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Número de publicaciónUS20060140984 A1
Tipo de publicaciónSolicitud
Número de solicitudUS 10/532,618
Número de PCTPCT/IB2003/005527
Fecha de publicación29 Jun 2006
Fecha de presentación24 Oct 2003
Fecha de prioridad25 Oct 2002
También publicado comoCA2502986A1, CA2502986C, EP1556009A2, EP1556009B1, US8722021, US8840869, US9713643, US20050271598, US20080138293, US20130183250, US20140241998, US20160354473, US20170274084, WO2004037225A2, WO2004037225A3
Número de publicación10532618, 532618, PCT/2003/5527, PCT/IB/2003/005527, PCT/IB/2003/05527, PCT/IB/3/005527, PCT/IB/3/05527, PCT/IB2003/005527, PCT/IB2003/05527, PCT/IB2003005527, PCT/IB200305527, PCT/IB3/005527, PCT/IB3/05527, PCT/IB3005527, PCT/IB305527, US 2006/0140984 A1, US 2006/140984 A1, US 20060140984 A1, US 20060140984A1, US 2006140984 A1, US 2006140984A1, US-A1-20060140984, US-A1-2006140984, US2006/0140984A1, US2006/140984A1, US20060140984 A1, US20060140984A1, US2006140984 A1, US2006140984A1
InventoresDov Tamarkin, Doron Friedman, Meir Eini
Cesionario originalFoamix Ltd.
Exportar citaBiBTeX, EndNote, RefMan
Enlaces externos: USPTO, Cesión de USPTO, Espacenet
Cosmetic and pharmaceutical foam
US 20060140984 A1
Resumen
The invention relates to an alcohol-free cosmetic or pharmaceutical foam carrier comprising water, a hydrophobic solvent, a foam adjuvant agent, a surface-active agent and a water gelling agent. The cosmetic or pharmaceutical foam carrier does not contain aliphatic alcohols, making it non-irritating and non-drying. The alcohol-free foam carrier is suitable for inclusion of both water-soluble and oil soluble pharmaceutical and cosmetic agents.
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Reclamaciones(87)
1. An alcohol-free foamable pharmaceutical or cosmetic carrier, comprising:
(a) a foamable composition comprising:
about 2-75% by weight of composition of a liquid, non-volatile hydrophobic solvent;
about 80-98% by weight of composition of water;
about 0.1% to 5% by weight of composition of a foam adjuvant agent selected from the group consisting of fatty alcohols, fatty acids, hydroxyl-substituted fatty alcohols, hydroxyl-substituted fatty acids, and fatty acids and fatty alcohols including at least one double bond in its carbon atom chain;
about 0.1% to 5% by weight of composition of a surface-active agent; and
about 0.1% to 5% by weight of composition of a water gelling agent and
(b) a liquefied or compressed gas propellant in a container,
which upon release provides a breakable foam suitable for topical or muscosal administration.
2. The foamable carrier of claim 1, wherein the hydrophobic solvent comprises about 5-10% by weight of composition.
3. The foamable carrier of claim 1, wherein the hydrophobic solvent comprises about 10-20% by weight of composition.
4. The foamable carrier of claim 1, wherein the hydrophobic solvent comprises about 20-75% by weight of composition.
5. The foamable carrier of claim 1, wherein the hydrophobic solvent comprises a mixture of mineral oil and an emollient in a ratio between 2:8 and 8:2 on a weight basis.
6. The foamable carrier of claim 1, wherein at least 2% of the foamable composition is a silicone oil.
7. (canceled)
8. The foamable carrier of claim 1, wherein the surface-active agent is a mixture of a non ionic surfactant and an anionic surfactant in a 20:1 to 1:1 ratio.
9. The foamable carrier of claim 1, wherein the surface-active agent is a mixture of a non-ionic surfactant and an ionic surfactant in a 100:1 to 6:1 ratio.
10. The foamable carrier of claim 1, wherein the surface-active agent consists essentially of one or more non-ionic surfactants.
11. The foamable carrier of claim 1, wherein the surface-active agent has HLB value of more than 9.
12. The foamable carrier of claim 10, wherein the non-ionic surfactant comprises a sucrose ester.
13. The foamable carrier of claim 1, wherein the hydrophobic solvent is selected from the group comprising vegetable oils, marine oils, mineral oils, emollients, silicone oils, plant-derived therapeutic oils and mixture thereof.
14. The foamable carrier of claim 1, wherein the combined amount of foam adjuvant agent, surface-active agent and water gelling agent is less than about 8% (w/w).
15. The foamable carrier of claim 1, wherein the combined amount of foam adjuvant agent, surface-active agent and water gelling agent is less than about 5% (w/w) of the foamable composition.
16. A pharmaceutical or cosmetic composition, comprising:
(a) a foamable composition comprising:
about 2-75% by weight of composition of a liquid, non-volatile hydrophobic solvent;
about 80-98% by weight of composition of water;
about 0.1% to 5% by weight of composition of a foam adjuvant agent selected from the group consisting of fatty alcohols, fatty acids, hydroxyl-substituted fatty alcohols, hydroxyl-substituted fatty acids, and fatty acids and fatty alcohols including at least one double bond in its carbon atom chain;
about 0.1% to 5% by weight of composition surface-active agent; and
about 0.1% to 5% by weight of composition water gelling agent;
(b) a therapeutically effective amount of an active agent; and
(c) a liquefied or compressed gas propellant in a container,
which upon release provides a breakable foam suitable for topical or muscasol administration.
17. The pharmaceutical or cosmetic composition of claim 16, wherein the hydrophobic solvent comprises about 5-10% by weight of composition.
18. The pharmaceutical or cosmetic composition of claim 16, wherein the hydrophobic solvent comprises about 10-20% by weight of composition.
19. The pharmaceutical or cosmetic composition of claim 16, wherein the hydrophobic solvent comprises about 20-75% by weight of composition.
20. (canceled)
21. The pharmaceutical or cosmetic composition of claim 16, wherein the active agent is a cosmetically effective agent.
22. The pharmaceutical or cosmetic composition of claim 16, wherein the hydrophobic solvent is selected from the group comprising vegetable oils, marine oils, mineral oils, emollient, silicone oils, plant-derived therapeutic oils and mixture thereof at any proportion.
23. The pharmaceutical or cosmetic composition of claim 16, further comprising excipients selected from the group consisting of antioxidants, humectants, flavoring, colorant and odorant agents.
24. The pharmaceutical or cosmetic composition of claim 16, wherein the hydrophobic solvent comprises a mixture of mineral oil and an emollient in a ratio between 2:8 and 8:2 on a weight basis.
25. The pharmaceutical or cosmetic composition of claim 16, wherein at least 2% of the composition is a silicone oil.
26. The pharmaceutical or cosmetic composition of claim 16, wherein the surface-active agent is a mixture of a non ionic surfactant and an anionic surfactant in a 20:1 to 1:1 ratio.
27. The pharmaceutical or cosmetic composition of claim 16, wherein the surface-active agent consists essentially of one or more non-ionic surfactants.
28. The pharmaceutical or cosmetic composition of claim 16, wherein the surface-active agent is a mixture of a non-ionic surfactant and an ionic surfactant in a 100:1 to 6:1 ratio.
29. The pharmaceutical or cosmetic composition of claim 16, wherein the combined amount of foam adjuvant agent, surface active agent and water gelling agent is less than about 8% (w/w).
30. The composition of claim 16, further comprising an effective concentration of a penetration enhancer.
31. The pharmaceutical or cosmetic composition of claim 16, wherein the combined amount of foam adjuvant agent, surface active agent and water gelling agent is less than about 5% (w/w).
32. The pharmaceutical or cosmetic composition of claim 16, wherein the active agent is selected for the treatment of a disease, the etiology of which is bacterial, fungal, viral, parasitic, inflammatory, autoimmune, allergic, hormonal, malignant and combinations thereof.
33. (canceled)
34. The composition of claim 16, wherein the active agent is selected for the treatment of a disorder of the skin, mucosal membrane, vagina and rectum.
35. The composition of claim 16, wherein the active agent is selected for the treatment of a disorder, selected from the group of dermatosis, dermatitis, bacterial Infections, fungal Infections, parasitic infections, viral infections, disorders of hair follicles and sebaceous glands, acne, rosacea, scaling papular diseases, benign tumors, malignant tumors, reactions to sunlight, bullous diseases, pigmentation disorders, disorders of cornification, pressure sores, disorders of sweating, inflammatory reactions, xerosis, ichthyosis, allergy, burn, wound, cut, and non-dermatological disorders, which respond to transdermal delivery of said drug.
36. (canceled)
37. The composition of claim 16, wherein the active agent is selected from the group consisting of antibacterial agents, antifungal agents, antiviral agents, insecticides, insect repellents, anti-inflammatory or antiallergic agents, anticancer agents, photodynamic therapy agents, local anesthetics, nonsteroidal anti-inflammatory drugs (NSAIDs), and an herbal extract, a radical scavenger, and an anti-acne cream.
38. (canceled)
39. (canceled)
40. (canceled)
41. (canceled)
42. (canceled)
43. (canceled)
44. (canceled)
45. (canceled)
46. (canceled)
47. The composition of claim 21, wherein the active agent is selected from the group consisting of retinoids. anti-wrinkle agents, skin whitening agents. self-tanning agents, herbal extracts, radical scavengers, anti-acne agents, and figure forming agents.
48. (canceled)
49. (canceled)
50. The composition of claim 16, wherein said active agent is selected from the group comprising sulfur-containing amino acids, thiol compounds, alpha hydroxy acids, lactic acid and its derivatives and salts, glycolic acid and its derivatives and salts, beta-hydroxy acids, salicylic acid and salicylic acid salts and derivatives, phytic acid, lipoic acid, lysophosphatidic acid, skin peel agents, phenol, resorcinol, vitamin B3 compounds, niacinamide, nicotinic acid and nicotinic acid salts and esters, tocopheryl nicotinate, nicotinyl amino acids, nicotinyl alcohol esters of carboxylic acids, nicotinic acid N-oxide and niacinamide N-oxide, retinoids, retinol, retinal, retinoic acid, retinyl acetate, retinyl palmitate, retinyl ascorbate, caffeine, theophiline, pentoxyphilline, dihydroxy acetone kojic acid, arbutin, nicotinic acid and its precursors, salts and derivatives, arbutin, ascorbic acid and salts and derivatives thereof.
51. (canceled)
52. (canceled)
53. (canceled)
54. (canceled)
55. (canceled)
56. (canceled)
57. The composition of claim 21, wherein the active agent is an agent that influences hair growth, a hair growth stimulation agent, or a hair growth inhibiting agent.
58. (canceled)
59. (canceled)
60. The composition of claim 16, further comprising a sunscreen agent.
61. (canceled)
62. The composition of claim 16, wherein the active agent is a combination of a skin whitening agent and a sunscreen agent.
63. The composition of claim 16, wherein the active agent is a combination of a skin whitening agent and an inorganic sunscreen agent.
64. The composition of claim 16 wherein the active agent is intended for transdermal delivery.
65. The composition of claim 16, further comprising a decontaminating agent selected from the group comprising an oxidizing agent, iodine and iodine compounds, chlorohexidine, bleaching agents and surface-active agents.
66. A method of treating, alleviating or preventing a dermatological disorder, comprising:
administering topically to a subject having said dermatological disorder a therapeutically effective amount of a breakable foam composition comprising:
(a) a foamable composition comprising:
about 2-75% by weight of composition of a liquid, non-volatile hydrophobic solvent;
about 80-98% by weight of composition of water;
about 0.1% to 5% by weight of composition of a foam adjuvant agent selected from the group consisting of fatty alcohols, fatty acids, hydroxyl-substituted fatty alcohols, hydroxyl-substituted fatty acids, and fatty acids and fatty alcohols including at least one double bond in its carbon atom chain;
about 0.1% to 5% by weight of composition of a surface-active agent; and
about 0.1% to 5% by weight of composition of a water gelling agent.
(b) at least one active agent, which is intended to prevent, alleviate or cure said disorder; and
(c) a liquefied or compressed gas propellant.
67. The method of claim 66, wherein at least 2% of the composition is a silicone oil.
68. The method of claim 66, wherein the hydrophobic solvent comprises a mixture of mineral oil and an emollient in a ratio between 2:8 and 8:2 on a weight basis.
69. The method of claim 66, wherein the surface-active agent is selected from the groups of non-ionic surfactants, cationic surfactants, amphoteric and zwitterionic surfactants.
70. The method of claim 66, wherein the surface-active agent is a mixture of a non-ionic surfactant and an anionic surfactant in a 1:1 to 20:1 ratio.
71. The method of claim 66, wherein the surface-active agent is non-ionic.
72. The method of claim 66, wherein the surface-active agent has HLB value of more than 9.
73. The method of claim 66, wherein the non-ionic surfactant comprises a sucrose ester.
74. The method of claim 66, wherein the active agent is intended for the treatment of a disease, the etiology of which is bacterial, fungal, viral, parasitic, inflammatory, autoimmune, allergic, hormonal, malignant and combinations thereof.
75. The method of claim 66, wherein the active agent is selected from the group comprising antibacterial, antifungal, anti-inflammatory, antiallergic, nonsteroidal anti-inflammatory, retinoid, alpha hydroxy acid, beta hydroxy acid, keratolytic, antiproliferative, anticancer and anti-pigmentation drugs.
76. The method of claim 66, wherein the active agent is selected from the group comprising insecticides, insect repellents, and figure forming agents.
77. The method of claim 66, wherein said active agent is applied topically to an affected area.
78. The method of claim 66, wherein said dermatological disorder is a disorder selected from the group, consisting of dermatosis, dermatitis, bacterial Infections, fungal Infections, parasitic infections, viral infections, disorders of hair follicles and sebaceous glands, scaling papular diseases, benign tumors, malignant tumors, reactions to sunlight, bullous diseases, pigmentation disorders, disorders of comification, pressure sores, disorders of sweating, inflammatory reactions, xerosis, ichthyosis, allergy, bum, wound, cut, and non-dermatological disorders, which respond to transdermal delivery of said active agent.
79. (canceled)
80. The method of claim 66, wherein the active agent is selected from the group consisting of an agent that influences hair growth, a hair growth stimulating agent, and a hair growth inhibiting agent.
81. (canceled)
82. (canceled)
83. The method of claim 66, further comprising a sunscreen agent.
84. (canceled)
85. The method of claim 66, wherein the active agent is a combination of a skin whitening agent and a sunscreen agent.
86. (canceled)
87. The method of claim 66, comprising an effective concentration of a penetration enhancer.
Descripción
  • [0001]
    This application claims priority to Related Applications of Israeli patent application No. 152486 filed Oct. 25, 2002 entitled “Alcohol-free Cosmetic and Pharmaceutical Foam Carrier”, and to U.S. provisional patent application No. 60/495,546, filed Nov. 29, 2002, entitled “Cosmetic and Pharmaceutical Foam”, which are incorporated herein in their entirety.
  • FIELD OF THE INVENTION
  • [0002]
    The invention relates to an alcohol-free, cosmetic or pharmaceutical foam carrier and its use. More specifically, the invention relates to a cosmetic or pharmaceutical foam carrier suitable for inclusion of both water soluble and oil soluble pharmaceutical and cosmetic agents.
  • BACKGROUND OF THE INVENTION
  • [0003]
    External topical administration is an important route for the administration of drugs in disease treatment. In external topical administration, the drug is absorbed into and/or through skin, mucous membrane or wound tissue. Many groups of drugs, including, for example, antibiotic, anti-fungal, anti-inflammatory, anesthetic, analgesic, anti-allergic, corticosteroid, retinoid and anti-proliferative medications are preferably administered in hydrophobic media, e.g. ointments or oils. However, due to the undesirable consistency of these hydrophobic carriers, their use is limited. For instance, ointments containing white petrolatum, e.g., Vaseline petroleum jelly, as the carrier often form an impermeable barrier, so that metabolic products and excreta from the wounds to which they are applied are not easily removed or drained away. Furthermore, it is difficult for the active drug dissolved in the carrier to pass through the white petrolatum barrier layer into the wound tissue, so the efficacy of the drug is reduced.
