MXPA99005852A - Pharmaceutical compositions containing gellantsin the form of alkyl amides of di- and tri-carboxylic acids - Google Patents

Abstract

The present invention relates to pharmaceutical compositions useful as carriers for topical skin actives such as moisturizers, protectants, antiperspirants, deodorants and the like;and more particularly, to such pharmaceutical compositions in the form of a gel or gel stick.

Description

PHARMACEUTICAL COMPOSITIONS CONTAINING GELIFIERS IN THE FORM OF ALKYLAMIDS OF DI- AND TRI-CARBOXYLIC ACIDS FIELD OF THE INVENTION The present invention relates to compositions useful as carriers for pharmaceutical active ingredients such as antiseptics, antifungals, sunscreens, deodorants and the like; and more particularly, to such pharmaceutical compositions in the form of a gel or gel stick.

BACKGROUND OF THE INVENTION Topically effective pharmaceutical active ingredients for treating dermatological conditions are generally delivered by means of ointment, gel, solid gels, lotion or cream vehicles. Such vehicles provide varying degrees of emolliency and barrier protection for the skin, thus promoting uniform application and effective transdermal absorption of the active ingredients. Conventional examples of such vehicles are described in Sagarin, Cosmetics Science and Technology, 2nd Edition, Vol. 1, Wiley Interscience (1972) and Encyclopedia of Chemical Technology, Third Edition, Volume 7. In recent years, solid gel vehicles have become increasingly popular in view of its easy application form "without touching" them, as well as the discovery of formulations with less visible residue. The bar shape is distinguished from gels or pastes because the bar can maintain its shape for extended periods of time outside the packaging (although some shrinkage occurs due to evaporation of solvent). Alternatively, one can adjust the amount of stearyl alcohol and castor wax and / or modify the manufacturing process to produce a viscous gel or paste instead of the bar. These gels or pastes can be suitably packaged in containers that have the appearance of a bar, but are supplied through openings arranged on the upper surface of the package. These products are typically called soft-ons. A more detailed description of soft gels is found in US Patent No. 5,102,656 given to Kasat, US Patent No. 5,069,897 given to Orr, and US Patent No. 4,937,069 given to Shin, each of which is incorporated in US Pat. the present by reference in its entirety. As alluded to above, however, a major disadvantage of the hard gel stick carriers remains the visible residue associated with their application. This visible residue tends to stain fabrics and is therefore considered undesirable by consumers. Additionally, when formulating gel stick carriers, the active ingredients are typically suspended in a carrier such as cyclomethicone. Such suspensions generally result in problems of syneresis and / or runoff that adversely affect the stability of the formula and the aesthetic properties; This is particularly true when it is sent to hot climates and / or high altitudes. Attempting to satisfy these concerns, researchers have suggested varying the type of gelling agent used. One proposal involved the use of dibenzylidene alditols. A problem with dibenzylidene alditols, however, is related to their inherent instability in acidic environments. On the other hand, solid gel sticks that are combined with gelling agents with certain active ingredients (eg, solubilized antiperspirant active ingredients) resulted in solid gel sticks having a tactile sticky feel. Another attempt involved the use of N-acyl amino acid gelling agents. The information related to the use of these gelling agents is found in: US Patent No. 3,969,087 published July 13, 1976 given to Saito et al .; Japanese Patent Application 1-207223, published August 21, 1989; Japanese Patent Application 1-207223 which was published on August 21, 1989; and Japanese Patent Application 2-180805 which was published on July 13, 1988. While the prior art discloses a variety of gelling agents useful in the formulation of soft gel compositions or gel bars, there is still a need for additional formulations that reduce the visible residue associated with such compositions. The present inventors have found that soft gel pharmaceutical compositions or gel sticks incorporating gelling agents in the form of alkylamides of di- and tri-basic carboxylic acids provide such compositions with reduced visible residue.

Accordingly, it is an object of the present invention to provide improved pharmaceutical compositions. It is also an object of the present invention to provide improved pharmaceutical compositions in the form of a solid gel or gel stick. It is another object of the present invention to provide improved pharmaceutical compositions of solid gel or soft gel bars that additionally comprise a pharmaceutically acceptable active ingredient. It is a further object of the present invention to provide improved pharmaceutical compositions of solid gel stick or gel for topical application to the skin or mucosal tissue of mammals, containing a pharmaceutically acceptable active ingredient and a gelling agent, which have good structural integrity with a reduced visible residue. Still a further object of the present invention is to provide methods for delivering pharmaceutically acceptable active ingredients. These and other objects will become readily apparent from the description that follows.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to pharmaceutical compositions, comprising: A.) an effective and safe amount of at least one active pharmaceutical ingredient; B.) a gelling agent of the formula: • X -Y -Z -R, 0 R10 R6 wherein: a) Ri is zero or zero, hydroxy, hydrogen, aryl, siloxane or alkyl of 1 to 22 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 22 atoms carbon, alkoxy of 1 to 22 carbon atoms, alkyl esters of 1 to 22 carbon atoms, alkyl ethers of 1 to 22 carbon atoms, or aryl substituted with alkyl of 1 to 22 carbon atoms; b) R2, R4, R5 and R6 are independently or together hydrogen, hydroxy, aryl, siloxane or alkyl of 1 to 22 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 22 carbon atoms, alkoxy of 1 to 22 carbon atoms, alkyl esters of 1 to 22 carbon atoms, alkyl ethers of 1 to 22 carbon atoms, or aryl substituted with alkyl of 1 to 22 carbon atoms; c) R3 is nil, hydroxy, hydrogen, saturated or unsaturated, substituted or unsubstituted, 1 to 4 carbon atoms, straight chain, branched or cyclic, alkenyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 atoms of carbon, alkyl esters of 1 to 4 carbon atoms or alkyl ethers of 1 to 4 carbon atoms; d) R7 and Re are independently or together nothing, hydrogen, hydroxy, aryl, siloxane or alkyl of 1 to 22 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 22 atoms carbon, alkoxy of 1 to 22 carbon atoms, alkyl esters of 1 to 22 carbon atoms, alkyl ethers of 1 to 22 carbon atoms, or aryl substituted with alkyl of 1 to 22 carbon atoms; e) Rg is nothing or hydrogen; f) Rio and Rn are independently or together nothing, hydrogen, hydroxy, aryl, siloxane or alkyl of 1 to 6 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 6 atoms carbon, alkoxy of 1 to 6 carbon atoms, alkyl esters of 1 to 6 carbon atoms, alkyl ethers of 1 to 6 carbon atoms, or aryl substituted with alkyl of 1 to 6 carbon atoms; g) X is nothing, nitrogen, aryl or - (CH2) n ~ where n is an integer from 1 to 6; h) And it is nothing, acyl or carbonyl; i) Z is nothing, hydrogen, hydroxy, aryl, siloxane, nitrogen or alkyl of 1 to 22 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 22 carbon atoms, alkoxy of 1 to 22 carbon atoms, alkyl esters of 1 to 22 carbon atoms, alkyl ethers of 1 to 22 carbon atoms, or aryl substituted with alkyl of 1 to 22 carbon atoms; and j) whenever (i) when X is nothing, Y, Z, R3, R7 and R are nothing, C is directly connected to C "and Ri is not a hydrogen, (ii) when X and Z are nothing and Y is nothing, X is directly linked to Z, (iii) when Z is nothing, a hydrogen or a hydroxy, R7 and R8 are nothing, and (iv) when "a" is a double bond, R3 and Rg are nothing; and C.) an anhydrous liquid carrier. The present invention further relates to methods for delivering to the skin materials and pharmaceutical active ingredients with reduced residue. By "acyl" or "carbonyl" as used herein, is meant a radical formed by the removal of the hydroxy and alkyl portions of a carboxylic acid (i.e., -C-). By "alkyl" as used herein, it is meant an unsubstituted or substituted saturated hydrocarbon chain radical having from 1 to 22 carbon atoms, preferably from 1 to 8 carbon atoms. Preferred alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, hexyl and octyl. By "alkenyl" as used herein, is meant an unsubstituted or substituted hydrocarbon chain radical having from 2 to 22 carbon atoms, preferably from 2 to 8 carbon atoms, and having at least one double bond olefinic By "aryl" as used herein, an aromatic carbocyclic ring radical is meant. Preferred aryl groups include, but are not limited to, phenyl, tolyl, xylyl, cumenyl and naphthyl. By "alkoxy" as used herein, is meant an oxygen radical having a hydrocarbon chain substituent, wherein the hydrocarbon chain is an alkyl or alkenyl (i.e., -O-alkyl or -O-alkenyl ). Preferred alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy and allyloxy. By "siloxane" as used herein, is meant a linear compound consisting of silicon atoms bonded by a single bond to oxygen, and arranged in such a way that each silicon atom is bonded with two or four oxygen atoms (ie, -Yes (0) 2RR ', wherein R and R', independently, are, but are not limited to, alkyl, alkyl esters or alkyl ethers). By "cyclic chain" as used herein, is meant an unsubstituted or substituted, saturated, unsaturated or aromatic hydrocarbon chain ring radical. The cyclic chains are monocaine, or are systems of polycyclic rings fused, bridged or spiro. As defined above and as used herein, the substituent groups may themselves be substituted. Such substitution may be with one or more substituents. Such substituents include (for example) those listed in C. Hansch and A. Leo, Substituent Constants for Correlation Analysis in Chemistry and Biology (1979), incorporated by reference herein. Preferred substituents include (for example) alkyl, alkenyl, alkoxy, hydroxy, oxo, nitro, amino, aminoalkyl (for example aminomethyl, etc.), cyano, halo, carboxy, alkoxyacyl (e.g., carboethoxy, etc.), thiol , aryl, cycloalkyl, heteroaryl, heterocycloalkyl (eg, piperidinyl, morpholinyl, pyrrolidinyl, etc.), imino, thioxo, hydroxyalkyl, aryloxy, arylalkyl, and combinations thereof.

