Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
  • A61K8/23—Sulfur; Selenium; Tellurium; Compounds thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
  • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
  • A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
  • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
  • A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/06—Antipsoriatics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/10—Anti-acne agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q5/00—Preparations for care of the hair
  • A61Q5/006—Antidandruff preparations
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q5/00—Preparations for care of the hair
  • A61Q5/02—Preparations for cleaning the hair

Definitions

• the invention relates to methods for using compositions comprising dichlorophenyl imidazoldioxolan in treating the symptoms associated with seborrheic dermatitis, dandruff, psoriasis, and acne and the compositions used therein.
• Traditional approaches for treating skin and scalp diseases such as dandruff, seborrheic dermatitis, psoriasis, and acne include the topical administration of an agent capable of :1) inhibiting microorganism growth on the skin surface; 2) reducing skin surface irritation; and/or 3) reducing the sebum production on the skin surface.
• ketoconazole was useful in the topical treatment of psoriasis and seborrheic dermatitis.
• Shampoos containing 2% ketoconazole are known to show a beneficial effect in treating seborrheic dermatitis after topical application. It is further known that stable shampoos which exhibit better cosmetic attributes such as lathering and conditioning have been formulated to contain less than 2 % active ingredient . See United States Patent No. 5,456,851.
• a second known approach for treating one or more of the above-mentioned diseases involves the reduction of the symptoms, i.e. scaling, flaking, and itching, associated with these diseases.
• One such method is via the topical application of a keratinolytic agent, i.e. one which is effective in "sloughing -off" the excess ceils which build up on the surface of the skin. See i 113057.
• Other methods for reducing the itching, irritation and skin dryness involve the regulation of the types and amounts of detergents used therein.
• aqueous detergent compositions comprising from about 4 to about 12 % by weight of an anionic surfactant, an amphoteric surfactant at a level of at least about 0.75 parts by weight per part by weight of said anionic surfactant, and one or more of 11 listed therapeutic agents).
• coal tar is only somewhat effective in inhibiting Malassezia furfur growth, it is known to be effective in suppressing DNA synthesis and thus also in inhibiting cell division. Since cell proliferation and buildup create symptoms of scaling, flaking, and itching, the ability of coal tar to inhibit cell division appears to alleviate these symptoms.
• WO-96/29045 genericaily discloses combinations of cytotoxic agents and antifungal agents for the treatment of seborrheic dermatitis of the scalp; however, it specifically discloses the combined use of an unidentified composition comprising 1.8 % coal tar and an unidentified solution comprising 2% ketoconazole.
• a third approach for treating seborrheic dermatitis, dandruff, psoriasis, and acne is via the reduction of sebum production on the skin surface, a frequent symptom of those who suffer from these diseases. It is believed that the presence of a high degree of sebum trapped on the skin surface by the proliferation of surface skin ceils may provide a beneficially nurturing environment for microorganisms. Agents such as alcohols, solvents, and surfactants have been incorporated into various treatments for the purpose of reducing sebum production; however, these agents are very irritating to the skin and are ineffective against inhibting the growth of M. furfur.
• compositions for treatment of seborrheic dermatitis, dandruff, psoriasis, acne and the like which not only inhibited microorganism growth, but which also effectively sloughed-off excess skin cells from the skin surface and reduced the sebum-production on the skin surface without any of the above disadvantages.
• a method for treating seborrheic dermatitis, dandruff, and psoriasis comprising, consisting essentially of or consisting of: a) applying to the skin or hair an effective amount of a composition comprised of 1) dichlorophenyl imidazoldioxolan; and
• a therapeutic component selected from salicylic acid, coal tar and derivatives thereof, piroctone olamine (Octopirox), selenium sulfide, ciclopirox olamine, or mixtures thereof.
• compositions comprising, consisting essentially of or consisting of: a) dichlorophenyl imidazoldioxolan; and b) a therapeutic component selected from salicylic acid, coal tar and derivatives thereof, piroctone olamine (Octopirox), selenium sulfide, ciclopirox olamine, or mixtures thereof.
• This composition may be combined with art known body or hair cleansing product ingredients to form various body and hair cleansing products such as soaps, gels, and shampoos.
