "by the vehicle alone, and did not lack sensation (s) normal (s). The protonated polyarms of the present invention include straight or branched chain polyarnines, as well as heterocyclic amines. The protonated portions of these polyamine molecules can be primary, secondary, tertiary or quaternary arnine functions. In addition to the amino acid compounds described herein, polylactic antimicrobial compounds are preferably selected from the group consisting of esperrnin, esperrnidma, putresema, pr-ot amine, HFPES, irnidazole and piperazma, since these pol They have two or more ammonium protonated groups or acidity conditions (pH ba). When the pollamines of the present invention are amino acids, they are preferably selected from the group consisting of rgmin, lysine, histidine and ornithma, since these amino acids have, in addition to a positively charged ammo N-or portion, a chain amino function laterally positively charged at the physiological and lower pH. The argmin, histidine and orn t a possess two predominantly positive charges at the pH aunt or hp < 5), a positive charge in the amino group of side chain and another positive charge in the Na terminal of the amino acid backbone. It was believed that the protonated state several times of these amino acids at pH ba contributes to the properties ant 1 rp tantes of these corp? et os. In addition to the amino acids mentioned, forms substituted or derivatively of such amino acids are also within the scope of the present invention. In the present, the derived amino acids also include analogous forms of the amino acids. Preferred substituents include substituents (either on either or both ex-terminals of the terminus Nw and the C terminus of the amino acid) at the N-or terminal of the amino acid of the RCO-i R- form, terminal substituents (C ) carboxyl of the form -NH2, -NI-INH2 and -NI-IR, where each R is independently substituent or substituted alkyl, alkenyl or alkylo (either straight or branched chain, and preferably 1 ak carbons), or alkyl, alkali, aralkyl or cycloalkyl (preferably about 3 to 20 carbons), or, in the case of NR2, the R- groups together are a cyclized group formed (in conjunction with the nitrogen atom) a heterocyclic ring. 5-8 member co-containing optionally an oxygen or nitrogen as an additional ring heteroatom.

An acetyl terminal-to-ino substituent is a replacement for the amino acid compounds. Substituents are used for bonding or storing of terminal boxes formed from sand substituted or substituted with lower alkyl, or lower alkoxy or single ring aploxy, groups, and groups of - H2, -OCH3, - are preferred. OCH2CH3, are especially preferred. Sust ituyent is for training they are particularly recommended. When a group of amidation of the structure -NR2 is going to be cyclical in shape, the heterocyclic structure is preferred. Other suitable agents are commercially available or can be prepared and evaluated by a person skilled in the art with antirust activity with routine tests. In addition, it has been found that both the D-form and the L of the antisense amino acid components of the present invention exhibit irritant-reducing activity. It is believed that guadmium, a side-chain constituent of arginine, can also be effective in reducing irritation. In a similar way, other isomeric forms, homologs and suitable salts of amino acid compounds are predicted to be active.

FORMULATIONS OF THE INVENTION The topical anti-inflammatory formulations of the invention comprise a topical vehicle suitable for administration to the skin of the animal (particularly a human being), and an amount of one or more effective anti-inflammatory compounds to reduce, inhibit or inhibit eliminate irritation of existing or potential skin. In one embodiment, antitumor topical formulations furthermore contain an irritant ingredient that by itself is capable of inducing skin irritation such as symptoms associated with inflammation, such as, for example, a cosmetic or care product ingredient. of the skin, or a pharmaceutically active ingredient or a pharmaceutically active drug ingredient. The antipyretic compounds before polyarnine to be used in the antimicrobial formulations of the invention are contained in an effective concentration to prevent or reduce (hereinafter "inhibit") the symptoms of skin irritation (such as inflammation). ) that it is intended to eliminate. The formulation preferably contains the selected compound in a suitable topical carrier at a total concentration of about 10 to about 3000 mM, most preferably about 50 to about 2000 rnM, and most preferably still about 100 to about 1000 mM. The right concentration can be achieved using? N l'R only the anti-irritant component of polyamine of the invention, or many different components can be combined to produce the desired total concentration. If other intervening compounds are included in the formulation, then lower concentrations of the compounds of the invention may be used. Preferred concentrations can also be expressed in terms of weight / volume or weight / weight percentage which will vary a little depending on the density of the vehicle and other components of the formulation. Therefore, to take * an example in which the vehicle has a density of 0.93 g / rnl (as in a mixture of 50:50 Ten volume] of 95% ethyl alcohol and water) and the