All concentrations and ratios are by weight of the total composition, unless indicated otherwise. Additionally, all measurements were made at 25 ° C unless otherwise specified. By the phrase "room temperature" as used herein, the surrounding conditions are understood to be under about 1033 kg / cm2 (one atmosphere) of pressure, at about 50% relative humidity, and about 25 ° C, at unless otherwise specified. The pharmaceutical compositions of the present invention may comprise, consist of, or consist essentially of the essential elements and limitations of the invention described herein, as well as any of the additional or optional ingredients, components, or limitations described herein.

DETAILED DESCRIPTION OF THE INVENTION The essential components, as well as the optional components of the compositions of the present invention are described in the following paragraphs.

ESSENTIAL COMPONENTS Pharmaceutically acceptable active ingredient An essential component of the present invention are pharmaceutically acceptable active ingredients. By the phrase "pharmaceutically acceptable active ingredient", as used herein, is meant active ingredients administered topically to the skin or mucosal tissue as a form of treatment, or to produce a benefit. Such active ingredients include, but are not limited to, antiseptics or antibacterials, antifungals, exfoliating agents, topical NSAIDS, sunscreens, anti-dandruff agents, deodorants, antiperspirants, and the like. The phrase "effective and safe amount", as used herein, means an amount of an active ingredient sufficiently high to significantly or positively modify the condition to be treated, but sufficiently low to avoid serious side effects (in a relationship reasonable benefit / risk), within the scope of sound medical judgment. A safe and effective amount of the pharmaceutically acceptable active ingredient will vary with the specific active ingredient, the ability of the composition to penetrate the active ingredient through the skin, the amount of composition to be applied, the particular condition being treated, the age and physical condition of the patient being treated, the severity of the condition, the duration of the treatment, the nature of the concurrent therapy, and similar factors. The pharmaceutical active ingredient of the present invention can be an antiseptic or antibacterial active ingredient. Preferred antiseptic or antibacterial active ingredients include (but are not limited to): 2-hydroxy-4, 2 ', 4' -trichlorodiphenyl ether (TCS); 2,6-dimethyl-4-hydroxychloro-benzene (PCMX); 3, 4, 4 '-trichlorocarbanilide (TCC); 3-trifluoromethyl-4, '-dichlorocarbanilide (TFC); 2,2'-dihydroxy-3, 3 ', 5, 5', 6,6'-hexachlorodi phenyl-methane; 2,2'-dihydrqxy-3, 3 ', 5,5'-tetrachlorodiphenylmethane; 2,2'-dihydroxy-3,3'-dibromo-5,5'-dichlorodiphenylmethane; 2-hydroxy-4,4'-dichlorodiphenyl ether; 2-hydroxy-3, 5 ', 4-tribromodiphenyl ether; l-hydroxy-4-methyl-6- (2,4-, 4-trimethylpentyl) -2 (1H) -pyridinone (Octopirox); nitrofurantoin; phenazopyridine; acyclovir; chlorhexidine; peroxides; benzalkonium chloride; benzethonium chloride; iodo; povidone-iodine; methylbenzethonium chloride; rapamycin derivatives and mixtures thereof. The antiseptic or antibacterial active ingredient may be present in a concentration from about 0.01% to about 10%, typically from about 0.1% to about 10% and preferably from about 0.5% to about 10%. The concentration is selected to provide the desired level of antiseptic or antibacterial activity, and can be modified as desired. The pharmaceutical agent can also be an antifungal agent. Suitable antifungal agents for use in the articles of the present invention are selected from the group consisting of butoconazole, clotrimazole, econazole, fluconazole, itraconazole, ketoconazole, miconazole, terconazole, sulconazole, nystatin, haloprogin, tolnaftate, their pharmacological salts and mixtures thereof. the same. Preferred for use herein are the ethers and amines of 1- (β-aryl) ethyl-imidazole described in US Patent No. 3,717,655 given to Godefroi et al., Published on February 20, 1973, derivatives of substituted N-alkylimidazoles. described in U.S. Patent No. 4,078,071 to Walker, published March 7, 1978. Other preferred antimicrobial agents include the tin-containing polymers described in U.S. Patent No. 5,043,463 given to Carraher Jr. , and collaborators, published August 27, 1991. All of these patents are incorporated by reference herein. The antifungal agent can be present in a concentration from about 0.01% to about 4%, typically from about 0.1% to about 2%, and preferably from about 0.5% to about 2%. The concentration is selected to provide the desired level of antifungal activity, and can be modified as desired. Other useful components include hormones such as pregnenolone and estrogens. Exfoliating agents such as salicylic acid and salicylic acid derivatives can be incorporated in the present invention. Also useful are alpha- or beta-hydroxy acids or alpha-keto acids or derivatives thereof described in U.S. Patent No. 4,234,599 to Van Scott et al., Published November 18, 1980, which is incorporated by reference. at the moment. Useful members of this class include alpha-hydroxybutyric acid, alpha-hydroxy-isobutyric acid, alpha-hydroxy-isocaproic acid, alpha-hydroxy-isovaleric acid, a-lactic acid, beta-hydroxybutyric acid, beta-phenyl-lactic acid, acid beta-phenylpyruvic, citric acid ethylpiruvate, galacturonic acid, glucoheptonic acid, glucoheptono-1,4-lactone, gluconic acid, gluconolactone glucuronic acid, glucuronolactone, glycolic acid, isopropyl pyruvate, lactic acid, malic acid, mandelic acid, pyruvate methyl, musician acid, pyruvic acid, saccharic acid, saccharic acid 1,4-lactone, tartaric acid and tartronic acid. The compositions of the present invention may also include topical analgesic agents such as, but not limited to, hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone phosphate, beclomethasone dipropionate, clobetasol valerate, desonido, desoximetasone, deoxycorticosterone acetate, dexamethasone. , dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flu etasone pivalate, fluosinolone acetonide, fluocinonide, flucortin butyl ester, fluocortolone, fluprednidene acetate (fluprednilidene), flurandrenolone, halcinonide, hydrocortisone, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, shortdoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone acetonide, medrisone, amcinafel, amcinafide, betamethasone and the balance of their esters, chloroprednisone, chlorprednisone acetate , clocortelone, clescinolone, dichlorisone, difluprednate, flucloronide, flunisolide, fluorometalone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortamate, meprednisone, for etasone, prednisolone, prednisone, beclomethasone dipropionate, triamcinolone, peroxicam, isoxicam, tenoxicam, sudoxicam, CP-14,304, aspirin, disalcid, benorilate, trilisate, safapirin, solprin, diflunisal, and fendosal, diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, thiopinac, zidomethacin, acemetacin, fentiazac, zomepiract, clidanac, oxepinac , and felbinac, mefenamic, meclofenamic, flufenamic, niflumic, and tolfenamic acid, ibuprofen, naproxen, benoxaprofen, flubiprofen, ketoprofen, fenoprofen, fenbufen, indoprofen, pirprofen, carprofen, oxaprozin, pranoprofen, miroprofen, thioxaprofen, suprofen, alminoprofen, and tiaprofenic , fenibutezone, oxyphenbutezone, feprazone, azapropezone, and trimetazone and mixtures thereof. The sunscreen active ingredients can also be incorporated in the present invention. Suitable sunscreen agents include, but are not limited to, p-aminobenzoic acid, its salts and its derivatives (ethyl, isobutyl, glyceryl esters).; p-dimethylaminobenzoic acid); anthranilates (ie, o-aminobenzoates; 5-methyl, menthyl, phenyl, benzyl, phenylethyl, linallyl, terpinyl, and cyclohexenyl esters); salicylates (amyl, phenyl, benzyl, methyl, glyceryl, and dipropylene glycol esters); cinnamic acid derivatives (methyl and benzyl esters, a-phenylcinnamonitrile, butylcinnamoyl pyruvate); dihydroxycinnamic acid derivatives (umbelliferone, methylumbelliferone, methylaceto-umbelliferone); trihydroxycinnamic acid derivatives (esculetin, methylesculene, daphnetin, and the glycosides esculin and daphnin); hydrocarbons (diphenylbutadiene, stilbene); dibenzalacetone and benzalacetophenone; naphtholsulfonates (sodium salts of 2-naphthol-3,6-disulfonic and 2-naphthol-6,8-disulfonic acids); dihydroxynaphthoic acid and its salts; o- and p-hydroxybiphenyldisulfonates; coumarin derivatives (7-hydroxy, 7-methyl, 3-phenyl); diazoles (2-acetyl-3-bromoindazole, phenylbenzoxazole, methylnaphthoxazole, various arylbenzothiazoles); quinine salts (bisulfate, sulfate, chloride, oleate, and tannate); quinoline derivatives (salts of 8-hydroxyquinoline, 2-phenylquinoline); benzophenones substituted with hydroxy- or methoxy; uric acid and viliuric acid; tannic acid and its derivatives (for example hexaethyl ether); ether (butylcarbotol) (6-propyl piperonyl); hydroquinone; benzophenones (oxibenzene, sulisobenzone, dioxybenzone, benzoresorcinol, 2,2 ', 4,4'-tetrahydroxybenzophenone, 2,2'-dihydroxy-4,' di-ethoxybenzophenone, octabenzone, 4-isopropyl-dibenzoylmethane, butylmethoxydibenzoylmethane, ethacrylene; isopropyl-dibenzoylmethane and mixtures thereof The compositions of the present invention may also include antioxidants or radical scavengers Suitable antioxidants or radical scavengers include, but are not limited to, butylated hydroxybenzoic acids, 6-hydroxy-2 acid, 5, 7, 8-tetramethylchroman-2-carboxylic acid, gallic acid, propyl gallate, uric acid, sorbic acid, fatty acid ascorbic esters, amines, sulfhydryl compounds, dihydroxyfenic acid, pharmaceutically acceptable salts thereof, alkyl esters of the same, derivatives thereof and mixtures thereof The compositions of the present invention may also include topically administered vitamins. Vitamins include, but are not limited to, Vitamin A, ascorbic acid, Vitamin B, biotin, pantothenic acid, Vitamin D, Vitamin E and mixtures thereof and derivatives thereof. Derivatives or analogs of these vitamins can also be used, such as the synthetic analogs of Vitamin A, natural analogs of Vitamin A, geometric isomers and stereoisomers and mixtures thereof. Other useful active ingredients that are useful in the present compositions include anti-dandruff active ingredients such as zinc pyrithione, octopirox, selenium disulfide, sulfur, coal tar, and the like. The deodorant active ingredients (for example bacteriostats, deodorant fragrances, odor absorbers, odor prevention agents, etc.) are described in the chapter entitled "Deodorant Ingredients" by EP Seitz, et al., In Antiperspirants and Deodorants, (K. Laden, et al. Ed. 1988), pages 345-390. Antiperspirants and Deodorants is volume 7 of the Pharmaceutical Science and Technology Series. This chapter, entitled "Deodorant Ingredients" is incorporated herein by reference in its entirety. Suitable deodorant bacteriostats include 2,2 '-methylenebis (3,4,6-trichlorophenol), 2,4,4'-trichloro-2'-hydroxy (diphenyl ether), zinc phenolsulfonate, 2,2'-thiobis ( 4,6-dichlorophenol), p-chloro-m-xylenol, dichloro-m-xylenol and the like. More preferred is 2, 4, 4 '-trichloro-2' -hydroxy (diphenyl ether), which is known generically as triclosan and is available from the Ciba-Geigy Corporation under the registered trademark Irgasan DP-300 Registered Trade Mark. When triclosan is used, it will be present in a range from about 0.05 to about 0.9%, preferably from about 0.1 to about 0.5% by weight of the composition. Other types of bacteriostats include sodium N-lauroyl sarcosinate, sodium N-palmi toilsarcosinate, lauroyl sarcosine, N-myristoylglycine, potassium N-lauroyl sarcosinate and aluminum chlorohydroxy lactate (sold by Reheis Chemical Company under the trademark of Chloracel).