• Yet another embodiment of this invention is directed to a process for preparing a body and hair cleansing formulation comprising, consisting essentially of or consisting of:
• in yet another embodiment is a method for inhibiting the growth of bacterium on the surface of skin comprising, consisting essentially of, and/or comprising: topically applying to the skin an effective amount of a composition comprised of dichlorophenyl imidazoldioxolan.
• dichlorophenyl imidazoldioxolan and compositions comprised thereof were superior in inhibiting the growth of microorganisms such as ⁇ f. furfur and Propionibacterium acnes (P. acne).
• the combination of dichlorophenyl imidazoldioxolan with one or more therapeutic components often provided significant improvement and/or synergism over prior art shampoos and cleansers which contained the components alone.
• the concentration of one or both of the different types of components can be lowered, thus increasing its toierabiiity by the user.
• MEA shall include a mono-ethanoiamide of formula RCO-NH-CH2CH2- OH
• DEA shall include a di-ethanol amide of formula RCO-N(CH2CH2-OH)2
• MIPA shall include a mono-isopropanol amide of formula RCO-NH-CH2-CHOH-CH3, wherein each RCO-group is a fatty acid residue, such as a C13.19 alkylcarbonyl or C13-19 alkenylcarbonyi group
• TAA shall mean triethanolammonium.
• ammo acid containing both ammo (basic) and acid (e.g., carboxylic acid, acidic) functional groups
• zwitterionic molecules which possess both positive and negative charges within the same molecule.
• the charges of the latter may be either dependent on or independent of the pH of the composition.
• Dichlorophenyl imidazolodioxalan is commercially available from Janssen Pharmaceutica, N.V., under the tradename, "Elubiol.” Although the amount of dichlorophenyl imidazoldioxolan used in the composition of the present invention may depend upon, for example, the type of symptoms present and the amount of other ingredients combined therewith, one skilled in the art could readily determine, without undue expe ⁇ mentation, that the dichlorophenyl imidazoldioxolan may be used in an amount, based upon the total weight of the composition, from about 0.1 % to about 2 %, preferably from about 0.25 % to about 1 %, and more preferably from about 0.25% to about 1 %.
• composition of the present invention further includes a therapeutic component effective in achieving a therapeutic result in the treatment of dandruff, seborrheic dermatitis, and psoriasis selected from salicylic acid, coal tar and derivatives thereof such as anthralin, piroctone olamine (Octopirox), selenium sulfide, ciclopirox olamine, other known anti-dandruff agents or mixtures thereof.
• Salicylic acid is the therapeutic component of choice.
• the amount of the therapeutic component may vary for reasons similar to those set forth above, one skilled in the art could readily determine, without undue experimentation, that the therapeutic component may be used in an amount, based upon the total weight of the composition, from about 0.5 % to about 3 %, and preferably from about 1 % to about 2 %.
• the dichlorophenyl imidazoldioxolan and the therapeutic component(s) are present in quantities which produce a significant improvement and/or mutual synergistic effect on the inhibition of the growth of dermatophyte fungi, in particular the species associated with dandruff and seborrheic dermatitis, i.e. Malessezia furfur (Pityrosporum ovale), but also on the growth of other species such as Epidenmophyton, Microsporum, and Trichophyton spp. associated with, for example, tinea capitis, tinea corporis and the like.
• the ratio of the quantities of the dichlorophenyl imidazoldioxolan and the therapeutic component(s) will depend on the nature of the therapeutic component(s) and on the target species. Particularly, it is contemplated that the weight : weight ratio between the dichlorophenyl imidazoldioxolan and the therapeutic component may range from about 0.1 : 3 to about 2 : 0.5 , and preferably from about 0.25 : 2 to about 0.5 : 1.0.
• the composition may contain dichlorophenyl imidazoldioxolan, salicylic acid, and, based upon the total weight of the composition, from about 0% to about 1%, preferably from about 0.25 % to about 1%, and more preferably from about 0.50 % to about 0.75 % piroctone olamine (Octopirox).