mtrogenic compound is incorporated in form of hietidma (weight of formula 155), representative values of representativeness correspond approximately to 100 rnM: 0.78% (w / v) 0.83% μ / μ) 500 mM: 3.88% (w / v) 4.17% (p / p) 1000 inM: 7.75 (p / v /) 8"33% (p / p) The above-mentioned preferred concentration scales contemplate that a typical topical dose will be approximately 0.5 grams of formulation in an area of 5 cm x 5 crn of skin (25 crn2). Clinical studies have shown that such preferred concentration scales are generally effective in inhibiting skin irritation. In typical topical vehicles, the compositions are easily formulated and do not leave any visible residue ignificant when applied to the skin. Forms of higher concentration, such as saturated pastes or other forms, can also be used successfully, particularly where visible appearance is not a limiting consideration (as in the case of selective applications), Furthermore, routine clinical evaluations such as those described below can be easily employed, it would be convenient to optimize the concentration of this antimicrobial agent (s) of the invention and to confirm if the lower or higher are appropriate for a given formulation or indication of irritation given. For example, the concentration can be adjusted to account for the amount of formulation that will typically be applied to a skin area given by the user, which will depend to some degree on the physical nature of the topical vehicle (e.g., lotion). in comparison with liquid spray vehicles). Also, the amount of the compound required may be reduced in cases where the formulation contains an increased ingredient of skin penetration or other agent that increases the ability of the compounds to penetrate the stratum corneum to its site of anti-irritant activity. . Preferably, the formulations of the invention include an amount of anti-irritant compound (or compounds) of polyarynin layer: to inhibit irritation in susceptible individuals by at least about 10% or more, as measured by an average reduction in cumulative irritation. at the end of a susceptible test population as illustrated in the clinical protocols described above. Alternatively, the formulations of the invention include an amount of anti-irritant compound cap to inhibit 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 a base from individual to individual (treated areas vs. control areas). This latest measure of effectiveness reflects the fact that the present formulations, similar to many therapeutic products, in some cases can be effective to provide a significant benefit to a part, but not all, of the susceptible population. The optimal concentration of a compound of the invention can also be reduced * below (or within) the preferred scales discussed above if some other antiretentive component is included in the formulation together with the antigenic compound of polyane. of the invention. In particular, it is contemplated that lower (ie, half) amounts of antimatter species may be used *, while still maintaining comparable levels of anthurriot activity, and also showing an approximately equal concentration of, for example, a calcium channel blocking or regulating agent, or other antimicrobial agent such as a steroidal or nonsteroidal anti-inflammatory agent. Examples of suitable additional irritant ingredients are described in the U.S. Patent Applications. Applicants of the present invention Series Nos. 8/362, LOO, 08 / 362,101, 08 / 362,097, 08 / 362,055 and 08 / 362,058 (entitled "For ulat íons and Methods for Reducing Sl-in Trp t at ion "), filed on December 21, 1994 and incorporated herein by reference in its entirety. Other anti-frying ingredients such as aloe vera, chamomile, or-bisabolol, clear cola extract, green tea extract, tea tree oil, licorice extract, alantoma, urea, caffeine or other xanthines and cirrhotic acid and their derivatives may also be beneficially incorporated into the formulations of the invention to inhibit the effects or symptoms of irritation. The compounds of the invention are typically incorporated into the formulations herein by mixing an appropriate amount of a sufficiently soluble form of the selected compound in the chosen formulation vehicle., at an appropriate pH so that the polyamine is protonated several times (eg, where the side chains of the amino acid compounds are positively charged), together with other skin care components as desired. From a formulation point of view, it is preferred that the selected compound be sufficiently soluble in the formulation vehicle to allow a consistent formulation having desired physical and topical application characteristics. It is also highly preferred that the '- *' .