  • [0004]
    In addition, ointments and creams often do not create an environment for promoting respiration of the wound tissue and it is not favorable to the normal respiration of the skin. An additional disadvantage of petroleum jelly-based products relates to the greasy feeling left following their topical application onto the skin, mucosal membranes and wounds. Besides petroleum jelly, hydrophobic pharmaceutical carriers now in use include liquid paraffin, lanolin, beeswax, vegetable oil, glycerin monostearate, higher alcohols, polyethylene glycol and some emulsifying agents, which also have undesirable flow properties and skin feel.
  • [0005]
    Several hydrophobic liquid and semi-solid oils, e.g., mono- and poly-unsaturated oils from vegetable and marine sources, mineral oils, silicone oils, and liquid hydrophobic plant-derived oils, are known for their therapeutic benefits when applied topically, yet, their application in liquid form is not practical. Oils can also contain essential nutritional constituents, such as oil-soluble vitamins (e.g., vitamin A and vitamin E), minerals and other therapeutically beneficial constituents. Another class of therapeutic oils includes mineral and silicon oils useful for the treatment of skin dehydration and other medical disorders, which oils are liquid at ambient temperature. Such therapeutic oils unfortunately, cannot be applied by users in amounts sufficient to exert therapeutic affects because of they typically are liquid at use temperatures.
  • [0006]
    Other pharmaceutical active ingredients are water-soluble and require a water component in the carrier.
  • [0007]
    While semi-solid cosmetic and pharmaceutical formulations, such as creams, lotions, gels and ointments are commonly used by consumers, new forms are desirable, in order to achieve better control of the application, while maintaining or bestowing the skin beneficial properties of such products. Thus, the development of a new composition, having breakable foam consistency when extruded out of a container and liquid properties when applied onto the skin is advantageous. Ideally a foam should contain hydrophobic substances (solvents), which can act as emollients and provide the skin with soothing and nourishing properties. However, such hydrophobic solvents are difficult to formulate into a lather-producing or foam-producing product because the hydrophobic solvents interfere with the lather forming ability of the surfactant. Furthermore, addition of oils and other emollients to topical formulations can result in an unpleasant or annoying skin residue.
  • [0008]
    Use of emulsions in foam compositions is known. Emulsion systems provide a two-phase system including lipophilic or hydrophobic components in one phase and hydrophilic components in the second phase. The foamed emulsion typically is an oil-in-water emulsion in which the hydrophobic component is dispersed in the aqueous continuous phase. Surfactants for reducing surface tension and emulsifiers for improving foam stability are included in the foam composition.
  • [0009]
    Foams and, in particular, foam emulsions are complicated systems which do not form under all circumstances. Slight shifts in foam emulsion composition, such as by the addition of active ingredients, may destabilize the foam. Furthermore, many emulsions do not provide the high foam capacity, foam stability and/or fast-breaking action under stress or temperatures that are desired in a topical foam composition.
  • [0010]
    A particularly desirable type of oil-containing foam is such wherein all or part of the oil phase comprises silicone oil. Silicone oil is known for its skin protective features and its incorporation in topical products is beneficial. However, it is not obvious to produce silicone oil-based foams, since many silicone oils possess anti-foaming properties.
  • [0011]
    U.S. Pat. No. 6,126,920 discloses treatment of various skin diseases, and in particular, scalp psoriasis, using a foamable pharmaceutical composition containing a corticosteroid active substance, an aliphatic alcohol, water, a fatty alcohol, a surface-active agent, a propellant and a buffering agent. The foamable composition contains 40-90% w/w composition of an aliphatic alcohol. U.S. Pat. No. 6,126,920 is typical of many compositions that use aliphatic alcohols in the foam composition. The alcohol promotes fast drying and thereby attempts to address the sticky feeling left by many topical formulations after application; however, alcohols, and in particular the methyl, ethyl and isopropyl alcohols preferred in the '920 patent, are defatting agents and may cause skin to become dry and cracked. Hence, the presence of aliphatic alcohol in a therapeutic foam for external topical administration as taught in U.S. Pat. No. 6,126,920 is undesirable.
  • [0012]
    U.S. Pat. No. 5,536,743 to Borgman describes a buffered non-flowing composition suitable for the treatment of bacterial vaginosis which contains metronidazole. Suitable formulations include oil-in-water emulsions including an internal oil phase of about 10-40 wt % oil and anionic, cationic or nonionic surfactants. Suitable components of the oleaginous phase include long chain alcohols, esters, and acids, vegetable and animal oils and waxes. No other stabilizing agents are disclosed for use in foam aerosol compositions.
  • [0013]
    EP 0,598,412 describes a composition that is useful for skin protection against drying and harsh environmental substances. The protection is derived from the inclusion of poly(tetrafluoroethylene) (PTFE) in the composition. The composition includes low levels of both hydrophilic emollients and hydrophobic emollients. The compositions include high levels of surfactants, including ionic surfactants, and co-emulsifiers resulting in thick emulsions which are not flowable, and thus providing products which are inefficient foamers (or non-foaming) and too thick for spreading over large skin areas.
  • [0014]
    U.S. Pat. No. 6,423,323 describes an aqueous foam emulsion. The composition includes a hydrophobic phase including fatty acids, emulsifiers and co-emulsifiers, and an aqueous phase containing hydrophilic moisturizers and emulsifiers. An optional ingredient according to U.S. Pat. No. 6,423,323 is one or more refatting substances, in preferable concentrations of 0.5 to 2%, if the product is to be used for normal skin; and 3 to 6% for dry skin. Addition of high levels of co-emulsifiers such as fatty alcohols and fatty acids suggest that the foam is not stable. No other stabilizing agents are disclosed.
  • [0015]
    U.S. Pat. No. 5,635,469 describes a foamable cleansing liquid composition comprising about 0.05% to about 10% of an emollient, in addition to cleansing surfactants, humectants and water soluble cationic or nonionic polymers, but no propellants. Low density foams are achieved using a novel non-aerosol foam dispenser. The foaming is achieved by operating a manual pump, which is not convenient for operation. Emollients and humectants are included to improve the level of hydration and/or lipid content of the skin. However, the patent notes that emollients and humectants interfere with the lather forming ability of the surfactant.
  • [0016]
    U.S. Pat. No. 6,113,888 teaches a single water phase composition comprising a self-tanning agent, a nitrogen-free polymer, a nitrogen-free surfactant, and water.
  • [0017]
    U.S. Pat. No. 5,679,324 to Lisboa pertains to an aerosol foamable fragrance composition, translucent in its pre-dispensed state, which forms a fast breaking foam. Apparently the foam breaks spontaneously upon discharging from an aerosol container (with no need of any rubbing or sheer force application), thus, making is impractical for spreading over a skin surface. The composition contains surfactant, a propellant, a fragrance, a thickener, and a cosmetic vehicle (preferably water) wherein the ratio of the surfactant to propellant is from about 1:1 to about 1:10. Emollients including silicone oils, mineral oils and hydrocarbon oils may be included.
  • [0018]
    U.S. Pat. No. 6,251,369 discloses foamable dental fluoride compositions containing a water-soluble fluoride component, whereby said compositions include an oil in water emulsion. However, the patent fails to specify the identity or concentration of the oil component of the emulsion; and none of the compositions presented in the examples contain any oil component.
  • [0019]
    U.S. Pat. No. 5,961,957 describes a barrier foam composition comprising from 70 to 90% of water, from 7 to 9% of butane, from 2 to 4% of glyceryl monostearate, from 1.5 to 3.50% of dimethicone copolyol (a water-soluble silicone compound), from 1 to 3% of propane, from 0.5 to 2.5% of lanolin, from 0.5 to 2.5% of stearic acid and from 0.05 to 1.05% of at least one of methylchloroisothiazolinone and methylisothiazolinone.
  • [0020]
    A few dermatological foam products are available on the market.
  • [0021]
    Olux™ Foam, produced by Connetics, Inc., contains clobetasol propionate. Each gram of Olux™ Foam contains 0.5 mg clobetasol propionate, USP, in a thermolabile foam, which consists of ethanol (60%), purified water, propylene glycol, cetyl alcohol, stearyl alcohol, polysorbate 60, citric acid, and potassium citrate. It is dispensed from an aluminum can pressurized with a hydrocarbon propellant (propane/butane). Luxiq™ is another corticostroid foam medication, containng 1.2 mg betamethasone valerate per gram, in a vehicle, comprising ethanol (60.4%), purified water, propylene glycol, cetyl alcohol, stearyl alcohol, polysorbate 60, citric acid, and potassium citrate, and pressurized with a hydrocarbon propellant.
  • [0022]
    Cortifoam, a hydrocortisone acetate rectal foam is produced by Schwartz Pharma GmbH, wherein the hydrocortisone is present at 10% in a foam vehicle. Nonmedicinal ingredients of Cortifoam include cetyl alcohol, ethoxylated stearyl alcohol, methylparaben, polyoxyethylene-10 stearyl ether, propylene glycol, propylparaben, triethanolamine, water, and inert propellants, isobutene, and propane.
  • [0023]
    Thus, foam compositions for topical treatment, containing higher concentrations of oils, and do not comprise alcohol are still desirable. Foam compositions that are robust and suitable for inclusion of a wide range of active ingredients are desired.
  • SUMMARY OF THE INVENTION
  • [0024]
    Despite the commonly known fact that hydrophobic solvents are difficult to formulate into a lather-producing or foam-producing product and that addition of conventional hydrophobic solvents interferes with the lather forming ability of the surfactant, we have surprisingly discovered a series of foamable carrier compositions, which, upon admixing with a liquefied gas propellant in an aerosol container, produces a foamable composition that is suitable for topical administration. Upon discharge from an aerosol container, the composition forms a breakable foam, which is rich and creamy in appearance, and show very fine bubble structure. The foam does not break down immediately upon discharge, however, it collapses to spread easily onto a skin area upon slight rubbing.
  • [0025]
    In one or more embodiments of the present invention, the alcohol-free cosmetic or pharmaceutical foamable carrier composition includes water, a liquid, non-volatile hydrophobic solvent, a foam adjuvant agent selected from the group consisting of fatty acids and fatty alcohols, a surface-active agent and a water gelling agent. Such foamable carriers, when placed in an aerosol container and combined with a liquefied gas propellant, create an oil in water emulsion, which, upon release from the aerosol container, provides a therapeutically beneficial foam product. The foam retains its structure for a time sufficient for a user to apply and to rub the foam into the skin. The foam has a very low yield strength and, hence, it breaks upon touch and makes rubbing easy and efficient, and its application even.
  • [0026]
    In one or more embodiments of the present invention, the foamable carrier composition the hydrophobic solvent content is about 2-5% and has a composition as follows:
  • [0027]
    Class A Composition:
      • about 2-5% hydrophobic solvent;
      • about 80-98% water;
      • about 0.1% to 5% foam adjuvant agent;
      • about 0.1% to 5% surface-active agent; and
      • about 0.1% to 5% water gelling agent.
  • [0033]
    In one or more embodiments of the present invention, the foamable composition the hydrophobic solvent content is about 5-10% and has a composition as follows:
  • [0034]
    Class B Composition:
      • about 5-10% hydrophobic solvent;
      • about 75-95% water;
      • about 0.1% to 5% foam adjuvant agent;
      • about 0.1% to 5% surface-active agent; and
      • about 0.1% to 5% water gelling agent.
  • [0040]
    In one or more embodiments of the present invention, the foamable composition the hydrophobic solvent content is about 10-20% and has a composition as follows:
  • [0041]
    Class C Composition:
      • about 10-20% hydrophobic solvent;
      • about 60-90% water;
      • about 0.1% to 5% foam adjuvant agent;
      • about 0.1% to 5% surface-active agent; and
      • about 0.1% to 5% water gelling agent.
  • [0047]
    In one or more embodiments of the present invention, the foamable composition the hydrophobic solvent content is about 20-75% and has a composition as follows:
  • [0048]
    Class A Composition:
      • about 20-75% hydrophobic solvent;
      • about 25-75% water;
      • about 0.1% to 5% foam adjuvant agent;
      • about 0.1% to 5% surface-active agent; and
      • about 0.1% to 5% water gelling agent.
  • [0054]
    All % values are provided on a weight (w/w) basis, based on the composition with out propellant (unless otherwise specified).
  • [0055]
    The cosmetic or pharmaceutical foamable carrier composition is liquid. The foamable of the present invention does not contain short chain aliphatic alcohols, making it non-irritating and non-drying. Alcohols penetrate the skin's protective barrier and break down the intercellular matrix. In a recent publication by the American Academy of Dermatology (AAD), titled “Facing the Facts about Skin Care Products” it is stated “[i]ndividuals with dry skin should avoid astringents and any product with alcohol because they easily strip away moisture from the skin” (see: www.aad.org/PressReleases FacingFacts.html). Another AAD publication, titled “Sensitive About Your Skin?”, recommends to “[a]void solvents that penetrate the skin including, propylene glycol and ethanol” (see: www.aad.org/PressReleases/sensitive.html).
  • [0056]
    The alcohol-free foam carrier is formulated as an oil-in-water or water-in-oil emulsion, so that it is suitable for inclusion of either water-soluble and oil soluble active agents (or both). The foamable carrier composition of the present invention, when admixed with a propellant substance in an amount of about 5-25% by weight of the total composition in an aerosol container, produces lightweight breakable foam, suitable for facile application onto the skin, and other body areas, which may accept topically-applied products. Since the propellant, in the pressurized container is in liquid state, upon admixing the foamable carrier composition with the propellant, a stable emulsion, comprising the oil and the propellant (jointly as the “oil phase” component of such emulsion) is formed.
  • [0057]
    In one or more embodiments of the present invention, an alcohol-free cosmetic or pharmaceutical product is provided. The product includes a foam carrier composition according to one or more embodiments of the present invention and an active cosmetic or pharmaceutical ingredient in a therapeutically effective concentration. Cosmetic and pharmaceutical agents can be included in each of the compositions described above and in the detailed description that follows. Pharmaceutical products are intended for topical treatment of human and animal skin disorders, or any other disorder, that requires topical application of a drug. Cosmetic products are intended for beautifying the skin and improving its appearance.
  • [0058]
    Cosmetic and medical disorders that are best treated using the alcohol-free foam carrier and the alcohol-free cosmetic or pharmaceutical product are identified, and the advantages of such carrier and products is demonstrated as compared to currently available options.
  • [0059]
    The foam of the present invention is advantageous to current options, for one or more of the following reasons:
      • (1) The foam is lightweight and thus, economical.
      • (2) The foam contains a hydrophobic solvent, in any desirable concentration, which provides a refatting and skin soothing effect, as well as a carrier for hydrophobic active agents.
      • (3) The foam contains silicone oil in a therapeutically effective concentration
      • (4) The foam includes active agent, both water soluble and oil soluble.
      • (5) The foam is easily spreadable, allowing treatment of large areas such as the arms, back, legs and the breast.
      • (6) Due to its flow properties, it spreads effectively into folds and wrinkles, providing uniform distribution of the active agent without the need of extensive rubbing and absorbs into the skin.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0066]
    A more complete appreciation of the present invention and many of its advantages will be understood by reference to the following detailed description when considered in connection with the following drawings, which are presented for the purpose of illustration only are not intended to limit the scope of the appended claims, and in which:
  • [0067]
    FIG. 1 illustrates the improvement in the treatment of psoriasis using Bethasone valerate 0.12% foam; and
  • [0068]
    FIG. 2 illustrates the improvement in the treatment of atopic dermatitis using Bethasone valerate 0.12% foam.