• the shampoos according to the present invention can conveniently be formulated using art-known shampoo bases; the art-known shampoo ingredients comprise one or more of a surfactant, a foaming agent, a thickener sufficient to give the final formulation a viscosity in the range of about 4,000 to about 9,000 mPa.s at room temperature, a preservative system, an anti-oxidant system, and acid or base or buffer sufficient to give the shampoo a pH in the range of from about 3 to about 8.
• a single ingredient can have two or more functions, e.g. surfactant and foaming agent.
• Suitable surfactants for use in the shampoos according to the present invention include any commercially available nonionic surfactant, amphotenc surfactant, anionic surfactant, or mixtures thereof.
• suitable nonionic surfactants useful in the present invention include polyoxyethylene derivatives of polyol esters, wherein the polyoxyethylene de ⁇ vative of polyol ester (1) is de ⁇ ved from (a) a fatty acid containing from about 8 to about 22, and preferably from about 10 to about 14 carbon atoms, and (b) a polyol selected from sorbrtol, sorbitan, glucose, ⁇ - methyl glucoside, polyglucose having an average of about 1 to about 3 glucose residues per molecule, giyce ⁇ ne, pentaeryth ⁇ tol and mixtures thereof, (2) contains an average of from about
• Suitable nonionic surfactants includes long chain alkyl glucosides or polyglucosKJes, which are the condensation products of (a) a long chain alcohol containing from about 6 to about 22, and preferably from about 8 to about 14 carbon atoms, with (b) glucose or a glucose-containing polymer.
• the alkyl glucosides have about 1 to about 6 glucose residues per molecule of alkyl glucoside.
• Amphotenc surfactants suitable for use in the present invention include, but are not limited to amphocarboxylates, alkyl betames, amidoalkyi betaines, amidoalkyl suttaines, amphophosphates, phosphobetaines, pyrophosphobetaines, carboxyalkyl alkyl polyammes and mixtures thereof.
• Suitable anionic surfactants may be selected from alkyl sulfates, alkyl ether sulfates, alkyl monoglycerylether sulfates, alkyl monoglycende sulfates, alkyl monoglyce ⁇ de sulfonates, alkyl sulfonates, alkylaryl sulfonates, alkyl sulfosuccinates, alkyl ether sulfosuccinates, alkyl sulfosuccinamates, alkyl amidosulfosuccinates, alkyl carboxylates, alkyl amidoethercarboxylates, alkyl succinates, fatty acyl sarcosinates, fatty acyl ammo acids, fatty acyl taurates, fatty alkyl sulfoacetates, alkyl phosphates, and mixtures thereof.
• Preferred surfactants include sodium olefin sulfonates wherein the olefin has from about 14 to about 16 carbon atoms, sodium lauryl sulfate, TEA lauryl sulfate, sodium laureth sulfate, cocamidopropylamine oxide, lauryl amine oxide, lauramido DEA, cocamidopropyl betaine, lauryl dimethyl betaine, cocodimethyl sulfo-propyl betaine, sodium cocoyl sarcosmate, disodium oleamido MIPA sulfosuccmate, disodium cocamido MIPA sulfosuccinate, disodium laureth sulfosuccinate, cocoamphocarboxy-glycinate, disodium oleamido MEA sulfosuccinate, amine glycinates, amine propionates and amine sultaines, and mixtures thereof, with sodium
• a mixture of two or more different surfactants more preferably a mixture of anionic surfactants and amphoteric surfactants, and in particular sodium laureth sulfonate and sodium cocoyl sarcosinate, or sodium lauryl sulfonate, sodium laureth sulfonate, TEA lauryl sulfonate, cocoamidopropyiamine oxide, and cocamidopropyl betaine, may be used.
• the total amount of surfactants may range from, based upon the total weight of the composition, from about 30% to about 60%, and preferably from about 40% to about 50%.
• the shampoos contain, based upon the total weight of the shampoo, from about 15% to about 30%, and preferably from about 20% to about 25% of an anionic surfactant, from about 5% to about 20%, and preferably from about 10% to about 15% of a non-ionic surfactant, and from about 10% to about 30%, and preferably from about 20% to about 25% of an amphoteric surfactant.
• the weight of amphoteric surfactants is less than 15 % by weight of the total amount of surfactants.