The compositions of the present invention may also incorporate antiperspirant active ingredients. These antiperspirant active ingredients are preferably particulate astringent compounds having an average particle size between about 5-200 microns. Suitable astringent compounds include aluminum chloride, aluminum hydrochloride, aluminum sulfocarbolate, aluminum sulfate, aluminum zirconium hydrochloride, zinc sulfate, zinc sulfocarbolate, and zirconium hydrochloride. Preferred types of astringent compounds are aluminum chlorohydrates and aluminum-zirconium hydrochlorides, such as aluminum-zirconium tetrachlorohydrexglycine, which is commercially available as Rezal 36 GP Superultrafine (Reheis), and Reach AZP 908 (Reheis). The organometallic astringent compounds tend to have lower densities, which are advantageous for purposes of equalizing the density of the organic matrix phase and the particle phase dispersed in a pharmaceutical product. Mixtures of the above dermal active ingredients can be incorporated in the present invention.

Alkylamides of Carboxylic Acids Di- and / or Tri-basic O'tro essential component of the present invention are the gelling agents in the form of alkylamides of acids or di- and / or tri-basic carboxylic anhydrides. Alkylamides suitable for use in the present invention generally have the formula: or R1- c- -C-N -R R3-X -Y -Z -R8 where a main structure is formed from the junction of C, C "and X, and where a) Ri is zero or zero, hydroxy, hydrogen, aryl, siloxane or alkyl of 1 to 22 carbon atoms saturated or unsaturated , substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 22 carbon atoms, alkoxy of 1 to 22 carbon atoms, alkyl esters of 1 to 22 carbon atoms, alkyl ethers of 1 to 22 carbon atoms, or aryl substituted with alkyl of 1 to 22 carbon atoms, preferably alkyl of 4 to 18 carbon atoms, alkenyl of 4 to 18 carbon atoms, alkoxy of 4 to 18 carbon atoms, alkyl esters of 4 to 18 carbon atoms, alkyl ethers of 4 to 18 carbon atoms, or aryl substituted with alkyl of 4 to 18 carbon atoms, more preferably alkyl of 12 to 1 carbon atoms, alkenyl of 12 to 18 carbon atoms, alkoxy from 12 to 18 carbon atoms, alkyl esters of 12 to 18 carbon atoms, alkyl groups of 12 to 18 carbon atoms, or aryl substituted with alkyl of 12 to 18 carbon atoms; b) R2, R, R = and Re are independently or together hydrogen, hydroxy, aryl, siloxane or alkyl of 1 to 22 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 22 carbon atoms, alkoxy of 1 to 22 carbon atoms, alkyl esters of 1 to 22 carbon atoms, alkyl ethers of 1 to 22 carbon atoms, or aryl substituted with alkyl of 1 to 22 carbon atoms, preferably alkyl of 4 to 10 carbon atoms, alkenyl of 4 to 10 carbon atoms, alkoxy of 4 to 10 carbon atoms, alkyl esters of 4 to 10 carbon atoms, alkyl ethers of 4 to 10 carbon atoms, or aryl substituted with alkyl of 4 to 10 carbon atoms, more preferably alkyl of 4 to 8 carbon atoms, alkenyl of 4 to 8 carbon atoms, alkoxy of 4 to 8 carbon atoms, alkyl esters of 4 to 8 atoms of carbon, alkyl ethers of 4 to 8 carbon atoms, or aryl substituted with alkyl ilo of 4 to 8 carbon atoms; c) R3 is nil, hydroxy, hydrogen, saturated or unsaturated, substituted or unsubstituted, 1 to 4 carbon atoms, straight chain, branched or cyclic, alkenyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 atoms of carbon, alkyl esters of 1 to 4 carbon atoms or alkyl ethers of 1 to 4 carbon atoms, preferably an alkoxy of 1 to 4 carbon atoms, hydroxy or hydrogen, more preferably a hydroxy or hydrogen; d) R7 and R8 are independently or together nothing, hydrogen, hydroxy, aryl, siloxane or alkyl of 1 to 22 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 22 atoms of carbon, alkoxy of 1 to 22 carbon atoms, alkyl esters of 1 to 22 carbon atoms, alkyl ethers of 1 to 22 carbon atoms, or aryl substituted with alkyl of 1 to 22 carbon atoms, preferably alkyl from 4 to 10 carbon atoms, alkenyl of 4 to 10 carbon atoms, alkoxy of 4 to 10 carbon atoms, alkyl esters of 4 to 10 carbon atoms, alkyl ethers of 4 to 10 carbon atoms, or aryl substituted with alkyl of 4 to 10 carbon atoms, more preferably alkyl of 4 to 8 carbon atoms, alkenyl of 4 to 8 carbon atoms, alkoxy of 4 to 8 carbon atoms, alkyl esters of 4 to 8 carbon atoms , alkyl ethers of 4 to 8 carbon atoms, or aryl substituted with alkyl 4 to 8 carbon atoms; e) R9 is nothing or hydrogen; f) Rio and n are independently or together nothing, hydrogen, hydroxy, aryl, siloxane or alkyl of 1 to 6 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 6 carbon atoms carbon, alkoxy of 1 to 6 carbon atoms, alkyl esters of 1 to 6 carbon atoms, alkyl ethers of 1 to 6 carbon atoms, or aryl substituted with alkyl of 1 to 6 carbon atoms, preferably alkyl of 1 to 4 carbon atoms, alkenyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkyl esters of 1 to 4 carbon atoms, alkyl ethers of 1 to 4 carbon atoms, or aryl substituted with alkyl of 1 to 4 carbon atoms, or hydrogen, more preferably a hydrogen; g) X is nothing, nitrogen, aryl or - (CH2) n- where n is an integer from 1 to 6, preferably - (CH2) n- where n is an integer from 1 to 3; h) And it is nothing, acyl or carbonyl; i) Z is nothing, hydrogen, hydroxy, aryl, siloxane, nitrogen or alkyl of 1 to 22 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 22 carbon atoms, alkoxy of 1 to 22 carbon atoms, alkyl esters of 1 to 22 carbon atoms, alkyl ethers of 1 to 22 carbon atoms, or aryl substituted with alkyl of 1 to 22 carbon atoms, preferably alkyl of 4 to 10 carbon atoms, alkenyl of 4 to 10 carbon atoms, alkoxy of 4 to 10 carbon atoms, alkyl esters of 4 to 10 carbon atoms, alkyl ethers of 4 to 10 carbon atoms, or aryl substituted with alkyl of 4 to 10 carbon atoms, more preferably alkyl of 4 to 8 carbon atoms, alkenyl of 4 to 8 carbon atoms, alkoxy of 4 to 8 carbon atoms, alkyl esters of 4 to 8 carbon atoms, alkyl ethers of 4 to 8 carbon atoms, or aryl substituted with alkyl of 4 to 8 carbon atoms carbon; and j) "a" is a double or single bond provided that: (i) when X is nothing, Y, Z, R3, 'R7 and R8 are nothing, C is directly attached to C "and Ri is not hydrogen; ii) when X and Z are nothing and Y is nothing, X is directly linked to Z, (iii) when Z is nothing, a hydrogen or a hydroxy, R7 and R8 are nothing, and (iv) when "a" is a double bond, R3 and R9 are nil The acid alkylamides or di- and tri-basic carboxylic anhydrides suitable for use in the present invention include the alkylamides of citric acid, tricarballic acid, aconitic acid, nitrilotriacetic acid, succinic acid and itaconic acid such as 1,2,3-propanedibutyl amide, 2-hydroxy-1,2,3-propanedibutyl amide, 1-propen-1,2,3-trioctylamide, N, N ', N "- tri (acetodecylamide) amine, 2-dodecyl-N, N'-dihexy lsuccinamide, and 2-dodecyl-N, N'-dibutyl succinamide. Preferred for use in the present invention are the alkylamides of dicarboxylic acids such as the di-amides of alkylsuccinic acids, alkenylsuccinic acidsAnhydrides and alkylsuccinic alkenylsuccinic anhydrides, more preferably 2-dodecyl-N, N'-dibutilsuccinamida. The alkylamide gelling agents, preferably, have opposite and substantially parallel end chains that extend outward from the main structure of the gelling agent. Without being limited by theory, it is believed that this spatial disposition, or structural configuration of "pitch", facilitates the formation of networks essential to the formulation of the compositions of gel or stick. By the phrase "tuning fork configuration" used herein means any configuration resembling an article or implement having a handle portion which extends longitudinally at one end to form two prongs. It is also preferred that the end chains are attached to the main structure of the gelling agent by means of acyl-amide linkages wherein the acyl portion of the acyl-amide linkage is directly attached to the main structure of the gelling agent.

The alkylamides of the present invention are synthesized using any of the following one or two step reaction procedures. The one-step process involves direct amidation of the di- or tri-basic organic acid or anhydride with the appropriate alkylamine at reaction temperatures typically at or near the boiling point of the alkylamine, preferably from about 30 ° C to about 200 ° C, followed by removal of excess amine. Certain reactions, due to their exothermic nature, may not require external heating. The two-stage process involves the esterification of the di- or tri-basic organic acid or anhydride with methanol using a boron trifluoride catalyst or other Lewis acid at a temperature from about 30 ° C to about 100 ° C, followed by by removing excess methanol and catalyst. The resulting trimethyl ester is then amidated as described in the one step process above using the appropriate alkylamine, followed by removal of the excess amine. Preferably, the alkylamides of the present invention are non-polymeric.

When the alkylamide of the present invention is included in lower concentrations in the composition, a gel is formed. At higher concentrations, or when other gelling agents are included in the composition, the hardness of the composition increases, to form a hard bar. The alkylamides of the di- and tribasic carboxylic acids are preferably present in a concentration from about 0.1% to about 25%, more preferably from about 1% to about 15%, more preferably from about 1% to about 10% Anhydrous Liquid Carrier The pharmaceutical compositions of the present invention comprise an anhydrous liquid carrier for the alkylamide of the present invention, wherein the pharmaceutical carrier comprises one or more anhydrous liquids, each of which or collectively have a solubility parameter from about 3 to about 20 (calories / cm3) 1/2, preferably from about 5 to about 16 (calories / cm3) 1/2, more preferably from about 5 to about 11 (calories / cm3) 1 2. The anhydrous carrier is a liquid under environmental conditions.

The solubility parameters for liquid carriers or other materials, and the means for determining such parameters are well known in the chemical art. A description of the solubility parameters and the means to determine them are described by C.D. Vaughan, "Solubility Effects in Product, Package, Penetration and Preservation" 103 Pharmaceuticals and Toiletries 47-69, October 1988; and C. D. Vaughan, "Using Solubility Parameters in Pharmaceutical Formulation," 36 J. Soc. Pharmaceutical Chemists 319-333, September / October 1988, the disclosures of which are incorporated herein by reference. The concentrations of the anhydrous liquid carrier in the pharmaceutical composition will vary with the type of carrier selected, the type of gelling agent used in combination with the carrier, and the solubility of the selected gelling agent in the selected carrier, etc. Preferred concentrations of the anhydrous liquid carrier are in the range of about 10% to about 80%, preferably from about 30% to about 70%, more preferably from about 45% to about 70% by weight of the composition.