  • DETAILED DESCRIPTION OF THE INVENTION
  • [0069]
    Hydrophobic Solvent
  • [0070]
    A hydrophobic solvent according to the present invention is a liquid material having solubility in distilled water at ambient temperature of less than about 1 gm per 100 mL, more preferable less than about 0.5 gm per 100 mL, and most preferably less than about 0.1 gm per 100 mL. It is liquid at ambient temperature.
  • [0071]
    The total content of hydrophobic solvent may vary from 2% to 75% (w/w) of the foamable composition. However, different ranges (herein “composition classes A-D”) have been designated, in order to facilitate a choice of an appropriate class, according to the anticipated cosmetic or pharmaceutical need. As a rule of thumb, higher hydrophobic solvent concentrations are more appropriate for the treatment of dry skin, and/or for the treatment of a disease, which is more responsive to drugs delivered in an oily vehicle. Likewise, the higher oil-content composition classes provide an enhanced occlusive effect, which in turn induces the skin penetration of an active agent. Another consideration relates to user acceptance of a product containing a high concentration of the hydrophobic solvent (from about 25% of the composition), which would leave some oily feeling post-application. Thus, a particular composition of the present invention is selected having a hydrophobic solvent concentration in view of the target population and its specific needs.
  • [0072]
    In one or more embodiments of the present invention, the hydrophobic solvent is mineral oil. Mineral oil (Chemical Abstracts Service Registry number 8012-95-1) is a mixture of aliphatic, naphthalenic, and aromatic liquid hydrocarbons that are derived from petroleum. It is typically liquid; its viscosity is in the range of about 35 CST to about 100 CST (at 40° C.), and its pour point (the lowest temperature at which an oil can be handled without excessive amounts of wax crystals forming) is below 0° C. By contrast, white petrolatum, also termed “Vaseline”, is disadvantageous, due to its waxy nature. It is known to leave waxy and sticky feeling after application and occasionally stain cloths. Thus, white petrolatum and other semi-solid oils are not a preferred hydrophobic solvent according to the present invention.
  • [0073]
    Yet another preferred hydrophobic solvents are liquid oils from vegetable, marine or animal sources. By way of example, the unsaturated oil may be selected from the group consisting of olive, corn, soybean, canola, cottonseed, coconut, sesame, sunflower, borage seed, syzigium aromaticum, hempseed, herring, cod-liver, salmon, flaxseed, wheat germ and evening primrose oils and mixtures thereof, at any proportion.
  • [0074]
    A particularly preferred class of oils includes polyunsaturated oils, e.g., esters, and in particular glyceryl esters, of omega-3 and omega-6 fatty acids. Examples of such polyunsaturated fatty acids are linoleic and linolenic acid, gamma-linoleic acid (GLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Thus, in one or more embodiments of the present invention the hydrophobic solvent includes at least 6% by weight foamable composition of an oil selected from omega-3 oil, omega-6 oil, and mixtures thereof.
  • [0075]
    Another class of oils suitable for use as a phydrophobic solvent is liquid hydrophobic plant-derived oils, or essential oils, e.g. “therapeutic oils” containing active biologically occurring molecules that have a therapeutic effect when applied topically. Examples of such oils include rosehip oil, which contain retinoids and is known to reduce acne and post-acne scars, and tea tree oil, which possess antibacterial, antifungal and antiviral properties. Other examples of essential oils are oils of basil, camphor, cardamom, carrot, citronella, clary sage, clove, cypress, frankincense, ginger, grapefruit, hyssop, jasmine, lavender, lemon, mandarin, marjoram, myrrh, neroli, nutmeg, petitgrain, sage, tangerine, vanilla, verbena, as well as any other therapeutically beneficial oil, know in the art of herbal medication.
  • [0076]
    In one or more embodiments of the present invention, the hydrophobic solvent is an “emollient”. An emollient is a hydrophobic agent that softens, smoothens and improves lipid content of the skin or other mucous membranes. In one or more embodiments of the present invention, the emollient is a liquid. Without derogating the generality of this definition, examples of suitable emollients for use include isostearic acid derivatives, isopropyl palmitate, lanolin oil, diisopropyl dimerate, diisopropyl adipate, dimethyl isosorbide, maleated soybean oil, octyl palmitate, isopropyl isostearate, cetyl lactate, cetyl ricinoleate, tocopheryl acetate, acetylated lanolin alcohol, cetyl acetate, phenyl trimethicone, glyceryl oleate, tocopheryl linoleate, wheat germ glycerides, arachidyl propionate, myristyl lactate, decyl oleate, propylene glycol ricinoleate, isopropyl lanolate, pentaerythrityl tetrastearate, neopentylglycol dicaprylate/dicaprate, hydrogenated coco-glycerides, isononyl isononanoate, isotridecyl isononanoate, myristyl myristate, triisocetyl citrate, octyl dodecanol, octyl hydroxystearate and mixtures thereof. Other examples of other suitable emollients can also be found in the Cosmetic Bench Reference, pp. 1.19-1.22 (1996). In one or more embodiments, the hydrophobic solvent is a mixture of a mineral oil or silicone oil and an emollient.
  • [0077]
    In one or more embodiments of the present invention, silicone oil is a component of the hydrophobic solvent. Silicone oils are used in the foamable compositions due to their known skin protective and occlusive properties. Suitable silicone oils for use in the invention include non-volatile silicones, such as polyalkyl siloxanes, polyaryl siloxanes, polyalkylaryl siloxanes and polyether siloxane copolymers, polydimethylsiloxanes (dimethicones) and poly(dimethylsiloxane)-(diphenyl-siloxane) copolymers. These are preferably chosen from cyclic or linear polydimethylsiloxanes containing from about 3 to about 9, preferably from about 4 to about 5, silicon atoms. Volatile silicones such as cyclomethicones can also be used. Water-soluble silicones, such as dimethicone copolyol are not included in the definition of silicone oils (as hydrophobic solvents) according to the present invention.
  • [0078]
    In one or more embodiments of the present invention, the composition comprises at least 2% (w/w foamable composition) silicone oil, alone or as part of the hydrophobic solvent. Yet, in other embodiments, the composition comprises at least 5% (w/w) silicone oil alone or as part of the hydrophobic solvent.
  • [0079]
    The hydrophobic solvent of the present invention may comprise a mixture of two or more of the above hydrophobic solvents in any proportion.
  • [0080]
    Foam Adjuvant Agents
  • [0081]
    Foam adjuvants are included in the foamable compositions of the present invention to increase the foaming capacity of surfactants and/or to stabilize the foam. In one or more embodiments of the present invention, the foam adjuvant agents includes fatty alcohols having 15 or more carbons in their carbon chain, such as cetyl alcohol and stearyl alcohol (or mixtures thereof). Other examples of fatty alcohols are arachidyl alcohol (C20), behenyl alcohol (C22), 1 -triacontanol (C30), as well as alcohols with longer carbon chains (up to C50). Fatty alcohols, derived from beeswax, including a mixture of alcohols, a majority of which has at least 20 carbon atoms in their carbon chain, are especially well suited as foam adjuvant agents according to the present invention. The concentration of the fatty alcohol, required to support the foam system is inversely related to the length of its carbon chains.
  • [0082]
    In one or more embodiments of the present invention, the foam adjuvant agent includes fatty acids having 16 or more carbons in their carbon chain, such as hexadecanoic acid (C16) stearic acid (C18), arachidic acid (C20), behenic acid (C22), octacosanoic acid (C28), as well as fatty acids with longer carbon chains (up to C50), or mixtures thereof.
  • [0083]
    Optionally, the carbon atom chain of the fatty alcohol or the fatty acid may have at least one double bond. A further class of foam adjuvant agent according to the present invention comprises a long chain fatty alcohol or fatty acid, wherein the carbon atom chain is branched. The carbon chain of the fatty acid or fatty alcohol can be substituted with a hydroxyl group, such as 12-hydroxy stearic acid.
  • [0084]
    The foam adjuvant agent according to one or more embodiments of the present invention includes a mixture of fatty alcohols, fatty acids and hydroxy fatty acids and derivatives thereof in any proportion, providing that the total amount is 0.1% to 5% (w/w) of the carrier mass. More preferably, the total amount is 0.4% - 2.5% (w/w) of the carrier mass.
  • [0085]
    While fatty alcohols and fatty acids serve to stabilize the resultant foam composition, they often provide additional therapeutic properties. Long chain saturated and mono unsaturated fatty alcohols, e.g., stearyl alcohol, erycyl alcohol, arachidyl alcohol and docosanol have been reported to possess antiviral, anti infective, anti-proliferative and anti-inflammatory properties (U.S. Pat. No. 4,874,794). Longer chain fatty alcohols, e.g., tetracosanol, hexacosanol, heptacosanol, octacosanol, triacontanol, etc. are also known for their metabolism modifying properties and tissue energizing properties. Long chain fatty acids have also been reported to possess anti-infective characteristics. Thus, the pharmaceutical or cosmetic carrier, containing the foam adjuvant agent of the present invention provides an extra therapeutic benefit in comparison with currently used vehicles, which are inert and non-active.
  • [0086]
    Surface-active Agents
  • [0087]
    Surface-active agents, according to the present invention include any agent linking oil and water in the composition.
  • [0088]
    The surface-active agent is suitably selected from anionic, cationic, nonionic, zwitterionic, amphoteric and ampholytic surfactants, as well as mixtures of these surfactants. Such surfactants are well known to those skilled in the pharmaceutical and cosmetic formulation art. Nonlimiting examples of possible surfactants include polysorbates, such as polyoxyethylene (20) sorbitan monostearate (Tween 60) and poly(oxyethylene) (20) sorbitan monooleate (Tween 80); poly(oxyethylene) (POE) fatty acid esters, such as Myrj 45, Myri 49 and Myrj 59; poly(oxyethylene) alkylyl ethers, such as poly(oxyethylene) cetyl ether, poly(oxyethylene) palmityl ether, polyethylene oxide hexadecyl ether, polyethylene glycol cetyl ether, brij 38, brij 52, brij 56 and brij W1; sucrose esters, partial esters of sorbitol and its anhydrides, such as sorbitan monolaurate and sorbitan monolaurate; mono or diglycerides, isoceteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyl taurate, sodium lauryl sulfate, triethanolamine lauryl sulfate and betaines.
  • [0089]
    A combination of surface active agents is possible. Any surface-active agent or combinations thereof may be used as surface-active agent. According to one or more embodiments of the present invention, the surface-active agent (or agents) has an HLB of higher than 9.
  • [0090]
    In one or more embodiments of the present invention, the surface-active agent is selected from the groups of non ionic surfactants, cationic surfactants, amphoteric and zwitterionic surfactants, and, in particular, the surface-active agent is a non-ionic surfactant. Ionic surfactants (including cationic, anionic, amphotheric and zwitterionic surfactants) are known to be skin irritants. Therefore, non-ionic surfactants are preferred in applications including sensitive skin such as found in most dermological disorders. We have surprisingly found that non-ionic surfactants alone provide foams of excellent quality, i.e. a score of “E” according to the grading scale discussed below.
  • [0091]
    In one or more embodiments of the present invention, the surface active agent is solely non-ionic, comprising one or more non-ionic surfactants.
  • [0092]
    In one or more embodiments of the present invention, the surface active agent include a ratio of non-ionic surfactants to ionic surfactants in the range of 100:1 to 6:1; in some embodiments the non-ionic to ionic surfactant ratio is greater than 6:1, or greater than 8:1; or greater than 14:1, or greater than 16:1, or greater than 20:1.
  • [0093]
    Exemplary non-ionic surfactants include polyethoxylated fatty acids, fatty acid diesters, polyethylene glycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglycerized fatty acids, sterol and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, sugar esters, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters and lower alcohol fatty acid esters.
  • [0094]
    Although polyethylene glycol (PEG) itself does not function as a surfactant, a variety of PEG-fatty acid esters have useful surfactant properties. Exemplary monoesters include esters of lauric acid, oleic acid, and stearic acid, e.g., PEG-8 laurate, PEG-8 oleate, PEG-8 stearate, PEG-9 oleate, PEG-10 laurate, PEG-10 oleate, PEG-12 laurate, PEG-12 oleate, PEG-15 oleate, PEG-20 laurate and PEG-20 oleate. Polyethylene glycol fatty acid diesters suitable for use as non-ionic surfactants in the compositions of the present invention include PEG-20 dilaurate, PEG-20 dioleate, PEG-20 distearate, PEG-32 dilaurate and PEG-32 dioleate. Suitable polyethylene glycol glycerol fatty acid esters include PEG-20 glyceryl laurate, PEG-30 glyceryl laurate, PEG-40 glyceryl laurate, PEG-20 glyceryl oleate, and PEG-30 glyceryl oleate.
  • [0095]
    A large number of surfactants of different degrees of hydrophobicity or hydrophilicity can be prepared by reaction of alcohols or polyalcohols with a variety of natural and/or hydrogenated oils. Most commonly, the oils used are castor oil or hydrogenated castor oil, or an edible vegetable oil such as corn oil, olive oil, peanut oil, palm kernel oil, apricot kernel oil, or almond oil. Preferred alcohols include glycerol, propylene glycol, ethylene glycol, polyethylene glycol, sorbitol, and pentaerythritol. Among these alcohol-oil transesterified surfactants, preferred hydrophilic surfactants are PEG-35 castor oil (Incrocas-35), PEG-40 hydrogenated castor oil (Cremophor RH 40), PEG-25 trioleate (TAGAT® TO), PEG-60 corn glycerides (Crovol M70), PEG-60 almond oil (Crovol A70), PEG-40 palm kernel oil (Crovol PK70), PEG-50 castor oil (Emalex C-50), PEG-50 hydrogenated castor oil (Emalex HC-50), PEG-8 caprylic/capric glycerides (Labrasol), and PEG-6 caprylic/capric glycerides (Softigen 767). Preferred hydrophobic surfactants in this class include PEG-5 hydrogenated castor oil, PEG-7 hydrogenated castor oil, PEG-9 hydrogenated castor oil, PEG-6 corn oil (Labrafil® M 2125 CS), PEG-6 almond oil (Labrafil® M 1966 CS), PEG-6 apricot kernel oil (Labrafil® M 1944 CS), PEG-6 olive oil (Labrafil® M 1980 CS), PEG-6 peanut oil (Labrafil® M 1969 CS), PEG-6 hydrogenated palm kernel oil (Labrafil® M 2130 BS), PEG-6 palm kernel oil (Labrafil® M 2130 CS), PEG-6 triolein (Labrafil® b M 2735 CS), PEG-8 corn oil (Labrafil® WL 2609 BS), PEG-20 corn glycerides (Crovol M40), and PEG-20 almond glycerides (Crovol A40). The latter two surfactants are reported to have HLB values of 10, which is generally considered to be the approximate border line between hydrophilic and hydrophobic surfactants.
  • [0096]
    Alcohol-oil transesterification derivatives of oil soluable vitamins (e.g., vitamins A, D, E, K, etc.), such as tocopheryl PEG-100 succinate (TPGS, available from Eastman), are also suitable surfactants.
  • [0097]
    Polyglycerol esters of fatty acids are also suitable non-ionic surfactants for the present invention. Among the polyglyceryl fatty acid esters, exemplary use hydrophobic surfactants include polyglyceryl oleate (Plurol Oleique), polyglyceryl-2 dioleate (Nikkol DGDO), and polyglyceryl-10 trioleate. Preferred hydrophilic surfactants include polyglyceryl-10 laurate (Nikkol Decaglyn 1-L), polyglyceryl-10 oleate (Nikkol Decaglyn 1-0), and polyglyceryl-10 mono, dioleate (Caprol® PEG 860), Polyglyceryl polyricinoleates (Polymuls) are hydrophilic and hydrophobic surfactants of this class.