• the shampoo may comprise, based upon the total weight of the composition, from about 20 % to about 25% of an anionic surfactant such as sodium olefin sulfonate, and from about 20 % to about 25% of an amphoteric surfactant comprising, based upon the total weight of the amphoteric surfactant, from about 1.0 % to about 5.0% cocamidopropylamine oxide and from about 20% to about 25% cocamidopropyl betaine.
• an anionic surfactant such as sodium olefin sulfonate
• an amphoteric surfactant comprising, based upon the total weight of the amphoteric surfactant, from about 1.0 % to about 5.0% cocamidopropylamine oxide and from about 20% to about 25% cocamidopropyl betaine.
• Suitable foaming agents for use in the composition of the present invention include, but are not limited to fatty acid mono- and dialkanol- amides and mixtures thereof.
• Suitable foaming agents are cocamide MEA, cocamide DEA, oieamide MEA, oleamide DEA and mixtures thereof.
• the foaming agent may be present in a range from about 0 to about 10 % (wtw), preferably from about 2 to about 6 % (wtw), in particular about 4 to about 5 % (w/w). These ingredients typically also have a thickening effect on the formulation.
• Suitable preservatives for use in the present shampoos are dermatologically acceptable preservatives, e.g. sodium EDTA, methylparaben, propylparaben, butylparaben, ethylparaben, imidazolidinyi urea, diazolidinyl urea, phenoxyethanol, quatemium 15, citric acid, preferably in combinations with one another.
• Sodium EDTA and citric acid also function as chelating agents.
• the preservatives are used in an amount effective to retard degradation of the final composition in order to give adequate shelf life.
• Effective stability is considered to be a loss of active ingredient during storage of not more than about 10 percent.
• the proportion of BHT or BHA that has been found to be most effective is within the range of from about 0.01 % to about 1 % (w/w). Proportions greater than this amount do not stabilize dichlorophenyl imidazoldioxolan as effectively for the 13-week accelerated aging period.
• stability testing for 13 weeks at 50°C is quite sufficient to predict product stability during normal shelf life storage for two (2) years at room temperature. It is also equally important that, for safety reasons (that is, to minimize the potential for skin sensitization), it is desired to use as small an amount as possible of BHT or BHA.
• a suitable thickener is a carbomer or polycarboxylic acid, such as Carbopol TM 1342, which is thickened by the addition of sodium hydroxide or sodium chloride at the end of the preparation.
• Other suitable thickeners are xanthan gum, veegum, and the foaming agents mentioned hereinabove, preferably cocamide MEA.
• the amount of thickener used will depend upon the viscosity desired, typically the amount of thickener used may range, based upon the total weight of the shampoo, from about 0 % to about 2%, and preferably from about 0.2% to about 1.3%.
• Suitable pH adjusters or buffers for use in the present invention include, but are not limited to sodium citrate, citric acid, and mixtures thereof.
• the pH of the shampoos according to the present invention are conveniently established using dermatologically acceptable acids, bases and buffers.
• the pH can range from about 3.0 to about 8.0, but preferably is in the range of about 3.5 to about 5.0, in particular from about 3.7 to about
• Optional solubilizers for use in the present invention include, but are not limited to hexylene glycol, propylene glycol, butylene glycol and mixtures thereof. These solubilizers should be used in an amount effective for dissolving substantially ail of the solids in a given solution.
• the shampoo may optionally comprise a conditioner in an amount, based upon the total weight of the shampoo, from about 0 to about 5%, and preferably from about 1% to about 3%.
• suitable conditioners include, but are not limited to a cationic cellulose derivative; a cationic guar derivative; silicon substances such as cyciomethicone, dimethicone, and a giyceryl-derivative such as linoleamidopropyl poiyglycol dimonium chloride, and mixtures thereof; a homopolymer or copolymer of a cationic monomer selected from: a. a monomer having formula I.
• R is H or CH 3 ,
• Y is O or NH
• R- is an alkylene group having from about 2 to about 6, and preferably from about 2 to about 3 carbon atoms
• R 2 , R 3 and R are each independently an alkyl group having from about 1 to about 22, and preferably from about 1 to about 4 carbon atoms
• X is a monovalent anion selected from halide and alkyl sulfate, or b. diallyldimethylammonium chloride; or mixtures thereof.