- * The chosen compound (or compounds) are sufficiently soluble in water such that, when applied to the skin, the compounds of the component are brought to the medium of the skin containing water. In addition, it will be clear that the chosen anti-irritants should be topically acceptable and preferably not be irritating, toxic or ot-a-way, as the user will trust. Typical vehicles suitable for use with the formulations of the invention are well known in the cosmetic and pharmaceutical arts and include vehicles (or vehicle components) such as water; organic solvents such as alcohols (particularly lower alcohols readily capable of evaporating from the skin such as ethanol), glicoles (such as glycerin), alicyclic 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, acylgliotols (including oils, such as mineral oil, and gripes of natural or synthetic origin), phospholyses, spindles, and waxes; protein-based materials such as collagen and gelatin; liquefied materials (non-volatile and volatile) such as cyclomet cona, dimethiconol and di et iconcopol isl (Dou Corning); hydrocarbon-based materials such as petrolatum and squalene; ammonium, cationic and amphoteric surfactants and soaps; sustained releasing vehicles such as rniorospores and polymer matrices; stabilizing and suspension agents; ernulous agents; and vehicle vehicles and components that are suitable for administration to the skin, as well as mixtures of typical vehicle components as previously identified or otherwise known in the art. The vehicle may further include components adapted to improve the stability or effectiveness of the applied formulation, such as presenters, anti-oxidants, skin penetration mcrenents, sustained release materials and the like. Examples of said vehicle, and vehicle components are well known in the art and are described in reference works such as Marti ndale - The Extra Pharrnacopoeia (Phar Aceut Cal Press, London 1993) and Mar't in (ed. .), Rern nqton's Pharmaceut i cal Sciences. The choice of a suitable vehicle will depend on the particular physical form and the mode of assortment that the formulation will achieve. Examples of suitable forms include liquids (including dissolved forms of the compounds of the invention as well as suspensions, emulsions and the like); solids and selenides such as gels, foams, pastes, creams, "bar-ras" ointments (as in lipsticks or deodorant sticks), powders and similar formulations containing liposomes or other assortment vesicles; rectal or vaginal suppositories, creams, foams, gels or ointments, enemas and washes; and other forms. Typical assortment modes include the J < using the fingers, application using a physical api icator such as a cloth, fabric, swab, bar or brush (as is achieved, for example, by soaking the applicator with the formulation just before application or applying or adhering to a prepared applicator that already contains the formulation - such as a tr-tied or pre-moistened bandage, fabric, wash cloth or bar - for the skin); sprinkling (including steam, spray or foam spray, such as nasal sprinklers); drip application (eg, ear drops or pair-to-eyes); splash (a suitable powder form of the formulation); soaking; and injection (particularly intradermal or subcutaneous injection). Lontophoresis or other electromagnetically increased delivery systems can also be used, for example, to increase the assortment to the dermis. Metrology and materials for preparing formulations in a variety of ways are also described in Anthony L.L. Hun + ing (od.), "A Forrnulary of Cosme + ic Preparations (Vol. 2) - Crea s, Lotions and Mil s", Micelle Press (England, N.. 1993). See, for example, Chapter 7, pp. 5-14 (oils and gels); Chapter 8, pp 15-98 (bases and emulsions); Chapter 9, pp. 101-120 ("products for all purposes"); chapter 10, pp. 121-184 (chewing cleansers, creams, lotions); Chapter 11, pp. 185-208 (base, base creams and day creams); Chapter 12, pp. 209-254 (emollients); Chapter 13, pp. 297-324 (products for facial treatment); Chapter 14, pp. 325-380 (products for i '-t hands); Chapter 15, pp. 381-460 (creams and lotions for the body and for the skin); and Chapter 16, pp. 461-484 (baby trust products); whose contents are incorporated here by reference. The formulations of the invention are formulated most preferably in the manner that the formulation (as with any accompanying components) is substantially invisible when applied 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 is not visible even when applied to unexposed portions of the body. It is recognized that in some cases, par cularly with colored facial skin care products such as blushes, imperfections, lipsticks and the like, the formulation will be designed to be visible on skin; in such cases it is desirable that the anti-tarnish component of polina by itself be "invisible", that is, not adversely change the appearance of the overall formulation as it is applied to the skin. In another embodiment of the invention, the anti-irritant species of the invention can be formulated in a form for topical oral administration to treat pain or irritation in the mouth, throat or other parts of the upper gastrointestinal tract such as those due to sore throat, small sores of the mouth, irritation or inflammation of the gum or the like, including irritation such as may be exacerbated by es or acid foods, for example, in the case of ulcers or heartburn. The < suitable forms for said oral administration include liquids (e.g., mouthwash, or solutions for g rgas), troches, tablets, pills and capsules. As with other topical forms described herein, the components used in such oral formulations should be chosen so that they are non-toxic. Methods for preparing oral formulations suitable for use in the present invention are well known in the art. Similarly, formulations suitable for rectal, vaginal, nasal, pulmonary, reatory, nonaphogenic, otic, and ocular uses are contemplated and can be easily prepared.