  • [0098]
    Sterols and derivatives of sterols are suitable surfactants for use in the present invention. These surfactants can be hydrophilic or hydrophobic. Preferred derivatives include the polyethylene glycol derivatives. An exemplary hydrophobic surfactant in this class is cholesterol. An exemplary hydrophilic surfactant in this class is PEG-24 cholesterol ether (Solulan C-24).
  • [0099]
    A variety of PEG-sorbitan fatty acid esters are suitable for use as non-ionic surfactants in the present invention. In general, these surfactants are hydrophilic, although several hydrophobic surfactants of this class can be used. Among the PEG-sorbitan fatty acid esters, exemplary hydrophilic surfactants include PEG-20 sorbitan monolaurate (Tween-20), PEG-20 sorbitan monopalmitate (Tween-40), PEG-20 sorbitan monostearate (Tween-60), and PEG-20 sorbitan monooleate (Tween-80).
  • [0100]
    Ethers of polyethylene glycol and alkyl alcohols are suitable non-ionic surfactants for use in the present invention. Exemplary hydrophobic ethers include PEG-3 oleyl ether (Volpo 3) and PEG-4 lauryl ether (Brij 30).
  • [0101]
    The polyoxyethylene-polyoxypropylene (POE-POP) block copolymers are a unique class of polymeric surfactants. The unique structure of the surfactants, with hydrophilic POE and hydrophobic POP moieties in well-defined ratios and positions, provides a wide variety of surfactants suitable for use in the present invention. These surfactants are available under various trade names, including Synperonic PE series (ICI), Pluronic® series (BASF), Emkalyx, Lutrol (BASF), Supronic, Monolan, Pluracare, and Plurodac. The generic term for these polymers is “poloxamer” (CAS 9003-11-6). Exemplary hydrophilic surfactants of this class include Poloxamers 108, 188, 217, 238, 288, 338, and 407. Exemplary hydrophobic surfactants in this class include Poloxamers 124, 182, 183, 212, 331, and 335.
  • [0102]
    Sorbitan esters of fatty acids are suitable non-ionic surfactants for use in the present invention. Among these esters, preferred hydrophobic surfactants include sorbitan monolaurate (Arlacel 20), sorbitan monopalmitate (Span-40), sorbitan monooleate (Span-80), sorbitan monostearate, and sorbitan tristearate.
  • [0103]
    Esters of lower alcohols (C2 to C4) and fatty acids (C8 to C18) are suitable non-ionic surfactants for use in the present invention. Among these esters, preferred hydrophobic surfactants include ethyl oleate (Crodamol EO), isopropyl myristate (Crodamol IPM), and isopropyl palmitate (Crodamol IPP).
  • [0104]
    In one or more embodiments of the present invention, the surface-active agent comprise mono-, di- and tri-esters of sucrose with food fatty acids (sucrose esters), prepared from sucrose and methyl and ethyl esters of food fatty acids or by extraction from sucroglycerides. Exemplary sucrose esters include sucrose monopalmitate and sucrose monolaurate. Suitable sucrose esters include those having a high monoester content, which have higher HLB values.
  • [0105]
    In one or more embodiments of the present invention, a combination of a non-ionic surfactant and an anionic surfactant (such as sodium lauryl sulphate) is employed, at a ratio of between 1:1 and 20:1, or at a ratio of 4:1 to 10:1. The resultant foam has a low specific gravity, e.g., less than 0.1 g/ml, which upon rubbing (shear stress) onto the skin collapses easily, to allow facile absorption.
  • [0106]
    Unlike prior art foamable compositions, the total surfactant employed to obtain a foam that is stable, of low specific gravity and has a fine bubble structure is low. Lower surfactant levels, particularly of ionic surfactants, are preferred to reduce skin irritations. Total surfactant is in the range of 0.1 to 5.0 wt % of the foamable composition, and is typically less than 2 wt %, or even less than 1 wt %.
  • [0107]
    Water Gelling Agents The water gelling agent according to one or more embodiments of the present invention stablizes the acqueons phase by, for example, increasing viscosity and linking capability. Exemplary water gelling agents that can be used in accordance with one or more embodiments of the present invention include for example, but are not limited to, naturally-occurring polymeric materials such as, locust bean gum, sodium alginate, sodium caseinate, egg albumin, gelatin agar, carrageenin gum sodium alginate, xanthan gum, quince seed extract, tragacanth gum, starch, chemically modified starches and the like, semi-synthetic polymeric materials such as cellulose ethers (e.g. hydroxyethyl cellulose, methyl cellulose, carboxymethyl cellulose, hydroxy propylmethyl cellulose), polyvinylpyrrolidone, polyvinylalcohol, guar gum, hydroxypropyl guar gum, soluble starch, cationic celluloses, cationic guars and the like and synthetic polymeric materials such as carboxyvinyl polymers, polyvinylpyrrolidone, polyvinyl alcohol polyacrylic acid polymers, polymethacrylic acid polymers, polyvinyl acetate polymers, polyvinyl chloride polymers, polyvinylidene chloride polymers and the like. Mixtures of the above compounds are contemplated.
  • [0108]
    Further exemplary water gelling agents include the acrylic acid/ethyl acrylate copolymers and the carboxyvinyl polymers sold, for example, by the B.F. Goodrich Company under the trademark of Carbopol Registered TM resins. These resins consist essentially of a colloidal water-soluble polyalkenyl polyether crosslinked polymer of acrylic acid crosslinked with from 0.75% to 2% of a crosslinking agent such as polyallyl sucrose or polyallyl pentaerythritol. Examples include Carbopol 934, Carbopol 940, Carbopol 950, Carbopol 980, Carbopol 951 and Carbopol 981. Carbopol 934 is a water-soluble polymer of acrylic acid crosslinked with about 1% of a polyallyl ether of sucrose having an average of about 5.8 allyl groups for each sucrose molecule.
  • [0109]
    The gelling agent is present in an amount in the range of about 0.1% to about 5.0 wt % of the foamable composition. In one or more embodiments, it is typically less than 1 wt % of the foamable composition.
  • [0110]
    “Alcohol free”
  • [0111]
    Unlike the composition disclosed in U.S. Pat. No. 6,126,920, which contains a 40-90 wt % aliphatic alcohol, the composition of the present invention does not contain such amount alcohols. For the purpose of the present application, the term “alcohol free” shall mean that the composition contains no more than an incidental amount of an aliphatic alcohol, e.g. less than about 7.5% of any aliphatic alcohol, having one to six carbon atoms in their carbon backbone, or no more than 7.5% of any mixture of such aliphatic alcohols. Alcohols at these low levels are not considered to have a negative effect on skin or mucous membranes. In one or more embodiments, the foamable compositions do not contain any alcohol.
  • [0112]
    Optional Ingredients
  • [0113]
    The pharmaceutical or cosmetic foam carrier of the present invention may further optionally comprise a variety of pharmaceutical or cosmetic ingredients, which are added in order to fine-tune the consistency of the formulation, protect the formulation components from degradation and oxidation and bestow their cosmetic acceptability. Such excipients, may be selected, for example, from the group consisting of diglycerides, triglycerides, stabilizing agents, antioxidants, humectants, flavoring, colorant and odorant agents and other formulation components, used in the art of pharmaceutical and cosmetic formulary. A pharmaceutical or cosmetic composition manufactured using the foam carrier according to the present invention is very easy to use. When applied onto the afflicted body surface of humans or animals, it is in a foam state, allowing free application without spillage. Upon further application of a mechanical force, e.g., by rubbing the composition onto the body surface, it freely spreads on the surface and is rapidly absorbed.
  • [0114]
    Propellant Aerosol
  • [0115]
    Aerosol propellants are used to generate and administer the foamable composition as a foam. The total composition including propellant, foamable compositions and optional ingredients is referred to as the foamable carrier. The propellant makes up about 5-25 wt % of the foamable carrier. Examples of suitable propellants include volatile hydrocarbons such as butane, propane, isobutane or mixtures thereof, and fluorocarbon gases.
  • [0116]
    Composition and Foam Physical Characteristics
  • [0117]
    1. Composition Flow Properties:
  • [0118]
    It is important to have a composition, including water, hydrophobic solvents, formulation excipients and propellant, in a stable emulsion, which ascertain acceptable shelf-life of the product.
  • [0119]
    Yet, another crucial property is that said composition has to be free flowing, since otherwise, it cannot flow through the dip-tube of the aerosol container and create acceptable foam. It has been noted that in the context of the composition of the present invention, compositions comprising semi-solid hydrophobic solvents, e.g., white petrolatum, are excessively viscous and demonstrate poor flowability.
  • [0120]
    The combination of a surface active agent, foaming adjuvant and water gelling agent according to one or more embodiments of the invention provides a low specific gravity foam having superior flow properties and sheer breakability (among other attributes). According to one or more embodiments of the present invention, the total amount of surface active agent, foaming adjuvant and water gelling agent, in combination does not exceed 8% (w/w) of foamable composition. In other embodiments, the combined amounts of surface active agent, foaming adjuvant and water gelling agent is less than 5% (w/w) of foamable composition. The low solids content improves the flow properties of the foam, reduces unpleasant skin residue and reduces the cost of manufacture. As is demonstrated herein, the foam quality and foam breakability is excellent, despite the low levels of these components in the foam.
  • [0121]
    2. Foam Properties:
  • [0122]
    The following scale for foam quality is used to evaluate foams.
  • [0123]
    E (excellent): very rich and creamy in appearance, does not show any bubble structure or shows a very fine (small) bubble structure.
  • [0124]
    G (good): rich and creamy in appearance, very small bubble size, “dulls” more rapidly than an excellent foam.
  • [0125]
    FG (fairly good): a moderate amount of creaminess noticeable, bubble structure is noticeable.
  • [0126]
    F (fair): very little creaminess noticeable, larger bubble structure than a “fairly good” foam.
  • [0127]
    P (poor): no creaminess noticeable, large bubble structure.
  • [0128]
    VP (very poor): dry foam, large very dull bubbles, difficult to spread on the skin.
  • [0129]
    Foams, adequate for topical administration according to the present invention have to be of quality grade E or G, upon release from the aerosol container. Smaller bubbles mean more stable foam, which does not collapse spontaneously immediately upon discharge from the container. The finer foam structure looks and feels smoother, thus increasing its usability and appeal.
  • [0130]
    A crucial aspect of foam properties, according to the present invention is breakability. Sheer-force breakability of the foam, as attained by the composition of the present invention is clearly advantageous to thermally-induced breakability, present, for example in U.S. Pat. No. 6,126,920, and the respective Olux and Luxiq products, as demonstrated by the fact that according to the use instructions of Olux and Luxiq, the foam cannot be applied on the hand and afterwards delivered to the afflicted area, since it immediately collapses upon exposure to skin temperature.
  • [0131]
    Yet, another important property is specific gravity of the foam, as measured upon release from the aerosol can. Typically, foams according to the present invention have specific gravity of less than 0.1 g/mL and more preferably, less than 0.05 g/mL.
  • FIELDS OF PHARMACEUTICAL APPLICATIONS
  • [0132]
    By including an appropriate therapeutic agent in the foamable carrier, the foam composition of the present invention is useful in the therapy of a variety of dermatological disorders (also termed “dermatoses”), including, in a non-limiting exemplary manner:
  • [0133]
    Dermatitis
      • Contact Dermatitis
      • Atopic Dermatitis
      • Seborrheic Dermatitis
      • Nummular Dermatitis
      • Chronic Dermatitis Of The Hands And Feet
      • Generalized Exfoliative Dermatitis
      • Stasis Dermatitis
      • Lichen Simplex Chronicus
  • [0142]
    Bacterial Infections
      • Cellulitis
      • Acute Lymphangitis
      • Lymphadenitis
      • Erysipelas
      • Cutaneous Abscesses
      • Necrotizing Subcutaneous Infections
      • Staphylococcal Scalded Skin Syndrome
      • Folliculitis
      • Furuncles
      • Hidradenitis Suppurativa
      • Carbuncles
      • Paronychial Infections
      • Erythrasma
  • [0156]
    Fungal Infections
      • Dermatophyte Infections
      • Yeast Infections
  • [0159]
    Parasitic Infections
      • Scabies
      • Pediculosis
      • Creeping Eruption
  • [0163]
    Viral Infections
  • [0164]
    Disorders of Hair Follicles and Sebaceous Glands
      • Acne
      • Rosacea
      • Perioral Dermatitis
      • Hypertrichosis (Hirsutism)
      • Alopecia, including male pattern baldness, alopecia areata, alopecia universalis and alopecia totalis
      • Pseudofolliculitis Barbae
      • Keratinous Cyst
  • [0172]
    Scaling Papular Diseases
      • Psoriasis
      • Pityriasis Rosea
      • Lichen Planus
      • Pityriasis Rubra Pilaris
  • [0177]
    Benign Tumors
      • Moles
      • Dysplastic Nevi
      • Skin Tags
      • Lipomas
      • Angiomas
      • Pyogenic Granuloma
      • Seborrheic Keratoses
      • Dermatofibroma
      • Keratoacanthoma
      • Keloid
  • [0188]
    Malignant Tumors
      • Basal Cell Carcinoma
      • Squamous Cell Carcinoma
      • Malignant Melanoma
      • Paget's Disease Of The Nipples
      • Kaposi's Sarcoma
  • [0194]
    Reactions To Sunlight
      • Sunburn
      • Chronic Effects of Sunlight
      • Photosensitivity
  • [0198]
    Bullous Diseases
      • Pemphigus
      • Bullous Pemphigoid
      • Dermatitis Herpetiformis
      • Linear Immunoglobulin A Disease
  • [0203]
    Pigmentation Disorders
      • Hypopigmentation
        • Vitiligo
        • Albinism
        • Postinflammatory hypopigmentation
      • Hyperpigmentation
        • Melasma (chloasma)
        • Drug-induced hyperpigmentation
        • Postinflammatory hyperpigmentation
  • [0212]
    Disorders of Cornification
      • Ichthyosis
      • Keratosis Pilaris
      • Calluses And Corns
      • Actinic keratosis
  • [0217]
    Pressure Sores
  • [0218]
    Disorders of Sweating
  • [0219]
    Inflammatory reactions
      • Drug Eruptions
      • Toxic Epidermal Necrolysis
      • Erythema Multiforme
      • Erythema Nodosum
      • Granuloma Annulare
  • [0225]
    In one or more embodiments of the present invention, the foam composition of the present invention is useful in the therapy of non-dermatological disorders, which respond to transdermal delivery of an active agent. By way of example, such disorders include localized pain in general, as well as joint pain, muscle pain, back pain, rheumatic pain, arthritis, ostheoarthritis and acute soft tissue injuries and sports injuries. Other disorders of this class include conditions, which respond to hormone therapy, such as hormone replacement therapy, transdermal nicotine administration, and other respective disorders, known in the art of drug delivery. The foam composition of the present invention is also useful in the delivery of local anesthetic agents.
  • ACTIVE PHARMACEUTICAL AGENTS (DRUGS)
  • [0226]
    The active pharmaceutical agents, also referred to as “drug(s)”, may consist of a single drug or a combination of drugs that can be dissolved in the water phase or the hydrophobic phase of the carrier composition. Examples of such drugs are antibiotic, antibacterial, antifungal, antiviral, antiinflammatory, anesthetic, analgesic, antiallergic, corticosteroid, retinoid and antiproliferative medications and mixtures thereof at any proportion. The concentration of drugs may be adopted to exert a therapeutic effect on a disease when applied to an afflicted area.
  • [0227]
    Antibacterial Agents
  • [0228]
    One important class of drugs comprises antibacterial agents. It is well known that bacterial infections are involved in a variety of superficial disorders of the skin, eye, mucosal membrane, oral cavity, vagina and rectum. The antibacterial drug can be active against gram positive and gram-negative bacteria, protozoa, aerobic bacteria and unaerobic ones.