• each conditioner component may range, based upon the total weight of the composition, from about 0.01 percent to about 1.0 percent, preferably from about 0.01 percent to about 0.5 percent, and more preferably from about 0.01 to about 0.2 percent.
• the cationic cellulose derivative includes a polymeric quaternary ammonium salt such as polyquaternium-7, polyquatemium -22, polyquatemium-10, or mixtures thereof with polyquartemium 22 being preferred.
• a polymeric quaternary ammonium salt such as polyquaternium-7, polyquatemium -22, polyquatemium-10, or mixtures thereof with polyquartemium 22 being preferred.
• the cationic guar derivative is preferably a guar hydroxypropyltrimonium chloride, available commercially from Rhone-Poulenc Inc., of Cranbury, New Jersey under the tradename, "Jaguar C-17.”
• Another preferred cationic polymer includes those compounds derived from acrylamkJopropyl trimonium chloride which has the formula:
• cationic conditioning polymers are those derived from the monomer diallyldimethylammonium chloride.
• the homopolymer of this monomer is Polyquatemium-6, which is available commercially form Allied Colloids of Suffolk, Virginia under the tradename,
• Salcare SC30 The copolymer of diallyldimethylammonium chloride with acrylamide is known as Polyquatemium-7, and is also available from Allied Colloids under the tradename “Salcare SC10.”
• the shampoo may optionally comprise pearlizing agents in an amount, based upon the total weight of the shampoo, of from about 0% to about 3%, and preferably from about 1% to about 1.5%.
• suitable peariizing agents include, but are not limited to, ethylene glycol distearate, ethylene glycol monostearate and mixtures thereof.
• the shampoos may further compnse one or more fragrances and/or colorants.
• composition should be applied in an amount effective to ameliorate the symptoms associated with dandruff, seborrheic dermatitis, psonasis, and/or acne.
• amount effective shall mean an amount sufficient to cover the region of skin surface where the symptom exists and to ameliorate the symptoms associated with the respective disease.
• the composition should be topically applied to affected body parts at regular intervals, and preferably from about 1 to about 7 times per week. More preferably, the composition is applied more frequently dunng the initial stages of treatment, e.g. from about 4 to about 7 times per week until the desired effect is achieved, then less frequently when maintenance is desired, e.g. from about 1 to about 2 times per week.
• the composition may be applied to the desired area in the form of, for example, a lotion, cream, gel or the like which is designed to be left on the skin and not washed shortly after application. Alternatively, the composition may be applied to the desired area in the form of, for example, a lotion, cream, gel, soap, shampoo or the like which is designed to be ⁇ nsed off within a given amount of time after application.
• the shampoo is applied to wet hair, and the hair is washed in accordance with known practices. More preferably, the composition remains on the hair for greater than about 0 to about 10 minutes, and preferably from about 4 to about 7 minutes before nnsmg.
• compositions comp ⁇ sing dichlorophenyl imidazoldioxolan, a known sebum-redu ⁇ ng agent, see WO- 93/18743, were topically applied to the skin or hair of a mammal, the proliferation of
• compositions comp ⁇ sing dichlorophenyl imidazoldioxolan not only possess sebum-redu ⁇ ng properties, but it also possess supenor Malassezia furfur and Propionibacte ⁇ um acnes growth inhibition properties, they are supenor relative to other known therapeutic agents in ameliorating the symptoms associated with dandruff, acne, and the like
• compositions also include salicylic acid, a known keratinolytic agent
• the resulting composition possesses properties which are effective for treating dandruff and the like via all three traditional approaches
• the invention illustratively disclosed herein suitably may be practiced in the absence of any component, ingredient, or step which is not specifically disclosed herein.
• Example 3 Preparation of Shampoo Base Containing Salicylic Acid and Piroctone olamine.