CLINICAL RESULTS The antimicrobial efficacy of the formulations of the present invention was tested and confirmed in numerous clinical tests, the results of which are described in the following examples. Although these examples further illustrate various aspects and preferred embodiments of the invention as described herein, they are illustrative only and should not be construed as limiting the scope of the invention as set forth in the claims. 7 EXAMPLE 1 CLINICAL STUDIES OF ANTIRIRATION ACTIVITY The objective of the clinical trials was to determine whether and to what degree the compounds of the present invention reduced or prevented skin irritation caused by lactic acid, a hydroxyaccarboxylic acid known for its potential to irritate the skin. The tests were conducted in a double blind, randomized, vehicle controlled manner. Various formulations of this invention were tested in more than 250 pe. 1. Pro ocolo The subjects were women who had been selected and who showed normal susceptibility up to * above normal to irritation by the tested irritant. The tests were conducted in multiple panels of 7 to 12 subjects each. The subjects were instructed to not use makeup or facial lotions when they went to the clinic on the day of the test. The subjects were instructed to wash their face with Tvory bar soap in the clinic before applying the test solutions. The skin irritating lactic acid compositions were formulated in an appropriate vehicle before being applied to the skin of the subjects. In most tests, the irritant composition was 7.5% lactic acid dissolved in a 10% ethanol solution in water. Other tests for the skinIn addition, those using capsaicin or benzoyl peroxide are also suitable for evaluating the anti-irritant activity of the compounds. The test an irritant formulations were prepared by combining measured quantities of antimalarials (Sigma or Aldrich) of the present invention (concentration of 250 rnM) in the lactic acid irritant composition. The test formulation was applied to a defined portion of the subject's skin, typically the skin. Controls were performed by applying a corresponding formulation without adding any anti-polyamine irritant to a contralateral portion of the subject's skin. All test solutions (including controls) were applied in a double-blind, randomized manner, using prepared solutions as previously placed in coded bottles designed to be used either on the right or left side of the face (or test area) . Solutions were typically applied using a cotton swab (6 strokes) or sponge applicator to the face and cheekbone extending from the midline of the nose to the center of the cheek and cheekbone to the line of the jaw. The application was made first on the right side and then on the left side. Sensory evaluation scores were recorded for each treated side of the subject's skin every minute for 10 minutes or until 3 consecutive "zero" irritation scores were obtained. The following scores were used on a par-scale to sensory evaluation -. Score Description of irritation 0 No irritation 1 Light irritation - (Itching, burning or itching barely perceptible) 2 Mild irritation - (defined itching, burning or stinging) 3 Moderate irritation - (itching, burning * or distinctly uncomfortable itching, constantly aware of irritation) 4 severe irritation - (itching, burning * or continuous itching, e intensely uncomfortable, would interfere with daily routing) Symptom scores were accumulated, separately for areas treated with irritants and treated with control, for each individual and also for the panel as a whole. Individuals who do not report a cumulative score of at least "7" on at least one treatment area were excluded (in a blinded manner) from further analysis to achieve anti-irritant efficacy with respect to the subjects test more severely susceptib es. From a practical point of view, the scores "0" and "1" in the previous scale would be considered highly desirable for a commercial product because said response would not result in a consumer ceasing to use a product. Some consumers, in fact, might see barely perceptible "sensations" represented by a score of 1 as an indication that a facial skin care product (especially an exfoliator) was working or an advertising product. Conversely, irritation scores of "2", "3" and "4" would likely result in the consumer never buying the product again. In those subjects and skin samples where the irritation was detected, irritation commonly involved a spectrum of heartburn reactions. dogfish -comezón with time. For example, a subject could first experience itching, but moments later he could experience itching without itching. The higher levels of irritation experienced by the subjects (eg, "3" or "4" scores) occasionally showed erythema (visually observable inflammation) as well as effects of sensory irritation. 2. Resul ts The clinical tests, performed as generally deprecated, demonstrated that the polyamine anti-irritant compounds of the invention have significant and reproducible anthrrug effects parcularly if administered concurrently with an irritant compound. . A representative set of test results performed using anti-irri concentrations before acid of 250 mM, shown in the tables and 1 2 below. Table 1 reports representative tests resulting from vains straight chain, branched chain and polyam to heterocyclic. The representative test results are shown in Table 2 for the amino acid compounds of lysine, histidine and ornithine families, including several amino acid derivatives. Where multiple panels were studied (n > l), the percent inhibition was reported as the average of the observed values and representing the inhibition value of cumulative irritation.

ANTI-HAIR DATA TABLE 1 TABLE 2 * Unless stated otherwise, n = l. Appreciating that n = number of panels, not subjects. Figures 1 to 8 show more detailed information of the experiments of two panels conducted using L-argmina (Figures 1-4) and L-lysine (Figures 5-T) (250 M each) as anti-irritant components of the subject formulations. The kl Figures 1 and 5 show the time course of the irritation responses for both skin portions-treated with anti- irritant and untreated (control) panels, Figures 2 and 6 show the cumulative irritation during the time of the symptoms. Test panels, while Figures 3-4 and 7-H show the suppression of cumulative irritation and responses to treated / untreated irritation on an etio-by-subject basis. While the individual responses go a little, the overall effectiveness of the subject formulations is evident. As mentioned above, the anti-enhancing compounds of the invention are preferably chosen from the compounds that are non-irritating in themselves for the user. The lenediam et, a small straight-chain polyamm, is an example of a compound that is reported to have irritant properties (Merck Index, llü edition). Preliminary clinical tests of etiology using the protocol described above yielded variable results and suggested that the compound has low relative reactive properties (<20% inhibition) for some subjects and can actually increase irritation (less than 20%) in some users.

EXAMPLE 2 Dose response studies A study of anti-irritant activity was conducted using different concentrations of L-argyne to achieve the dose-response behavior of the present formulations. The lactic acid protocol described above was used. The inhibition data of irritation were recorded in the following table and indicate the activity ant i rritant e at low concentration (125 mM).