  • [0229]
    By way of example, the antibacterial drugs can be selected from the group of chloramphenicol, tetracyclines, synthetic and semi-synthesic penicillins, beta-lactames, quinolones, fluoroquinolnes, macrolide antibiotics, metronidazlole and its derivatives and analogs, dicarboxylic acids, such as azelaic acid, slicylates, peptide antibiotics, cyclosporines and any combination thereof at a therapeutically effective concentration. Another group of antibacterial agents which is non-specific, comprises strong oxidants and free radical liberating compounds, such as hydrogen peroxide, bleaching agents (e.g., sodium, calcium or magnesium hypochloride and the like) iodine, chlorohexidine and benzoyl peroxide.
  • [0230]
    Antibacterial compositions according to the present invention may be used to treat infections of the skin. An example of a very common skin infection is acne, which involve infestation of the sebaceous gland with p. acnes, as well staphylococus aurus and pseudomonas. Various antibacterial agents have been utilized to treat acne, however, their efficacy is limited due to their low penetration into the hydrophobic environment of the skin layers and sebaceous glands. The composition of the present invention, comprising a hydrophobic component, would facilitate an enhanced rate of penetration. Furthermore, the intrinsic antibacterial and antiinflammatory effects of the foam adjuvant agents, i.e., fatty alcohols and acids, provides a combined effect that should result in a better therapeutic response to treatment.
  • [0231]
    The composition of the present invention is particularly useful and beneficial in the prevention and treatment of secondary infections, accompanying skin-structure damage, such as in cuts, wounds, burns and ulcers. In all such cases, the present formulation is easy to use, being in foam state when applied and becoming liquid instantly upon rubbing onto the skin.
  • [0232]
    While being useful in the prevention and treatment of infections, the antibacterial foam of the present invention is also applicable for decontaminating areas, afflicted with bacterial warfare organisms, such as anthrax and smallpox.
  • [0233]
    The same advantage is expected when the composition of the present invention is topically applied to mucosal membranes, the oral cavity, the vagina and the rectum.
  • [0234]
    Anti-fungal Agents
  • [0235]
    Fungal infections are another object of treatment using the composition of the present invention. Superficial fungal infection of the skin is one of the commonest skin diseases seen in general practice. Dermatophytosis is probably the most common superficial fungal infection of the skin. It is caused by a group of fungi, which are capable of metabolizing the keratin of human epidermis, nails or hair. There are 3 genera of dermatophytes causing dermatophytosis, i.e, microsporum, trichophyton and epidermophyton.
  • [0236]
    Candidiasis is an infection caused by the yeast like fungus candida albicans or occasionally other species of candida. Clinical syndromes of candidiasis include: (a) oral candidiasis (oral thrush); (b) candidiasis of the skin and genital mucous membrane; and (c) candida paronychia, which inflicts the nail.
  • [0237]
    The pharmaceutical composition may comprise an antifungal drug, which is active against dermatophytes and candida, selected from the group of, but not limited to azoles, diazoles, triazoles, miconazole, fluconazole, ketoconazole, clotrimazole, itraconazole griseofulvin, ciclopirox, amorolfine, terbinafine, Amphotericin B, potassium iodide, flucytosine (5FC) and any combination thereof at a therapeutically effective concentration.
  • [0238]
    It is useful, for example for the treatment of tinea corporis, tinea pedis, tinea rubrum, tinea unguium, tinea cruris, tinea barbae and tinea versicolor, as well as yeast Infections, such as candidiasis, and candidal vaginitis
  • [0239]
    Anti-viral Agents
  • [0240]
    The composition of the present invention is particularly beneficial in the case of viral infections. Cold sores are caused by the herpes simplex Type 1 virus and are sometimes referred to as facial herpes. Mollusca are small viral growths that appear singly or in groups on the face, trunk, lower abdomen, pelvis, inner thighs, or penis. Shingles (herpes zoster), which usually only occurs once in a lifetime, appears as a rash (clusters of blisters with a red base). It is caused by the same virus responsible for chickenpox. Warts are a common, benign skin tumor caused by viral infection.
  • [0241]
    Viral infections are currently treated with various antiviral agents, as summarized in the following table:
    Chemical
    Drug Viruses Type
    Vidarabine Herpesviruses Nucleoside
    analogue
    Acyclovir Herpes simplex Nucleoside
    (HSV) analogue
    Gancyclovir Cytomegalovirus Nucleoside
    (CMV) analogue
    Nucleoside-analog reverse Retroviruses (HIV) Nucleoside
    transcriptase inhibitors (NRTI): analogue
    AZT (Zidovudine), ddl (Didanosine),
    ddC (Zalcitabine), d4T
    (Stavudine), 3TC (Lamivudine)
    Non-nucleoside reverse transcriptase Retroviruses (HIV) Nucleoside
    inhibitors (NNRTI): Nevirapine, analogue
    Delavirdine
    Protease Inhibitors: Saquinavir, HIV Peptide
    Ritonavir, Indinavir, Nelfinavir analogue
    Ribavirin Broad spectrum: Triazole
    HCV, HSV, carboxamide
    measles, mumps,
    Lassa fever
    Amantadine/Rimantadine Influenza A strains Tricyclic
    amine
    Interferons Hepatitis B and C Protein
  • [0242]
    Any of the above antiviral drugs, in a therapeutically effective concentration, can be incorporated in the foam composition of the present invention. The composition of the present invention, which comprises a hydrophobic solvent, would facilitate an enhanced rate of penetration and better topical distribution of any of the above listed antiviral drugs. Furthermore, the intrinsic antiviral effects of the foam adjuvant agents, i.e., fatty alcohols and acids, provides a combined effect that should result in a better therapeutic response to treatment.
  • [0243]
    Antiinflammatory or Antiallergic Agents
  • [0244]
    Yet, according to another embodiment according to the present invention the drug is an antiinflammatory or antiallergic agent. Antiinflammatory or antiallergic agent can be selected from the group of corticosteroids, non-steroidal antiinflammatory drugs (NSAIDs), anti-histamines, immunosuppressants and any combination thereof at a therapeutically effective concentration.
  • [0245]
    The following table provides a summary of currently available corticosteroid agent and their typical therapeutically effective concentration.
    Potency Compound Formulation
    Very high Clobetasol proprionate Cream or ointment 0.05%
    Halobetasol proprionate Cream or ointment 0.05%
    High Betamethasone diproprionate Cream or ointment 0.05%
    Betamethasone valerate Ointment 0.1%
    Fluocinolone acetonide Cream 0.02%
    Halcinonide Cream or ointment 0.1%
    Medium Betamethasone valerate Cream 0.1%
    Fluocinolone acetonide Cream or ointment 0.020%
    Hydrocortisone valerate Cream or ointment 0.2%
    Triamcinolone acetonide Cream, ointment, or lotion
    0.1% or 0.020%
    Low Hydrocortisone Cream, ointment, or lotion
    1.0% or 2.5%
  • [0246]
    The concentrations of corticosteroid drugs, as presented in the above table are provided herein only as example, and any therapeutically effective concentration of such corticosteroids can be incorporated in the composition of the present invention.
  • [0247]
    Since all corticosteroid drugs are typically hydrophobic, the carrier of the present invention, comprising a hydrophobic solvent, is most suitable as a vehicle to facilitate better topical distribution and an enhanced rate of penetration of any of the above listed drugs. Furthermore, the intrinsic antiviral, antibacterial and antiinflammatory effects of the foam adjuvant agents, i.e., fatty alcohols and acids, provides a combined effect that should result in a better therapeutic response to treatment.
  • [0248]
    Psoriasis is a very common chronic skin disease, which may be the target of treatment using the composition of the present invention. It is marked by periodic flare-ups of sharply defined red patches covered by a silvery, flaky surface.
  • [0249]
    Corticosteroid ointments, greasy preparations containing little or no water, are commonly used for treating psoriasis. Their main disadvantage is in their sticky feeling, which remains so long after treatment is over. By contrast, the foam of the present invention, while comprising considerable concentration of an oil (hydrophobic solvent), spreads very easily throughout the afflicted area and absorbs into the skin without leaving any untoward sensation or look. Examples of other inflammatory disorders, which can be treated by the composition of the present invention, wherein the drug is a steroid are atopic dermatitis, seborrhea, seborrheic dermatitis of the face and trunk, seborrheic blepharitis, contact dermatitis, stasis dermatitis (gravitational eczema; varicose eczema), exfoliative dermatitis (erythroderma), lichen simplex chronicus, pityriasis rosea and pemphigus.
  • [0250]
    Topical antihistaminic preparations currently available include 1% and 2% diphenhydramine (Benadryl® and Caladryl®), 5% doxepin (Zonalon®) cream, phrilamine maleate, chlorpheniramine and tripelennamine, phenothiazines, promethazine hydrochloride (Phenergan®) and dimethindene maleate. These drugs, as well as additional antihistamins can also be incorporated in the composition of the present invention.
  • [0251]
    It is pointed out that polyunsaturated fatty acids, containing omega-3 and omega-6 fatty acids (e.g., linoleic and linolenic acid, gamma-linoleic acid (GLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are beneficial in the treatment of psoriasis and other skin inflammation conditions.
  • [0252]
    A second class of anti-inflammatory agents, which is useful in the foam of the present invention, includes the nonsteroidal anti-inflammatory agents (NSAIDs). The variety of compounds encompassed by this group is well-known to those skilled in the art. Specific non-steroidal anti-inflammatory agents useful in the composition invention include, but are not limited to:
  • [0253]
    1) Oxicams, such as piroxicam, isoxicam, tenoxicam, sudoxicam;
  • [0254]
    2) Salicylates, such as salicylic acid, ethyl salicylate, methyl salycilate, aspirin, disalcid, benorylate, trilisate, safapryn, solprin, diflunisal, and fendosal;
  • [0255]
    3) Acetic acid derivatives, such as diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin, acematacin, fentiazac, zomepirac, clindanac, oxepinac, felbinac, and ketorolac;
  • [0256]
    4) Fenamates, such as mefenamic, meclofenamic, flufenamic, niflumic, and tolfenamic acids;
  • [0257]
    5) Propionic acid derivatives, such as ibuprofen, naproxen, benoxaprofen, flurbiprofen, ketoprofen, fenoprofen, fenbufen, indopropfen, pirprofen, carprofen, oxaprozin, pranoprofen, miroprofen, tioxaprofen, suprofen, alminoprofen, and tiaprofenic; and
  • [0258]
    6) Pyrazoles, such as phenylbutazone, oxyphenbutazone, feprazone, azapropazone, and trimethazone.
  • [0259]
    Any further steroidal and nonsteroidal compounds, having the capacity to prevent, alleviate the symptoms of, treat or cure inflammation processes, are generally included, as possible anti-inflammatory agents, according to the present invention.
  • [0260]
    The pharmaceutical composition of the present invention may also comprise an antiinflammatory or antiallergic agent, wherein said agent reduces the occurrence of pro-inflammatory cytokines or inhibits the effect of pro-inflammatory cytokines.
  • [0261]
    Mixtures of such anti-inflammatory agents may also be employed, as well as the dermatologically acceptable salts, esters, amides, prodrugs and derivatives of these agents.
  • [0262]
    Topical application of a foam, comprising a safe and effective dose of an NSAID can be useful in the prevention and/or alleviation of the symptoms of rheumatoid arthritis, osteoarthritis and pain. Topical NSAIDs, incorporated in the foam of the present invention can be also used in the treatment of dermatological disorders, such as acne, rosacea, hair growth disorders, actinic keratosis and certain skin cancer conditions.
  • [0263]
    Topical Anesthetics
  • [0264]
    The compositions of the present invention may contain a safe and effective amount of a topical anesthetic. Examples of topical anesthetic drugs include benzocaine, lidocaine, bupivacaine, chlorprocaine, dibucaine, etidocaine, mepivacaine, tetracaine, dyclonine, hexylcaine, procaine, cocaine, ketamine, pramoxine, phenol, and pharmaceutically acceptable salts thereof. Mixtures of such anesthetic agents may be synergistically beneficial.
  • [0265]
    Keratolytically Active Agents The term “keratolytically active agent” is used herein to mean a compound which loosens and removes the stratum corneum of the skin, or alters the structure of the keratin layers of skin.
  • [0266]
    Keratolytically active agents are used in the treatment of many dermatological disorders, which involve dry skin, hyperkeratiinization (such as prsoriasis), skin itching (such as xerosis), acne and rosacea.
  • [0267]
    Suitable keratolytically active agent include phenol and substituted phenolic compounds. Such compounds are known to dissolve and loosen the intracellular matrix of the hyperkeratinized tissue. As such, they are used in the treatment of dermatological disorders. Dihydroxy benzene and derivatives thereof have been recognized as potent keratolytic agents. Resorcinol (m-dihydroxybenzene) and derivatives thereof are used in anti-acne preparations. Hydroquinone (p-dihydroxybenzene), besides its anti-pigmentation properties, is also keratolytic. These compounds also exhibit antiseptic properties. Cresols also possess bactericidal and keratolytic properties.
  • [0268]
    Vitamin A and its derivatives, such as retinoic acid, isoretinoic acid, retinol and retinal are another preferred class of keratolytically active agents.
  • [0269]
    Another group of keratolytically active agents include alpha-hydroxy acids, such as lactic acid and glycolic acid and their respective salts and derivatives; and beta-hydroxy acids, such as Salicylic acid (o-hydroxybenzoic acid) and its salts and pharmaceutically acceptable derivatives, which typically possess antiinflammatory, as well as keratolytic, activity.
  • [0270]
    Yet, another class of preferred keratolytically active agents includes urea and its derivatives.
  • [0271]
    Retinoids Another preferred group of active agents comprise retinol, retinal, all trans retinoic acid and derivatives, isomers and analogs thereof, collectively termed “retinoids”. Etretinate, actiretin, isotretinoin, adapalene and tazarotene are further examples of said retinoid isomers and analogs. Compositions according to the present invention, which contain retinoids as the active drug, can be used for the treatment of acne, seborrhea, various dermatoses, inflammation of the skin, mucosal membranes, vagina and the rectum, psoriasis, actinic keratosis and skin cancers, by application onto the affected area.
  • [0272]
    Insecticide and Insect Repellents Agents
  • [0273]
    Insects, such as mosquitoes, biting flies, mites, gnats, fleas, chiggers, punkies, sand flies, lice and ticks can be annoying and sometimes pose a serious risk to human and animal health. In certain areas of the United States, mosquitoes can transmit diseases like equine and St. Louis encephalitis. Biting flies can inflict a painful bite that can persist for days, swell, and become infected. Ticks can transmit serious diseases like Lyme disease and Rocky Mountain spotted fever.
  • [0274]
    There are several types of insect repellents to use when protecting people and animals from flying or biting insects, spiders, ticks and mites. By way of example, these may include DEET (N, N-diethyl-m-toluamide), dimethyl phthalate, piperonyl butoxide and permethrin. Insect repelling terpenoids, have been reported by Hwang, et al, J. Chem. Ecol., 11, 1297 (1-985); and Ruledge, J. Am. Mosquito Control Assoc. 4, 414 (1988).
  • [0275]
    A particularly preferred group of insect repellents includes the terpenoid compounds, described in U.S. Pat. No. 5,411,992, including:
  • [0276]
    (1) Terpenoid-alcohol or terpene-ols are terpenoids which have at least one hydroxyl group. Examples of terpene-ols include: C10H16O compounds, perillyl alcohol, carveol, myrtenol, and cis-verbenol; C10H18O compounds, myrtanol, iso-pinocampheol, dihydrocarveol, isopulegol, terpineol, terpinen-4-ol, nerol, geraniol, and linalool, and C10H20O compounds, menthol, beta-citronellol, and dihydro-myrcenol.
  • [0277]
    (2) Terpenoid-esters are terpenoids, which have at least one ester group which is the product of the bonding of the hydroxyl group of a terpene-ol with an aliphatic carboxylic acid that can contain functional groups such as the hydroxyl or amine on the aliphatic chain. Examples of suitable aliphatic carboxylic acids include acetic acid, propionic acid, lactic acid, and various amino acids.