The anhydrous liquid carrier preferably comprises one or more anhydrous liquids suitable for topical application to human skin, the carrier or combination of liquid carriers are liquid under ambient conditions. The term "anhydrous" as used herein means that the pharmaceutical gel compositions of the present invention, and the essential or optional components thereof different from the pharmaceutically acceptable ingredients, are substantially free of added or free water. From a formulation point of view, this means that the pharmaceutical gel compositions of the present invention preferably contain less than about 5%, preferably less than about 3%, more preferably less than about 1%, more preferably zero percent by weight of free water or added, different from the water of hydration typically associated with pharmaceutically acceptable active ingredients prior to formulation. These anhydrous liquid carriers can be organic or contain silicone, be volatile or non-volatile, polar or non-polar, as long as the carrier can form a solution or other homogeneous liquid or homogeneous liquid dispersion with the selected gelling agent at the selected gelling concentration. a temperature from about 28 ° C to about 250 ° C, preferably from about 28 ° C to about 100 ° C, more preferably from about 28 ° C to about 78 ° C. The anhydrous liquid carrier preferably has a low viscosity to provide an improved spreadability efficiency on the skin. The anhydrous liquid carrier preferably comprises a modified or organofunctional silicone carrier selected from the group consisting of polyalkyl, loxanes, polyalkylarylsiloxanes, polyestersiloxanes, polyethersiloxane copolymers, polyfluorosiloxanes, polyaminosiloxanes, and combinations thereof. These modified silicone carriers should be liquid under ambient conditions, and have a viscosity of less than about 100,000 centistokes, preferably less than about 500 centistokes, more preferably from about 1 centistoke to about 50 centistokes, and even more preferably from about 1 centistoke to about 20 centistokes. These modified silicone carriers are generally known in the chemical art, some examples of which are described in 1 Cosme ti cs, Sci ence and Technolgy 27- 104 (M. Balsa and E. Sagarin editores 1972); U.S. Patent No. 4,202,879, issued to Shelton and published May 13, 1980; U.S. Patent No. 5,069,897, issued to Orr and published on December 3, 1991; whose descriptions are incorporated herein by reference. Modified silicone carriers suitable for use in pharmaceutical compositions include, but are not limited to, compounds or materials defined above, which are generally characterized as follows: silicone polyethers or silicone glycols (such as dimethicone copolyol); polyethers attached to silicone alkyl (such as EM-90 or EM-97 of Goldschmidt); siloxane surfactants of a pendant / rake / comb configuration, silicone surfactants of a trisiloxane configuration, and silicone surfactants of ABA / alpha-omega block copolymers (such as polyoxyalkylenes, ethoxylated polyoxyethylene, polyoxyethylene / ethoxylated polyoxypropylene / propoxylated); silicone emollients substituted with aromatic groups (such as phenyl, alpha-methylstyryl, styryl, methylphenyl, alkylphenyl); silicone copolymers with other functional groups including: hydrogen, alkyl, methyl, amino, trifluoropropyl, vinyl, alkoxy, arylalkyl, aryl, phenyl, styryl, polyethers, carboxylic esters; alkylmethylsiloxanes or silicone waxes (such as hexyl, octyl, lauryl, cetyl, stearyl); siloxane copolymers with nonionic functionality with silanol or trimethylsiloxy end groups; nonionic functionalized siloxanes with trisiloxane or methicone backbone groups attached; nonionic silicone surfactants; tetraethoxysilane; tetramethoxysilane; hexametoxy-silicone; oximetoxy trisiloxane; silicone emulsifiers; silicone or siloxane resins, alkylsilicone resins, polyoxyalkylene silicone resins; MQ resins such as Shiseido / Shin-etsu, for example from Japanese Patent Publication JP86143760 or from Walker Chem. 6MBH (described in EP722970); alkoxysiloxanes; alkoxysilanes; meticones (polymethylalkysiloxanes); and combinations thereof. Non-limiting examples of modified silicone carriers suitable for use in the pharmaceutical compositions herein include the following modified silicones available from Dow Corningn: DC-556 Cosmetic Grade Fluid (phenyl trimethicone); DC-704 Fluid for Diffusion Pump (Tetramethyl-Tetraphenyl-Trisiloxane); DC-705 Fluid for diffusion pump; DC-1784 Emulsion; DC-AF Emulsion; DC-1520-US Emulsion; DC-593 Fluid (Dimethicone [and] Trimethylsiloxysilicate); DC-3225C Fluid (Cyclomethicone [and] Dimethicone Copolyol); DC-190 Fluid (Dimethicone Copolyol); DC-193 Fluid (Dimethicone Copolyol); DC-1401 (Cyclomethicone [and] Dimethiconol); DC-5200 Fluid (Copolyol from Laurylmethicone); DC-6603 Polymer Powder; DC-5640 Powder; DC-Q2-5220 (Dimethicone Copolyol); DC Q2-5324 (Dimethicone copolyol); DC-2501 Cosmetic Wax (Dimethicone copolyol); DC-2502 Fluid (Cetyl Dimethicone); DC-2503 Wax '(Dimethicone Stearyl); DC-1731 Volatile Fluid (Caproyl Trimethicone); DC-580 Wax (It is tearoxitrime tilsilano [y] Alcohol Stearyl); DC-1-3563 (Dimethiconal); DC-X2-1286 (Dimeticonol); DC-X2-1146A (Cyclomethicone [y] Dimethiconol); DC-8820 Fluid (functionalized with Not me); DC Q5-0158A wax (stearoxitrimethylsilane); DC-Q2-8220 (Trimethyl s ili lamodimet icone); DC-7224 (Trimethylsilyllamodimethicone); DC-X2-1318 Fluid (Cyclomethicone [and] Vinylimetone icone); DC-QF1-3593A fluid (rimethylsiloxysilicate) and combinations thereof.