Concentration Percent of (inM) L-Arginine inhi lu c on 125 21% 250 53% The above examples are not intended to limit the scope of the present invention, which is described in the following recitations. In particular, those skilled in the art will recognize various equivalents and substitutions in view of the foregoing description, and it is contemplated that these are within the scope of the invention.

Claims (4)

1. NOVELTY OF THE INVENTION CLAIMS 1. - A composition for topical application to an animal subject comprising a topical vehicle; an irritant ingredient contained in an amount capable of inducing p-irritation in said subject and and an anti-irritant component comprising an anti-oxidant substance of one or more polylamines having a plurality of protonated ammo portions.
2. 2. The composition according to claim 1, further characterized in that said water-soluble polymer is selected from the group consisting of e < -permma, espermidma, put res a, protarnina, imidazola, , i,. < ? and HEPFS.
3. 3. The composition according to claim 1, further characterized in that said water-soluble polyamine is an amino acid having a positively charged nitrogen containing a side chain.
4. 4. The composition according to claim 3, further characterized in that said amino acid is selected from the group consisting of argm na, li ina, his idma and orm ina. 5.- A composition for topical application to a 6 animal subject comprising a topical vehicle; an irritant ingredient contained in an amount capable of inducing skin irritation in said subject; and an anti-oxidant component comprising a water-soluble amount of one or more soluble amino acids in water having a positively charged nitrogen containing side chain. 6 - The composition in accordance with the i oi ndi cation 5, also characterized in that said amino acid is selected from the group consisting of arginine, l i sma, h i i d i na and orn i t i n. 7. The composition according to claim 5, further characterized in that said anti-ratting component comprises at least one amino acid of r? Edido having a positively charged nitrogen containing side chain, said derived amino acid consists of an amino acid or a substituent selected from terminating substituents] Na of substituents RCO- and R ~, and substituents of C terminus of -NH2, -NHNI-12, -NHR, -NR2 and -OR (where each R is selected independently of unbranched and branched, lower-substituted and substituted alkyl, alkenyl, and alkynyl groups of from 1 to about 10 carbons, anlo, alkaryl, ara) and cycloalkyl groups of from about 3 to about 20 carbons , and, in the case of -NR2 of the cyclized groups that form (together with the nitrogen volume) a k / Heterocyclic co ring of 5-R members which optionally contains an oxygen or nitrogen as a heteroatom of a-ring cyano). 8. The composition according to claim 7, further characterized in that said derived amino acid is selected from derivatives of apginy, Usina, hi t a and orm t ina. 9. The composition according to claim 7, further characterized in that said its RCO is an active substance. 10. The composition according to claim 7, further characterized in that said amino acid is an ester form of the amino acid. 11. - The composition in accordance with the * - "d1 '*"' onos 1 or 5, characterized furthermore because said The anti-irritant is present in a concentration of approximately 10 nm to approximately 3000 mM. 12. The composition according to claim 1 or 5, further characterized in that said antagonist component is in a concentration of about 50 mM to about 2000 mM. 13. The composition of composition with claims 1 or 5, further characterized in that said anti-irritant component is in a concentration of about 100 mM to about 1000 nm. 14. The composition according to re-indications 1 or 5, further characterized in that it comprises a quantity of said anti-urinary component capable of inhibiting the average irritation of the skin attributable to said irritant ingredient in a susceptible human population in less approximately 20%,. 15. The composition according to claim 14, further characterized in that said inhibition of skin irritation represents an average reduction in one or more of itching, burning, eating in a human population susceptible to topical application of said composition. , compared to the level of irritation induced in said population by the application of a control formulation containing said irritant ingredient in a vehicle without said anhydride component. 16 .- The composition according to claim 1 or 5, comprising a can i of said component 11 rr11 ant e able to i nh bi r r at least approximately 40% of the cumulative irritation of the skin atr *? 17. The composition according to claim 16, further characterized in that said inhibition of pLel irritation represents an average reduction in one or more of itching. burning and itching in a human population susceptible to the topical application of said composition, in comparison with the level of irritation induced in said population by the application of a control formulation containing said irritant ingredient in a vehicle san said ant 11 rp component. so much. 18. The composition according to claim 1 or 5, further characterized in that said composition is a cosmetic product. 19. The composition according to claim 18, further characterized in that said composition comprises a skin exfoliator, skin peeler or skin cell renewing agent. 20. The composition according to claim 18, further characterized in that said irritant ingredient is selected from the group consisting of carboxylic acids, keto acids, a-hydroxyacids, (3-hydroxyacids, retinoids, peroxides and organic alcohols. - The composition according to claim 20, further characterized in that said irritant ingredient comprises lactic acid or a dehydrated salt.; l my mo. 22. The composition according to claim 20, further characterized in that said irritant ingredient comprises glycolic acid or a salt of the same. 23. The composition according to claim 20, further characterized in that said irritant ingredient comprises salicylic acid or a salt of the rni sin. 24. The composition according to claim 20, further characterized in that said irritant ingredient comprises a combination of lactic acid and cylindrical acid salt or salts thereof. 