  • [0000]
    Examples of terpenoid-esters include: carvyl acetate, carvyl propionate, and menthyl lactate.
  • [0278]
    (3) Essential oils which contain terpenoids and perfumes which contain terpenoids. Non-limiting examples of essential oils which have high content of terpene-ols and esters include bergamot (62% terpenoids); sage (>50% terpenoids); styrax (>50% terpenoids); peppermint (>50% terpenoids); and pine Siberian (75% terpenoids %). Terpenes, aldehydes and ketones vary in their usefulness but as a general group have potential as insect-repellent.
  • [0279]
    The foam of the present invention is particularly suitable for the effective uniform spreading of an insect repellent agent onto large areas of the skin of humans and animals. The hydrophobic solvent present in the foam composition helps retain the insect repellent on the skin surface for an extended period of time.
  • [0280]
    Yet, in a further embodiment, the foam is suitable for delivery of insect-killing agents (insecticides) to an afflicted external surface area of humans and animals. Thus, the pharmaceutical or cosmetic composition may comprise an insecticide, known in the art of parasitology. By way of example, such insecticide can be selected selected from the group of permethrin, hexachlorobenzene, carbamate, naturally occuring pyrethroids, permethrin, allethrin, malathion, piperonyl butoxide and any combination thereof at a therapeutically effective concentration. Its application is very convenient and it spreads easily, even over hairy areas. The hydrophobic solvent present in the foam composition helps retain the insecticide on the treated area for an extended period of time. Furthermore, the presence of a hydrophobic solvent in the foam eases mechanical removal of lice and nits with a comb.
  • [0281]
    Anti Cancer Drugs
  • [0282]
    Anti cancer drugs can also be used according to the present invention as the drug of choice from skin malignant tumors, such as basal cell carcinoma, squamous sell carcinoma, melanoma and Kaposi's sarcoma, as well as the pre-cancerous condition actinic keratosis. In certain cases, topical cytotoxic and antiproliferative drugs are used to treat or prevent such cancers, including 5-fluorouracil, also called 5-FU. 5-FU, as well as any other anti-cancer agents, know in the art of cancer medicine, can be incorporated in the foam at therapeutically effective levels.
  • [0283]
    A preferred family of anticancer drugs, suitable for usage in the foam of the present formulation comprises antiestrogens, such as tamoxifen. Tamoxifen blocks the effects of the hormone estrogen in the body. It is used to prevent or delay the return of breast cancer or to control its spread.
  • [0284]
    Photodynamic Therapy Agents
  • [0285]
    The foam composition of the present invention is also useful to deliver photo-sensitizing agents, known in the art of photodynamic therapy. By way of example, such photosensitizers can be selected from the group comprising modified porphyrins, chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbides, purpurins, m-THPC, mono-L-aspartyl chlorin e6, bacteriochlorins, phthalocyanines, benzoporphyrin derivatives, as well as photosensitiser precursors, such as aminolevulinic acid (ALA).
  • [0286]
    Active Agents for Burns, Wounds, Cuts and Ulcers
  • [0287]
    The treatment of burns, wounds, cuts and ulcers, using the composition of the present invention is particularly advantageous. The foam can include both anti-infective agents (against bacteria, fungi and/or viruses), antiinflammatory agents (steroidal and/or NSAIDs) and pain relieving components. Upon application, the foam spreads easily, covering the surface of the affected area, and without causing pain.
  • SKIN CARE ACTIVE AGENTS
  • [0288]
    The foam of the present invention is useful and advantageous for skin care and cosmetic care. The combination of oil and water, having moisture-retaining properties, in a spreadable foam form, can be used to substitute currently used cosmetic skin care creams, lotions, gels, etc. The cosmetic foam compositions of the present invention are suitable for the further application as “cosmeceutical” preparation (cosmetic products with therapeutic benefit), to treat “cosmetic” skin disorders, such as aging skin, wrinkles, hyperpigmentation (melasma, chloasma, freckles, etc.), scaly skin and other skin undesirable properties.
  • [0289]
    The CTFA Cosmetic Ingredient Handbook describes a wide variety of nonlimiting cosmetic and pharmaceutical ingredients commonly used in the skin care industry, which are suitable for use in the compositions of the present invention. Examples of these ingredient classes include: abrasives, absorbents, aesthetic components such as fragrances, pigments, colorings/colorants, essential oils, astringents, etc. (e.g., clove oil, menthol, camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazel distillate), anti-acne agents, antimicrobial agents (e.g., iodopropyl butylcarbamate), antioxidants, binders, biological additives, buffering agents, bulking agents, chelating agents, chemical additives, colorants, cosmetic astringents, cosmetic biocides, denaturants, drug astringents, external analgesics, film formers or materials, e.g., polymers, for aiding the film-forming properties and substantivity of the composition (e.g., copolymer of eicosene and vinyl pyrrolidone), opacifying agents, pH adjusters, propellants, reducing agents, sequestrants, skin bleaching and lightening agents (e.g., hydroquinone, kojic acid, ascorbic acid, magnesium ascorbyl phosphate, ascorbyl glucosamine), skin-conditioning agents (e.g., humectants, including miscellaneous and occlusive), skin soothing and/or healing agents (e.g., panthenol and derivatives (e.g., ethyl panthenol), aloe vera, pantothenic acid and its derivatives, allantoin, bisabolol, and dipotassium glycyrrhizinate), skin treating agents, thickeners, and vitamins and derivatives thereof.
  • [0290]
    In any embodiment of the present invention, however, the active agents useful herein can be categorized by the benefit they provide or by their postulated mode of action. It is to be understood that the active agents useful herein can in some instances provide more than one benefit or operate via more than one mode of action. Therefore, classifications herein are made for the sake of convenience and are not intended to limit the active to that particular application or applications listed.
  • [0291]
    Anti-acne Active Agents
  • [0292]
    The compositions of the present invention may contain a safe and effective amount of one or more pharmaceutically or cosmetically acceptable anti-acne active agents. Examples of useful anti-acne actives include resorcinol, sulfur, salicylic acid and salicylates, alpha-hydroxy acids, nonsteroidal anti-inflammatory agents, benzoyl peroxide, retinoic acid, isoretinoic acid and other retinoid compounds, adapalene, tazarotene, azelaic acid and azelaic acid derivatives, antibiotic agents, such as erythromycin and clyndamycin, zinc salts and complexes, and combinations thereof, in a therapeutically effective concentration.
  • [0293]
    Anti-wrinkle Active Agents/anti-atrophy Active Agents and Agents to Treat Dry and Scaly Skin (Xerosis and Ichthyosis)
  • [0294]
    The compositions of the present invention may further contain a safe and effective amount of one or more anti-wrinkle actives or anti-atrophy actives, which can be easily delivered by spreading a foam onto the skin. Exemplary anti-wrinkle/anti-atrophy active agents suitable for use in the compositions of the present invention include sulfur-containing D and L amino acids and their derivatives and salts, particularly the N-acetyl derivatives; thiols; hydroxy acids (e.g., alpha-hydroxy acids such as lactic acid and glycolic acid and their derivatives and salts; or beta-hydroxy acids such as salicylic acid and salicylic acid salts and derivatives), urea, hyaluronic acid, phytic acid, lipoic acid; lysophosphatidic acid, skin peel agents (e.g., phenol, resorcinol and the like), vitamin B3 compounds (e.g., niacinamide, nicotinic acid and nicotinic acid salts and esters, including non-vasodilating esters of nicotinic acid (such as tocopheryl nicotinate), nicotinyl amino acids, nicotinyl alcohol esters of carboxylic acids, nicotinic acid N-oxide and niacinamide N-oxide), vitamin B5 and retinoids (e.g., retinol, retinal, retinoic acid, retinyl acetate, retinyl palmitate, retinyl ascorbate). In the case of dry, scaly skin (xerosis) and ichthyosis such agents can alleviate the symptoms by temporary relief of itching associated with these conditions.
  • [0295]
    Anti-oxidants/radical Scavengers
  • [0296]
    A safe and effective amount of an anti-oxidant/radical scavenger may be added to the compositions of the subject invention, preferably from about 0.1% to about 10% (w/w), more preferably from about 1% to about 5% (w/w), of the composition.
  • [0297]
    Anti-oxidants/radical scavengers such as ascorbic acid (vitamin C) and its salts, ascorbyl esters of fatty acids, ascorbic acid derivatives (e.g., magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbate), tocopherol (vitamin E), tocopherol sorbate, tocopherol acetate, other esters of tocopherol, butylated hydroxy benzoic acids and their salts, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (commercially available under the tradename Trolox.sup.R), gallic acid and its alkyl esters, especially propyl gallate, uric acid and its salts and alkyl esters, sorbic acid and its salts, lipoic acid, amines (e.g., N,N-diethylhydroxylamine, amino-guanidine), sulfhydryl compounds (e.g., glutathione), dihydroxy fumaric acid and its salts, lycine pidolate, arginine pilolate, nordihydroguaiaretic acid, bioflavonoids, curcumin, lysine, methionine, proline, superoxide dismutase, silymarin, tea extracts, grape skin/seed extracts, melanin, and rosemary extracts may be used.
  • [0298]
    The foam of the present invention is suitable for delivering skin protecting and revitalizing anti-oxidants/radical scavengers. It is further pointed out that polyunsaturated fatty acids, containing omega-3 and omega-6 fatty acids (e.g., linoleic and linolenic acid, gamma-linoleic acid (GLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are beneficial in the treatment of psoriasis and other skin inflammation conditions. Likewise, emollients and silicone oils exert moisture-retaining and skin protective effects on the skin. Thus in a preferred embodiment, a skin protective foam is provided, wherein the hydrophobic solvent comprises in full or in part, a solvent, selected from the group of emollients, silicone oil and oils, rich in unsaturated fatty acids, thus, affording a synergistic therapeutic effect of the anti-oxidants/radical scavenger agent and the vehicle components.
  • [0299]
    Self-tanning Active Agents
  • [0300]
    The foam of the present invention is particularly suitable for the uniform delivery of a tanning active agent onto large areas of the skin. It is preferable that the compositions contain from about 0.1% to about 20%, more preferably from about 2% to about 7%, and still more preferably from about 3% to about 6%, of the composition, of dihydroxyacetone, or any other compound, know in the art as an artificial tanning active agent.
  • [0301]
    Skin Lightening and Whitening Agents
  • [0302]
    The foam of the present invention is particularly suitable for the uniform delivery of a skin lightening agent. When used, the compositions preferably contain from about 0.1% to about 10%, more preferably from about 0.2% to about 5%, of the composition, of a skin-lightening agent. Suitable skin lightening or whitening agents include those known in the art, including hydroquinone, azelaic acid and other related dicarboxylic acids, and salts and derivatives thereof, retinoids, kojic acid, arbutin, nicotinic acid and its precursors, salts and derivatives, arbutin, ascorbic acid and salts and derivatives thereof (e.g., magnesium ascorbyl phosphate or sodium ascorbyl phosphate), and herbal extracts (e.g., licorice extract, mulberry extract, placental extract).
  • [0303]
    In one or more embodiments of the present invention, the foam composition comprises a combination of a skin whitening agent and a sunscreen agent.
  • [0304]
    In one or more embodiments of the present invention, the foam composition comprises a combination of a skin whitening agent and an inorganic sunscreen agent. When inorganic sunscreen agents, e.g. TiO2, are rubbed onto the skin, they leave a white coating, which provides an immediate (although transient) whitening effect, which is highly desirable by the consumer, who wishes to see instant change in his/her appearance. The whitening agent, in combination with the inorganic sunscreen agent in the foam carrier can be easily and uniformly distributed on the skin surface, thereby affording an even instant whitening effect, unlike creams that are difficult to spread evenly on skin areas.
  • [0305]
    Sunscreens
  • [0306]
    Exposure to ultraviolet light can result in excessive scaling and texture changes of the stratum corneum. The foam of the present invention is advantageous for the delivery of sunscreen agents. Its application is very convenient and it spreads easily over large skin areas. The presence of a hydrophobic solvent in the foam ensures long lasting effect, even while bathing.
  • [0307]
    As used herein, “sunscreen active” or “sunscreen agent” includes both sunscreen agents and physical sunblocks. Suitable sunscreen actives may be organic or inorganic.
  • [0308]
    Inorganic sunscreens useful herein include the following metallic oxides; titanium dioxide having an average primary particle size of from about 15 nm to about 100 nm, zinc oxide having an average primary particle size of from about 15 nm to about 150 nm, zirconium oxide having an average primary particle size of from about 15 nm to about 150 nm, iron oxide having an average primary particle size of from about 15 nm to about 500 nm, and mixtures thereof. When used herein, the inorganic sunscreens are present in the amount of from about 0.1% to about 20%, preferably from about 0.5% to about 10%, more preferably from about 1% to about 5%, of the composition.
  • [0309]
    A wide variety of conventional organic sunscreen actives are suitable for use herein. Specific suitable sunscreen actives include, for example: p-aminobenzoic acid, its salts and its derivatives (ethyl, isobutyl, glyceryl esters; p-dimethylaminobenzoic acid); anthranilates (i.e., o-amino-benzoates; methyl, menthyl, phenyl, benzyl, phenylethyl, linalyl, terpinyl, and cyclohexenyl esters);
  • [0310]
    salicylates (amyl, phenyl, octyl, benzyl, menthyl, glyceryl, and di-pro-pyleneglycol esters); cinnamic acid derivatives (menthyl and benzyl esters, a-phenyl cinnamonitrile; butyl cinnamoyl pyruvate); dihydroxycinnamic acid derivatives (umbelliferone, methylumbelliferone, methylaceto-umbelliferone); trihydroxy-cinnamic acid derivatives (esculetin, methylesculetin, daphnetin, and the glucosides, esculin and daphnin); hydrocarbons (diphenylbutadiene, stilbene);
  • [0311]
    dibenzalacetone and benzalacetophenone; naphtholsulfonates (sodium salts of 2-naphthol-3,6-disulfonic and of 2-naphthol-6,8-disulfonic acids); di-hydroxynaphthoic acid and its salts; o- and p-hydroxybiphenyldisulfonates;
  • [0312]
    coumarin derivatives (7-hydroxy, 7-methyl, 3-phenyl); diazoles (2-acetyl-3-bromoindazole, phenyl benzoxazole, methyl naphthoxazole, various aryl benzothiazoles); quinine salts (bisulfate, sulfate, chloride, oleate, and tannate);
  • [0313]
    quinoline derivatives (8-hydroxyquinoline salts, 2-phenylquinoline); hydroxy- or methoxy-substituted benzophenones; uric and violuric acids; tannic acid and its derivatives (e.g., hexaethylether); (butyl carbotol) (6-propyl piperonyl) ether;
  • [0314]
    hydroquinone; benzophenones (oxybenzene, sulisobenzone, dioxybenzone, benzoresorcinol, 2,2′, 4,4′-tetrahydroxybenzophenone, 2,2′-dihydroxy-4,4′-dimethoxybenzophenone, octabenzone; 4-isopropyldibenzoylmethane; butylmethoxydibenzoylmethane; etocrylene; octocrylene; [3-(4′-methylbenzylidene bornan-2-one), terephthalylidene dicamphor sulfonic acid and 4-isopropyl-di-benzoylmethane.
  • [0315]
    A safe and effective amount of the organic sunscreen active is used, typically from about 1% to about 20%, more typically from about 2% to about 10% of the composition. Exact amounts will vary depending upon the sunscreen or sunscreens chosen and the desired Sun Protection Factor (SPF).
  • [0316]
    Agents for Hair Growth Disorders
  • [0317]
    Agents, which affect the pattern of hair growth, can be suitably incorporated in the foam of the present invention. Male patterrn baldness (MPB), the commonest cause of balding, is induced by the activity of the male hormone dihydrotestosterone (DHT), which converted from the hormone testosterone by the enzymes 5 alpha reductase. Current treatments of MPB include minoxidil and agents, which inhibit 5 alpha reductase, such as finasteride, spironolactone, azelaic acid and azelaic acid derivatives and salts. Such agents, as well as other agents known in the art, can be incorporated in the foam of the present invention.