Other non-limiting examples of modified silicone carriers suitable for use in the pharmaceutical compositions herein include the following modified silicones available from General Electric: GE SF-1023 (Dimethyl-Diphenyl Siloxane); GE CF-1142 (Methylphenyl Siloxane Fluid); GE SF-1153 (Dimethyl-diphenyl-Siloxane); GE SF-1265 (Diphenyl-Dimethyl-Siloxane); GE SF-1328; GE SF-1188 (Dimethicone Copolyol); GE SF-1188A (Silicone polyether copolymer); GE SF-1288 (silicone polyether copolymer, dimethyl-methyl-3-hydroxypropyl ethoxylate); GE SF-1318 (Siloxane methyl ester); GE SF-1328 (silicone surfactant, ethoxylated-propoxylated dimethyl-methyl-3-hydroxypropyl); GE SF-1550 (methylphenyl siloxane, hexamethyl-3-phenyl-3- [[trimethylsilyl] oxy] trisiloxane); GE SF-1632 (silicone wax); GE SS-4267 (Dimethicone [and] Trimethylsiloxysilicate). Other non-limiting examples of modified silicone carriers suitable for use in the pharmaceutical compositions herein include the following modified silicones available from Goldschmidt: Abil EM-90 (silicone emulsifier); Abil EM-97 (siloxane polyether); Abil Wax 9810 (silicone wax or C24-28 methicone); Abil Cera 2434 (Stearoxi Dimethicone); Abil Cera 9800D (Dimethicone from Stearyl); and Tegomer H-Si 2111, H-Si 2311, A-Si 2120, A-Si 2320, C-Si 2141, C-Si 2341, E-Si 2130, E-Si 2330, V-Si 2150, V-Si 2550, H-Si 6420, H-Si 6440, H-Si 6460 (Copolymers of Dimethicone Alpha-Omega). Other non-limiting examples of modified silicone carriers suitable for use in the pharmaceutical compositions herein include the following: Masyl 756 from PPG Industries (Tetrabutoxypropyl Trisiloxane); bis-phenylhexamethicone (available as Sibione Oils 70663 V30 from Rhone-Poulenc); Silbione Oils 70646 (dimethicone copolyols from Rhone-Poulenc); Silicone L-711, L-720, L-721 and L-722 (dimethicone copolyols from Union Carbide); Silicone L-7000, L-7001, L-7002, L-7004, L-7500, L-7600, L-7602, L-7604, L-7605, and L-7610 (Dimethicone copolyols from Union Carbide); Unisil SF-R (UPI dimethiconol); Silicate Cluster of Olin (tris [tributoxysiloxy] methylsilane); silicone copolymer F-754 (dimethicone copolyol from SWS Silicones); and combinations thereof. The anhydrous liquid carrier preferably comprises one or more volatile carriers, optionally in combination with one or more non-volatile carriers. In this context, the term "volatile" refers to carriers having a measurable vapor pressure under ambient conditions, and the term "non-volatile" refers to carriers that do not have a measurable vapor pressure under ambient conditions. These volatile silicone carriers can be cyclic, linear or branched chain silicones having the requirement volatility defined herein. Non-limiting examples of suitable volatile silicones are described in Todd et al., "Volatile Silicone Fluids for Cosmetics", Cosmetic and Toiletries, 91: 27-32 (1976), the descriptions of which are incorporated herein by reference, Pxeferides. among these volatile silicones are cyclic silicones having from about 3 to about 7, more preferably from about 4 to about 5, silicon atoms. More preferably are those that conform to the formula: wherein n is from about 3 to about 7, preferably from about 4 to about 5, more preferably 5. These volatile cyclic silicones generally have a viscosity value of less than about 10 centistokes. All viscosity values described herein are measured or determined under ambient conditions, unless otherwise specified. Volatile silicones suitable for use herein include, but are not limited to, Cyclomethicone D-5 (commercially available from G. E. Silicones); Dow Corning 344, and Dow Corning 345 (commercially available from Dow Corning Corp.); GE 7207, GE 7158 and Silicone Fluids SF-1202 and SF-1173 (available from General Electric Co.); SWS-03314, SWS-03400; F-222, F-223, F-250, F-251 (available from SWS Silicones Corp.); Silicones Volatiles 7158, 7207, 7349 (available from Union Carbide); Masil SF-V (available from Mazer) and combinations thereof. The anhydrous liquid carrier may also comprise a non-volatile silicone carrier different from or in addition to the preferred modified silicone carriers described above. These non-volatile silicone carriers are preferably linear silicones that include, but are not limited to, those that conform to any of the formulas: CH wherein n is greater than or equal to 1. These linear silicone materials will generally have values of viscosity of up to about 100,000 centistokes, preferably less than about 500 centistokes, more preferably from about 1 centistoke to about 200 centistokes, even more preferably from about 1 centistoke to about 50 centistokes, measured under ambient conditions. Examples of non-volatile linear silicones suitable for use in antiperspirant compositions include, but are not limited to, Dow Corning 2Q0, hexamethyldisiloxane, Rhodorsil Oils 70047 available from Rhone-Poulenc, Masil SF Fluid available from Mazer, Dow Corning 225, Dow Corning 1732, Dow Corning 5732, Dow Corning 5750 (available from Dow Corning Corp.); SF-96, SF-1066 and SF18 (350) Silicone Fluids (available from G.E. Silicones); Velvasil and Viscasil (available from General Electric Co.); and Silicone L-45, Silicone L530, Silicone L-531 (available from Union Carbide), and Siloxane F-221 and Silicone Fluid SWS-101 (available from SWS Silicones). The anhydrous liquid carrier may also contain fluorochemical compounds such as fluorosurfactants, fluorotelémeros, and perfluoro-polyethers, some examples of which are described in Cosmetics & Tailetries, Using Fluorinated Compounds in Topical Preparations, Vol. 111, pages 47-62, (October 1996), the disclosure of which is incorporated herein by reference. More specific examples of such liquid carriers include, but are not limited to, perfluoropolyimethyl isopropyl ethers, perfluoro-polypropyl ethers, fluorinated telomer of acrylamide, fluorinated amide surfactants, perfluorinated thiol surfactants. Other more specific examples include, but are not limited to, the polyperfluoropropyl ether ethers available from Dupont Performance Chemicals under the trademark Fluortress ™ PFPE oils, and the fluorosurfactant series from Dupont Performance Chemicals under the trademark Zonyl ™ Fluorosurfactants. The suitable organic liquid carrier includes polar or non-polar, saturated or unsaturated, substituted or unsubstituted, branched or linear or cyclic organic compounds, which are also liquid under ambient conditions. These carriers include hydrocarbon oils, alcohols, esters and organic ethers that are liquid under ambient conditions. Preferred organic carriers include mineral oil and other hydrocarbon oils, some examples of which are described in U.S. Patent No. 5,019,375, given to Tanner et al. On May 28, 1991, the disclosure of which is incorporated herein by reference. . Other suitable organic liquid carriers include Permethyl 99A, Permethyl 101A (Permethyl available from Persperse Corp.), the Isopar series of materials (available from Exxon), isohexadecane, diisopropyl adipate, butyl stearate, isododecane, light mineral oil, petrolatum and other similar materials. The anhydrous liquid carrier is preferably substantially free of water immiscible and polar organic solvents. In this context, "substantially free" means that the solid gel compositions preferably contain less than 7%, more preferably less than about 3%, and even more preferably zero percent by weight of an anhydrous polar organic solvent. These solvents are liquids under ambient conditions, and include mono- and polyhydric alcohols, fatty acids, esters of mono- and di-basic carboxylic acids with mono- and polyhydric