• the water - sodium olefin sulfonate mixture was made in accordance with the process set forth in Example 1 , with the exception that 440 g of purified water was used. After stirring the mixture for about 40 minutes while maintaining a constant intemal temperature and pressure therein, the mixture was then cooled to about 50 °C before the addition of 20 g of salicylic acid available from Spectrum Chemicals was added thereto with stirring for about 15 minutes until substantially all of the solids were dissolved. Temperature and pressure remained constant. 5 g of sodium citrate, 5 g of the "Phospholipid EFA " compound of Example 1 , and
• Example 4 Preparation of Shampoo Base Containing Dichlorophenyl Imidazoldioxolan. Salicylic Acid, and Piroctone olamine.
• Example 4 The process set forth in Example 4 was repeated, except that 5g of the dichlorophenyl imidazoldioxolan of Example 2 was stirred into the mixture of purified water and sodium olefin sulfonate, and the resulting mixture was then stirred for an additional 40 minutes until substantially all of the solids were dissolved before being cooled to 50 °C.
• Example 5 MIC of Shampoos against Pityrosporum ovale and Candida albicans
• Comparative shampoos "A” is a 0.5% coal tar-containing anti-dandruff shampoo available from Neutrogena Corporation, under the tradename "T-Gel”
• comparative shampoo “B” is a 1 % ketoconazole-containing anti-dandruff shampoo available from Neutrogena Corporation under the tradename "Neutrogena Long Lasting
• the shampoos were diluted directly into the culture medium, Diagnostic Sensitivy Test agar (DST ; Oxoid, UK) with the addition of Tween 80 (2 ml/1) and glyceryl monostearate (2.5 g/l) to give concentrations of 0.1 to 40 % of the shampoos in the culture medium. Consequently, the minimum inhibitory concentration (MIC) values are for the whole shampoo, and not only the active ingredient(s). As used herein, " MIC * means the lowest concentration of the shampoo at which a total inhibition of microorganism growth was observed.
• microorganisms were added onto the agar medium-filled plates in concentrations of 10 7 cell/ml (Malassezia furfur) and 10 6 cells/ml (C. albicans). These plates were incubated at 37°C and read after 1 , 2 and 3 days. All shampoos were tested in duplicate. The MIC results are presented in Table 2 below:
• Comparative shampoo "C” is a 2% ketoconazole-containing anti-dandruff shampoo available from Janssen Pharmaceutica N.V. under the tradename “Nizoral”. The shampoos were diluted 50-fold in sterile water, then further diluted in sterile water to generate a dilution series in two-fold concentration steps.
• the optical density of the wells was read with a model 3550 Bio-Rad automatic plate reader set at 570 nm.
• the growth (turbidity) of the M. furfur in the presence of the sample shampoos was caculated as a percentage of growth turbidity in drug-free control wells for each isolate.
• the maximal inhibitory dilution of a product for an isolate of M. furfur was defined as the highest dilution of test shampoo that reduced growth below 50% of control according to the spectrophotometric readings. The maximal inhibitory dilution results are presented in Table 3 below.
• Culture mediums were prepared in accordance with the procedure set forth in Example 5, but with formulations of dichlorophenyl imidazoldioxolan in water instead of shampoos. After P. acnes were added onto the agar medium-filled plates in concentrations of about 10 7 cell/ml , the plates were incubated and read in accordance with the procedure set forth in Example 5. This Example was repeated using two additional, different strains of P. acnes.
• the resulting MIC which in this example is the lowest concentration of the dichlorophenyl imidazoldioxolan at which a total inhibition of microorganism growth was observed, was 1 mg/ml for two strains and 10 mg/ml for the third strain.
• This Example shows that dichlorophenyl imidazoldioxolan is active against the growth of microorganisms involved in the pathogenesis of acne.
• Example 8 Comparative Testing of Elubiol. Salicylic Acid, and Benzoyl Peroxide
• BPO Cream Vanishing Cream
• the baseline absolute lesion count i.e. count for total comedones, open comedones, closed comedones, papules, pustules, cysts, and nodules, was calculated for each adult.
• Each adult was also given a rating on a qualitative scale from 0 (absent) to 3 (severe) for baseline acne symptoms, i.e. oiliness, erythema, dryness, peeling, burning, stinging, itching and tightness.