25. The composition according to claim 20, further characterized in that said irritant ingredient comprises capriloi isalicylic acid or a s l of the same. 26. The composition according to claim 20, further characterized in that said irritant ingredient comprises citric acid or a salt thereof. 27. The composition according to claim 20, further characterized in that said irritant ingredient is a retinoid selected from tretmoin, retinol, rot mal and derivatives thereof. The composition according to claim 20, characterized in addition because said irritant ingredient comprises benzoyl peroxide. 29. The composition according to claim 20, further characterized in that said irritant ingredient comprises acetic acid or a salt of the same. 30. The composition according to claim 20, further characterized in that said irritant ingredient comprises one or more of the group consisting of acid 1-p? Carboxylic acid, cappucilic acid, salicilic acid, cf-hydrox idecanoic acid, cx-hydroxyl acid, oxo-octanol, glycololone, ethoxypropylgluconate, oxalic acid, alic acid, tartaric acid, acid send! ico, benzyl acid, giucomco acid, pyruvic acid and phenol. 31"- The composition according to claim 20, further characterized in that said irritant ingredient comprises one or more chloroacetic acid or one of the same. 32.- The composition in accordance with the r * e? Vindication 20, further characterized in that the pH of the composition ranges from 1 to 6, 33.- The composition according to claim 20, characterized by the pH of the composition varies from 2 to 4. 34.- The composition of conformity with the rei indication 20, further characterized in that it has a concentration of said irritant ingredient of about 0.01% to about 50%. The composition according to claim 20, further characterized in that it has a concentration of said irritating ingredient around from 0.5% to approximately 20%. 36. The composition according to claim 1 or 5, further characterized in that said composition is an antitranspersive or deodorant p oduct. 37.- The composition < ie according to claim 1 or 5, further characterized in that said composition is a sunscreen product, sunscreen or for treatment of burns by the sun. 38.- The composition according to claim 1 or 5, further characterized in that said composition is an insect repellent product. 39.- The composition according to claim 18, characterized by adornas because said composition is a product for shaving or fiara hair removal, selected from the group consisting of depi products. Ladores, tonic, cream, foam, gel and after-dinner products. 40. The composition according to claim 18, further characterized in that said composition is a product for hair care or hair treatment. 41. The composition according to claim 40, further characterized in that said composition is selected from the group consisting of shampoo, conditioner, dye, dye, lightener, permanent hair undulators and hair malaxers. 42.- The composition according to claim 18, further characterized in that said composition is selected from the group consisting of cleaners, astringents, toners, enjà ¥ ages, serums and chew Lias 43. The composition according to claim 18, further characterized in that said composition is a product. of facial cosmetics. 44.- The composition according to the rei indication 18, further characterized because said composition is selected from the group consisting of creams, 1 oca and humeet ant e. 1 45.- The composition according to the i and vi ndications 1 or 5, characterized furthermore by said composition is selected from the group consisting of soaps and detergents. 46.- The composition according to claim 5 or 5, further characterized in that said composition is a topical drug product. 47.- The composition of >; according to claim 46, further characterized in that said irritant ingredient is capsaacin. 0 48. The composition according to claim 46, further characterized in that said composition is selected from the group consisting of products of antibiotics, analgesics, contraceptives, ani-acne and anti-dandruff. 49. The composition according to claim 48, further characterized in that said irritant ingredient is benzoyl peroxide. 50.- The composition according to claims L or 5, further characterized in that said composition is formulated with rectal or vaginal suppository, foam, cream, gel, ointment, l or enema. 51. The composition according to claims 1 or 5, further characterized in that said composition is formulated for administration to the mouth, gargantuan or lips. 52. The composition according to claim 51, formulated as a trocisco, mouth rinse or gargle. 53. The composition according to claim 1 or 5, formulated as a liquid, gel, cream, emulsion, suspension or bar. 54.- The composition according to claims 1 or 5, formulated as a physical api icator. 55. The composition according to claim 54, further characterized in that said physical ap- * icaror is selected from the group consisting of fabrics, tissues, swabs, bandages and wet towels. 56.- The composition according to the reivations 1 or 5, further characterized because said composition is formulated for administration to the respiratory system. 57.- The composition in accordance with the rei indication 56, formulated with a steam or spray. 58. The composition according to claim 1 or 5, further characterized in that said composition is formulated for otic admiration. 59. The composition according to claims 1 or 5, further characterized in that said composition is formulated for administration to the reproductive system. 60.- The composition according to claims L or 5, further characterized in that said composition is formulated for ocular administration. 61.- The composition according to claims 1 or 5, further characterized in that said composition is formulated for admi- stration to the gastrointesis system1. 62., - The composition according to 1 or 5, further characterized in that it comprises by * at least one second anpyritant agent. 63.