alcohols, polyoxyethylenes, polyoxypropylenes, polyalkoxylate ethers of alcohols, and combinations thereof. Examples of some anhydrous liquid organic polar solvents are described in Cosmetics, Science and Technology, Vol. 1, 27-104, edited by Balsarn and Sagarin (1972).; U.S. Patent No. 4,202,879 given to Shelton on May 13, 1980; and U.S. Patent No. 4,816,261 issued to Luebbe et al. on March 28, 1989, the descriptions of which are incorporated herein by reference. As discussed previously, the compositions of the present invention can be formulated either as a gel or as a gel stick. These gels or gel bars take the form of facial or body gels, soft gels, creams, lotions, movable ball packaging compositions, bar soaps, lip balms, facial moisturizers, sunscreens, anti-acne preparations, topical analgesics , antiperspirants, and deodorants. It is difficult to distinguish quantitatively between a pharmaceutical "gel" and a pharmaceutical "bar". For example, note the discussion in the article by Schmolka, "Gel Pharmaceuticals", in Pharmaceuticals & Toiletries, Vol. 99 (November 1984), pages 69-76. Generally, a gel is more viscous than a liquid, or a paste that can not retain its shape. It is not as rigid as a bar. Typically, it is understood that gels are soft and deformable products, while bars are freestanding solids.

OPTIONAL COMPONENTS Optionally, the pharmaceutical compositions of the present invention may additionally incorporate humectants and / or skin protectants.

Suitable cosmetic compositions include gel, bar soap, soft gel, cream, makeup, lotion, movable ball packages, facial moisturizers, or gel bars and the like. Useful humectants and / or skin protectants are described in Federal Register Volume 48, No. 32 and include aloe vera, allantoin, aluminum hydroxide gel, bismuth subnitrate, boric acid, calamine, cocoa butter, corn starch, dimethicone, glycerin, lanolin, kaolin, living cell derivative of yeast, petrolatum, shark liver oil, sodium bicarbonate, sulfur, tannic acid, white petrolatum, zinc acetate, zinc carbonate and zinc oxide, and mixtures thereof. The skin and / or humectant protector preferably comprises from about 0.001% to about 2%, more preferably from about 0.01% to about 1% of the pharmaceutical composition. Other ingredients conventionally incorporated in the gels and / or pharmaceutical bars can also be included. With regard to the var other ingredients that can be incorporated, attention is directed to optional components such as hardeners, boosters, chelating agents, dyes, perfumes, emulsifiers and fillers. These other optional components are further described in U.S. Patent No. 3,255,082 given to Barton; US Patent No. 4,049,792 given to Elsnau; U.S. Patent No. 4,137,306 given to Rubino et al .; U.S. Patent No. 4,279,658 to Hooper et al; Canadian Patent No. 1,164,347 which was given to Beckmeyer et al; European Patent Application No. 117,070 which was published on August 28, 1984; and in Geria, "Formulation of Stick Antiperspirants and Deodorants," Phamraceuticals and Toiletries, 99: 55-60 (1984), all of which are incorporated herein by reference in their entirety. Emulsifiers are particularly useful in the present invention. These emulsifiers include useful nonionic surfactants to form water-in-oil emulsions. The concentration of emulsifiers used in the present invention is typically less than about 10%, preferably less than about 5%. Examples of these emulsifiers include polyoxyethylene ethers of fatty alcohols, and polyoxyethylene-polysiloxane copolymers. Such emulsifiers are described in EPO Application 373,424 given to Raleigh et al., And in U.S. Ser. No. 530,671, given to Cedeno et al., Filed on July 2, 1991, all of which are hereby incorporated by reference in their entirety. Preferably, when the compositions of the present invention are in the form of a solid emulsion, the compositions include a surfactant. This ensures that the discontinuous phase remains dispersed with the cooling of the composition to form the gel. Preferred for use herein are surfactants that are easily rinsed from the skin. Thickeners are also useful in the present invention. Their selection and the concentration to which they are used should be such that they do not significantly affect the aesthetics of the gel compositions. Typical concentrations of thickeners are at levels of less than about 5%. Examples of the thickeners are described in US Patent No. 4,985,238 given to Tanner et al., Published January 15, 1991; incorporated herein by reference in its entirety. These thickeners include wax-like materials such as beeswax, cerasin, hydrogenated castor oil, synthetic waxes such as Fisher Tropsch waxes, microcrystalline waxes, polyethylene waxes, and mixtures thereof. In addition to the alkylamide gelling agent described above, the compositions of the present invention may also incorporate other gelling agents. Suitable additional gelling agents are described in U.S. Patent No. 5,429,816 given to Hofrichter et al., Published July 4, 1995, incorporated herein by reference in its entirety. The gelling agents included therein include those having the formula: 0 wherein Rx is OR2 or NR2R3, wherein R2 and R3 are, independently or together, a hydrogen, an aryl, a siloxane, an alkyl of 1 to 22 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkoxy of 1 to 22 carbon atoms, aryl substituted with alkyl of 1 to 22 carbon atoms, or an aryl radical substituted with alkyl of 1 to 22 carbon atoms, and wherein R2 is an alkoxy of 1 to 36 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight or branched chain. Preferred gelling agents from this group include 12-hydroxystearic acid, 12-hydroxyl tertiary methyl ester, 12-hydroxystearic acid ethyl ester, 12-hydroxystearic stearyl ester, 12-hydroxyl tertiary benzyl ester, 12-hydroxies tearic acid amide, 12-hydroxies tetraric acid isopropylamide, 12-hydroxystearic acid butylamide, 12-hydroxyestaric acid benzylamide, 12-hydroxystearic acid phenylamide, 12-hydroxystearic acid t-butyl lamide, cyclohexylamide 12-hydroxies tearic acid, 1-adamantyl amide of 12-hydroxystearic acid, 2-adamantyl acid of 12-hydroxystearic acid, diisopropylamide of 12-hydroxystearic acid, 12-hydroxylauric acid, 16-hydroxyhexadecanoic acid, derivatives thereof and mixtures of the same. Also in U.S. Patent No. 5,429,816 are the gelling agents having the formula: wherein Ri is an alkyl, aryl, arylalkyl branched, linear or cyclic radical, and has from about 6 to about 22 carbon atoms; and R2 and R3 are the same or different alkyl, aryl, or arylalkyl or alkyl, aryl or arylalkyl radical radicals, in which the alkyl portion is branched, linear or cyclic, and has from about 2 to about 20 carbon atoms. Preferred gelling agents of this type include N-lauroyl-glutamic acid diethylamide, N-lauroyl-glutamic acid dibutylamide, N-lauroyl-glutamic acid dihexylamide, N-lauroyl-glutamic acid dioctylamide, didecylamide. N-lauroyl- • glutamic acid, N-lauroyl- • glutamic acid didodecylamide, N-lauroyl- • glutamic acid tetradecylamide, N-lauroyl-glutamic acid dihexadecylamide, N-lauroyl-glutamic acid tearylamide, dibutylamide N-stearoyl- • glutamic acid, N-isosaroyl- • glutamic acid dihexylamide, N-stearoyl- • glutamic acid diheptylamide, N-tearoyl-glutamic acid dioctylamide, N-stearoyl-glutamic acid didecylamide, N-stearoyl-glutamic acid didodecylamide, N-stearoyl-glutamic acid tetradecylamide, N-stearoyl-glutamic acid dihexadecylamide, N-stearoyl-glutamic acid distearylamide and mixed of them. Mixtures of the additional gelling agents described above can also be incorporated in the pre invention.