  • [0318]
    It is further pointed out that polyunsaturated fatty acids, i.e., such which include any of the essential fatty acids (EFA's): linoleic and linolenic acid, gamma-linoleic acid (GLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are also known to contribute to hair growth. Thus in a preferred embodiment, a hair growth foam is provided, wherein the hydrophobic solvent comprises in full or in part, an oil, rich in such unsaturated fatty acids.
  • [0319]
    Figure-forming Agents; Agents to Treat Cellulite/Slimming
  • [0320]
    Figure forming agents such as used in the treatment of cellulite and in slimming products, can be suitably incorporated in the foam of the present invention. A non-limiting exemplary list of active agents, known in the treatment of cellulite and in the induction of a slimming effect include herbal extracts, such as baldderwack extract, butcher's, broom, cayenne, dandelion, red clover, ginkgo biloba, horse chestnut, witch hazel and borage oil, omega 3 and omega 6 oils, caffeic acid and salts and derivatives thereof, xanthine agents, such as caffeine, theophiline and pentoxyphilline, and nicotinic acid and salts and derivatives thereof.
  • [0321]
    Agents to Treat Sunburn, Heat Burn, Radiation Burn, Rash and Itch
  • [0322]
    Cosmetic and pharmaceutical ingredients which are known in the art of pharmacology and cosmetology to treat dermatitis, minor skin irritations, sunburn, heat burn, radiation burn, and inhibit inflammation can be beneficially incorporated in the foam of the present invention.
  • [0323]
    Examples of such active agents include chamomile extract (matricaria recutitia), cucumber distillate (cucumis sativus), lavender water (lavendula angustifolia), rose water (rosa damascena), witch hazel (hamamelis virginiana), allantoin, bisabolol, rosehip oil, calendula oil, azulaene, menthol and camphor.
  • [0324]
    Use of the Foam as a Lubricating and Protective Foam
  • [0325]
    There are several potential uses of the foam, particularly the silicone-oil based foam, as a lubricating foam. Typical examples are shaving foam, moisture protection foam and antifriction foam. For such purposes, the foam can be used in its basic composition (without additional formulation aids and active ingredients), or with the addition of such additives.
  • FOAM FOR NEUTRALIZATION AND/OR DECONTAMINATION OF HAZARDOUS CHEMICALS AND TREATMENT OF HEAT BURNS
  • [0326]
    It has been reported that povidone iodine antiseptic, a popular iodine product, can ameliorate damage to guinea pig skin exposed to mustard gas and other chemical irritants and further reduces, and many times prevents, damage to human skin after accidental heat burns caused by hot water, oil or hot steam.
  • [0327]
    Other active compound, having decontamination abilities, comprise strong oxidants and free radical liberating compounds, such as hydrogen oxide, bleaching agents (e.g., sodium, calcium or magnesium hypochloride and the like) iodine, chlorohexidine and benzoyl peroxide.
  • [0328]
    The alcohol-free foam of the present invention, comprising one or more of the above decontaminating and neutralizing agents can be applied onto the contaminated skin to form a preventive layer, prior to contamination measure or as a decontamination/neutralization means, right after contamination has occurred.
  • PENETRATION ENHANCERS
  • [0329]
    A penetration enhancer or permeation enhancer is an agent used to increase the permeability of the skin to a pharmacologically active agent to increase the rate at which the drug diffuses through the skin and enters the tissues and bloodstream. A chemical skin penetration enhancer increases skin permeability by reversibly altering the physiochemical nature of the stratum corneum to reduce its diffusional resistance. In a review of the technical and patent literature up to 1996, numerous chemical compounds were cited as skin penetration enhancers. Most of the compounds are generally recognized as safe (GRAS) ingredients that would often be considered inert by a formulator (Osborne D W, Henke J J, Pharmaceutical Technology, November 1997, pp 58-86.)
  • [0330]
    Examples of penetration enhancers, according to the present invention include: polyols, such as propylene glycol, hexylene glycol, diethylene glycol, propylene glycol n-alkanols, terpenes, di-terpenes, tri-terpenes, terpen-ols, limonene, terpene-ol, 1-menthol, dioxolane, ethylene glycol, other glycols, and glycerol; sulfoxides, such as dimethylsulfoxide (DMSO), dimethylformanide, methyl dodecyl sulfoxide, dimethylacetamide; monooleate of ethoxylated glycerides (with 8 to 10 ethylene oxide units); Azone (1 -dodecylazacycloheptan-2-one), 2-(n-nonyl)-1,3-dioxolane; esters, such as isopropyl myristate/palmitate, ethyl acetate, butyl acetate, methyl proprionate, capric/caprylic triglycerides, octylmyristate, dodecyl-myristate; myristyl alcohol, lauryl alcohol, lauric acid, lauryl lactate ketones; amides, such as acetamide oleates such as triolein; various surfactants, such as sodium lauryl sulfate; various alkanoic acids such as caprylic acid; lactam compounds, such as azone; alkanols, such as oleyl alcohol; dialkylamino acetates, and admixtures thereof.
  • [0331]
    Lower alcohols, such as ethanol, propanol, isopropanol, butanol, iso-butanol, t-butanol and pentanol are not considered appropriate penentartion enhancers according to the present invention, due to their skin drying and irritation properties.
  • [0332]
    Yet, another preferred class of penetration enhancers in the cyclodextrines and related compounds. Cyclodextrins are structurally related cyclic oligomaltoses which form a new group of pharmaceutical excipients. These are torus-shaped molecules with a hydrophilic outer surface and a lipophilic central cavity. Cyclodextrins are capable of forming water-soluble inclusion complexes with a wide variety of lipophilic water-insoluble drugs by taking up a whole drug molecule, or some part of it, into the cavity. The cyclodextrin molecules are relatively large (molecular weight ranging from almost 1000 to over 1500), with a hydrated outer surface, and under normal conditions, cyclodextrin molecules will only permeate the skin barrier with considerable difficulty. It is generally believed that the cyclodextrin molecules act as true carriers by keeping lipophilic drug molecules in solution and deliver them to the skin surface where they partition from the cyclodextrin cavity into the skin.
  • FURTHER TECHNICAL PARAMETERS
  • [0333]
    The composition of the present invention may be contained in and dispensed from a container capable of withstanding the pressure of the propellant gas and having an appropriate valve/nozzle for dispensing the composition as foam under pressure. A customary liquefied or compressed gas propellant can be added, in the amount of about 5-25% of the total composition. Liquefied propellants are gases that exist as liquids under pressure, including high purity hydrocarbons such as propane, isobutane and n-butane, dimethyl ether and chlorofluorocarbons (CFCs). Compressed gasses are exemplified by air, nitrogen and carbon dioxide.
  • [0334]
    A specific embodiment according to the present invention comprises placing the composition of the present invention on a patch, occlusive tape or the skin-contact compartment of a transdermal delivery apparatus and applying such object onto the skin, in order to attain effective superficial treatment or enhanced penetration of the drug into the skin or through the skin.
  • [0335]
    Utilizing such strategy, one can apply drugs, which are currently administered systemically or that require transdermal delivery, in the preferred therapeutic system of the present invention. Examples for such drugs are nicotine, testosterone and other male hormones and male hormone precursors, estrogen and other female hormones and hormone precursors, growth hormone, insulin, caffeine, steroidal and non-steroidal antiinflammatory agents and thyroid hormone substitutes.
  • [0336]
    The general process, as typically exemplified in Example 1 may be applied in order to produce the composition of the present invention. The pharmaceutical carrier according to the present invention can also be used to prepare cosmetics for beauty purpose by adding into skin care agents and perfume.
  • EXAMPLES
  • [0337]
    The invention is described with reference to the following examples. This invention is not limited to these examples and experiments. Many variations will suggest themselves and are within the full intended scope of the appended claims.
  • Example 1 General Procedure for Preparing Foamable Composition
  • [0338]
    Aqueous Phase: Water gelling agent and surface-active agent are dissolved in water, with agitation. The solution is warmed to 50-70° C. Water soluble cosmetic or pharmaceutical active ingredients and optional water soluble ingredients are added with agitation to the Aqueous Phase mixture.
  • [0339]
    Hydrophobic Phase: The hydrophobic solvent is heated to same temperature. Foam adjuvant agent is added to preheated hydrophobic solvent. Oil soluble cosmetic or pharmaceutical active ingredients* and optional oil soluble formulation ingredients are added with agitation to the Hydrophobic Phase mixture.
  • [0340]
    The warm Hydrophobic Phase is gradually poured into the warm Aqueous Phase, with agitation, followed by Ultraturax homogenization. The mixture is allowed to cool down to ambient temperature. In case of heat sensitive active ingredients, the active ingredient is added with agitation to the mixture after cooling to ambient temperature. The mixture, at ambient temperature, is added to an aerosol container, the container is sealed and appropriate amount of propellant (5-25 w % of the composition mass) is added under pressure into the container.
  • Example 2 Vegetable Oil-Based Foam Carrier Composition
  • [0341]
    Version Version Version
    No. 1 No. 2 No. 3
    Ingredient % (W/W)
    Hydrophobic solvent Soybean oil 40 30.5 20
    Water Water 48.5 32.5 61
    Foam adjuvant agent Stearyl Alcohol 0.8 1.05 0.73
    Surface-active agent Sucrose ester SP70 0.64 0.45 0.8
    Water gelling agent Xanthan Gum 0.16 0.11 0.1
    Methocel ELV15 0.32 0.22 0.28
    Other Ingredients Antioxidant 0.02 0.02 0.02
    Preservatives 0.3 0.3 0.3
    Fragrance 0.2 0.2 0.2
    Foam Specific gravity 0.10 0.15 0.065
    (gr/mL)
  • [0342]
    The compositions use a non-ionic surfactant and contain a combined amount of surface-active agent, foam adjuvant and water gelling agent ranging from 1.83% to 1.92% (w/w). The foam of this example is useful as a carrier of active pharmaceutical and/or cosmetic active ingredients, as exemplified below. It also can be used as a protective product. Additionally, it is also useful as lubricating foam, for various purposes.
  • Example 3 Silicone Oil-Based Foam Carrier Composition
  • [0343]
    Version Version
    No. 1 No. 2
    Specific Ingredient % (W/W)
    Hydrophobic solvent Dimeticone 350* 25 10
    Water Water 72 87
    Foam adjuvant agent Stearyl Alcohol 0.2 0.2
    Surface-active agent Sucrose ester SP70 0.8
    Myrj 49P 0.8
    Water gelling agent Xanthan Gum 0.2 0.2
    Methocel ELV15 0.4 0.4
    Other Ingredients Antioxidant 0.02 0.02
    Preservatives 1 1
    Fragrance 0.2 0.2
    Foam Specific gravity (gr/mL) 0.10 ND

    *Dimethylpolysiloxane of 350 cps viscosity.
  • [0344]
    The compositions use only non-ionic surfactant and contain a combined amount of surface-active agent, foam adjuvant and water gelling agent of 1.6% (w/w). The foam of this example is useful as a carrier of active pharmaceutical and/or cosmetic active ingredients, as exemplified below. It also can be used as a protective product. Additionally, it is also useful as lubricating foam, for various purposes.
  • Example 6 Mineral Oil-Based Foam Carrier Composition
  • [0345]
    Version Version Version Version Version
    No. 1 No. 2 No. 3 No. 4 No. 5
    Ingredient % (W/W)
    Hydrophobic solvent Mineral oil 69 50 50 25 25
    Water Water 28.4 46.7 46.7 71.88 71.9
    Foam adjuvant Stearyl Alcohol 0.7 1 1 0.5 0.5
    agent
    Surface-active Sucrose ester SP70 0.4 0.64 0 0.8 0
    agent PEG S-40 0 0 0.64 0 0
    Polysorbate-60 0 0 0 0 0.8
    Water gelling Xanthan Gum 0.1 0 0.14 0.2 0.2
    agent Methocel ELV15 0.2 0.4 0.32 0.4 0.4
    Other Antioxidant 0.02 0.02 0.02 0.02 0.02
    Ingredients Preservatives 1 1 1 1 1
    Fragrance 0.2 0.2 0.2 0.2 0.2
    Foam Specific ND ND ND ND 0.1
    gravity (gr/mL)
  • [0346]
    The compositions use only non-ionic solvents, and the total amount of surface active agent, foam adjuvants and water gelling agents ranges from 1.4 to 2.1% (w/w). The foam of this example is useful as a carrier of active pharmaceutical and/or cosmetic active ingredients, as exemplified in examples below. It is also useful as lubricating foam, for various purposes.
  • Example 7 Mixed Oils Foam Carrier Composition
  • [0347]
    Version Version
    No. 1 No. 2
    Ingredient 25% Oil 12.5% Oil
    Hydrophobic solvent Mineral oil 11.2% 5.6%
    Isopropyl myristate 5.0% 2.5%
    MCT oil 7.5% 3.8%
    Foam adjuvant agent Stearyl Alcohol 0.5% 0.25% 
    Water Water 73.0% 85.2% 
    Surface-active agent Sucrose ester SP70 0.8% 0.8%
    Distilled monoglyceride 1.2% 0.6%
    Sodium lauryl sulphate 0.1% 0.1%
    Water gelling agent Xanthan Gum 0.3% 0.3%
    Methocel ELV15 0.6% 0.6%
  • [0348]
    The foams of this example have a non-ionic surfactant to ionic surfactant ratio (w/w) of 20:1 and 14:1 for versions 1 and 2, respectively. Total amounts of surface active agent foam adjuvant and water gelling agent is in the range of 1.75-3.5% (w/w). It is useful as a carrier of active pharmaceutical and/or cosmetic active ingredients, as exemplified in examples below. It is also useful as lubricating foam, for various purposes.
  • [0349]
    The following examples, representing optional drug-containing foams, are prototype formulations, which have not been optimized for stability and inter-component compatibility. Such optimization is a customary need, which can be done, using means, known to those skilled in the art of pharmaceutical formulation
  • Example 8 Antibacterial Foam Composition
  • [0350]
    Version 2 Version 3 Version 4 Version 5
    Version 1 “Triple “Fucidic “Metro- “Triple
    Ingredient “Mupirocin” Antibiotic” Acid” nidazole” Antibiotic”
    Carrier Ingredients
    Mineral oil 48.8%  11.2%  48.8%  5.6% 5.6%
    Isopropyl myristate 5.0% 2.5% 2.5%
    MCT oil 7.5% 3.8% 3.8%
    Stearyl Alcohol 0.8% 0.5% 0.8% 0.25%  0.25% 
    Water  50% 73.0%   50% 85.2%  85.2% 
    Sucrose ester SP70 0.8% 0.8% 0.8%
    Myrj 40 0.8%
    Distilled 1.2% 0.6% 0.6%
    monoglyceride
    Tween 60 0.8%
    Sodium lauryl 0.05%  0.1% 0.1%
    sulphate
    Xanthan Gum 0.2% 0.3% 0.2% 0.3% 0.3%
    Methocel ELV15 0.2% 0.6% 0.2% 0.6% 0.6%
    Active Ingredients
    Mupirocin   2%
    Polymyxin B Sulfate 10,000 Units/gr 10,000 Units/gr
    Bacitracin Zinc   500 Units/gr   500 Units/gr
    Neomycin Sulfate* 0.05%  0.05% 
    Pramoxine HCl   1%   1%
    Fucidic acid   2%
    Metronidazole   1%
  • [0351]
    The foams of this example contain 100% non-ionic surfactant or have a non-ionic surfactant to ionic surfactant ratio ranging from 20:1 to 8:1. Total amounts of surface active agent, foam adjuvant and water gelling agent ranges from 2.05-3.5% (w/w). It is useful for the treatment of bacterial skin infection (general), cellulites, open wounds, cutaneous abscesses, furuncles, insect bite, impetigo, acne, acne-rosacea, and trichomonas vaginitis.