• Each adult was further rated for its baseline acne level, i.e. Grade I (comedonic acne); Grade II (papular-pustular acne) or Grade III (acne conglobata). At baseline, all adults were classified as having Grade II acne and as having nearly identical levels of acne symptoms.
• the absolute lesion count, the acne symptoms, and the acne level for each adult were recalculated.
• the cream containing 10% benzoyi peroxide also showed the fastest and more pronounced response against papules, with final lesion counts reduced by about 2/3 for users of the BPO Cream versus 1/3 for the other two groups. Pustules, cysts, and nodules were rarely seen in any of the adults.
• the group using the BPO Cream showed a 75% reduction in oiliness, versus a 55% reduction for users of the E Cream and a 35% reduction for users of the SA Cream.
• the elubiol treated group had a decrease in oiliness of 73%, versus decreases of 51% and 71% for salicylic acid and benzoyi peroxide, respectively.
• Erythema decreased by 39% within 1 week after the start of treatment in the elubiol group, versus a 30% decrease with salicylic acid and a 13% increase with benzoyi peroxide. At the end of the 12 weeks, erythema was reduced by 48%, 48% and 55% in the 3 groups, respectively.
• This Example showed that, in comparison to baseline values, only the elubiol treated patients shown significant reduction in erythema from the first week onwards.
• the irritation scores were more pronounced for adults in all groups. After the initial 2 week period, signs of irritation were reduced. At the end of the 12 weeks, the elubiol group showed the least amount of irritation (0/3.0), versus apparent irritation in the saiicyiic acid group (0.3/3.0) and the benzoyi peroxide group (0.38/3.0).
• This Example showed that the highest level of irritation was seen in the benzoyi peroxide group, followed by the saiicyiic acid group, and the elubiol group. Dryness and peeling were also assessed on the same severity scale. In particular, the benzoyi peroxide group showed a significantly greater amount of dryness and peeling than the salicylic acid group or the elubiol group.
• Stinging did not prove to be a problem with any of the users, and itching improved during the course of the study in the 3 groups. The fastest reduction in itching was observed in the group using the E cream.
• this Example showed that the 0.1 percent elubiol cream was comparatively faster acting and more efficacious than the 2% salicylic acid cream. While the .1 percent elubiol cream was not as fast-acting as the 10% benzoyi peroxide cream, the elubiol cream had comparatively minimal side effects and was better tolerated overall by the users than the benzoyi peroxide cream.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Dermatology (AREA)
• Epidemiology (AREA)
• Birds (AREA)
• Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Pharmacology & Pharmacy (AREA)
• Organic Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Medicinal Chemistry (AREA)
• General Chemical & Material Sciences (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Engineering & Computer Science (AREA)
• Inorganic Chemistry (AREA)
• Emergency Medicine (AREA)
• Cosmetics (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (3)

Publications (1)

Family

ID=21971188

Family Applications (1)

Country Status (12)

Cited By (1)

Families Citing this family (11)

Family Cites Families (5)

• 1998
  • 1998-06-29 AU AU82707/98A patent/AU8270798A/en not_active Abandoned
  • 1998-06-29 KR KR1019997012584A patent/KR20010020598A/ko not_active Application Discontinuation
  • 1998-06-29 WO PCT/US1998/013425 patent/WO1998052518A1/en not_active Application Discontinuation
  • 1998-06-29 DE DE19880535T patent/DE19880535T1/de not_active Withdrawn
  • 1998-06-29 CN CN98806837A patent/CN1262611A/zh active Pending
  • 1998-06-29 JP JP55076098A patent/JP2002510292A/ja active Pending
  • 1998-06-29 BR BR9810396-2A patent/BR9810396A/pt not_active Application Discontinuation
  • 1998-06-29 EP EP98932927A patent/EP0996410A1/en not_active Withdrawn
  • 1998-06-29 CA CA002294804A patent/CA2294804A1/en not_active Abandoned
  • 1998-07-01 AR ARP980103206A patent/AR013163A1/es unknown
  • 1998-07-01 ZA ZA9805781A patent/ZA985781B/xx unknown
  • 1998-07-02 CO CO98037373A patent/CO4940366A1/es unknown

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events