Mixtures of these gelling agents can also be incorporated in the pre invention. The particulate and filler materials may also be included in the pre compositions. These materials are typically used in concentrations from about 0.5% to about 5%, preferably no more than about 3%. Such materials are described in U.S. Patent No. 5,019,375, issued to Tanner et al., Published May 28, 1991, incorporated herein by reference in its entirety. Suitable filler materials include colloidal silica (such as Cab-O-Sil, sold by Cabot Corp.), clays (such as bentonite), hydrophobic clays (quaternized), silica / alumina thickeners, silicate powders such as talc, alumina silicate, and magnesium silicate, modified corn starches, metal stearates, and mixtures thereof. The use of such fillers and stabilizers in pharmaceutical bars is described in US Pat. No. 4, 126,679, given to Davy et al., Published on November 21, 1987, incorporated by reference in its entirety. Examples of other particulate materials include particulate hydrophilic polymers such as cellulose ether polymers, modified starches, polyamides, and polypeptides. A wash removal agent can be used to improve the ease with which the ingredients - particularly the gelling agent and the non-volatile non-volatile oils can be removed by washing. The wash removal agent is most preferably a non-liquid. The washout agent is typically in the pharmaceutical compositions in an amount from about 0.1% to about 10%. Typical wash-off agents are non-liquids selected from the group consisting of polyoxyethylene ethers having the formula Ri (OCH2CH2) nOH; polyoxyethylene esters having the formula RiCO (OCH2CH2) nOH; polyoxyethylene glyceryl esters having the formula (RiCOO) CH2CH (0H) CH2 (OCH2CH2) pOH or having the formula H0CH2CH (00CR1) CH2 (0CH2CH2) n0H; and polyoxyethylene glyceryl diesters having the formula R1COOCH2CH (00CR2) CH2 (0CH2CH2) n0H, preferably, the polyoxyethylene ethers wherein: Ri and R2 are the same or different alkyl, alkenyl, or aromatic hydrocarbon radicals, which may be substituted or unsubstituted, preferably an alkyl radical having from about 4 to about 22 carbon atoms; and n is from about 2 to about 80. Preferred examples of such washout agents include: from ceteh-2 to ceteh-30, from steareth-2 to steareth-30, from ceteareth-2 to ceteareth-30, from PEG-2 stearate to PEG-30 stearate, PEG-12 isostearate, PEG-16 hydrogenated castor oil, PEG-40 hydrogenated castor oil, and PEG-20 glyceryl stearate; more preferably, ceteareth-20, steareth-21, PEG-20 stearate, and PEG-16 hydrogenated castor oil; and more preferably, ceteareth-20.

METHODS OF MANUFACTURE The present invention can be made using any of the typical methods known to those skilled in the art, and described in Gels and Sticks Formular, 99 Pharmaceuticals & Toiletries 77-84, 1984; incorporated herein by reference. The methods that were found to be particularly useful follow below: Combine the gelling agent and the carrier in a vessel equipped with a heat source. Heat the mixture to between about 80 ° C and about 130 ° C with stirring, until the mixture forms a homogeneous molten solution. Preferably, the homogeneous molten solution is allowed to cool to a mixing temperature; typically between about 65 ° C and 120 ° C. Alternatively, the mixture can simply be heated to the mixing temperature until the mixture forms a homogeneous molten solution. This alternative method, however, typically takes more time than simply reheating and then cooling. Add the topical active ingredient (s) of dermal (s) and other ingredients, such as fragrances and colors, to the homogeneous molten solution in the top container with agitation. Allow the mixture to cool until it begins to thicken, and then pour the mixture into containers, allowing them to cool to room temperature. Although not preferred, the topical active ingredient (s) may be alternatively added together with the gelling agent and the liquid base material in the first stage. .

METHODS FOR USE The present invention provides methods for preventing perspiration and malodor associated with human perspiration. These methods comprise applying to the skin of a human a safe and effective amount of the pharmaceutical gel of the present invention. The term "a safe and effective amount" as used herein, is an amount that is effective to eliminate or substantially reduce the bad odor associated with perspiration of the human armpit, while being safe for human use in a relationship reasonable risk / benefit Typically, the safe and effective amount used is from about 0.1 grams to about 1.0 gram per skin surface area.

EXAMPLES The following examples further describe and demonstrate the embodiments within the scope of the present invention. These examples are for the purpose of illustration only, and are not to be construed as limitations of the present invention, since many variations are possible without departing from the spirit or scope thereof. The concentrations of the components in the examples below are expressed by total weight of the composition.

Table 1 includes examples of solid gel bar pharmaceutical compositions incorporating the alkylamide gelling agents of the present invention. The compositions are formed by combining and mixing the ingredients of each column using conventional technology.

Table 1 1 - . 1 - Dow Corning 245 Fluid; General Electric SF-1202 2 - . 2 - Farchem Jarcol 1-20 3 - Witco White Perfects 4 - Acme Hardesty 5 - Finsolv TN; Finetex Table 2 includes examples of soft gel pharmaceutical compositions incorporating the alkylamide gelling agents of the present invention. The compositions are formed by combining and mixing the ingredients of each column, using conventional technology.

Table 2 - Dow Corning 245 Fluid; General Electric SF-1202 - Farchem Jarcol 1-20 - Witco White Perfects - Acme Hardesty - Finsolv TN; Finetex

Claims (10)