- The composition according to claim 62, characterized also because the amount? < iad of anti-irritant component and said second agent is capable of inhibiting average cumulative skin irritation attributable to said irritant ingredient in a susceptible human population by at least about 20%. 64.- The composition according to claim 62, further characterized in that the amount of anti-fat component and said second agent is capable of inhibiting at least about 40% of the average cumulative skin irritation attributable to said irritant ingredient in said composition. at least 10% of the susceptible human population. The composition according to claim 62, further characterized in that the second agent is selected from the group consisting of mediators of potassium channels, regulatory agents or blockers, regulatory agents or calcium channel blockers, blocking agents of sodium channel, steroidal or non-steroidal anti-inflammatory agents, aloe era, chamomile, or-hisabolol, clear tail extract, green tea extract, tea tree oil, orozus extract, allanto, urea, caffeine and other xant as, and glycyrrhiza acid and its derivatives. 66.- A composition for inhibiting skin irritation in an animal subject that has an ant component. The composition comprises a quantity of antipoint of one or more water-soluble polyarms having a plurality of protonated portions. 67. The composition according to claim 66, further characterized in that said polia ina soluble in water is selected from the group consisting of esperrnma, esperrní di na, put resin, protamina, imidazola, p perazma and HEPES. (> 8. The composition according to claim 66, further characterized in that said water soluble polyamide is an amino acid having a positively charged nitrogen containing a side chain !. according to claim 68, further characterized in that said amino acid is selected from the group consisting of arganme, lyna, histidine and ornin-1 .. A composition for inhibiting skin irritation in an animal subject containing An irritant component comprising an anti-irritant amount of one or more water-soluble amino acids having a positively charged nitrogen containing side chain 71. The composition according to claim 70, further characterized by said soluble amino acid. In water it is selected from the group consisting of arganme, lisma, histadine and omityria 72. The composition according to claim 70, further characterized because The anti-irritant component comprises at least one amino acid derivative having a positively charged nitrogen containing a later-al chain, said derivatized amino acid consisting of an amino acid or a substituent selected from a substituent. terminal N-cr terminator of the RCO- and R ~ substituents, and C-terminal substituents of -NH2, -NHNH2, -NHR, -NR2 and -OR (where each R is independently selected from unbranched and branched, 5!) substituted and substituted lower alkyl, alkenyl, and alkylaryl groups of about 10 carbons, aplo, alkalyl, aralkyl and cycloalkyl groups of from about 3 to about 20 carbons, and, in the case of -NR2 of the cyclised groups they form (together with the nitrogen atom) a heterocyclic ring of 5-B members which optionally contains an oxygen or nitrogen as an additional ring heteroatom). 73. The composition according to claim 72, further characterized in that said derivatized amino acid is selected from aragamna, lysine, hi i dina and orn111 na derivatives. 74.- The conformational composition with claims 66 or 67 comprising said anti- propellant component in a concentration of about 10 in. To about 3,000 inM. 75. The composition according to claim 66 or 70 comprising said irritant component in a concentration of about 50 mM to about 2000 rnM. 76. The composition according to claim 56 or 70 comprising said anta- gating component in a concentration of about 100 mM to about 1000 mM. 77.- The composition according to claim 66 or 70, further characterized in that said 50 Inhibition of skin irritation represents a reduction in skin irritation attributable to a preexisting skin condition or skin irritation disorder. 78.- The composition according to claim 77, characterized further because said irritation < ie The skin is attributable to atopic dermatitis, non-atopic dermatitis, as, rhinitis, conjunctivitis, ecze- > ma, psoriasis or infectious disease. 7 < 3. The composition according to claim 67 or 70, further characterized in that said irritation of the skin is ocular irritation. 80.- The composition according to claims 67 or 70, characterized further because said skin irritation is irritation of the respiratory system. 81.- The composition in accordance with the The invention also relates to conditions 67 or 70, further characterized in that said skin irritation is irritation of the wound 82. The composition according to claim 66 or 70, further characterized by the skin irritation ee. irritation of the reproductive system 83. The composition according to claim 66 or 70, further characterized in that said irritation of the skin is irritation of a mucous membrane 84. The composition according to claim 66 or 70, characterized further because said skin irritation is skin epidermal irritation. 85. The composition according to claim 66 or 70, further characterized in that said skin irritation of the dermal skin. 86.- The composition according to the description 77, characterized in addition because said skin irritation is attributable to environmental exposure to one or more of sunlight, humidity, wind, cold temperature or hot or humid conditions. . 87. The composition according to claim 77, further characterized in that said skin irritation is susceptible to exposure to a chemical agent irri an e. 88.- The composition in accordance with rei indication 87, also characterized because said exposure to the irritant chemical agent is attributed to the application of a topical product. 8 < 3. The composition according to claim 88, further characterized in that said product is selected from the group consisting of antiperspirants, deodorants, sunscreens, sunscreens, treatment for sunburn, insect repellents, exfoliators, peeling. of the skin, skin cell renewers, fragrance, for shaving and hair removers, for head care or hair treatment, eye care solutions or contact lenses, ] Irritants, astringents, toni ficators, rinses, serum, hl face masks, cosmetics for the face, cream, moisturizing lotion, soap, detergent and drugs t peaks. 