1. A pharmaceutical composition characterized in that it comprises: A.) a safe and effective amount of at least one pharmaceutical active ingredient, preferably a pharmaceutical active ingredient selected from the group consisting of a deodorant active ingredient, an analgesic, an exfoliant, an agent sunscreen, a vitamin, an anti-dandruff agent, an antioxidant or radical scavenger, a hormone and mixtures thereof; B.) A gelling agent of the formula: or I R., - C'-C-N -R2 R3-X -Y -Z -R8 a) Ri is free, hydroxy, hydrogen, aryl, siloxane or alkyl of 1 to 22 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 22 carbon atoms, alkoxy 1 to 22 carbon atoms, alkyl esters of 1 to 22 carbon atoms, alkyl ethers of 1 to 22 carbon atoms, or aryl substituted with alkyl of 1 to 22 carbon atoms; b) R2, R, R5 and R6 are independently or together hydrogen, hydroxy, aryl, siloxane or alkyl of 1 to 22 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 22 carbon atoms, alkoxy of 1 to 22 carbon atoms, alkyl esters of 1 to 22 carbon atoms, alkyl ethers of 1 to 22 carbon atoms, or aryl substituted with alkyl of 1 to 22 carbon atoms; c) R3 is nil, hydroxy, hydrogen, saturated or unsaturated, substituted or unsubstituted, 1 to 4 carbon atoms, straight chain, branched or cyclic, alkenyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 atoms of carbon, alkyl esters of 1 to 4 carbon atoms or alkyl ethers of 1 to 4 carbon atoms; d) R7 and R8 are independently or together nothing, hydrogen, hydroxy, aryl, siloxane or alkyl of 1 to 22 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 22 atoms carbon, alkoxy of 1 to 22 carbon atoms, alkyl esters of 1 to 22 carbon atoms, alkyl ethers of 1 to 22 carbon atoms, or aryl substituted with alkyl of 1 to 22 carbon atoms; e) Rg is nothing or hydrogen; f) Rio and Rii are independently or together nothing, hydrogen, hydroxy, aryl, siloxane or alkyl of 1 to 6 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 6 atoms carbon, alkoxy of 1 to 6 carbon atoms, alkyl esters of 1 to 6 carbon atoms, alkyl ethers of 1 to 6 carbon atoms, or aryl substituted with alkyl of 1 to 6 carbon atoms; g) X is nothing, nitrogen, aryl or - (CH2) n ~ where n is an integer from 1 to 6; h) And it is nothing, acyl or carbonyl; i) Z is nothing, hydrogen, hydroxy, aryl, siloxane, nitrogen or alkyl of 1 to 22 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight chain, branched or cyclic, alkenyl of 1 to 22 carbon atoms, alkoxy of 1 to 22 carbon atoms, alkyl esters of 1 to 22 carbon atoms, alkyl ethers of 1 to 22 carbon atoms, or aryl substituted with alkyl of 1 to 22 carbon atoms; and j) provided that: (i) when X is nothing, Y, Z, R3, R7 and R8 are nothing, C is directly attached to C "and Ri is not a hydrogen, (ii) when X and Z are nothing and And it is nothing, X is directly linked to Z, (iii) when Z is nothing, a hydrogen or a hydroxy, R7 and R8 are nothing, and (iv) when "a" is a double bond, R3 and Rg are nothing; and C.) an anhydrous liquid carrier, preferably an anhydrous liquid carrier having a solubility parameter from 3 to 20 (calories / cm 3) 172.

2. A pharmaceutical composition according to claim 1, characterized in that the pharmaceutical composition comprises from 0.1% to 25% of the gelling agent, wherein the gelling agent is preferably selected from the group consisting of alkylamides of citric acid, tricarballylic acid, aconitic acid, nitrilotriacetic acid, alkylamides of alkylsuccinic acid, alkylamides of alkenyl succinic acid and anhydrides thereof.

3. A pharmaceutical composition according to any of the preceding claims, characterized in that it additionally comprises from 1% to 15% by weight of a secondary gelling agent having the formula: OR II wherein Ri is OR2 or NR2R3, wherein R2 and R3 are, independently or together, a hydrogen, an aryl, a siloxane, an alkyl of 1 to 22 carbon atoms saturated or unsaturated, substituted or unsubstituted, of re chain. cta, branched or cyclic, alkoxy of 1 to 22 carbon atoms, aryl substituted with alkyl of 1 to 22 carbon atoms, or an aryl radical substituted with alkyl of 1 to 22 carbon atoms, and wherein R 2 is an alkoxy of 1 to 36 carbon atoms saturated or unsaturated, substituted or unsubstituted, straight or branched chain, preferably a secondary gelling agent selected from the group consisting of 12-hydroxystearic acid, methyl ester of 12-hydroxystearic acid, ethyl ester of acid 12-hydroxystearic, 12-hydroxystearic acid stearyl ester, 12-hydroxystearic acid benzyl ester, 12-hydroxystearic acid amide, 12-hydroxystearic acid isopropylamide, 12-hydroxy acid butylamide stearic, 12-hydroxystearic acid benzylamide, 12-hydroxystearic acid phenylamide, 12-hydroxystearic acid t-butylamide, 12-hydroxystearic acid cyclohexylamide, 12-hydroxystearic acid 1-adamantylamide, 2-adamantylamide 12-hydroxystearic acid, diisopropylamide of 12-hydroxystearic acid, 12-hydroxylauric acid, 16-hydroxyhexadecanoic acid, derivatives thereof and mixtures thereof.

4. A pharmaceutical composition according to any of the preceding claims, characterized in that it additionally comprises a gelling agent a.dicion.1 having the formula: wherein Ri is an alkyl, aryl or arylalkyl radical which is branched, linear or cyclic, and has from about 6 to about 22 carbon atoms; and R2 and R3 are the same or different alkyl ester, aryl, arylalkyl or alkyl, aryl or arylalkyl amide radicals, in which the alkyl portion is branched, linear or cyclic, and has from 2 to about of 20 carbon atoms, preferably an additional gelling agent selected from the group consisting of N-lauroyl-glutamic acid diethylamide, N-lauroyl-glutamic acid dibutylamide, N-lauroyl-glutamic acid dihexylamide, N-lactyl-dioctylamide lauroyl-glutamic, didecylamide of N-lauroyl-glutamic acid, didodecylamide of N-lauroyl-glutamic acid, ditetradecylamide of N-lauroyl-glutamic acid, dihexadecylamide of N-lauroyl-glutamic acid, dies tearylamide of N-lauroyl-glutamic acid, N-stearoyl-glutamic acid dibutylamide, N-stearoyl-glutamic acid dihexylamide, N-stearoyl-glutamic acid diheptylamide, N-stearoyl-glutamic acid dioctylamide, sodium didacylamide N-stearoyl-glutamic acid, N-stearoyl-glutamic acid didodecylamide, N-stearoyl-glutamic acid tetradecylamide, N-stearoyl-glutamic acid dihexadecylamide, N-stearoyl-glutamic acid tearylamide and mixtures thereof.

5. A pharmaceutical composition according to any of the preceding claims, characterized in that the anhydrous carrier is selected from the group consisting of: non-polar volatile oils, preferably non-polar volatile oils selected from the group consisting of non-volatile polysiloxanes, paraffinic hydrocarbon oils, and mixtures thereof; relatively polar non-volatile oils; non-volatile non-polar oils; and mixtures thereof.

6. A pharmaceutical composition according to any of the preceding claims, characterized in that the non-volatile polysiloxanes are selected from the group consisting of polyalkylsiloxanes, polyarylsiloxanes, polyalkyl-arylsiloxanes, copolymers of polyethersiloxane, polyfluorosiloxane, polyaminosiloxane and mixtures thereof.

7. A pharmaceutical composition according to any of the preceding claims, characterized in that the paraffinic hydrocarbon oil is selected from the group consisting of mineral oils, petrolatums, isodecanes, permethyl, isohexadecanes, isododecane, and isoparaffins.

8. A pharmaceutical composition according to any of the preceding claims, characterized in that the carrier is in the form of a lip balm, a gel, bar soap, soft gel, cream, lotion, movable ball deodorant, facial moisturizer, gel bar , preparation of sunscreen, anti-acne preparation, topical analgesic preparation or deodorant, preferably a gel stick.

9. A pharmaceutical composition according to any of the preceding claims, characterized in that it additionally comprises a humectant or protector, preferably a humectant and protector selected from the group consisting of aloe vera, allantoin, aluminum hydroxide gel, bismuth subnitrate, boric acid, calamine, cocoa butter, corn starch, dimeric, glycerin, lanolin, kaolin, derived from living yeast cells, petrolatum, shark liver oil, sodium bicarbonate, sulfur, tannic acid, white petrolatum, zinc acetate, carbonate of zinc and zinc oxide, and mixtures thereof.

10. A pharmaceutical composition characterized in that it comprises: a) an effective and safe amount of at least one active pharmaceutical ingredient; b) a non-triglyceride gelling agent compound, comprising: i) a linear backbone of 2 to 12 carbon atoms, having terminal hydrogen bonding functional groups, each functional hydrogen bonding group carrying on the same a non-polymeric organic side chain; and ii) an additional non-polymeric organic side chain, attached to the main structure by an acyl-amide functional group,. such that the acyl portion of the acyl-amide functional group is attached to the main structure, wherein the side chains of the hydrogen-binding functional groups are arranged on the same axial side of the main structure, in such a way that the additional side chain is arranged on a flat side opposite the side chains of the hydrogen bonding functional groups, preferably wherein the side chains of the hydrogen bonding functional groups are attached to the hydrogen bonding functional group by groups functionalities of acyl-amide, such that the acyl portion of the acyl-amide functional group binds to the hydrogen-binding functional group; and c) an anhydrous liquid carrier.