90. The composition according to claim 88, further characterized in that said composition is packaged with instructions that direct the administration of the composition before, with or after the administration of said peak product. 91.- The composition according to claim 87, also characterized because said exposure to irritating chemical agents is punishable by stinging or biting of insects, or by exposure to plants. 92. The composition according to claim 76, further characterized in that said skin irritation is attributable to one or more shaving, cleansing or bathing for the skin, sweat and physical trauma to the skin. 93. The composition according to claim 56 or 70, further characterized by said skin irritation attributable to dry skin. 94. The composition according to claim 66 or 70 comprising an amount of said anti-irritant component capable of inhibiting said skin irritation in subjects experiencing the same at an average of at least 20%. The composition according to claim 66 or 70 comprising an amount of said anti-irritant component capable of inhibiting said skin irritation by at least 40% in at least 10% of the subjects experiencing the same. 96. The composition according to claim 66 or 70, further characterized in that said composition is formulated as a rectal or vaginal suppository, foam, cream, gel, ointment, enema or shower. 97. The composition according to claim 66 or 70, further characterized in that said arrangement is formulated to admire the mouth, throat or lips. 98.- The composition in accordance with claim 97, formulated as a trocine, mouth rinse or gargle. 99.- The composition according to claim 67 or 70, formulated with a liquid, gel, cream, mui ion, suspension or bar. 100.- The composition according to claim 67 or 70, formulated with a physical applicator. 101. The composition according to claim 66 or 70, further characterized in that said composition is formulated for administration to the respiratory tract system. 102.- The composition according to claim 101 formulated as a vapor or spray. 103.- The composition in accordance with the rei indications 66 or 70, also characterized because said i) 3 The composition is formulated to administer otic. 104.- The composition according to claim 66 or 70, further characterized in that said composition is formulated for administration to the gastrointestinal system. 105. The composition according to claim 66 or 70, further characterized in that said composition is formulated for ocular administration. 106.- The composition according to the vindications 66 or 70, characterized furthermore because said composition is formulated for administration to the reproductive system. 107. The composition according to claim 66 or 70, further characterized in that it comprises at least one second antireanitary agent. 108. The composition according to claim 107, charcterized also because-? and! The second agent is selected from the group consisting of mediators of potassium channels, regulatory agents or blockers, regulator agents or calcium channel blockers, sodium channel blocking agents, steroidal anti-inflammatory agents or non-steroidal agents. est eroids, aloe vera, chamomile, abyssolol, clear cola extract, green tea extract, tea tree oil, orozus extract, allanto, urea, caffeine and other xanthines, and glycyrrhizin and its derivatives. 109. - The use of the composition in accordance with claims 1 or 5 in the preparation of a medicament? inhibiting skin irritation associated with an irritant ingredient contained in a topical formulation applied to an animal subject. 110.- The use of the composition according to claims 66 or 70, in the preparation of a medicament for inhibiting the irritation of the skin in an animal subject. 11 L. The use according to claim 110, further characterized in that said medicament is administered within about three hours before the application to a subject of a second topical formulation containing an irritant ingredient. 112. The use according to claim 110, further characterized in that said medicament is administered substantially simultaneously with the application to the subject of a second topical formulation containing an irritant ingredient. 113. The use according to claim 110, further characterized in that said medicament is administered to inhibit skin irritation attributable to a skin disease or preexisting skin irritation condition of an animal or irritation disorder of the skin. skin. 114. The use according to claim 110, character *? Also because such skin irritation is eye irritation. 115. - The use according to claim 110, further characterized in that said irritation of the skin is irritation of the respiratory system. 116. The use according to claim 110, further characterized in that said irritation of the skin is irritation of the gastrointestinal system. 117. The use according to claim 110, further characterized in that said irritation of the skin is irritation of the reproductive system. 118.- The use in accordance with the claim 110, further characterized in that said skin irritation is irritation of a mucosal membrane. 119. The use according to claim 110, further characterized in that said irritation of the skin is irritation of the epidermal skin. 120. The use according to claim 110, further characterized in that said irritation of the skin is irritation of the dermal skin. 121. The use according to claim 113, further characterized in that said irritation of the skin is attributable to environmental exposure to one or more sunlight, low humidity, cold weather wind, or hot or humid conditions. 122. The use according to claim 113, also character- ized because said irritation of the skin is susceptible to exposure to an irritant chemical agent. H H 123. - The use according to claim 113, further characterized in that said skin irritation is attributable to one or more of shaving, cleansing or bathing of skin and physical trauma of the skin.