  • [0352]
    In certain embodiments, the foam of this example is useful for the prevention, decontamination and/or neutralization hazardous bacterial infestation (such as warfare organisms).
  • Example 9 Antifungal Foam Composition
  • [0353]
    Version 1 Version 2 Version 3 Version 4
    Ingredient “Terbinafine” “Clotrimazole” “Nystatin” “Nystatin”
    Carrier
    Ingredients
    Mineral oil 48.8%  11.2%  48.8%  5.6%
    Isopropyl 5.0% 2.5%
    myristate
    MCT oil 7.5% 3.8%
    Stearyl Alcohol 0.8% 0.5% 0.8% 0.25% 
    Water  50% 73.0%   50% 85.2% 
    Sucrose ester 0.8% 0.8% 0.8%
    SP70
    Myrj 40 0.8%
    Tween 80 0.8%
    Distilled 1.2% 0.6%
    monoglyceride
    Sodium lauryl 0.05%  0.1% 0.1%
    sulphate
    Xanthan Gum 0.2% 0.3% 0.2% 0.3%
    Methocel 0.2% 0.6% 0.2% 0.6%
    ELV15
    Active
    Ingredients
    Terbinafine   1%
    clotrimazole   2%
    Nystatin 100,000 100,000
    Units/gr Units/gr
  • [0354]
    The foams of this example have 100% non-ionic surfactant or have a non-ionic surfactant to ionic surfactant ratio ranging from 20:1 to 8:1. Total surface active agent, foaming adjuvant and water gelling agent ranges from 2.05 to 3.5% (w/w). It is useful in the treatment of dermatophyte infections, Tinea corporis, Tinea pedis, Tinea rubrum, Tinea unguium, Tinea cruris, Tinea barbae, and yeast infections, such as Candidiasis, Tinea versicolor and Candidal vaginitis.
  • Example 10 Corticosteroid Foam Composition
  • [0355]
    Version 1 Version 2 Version 3
    Ingredient “Hydrocortisone” “Betamethasone” “Dexamethasone”
    Carrier
    Ingredients
    Mineral oil 48.8%  11.2%  5.6%
    Isopropyl 5.0% 2.5%
    myristate
    MCT oil 7.5% 3.8%
    Stearyl Alcohol 0.8% 0.5% 0.25% 
    Water  50% 73.0%  85.2% 
    Sucrose ester 0.8% 0.4% 0.8%
    SP70
    Tween 80 0.4%
    Distilled 1.2% 0.6%
    monoglyceride
    Sodium lauryl 0.05%  0.1%
    sulphate
    Xanthan Gum 0.2% 0.3% 0.3%
    Methocel 0.2% 0.6% 0.6%
    ELV15
    Active
    Ingredients
    Hydrocortisone   1%
    Betamethasone 0.05% 
    dipropionate
    Dexamethasone 0.1%
    acetate
    Version 4 Version 5
    Ingredient “Triamcinolone” “Flumetasone”
    Carrier Ingredients
    Mineral oil 48.8%  48.8% 
    Stearyl Alcohol 0.8% 0.8%
    Water  50%  50%
    Sucrose ester SP70 0.8% 0.8%
    Sodium lauryl 0.05%  0.05% 
    sulphate
    Xanthan Gum 0.2% 0.2%
    Methocel ELV15 0.2% 0.2%
    Active Ingredients
    Triamcinolone 0.1%
    acetonide
    Flumetasone 0.02% 
    pivalate
  • [0356]
    The foams of this example have either 100% non-ionic surfactant or have a non-ionic surfactant to ionic surfactant ratio ranging from 20:1 to 16:1. Total surface active agent, foaming adjuvant and water gelling agent ranges from 2.05 to 3.5% (w/w). Indications include psoriasis, contact dermatitis, atopic dermatitis, seborrheic dermatitis, nummular dermatitis, inflammatory acne, chronic dermatitis of the hands and feet, generalized exfoliative dermatitis, stasis dermatitis, lichen simplex chronicus, herpes gestationis and pruritic urticarial papules and plaques of pregnancy.
  • Example 11 Antiviral Foam Composition
  • [0357]
    Version 1 Version 2 Version 3
    Ingredient “Acyclovir” “Acyclovir” “α-Interferon”
    Carrier Ingredients
    Mineral oil 48.8%  11.2%  5.6%
    Isopropyl myristate 5.0% 2.5%
    MCT oil 7.5% 3.8%
    Stearyl Alcohol 0.8% 0.5% 0.25% 
    Water  50% 73.0%  85.2% 
    Sucrose ester SP70 0.8% 0.8%
    Tween 80 0.8%
    Distilled monoglyceride 1.2% 0.6%
    Sodium lauryl sulphate 0.1%
    Xanthan Gum 0.2% 0.3% 0.3%
    Methocel ELV15 0.2% 0.6% 0.6%
    Active Ingredients
    Acyclovir   5%   5%
    α-Interferon 105 IU/g
  • [0358]
    The foams of this example have either 100% non-ionic surfactant or have a non-ionic surfactant to ionic surfactant ratio of 14:1. Total surface active agent, foaming adjuvant and water gelling agent ranges from 2.05 to 3.5% (w/w). Indications include Herpes simplex, Herpes zoster, Herpes gestationis and Herpes simplex genital ulcers.
  • Example 12 Insect Repellent Foam Composition
  • [0359]
    Ingredient %
    Isopropyl myristate 2.0%
    MCT oil 2.0%
    Stearyl Alcohol 1.2%
    Water 64.0% 
    Sucrose ester SP70 0.8%
    Sodium lauryl sulphate 0.1%
    Xanthan Gum 0.3%
    Methocel ELV15 0.6%
    Propylene glycol  15%
    DEET  15%
  • Example 14 Comparative Tolerability and Acceptability Study of a Corticosteroid Foam Composition Vs. a Conventional Ointment
  • [0360]
    A panel of eight testers was requested to apply about 0.5 gr. of the foam preparation of example 10, Version 2 on one arm and 0.5 gr. of commercial Betamethasone valerate ointment, in a double blind fashion. They were asked to describe their feeling about the ease of application, ease of spreading, spreadability and penetrability of each of the products and to give their general rating for each of the products on a scale of 0-3 (0=poor; 1=barely acceptable; 2=acceptable and 3=excellent).
  • [0361]
    As demonstrated in the following table, the foam preparation of example 10, Version 2 obtained higher rates in all aspects of the test.
    Commercial
    Betamethasone
    Foam Preparation Valerate Ointment
    Property Mean Rating Mean Rating
    Ease of application 2.3 1.6
    Ease of spreading 2.5 1.9
    Spreadability 2.9 1.2
    Penetrability 2.0 1.5
    Lack of sticky feeling 2.4 1.0
    Lack of greasy feeling 2.2 1.0
    Lack of shiny look 1.9 1.4
    Overall rating 2.5 1.4
  • Example 15 Human Safety and Efficacy Study of a Corticosteroid Composition in Psoriasis Patients
  • [0362]
    Two patients with mild to moderate psoriasis were administered topically a Betamethasone 0.1 2% foam (example 10, Version 2) twice daily for two weeks.
  • [0363]
    Both patients improved significantly, as manifested by clearance of the psoriatic plaques flattening of the thickened lesions. FIG. 1 provides an exemplary response to treatment in the elbows of one of these patients. While betamethasone is know for its effect in psoriasis, such a beneficial effect after 14 days treatment is exceptional. The accelerated effect was attributed to the improved convenience and therefore, improved compliance.
  • Example 16 Human Safety and Efficacy Study of a Corticosterold Composition in Psoriasis Patients
  • [0364]
    Four patients with moderate to severe, disseminated atopic dermatitis were administered topically a Betamethasone 0.12% foam (example 10, Version 2) twice daily for two weeks. All patients improved significantly, as manifested by complete clearance of all treated lesions. FIG. 2 provides exemplary responses to treatment in different body areas, after 10 days of treatment. While betamethasone is know for its effect in atopic dermatitis, such a beneficial effect after 10 days treatment is exceptional. The patients claimed that the use of the foam of the present invention was significantly more convenient than the corresponding cream and ointment. Thus, the accelerated effect was attributed to the improved convenience and therefore, improved compliance.
  • Example 17 Foam Compositions with Urea
  • [0365]
    EXAMPLE 1
    Foam Compositions with Urea
    Component % w/w
    Mineral oil 6.00 6.00 6.00 6.00
    Isopropylmeristat 6.00 6.00 6.00 6.00
    Glyceryl monostearate 0.50 0.50 0.50 0.50
    Stearyl alcohol 0.20 0.20 0.20 1.00
    Urea 10.00 10.00 10.00 10.00
    Xantan gum 0.30 0.30 0.30 0.30
    Methocel K100M 0.30 0.30 0.30 0.30
    Myrj 52 3.00
    TWEEN 80 1.00
    Myrj 49p 3.00
    TWEEN 60 1.00 1.00 1.00
    Cocamidopropylbetain 0.50 0.50
    Phenonip 0.30 0.30 0.30 0.30
    Water to 100.0 to 100.0 to 100.0 to 100.0
    Butane/propane 8.00 8.00 18.00 18.00
    FoamQuality E E E E
    Density n/a 0.023 n/a 0.024
  • Example 18 Compositions with Various Penetration Enhancers
  • [0366]
    Component % w/w
    Mineral oil 6.00 6.00 6.00 6.00 6.00
    Isopropyl myristate 6.00 6.00 6.00 6.00 6.00
    Glyceryl monostearate 0.50 0.50 0.50 0.50 0.50
    Stearyl alcohol 1.00 1.00 1.00 1.00 1.00
    Xantan gum 0.30 0.30 0.30 0.30 0.30
    Methocel K100M 0.30 0.30 0.30 0.30 0.30
    TWEEN 60 1.00
    TWEEN 80 1.00 1.00 1.00 1.00
    MYRJ 49p 3.00 3.00 3.00 3.00 3.00
    Propylen glycol 5.00
    Glycofurol 1.00 10.00
    Urea 10.00
    Cocoamidopropyl- 0.50 0.50 0.50 0.50 0.50
    bethaine
    Lidocain base 4.00 4.00 4.00 4.00 4.00
    Phenonip 0.30 0.30 0.30 0.30 0.30
    Water to 100 to 100 to 100 to 100 to 100
    Butane/propane 8 8 8 16 10
    Foam Quality E E E E E
    Density 0.020 0.018 0.019 0.019 0.018
    Component % w/w % w/w
    Isopropyl myristate 30.00 30.00
    Glyceryl monostearate 0.50 0.50
    Stearic acid 0.45 0.45
    Xantan gum 0.30 0.30
    Methocel K100M 0.30 0.30
    TWEEN 80 1.00 1.00
    MYRJ 49p 3.00 3.00
    Cocoamidopropylbethaine 0.50 0.50
    Transcutol p 20.00 20.00
    Hydrophilic drug Effective
    concentration
    Hydrophobic drug Effective
    concentration
    Phenonip 0.30 0.30
    Water to 100.0 to 100.0
    Butane/propane 8.00 8.00
    FoamQuality E E
    Density 0.020 0.020
Citas de patentes
Patente citada Fecha de presentación Fecha de publicación Solicitante Título
US2586287 *26 Oct 195019 Feb 1952Colagte Palmolive Peet CompanyAluminum sulfamate antiperspirant preparation
US2968628 *17 Oct 195817 Ene 1961Shulton IncPropellant composition
US3236457 *21 Ago 196322 Feb 1966John R KennedyComposite spray container assembly
US3298919 *26 Dic 196217 Ene 1967Dow CorningShaving cream containing polysiloxanes
US3301444 *12 Ago 196531 Ene 1967Oel IncAerosol metering valve
US3303970 *14 Jul 196414 Feb 1967Kurtz ConstanceDevice for simultaneously dispensing from plural sources
US3366494 *15 Feb 196730 Ene 1968Du PontPressurized aerosol food emulsions
US3369034 *27 Abr 196413 Feb 1968Eversharp IncProcess for separating saponifiables and unsaponifiables in marine animal oils
US3559890 *3 Sep 19682 Feb 1971William R BrooksFoam dispenser
US3561262 *26 Oct 19679 Feb 1971Magnaflux CorpWater soluble developer
US3563098 *28 Jun 196816 Feb 1971Rex Chainbelt IncAutomatic quick release mechanism
US3787566 *29 Mar 197122 Ene 1974Holliston Labor IncDisinfecting aerosol compositions
US3865275 *30 Jul 197311 Feb 1975Raymond Lee Organization IncApparatus for operating an aerosol can
US3866800 *12 Feb 196918 Feb 1975Alberto Culver CoNon-pressurized package containing self-heating products
US4001391 *16 Sep 19714 Ene 1977Plough, Inc.Means for depositing aerosol sprays in buttery form
US4001442 *17 Jul 19744 Ene 1977Elastin-Werk AktiengesellschaftCollagen-containing preparations
US4252787 *27 Dic 197624 Feb 1981Cambridge Research And Development GroupAnti-fertility composition and method
US4278206 *13 Abr 197914 Jul 1981Ae Development CorporationNon-pressurized dispensing system
US4309995 *28 Ene 198012 Ene 1982Sacco Susan MVaginal irrigation apparatus
US4310510 *3 Oct 198012 Ene 1982Sherman Kenneth NSelf administrable anti-fertility composition
US4427670 *10 Feb 198224 Ene 1984Mitsubishi Chemical Industries LimitedSkin preparation
US4725609 *20 Nov 198416 Feb 1988Burroughs Wellcome Co.Method of promoting healing
US4798682 *6 Jun 198617 Ene 1989Henkel Kommanditgesellschaft Auf AktienOil-in-water emulsions with increased viscosity under shear stress
US4804674 *19 Mar 198714 Feb 1989Euroceltique, S.A.Vaginal pharmaceutical composition
US4806262 *9 Nov 198721 Feb 1989The Procter & Gamble CompanyNonlathering cleansing mousse with skin conditioning benefits
US4808388 *18 Ago 198728 Feb 1989Merz + Co. Gmbh & Co.Foamable creams
US4897262 *22 Mar 198830 Ene 1990Playtex Jhirmack, Inc.Non-aerosol hair spray composition
US4902281 *16 Ago 198820 Feb 1990Corus Medical CorporationFibrinogen dispensing kit
US4981367 *28 Jul 19891 Ene 1991Stranco, Inc.Portable mixing apparatus
US4981677 *15 Nov 19881 Ene 1991L'orealPetrolatum-containing aerosol foam concentrate
US4981679 *27 Sep 19881 Ene 1991Briggs Joseph HMethod and composition for the treatment of burns
US4981845 *25 Ago 19891 Ene 1991Chesebrough Pond's U.S.A. Co., Division Of Conopco, Inc.Cosmetic composition
US4985459 *13 Oct 198915 Ene 1991Richardson-Vicks, Inc.Analgesic and anti-inflammatory compositions comprising diphenhydramine and methods of using same
US4992478 *4 Abr 198812 Feb 1991Warner-Lambert CompanyAntiinflammatory skin moisturizing composition and method of preparing same
US4993496 *8 Ene 199019 Feb 1991Total Walther Feuerschutz GmbhQuick release valve for sprinkler head
US5082651 *25 Abr 199021 Ene 1992Smith Kline & French Laboratories LimitedPharmaceutical compositions
US5087618 *11 Ene 198911 Feb 1992University Of FloridaRedox carriers for brain-specific drug delivery
US5089252 *30 Ago 198918 Feb 1992L'orealCosmetic composition for treating keratin fibres, and process for treating the latter
US5091111 *19 Sep 199025 Feb 1992S. C. Johnson & Son, Inc.Aqueous emulsion and aersol delivery system using same
US5279819 *21 Sep 199218 Ene 1994The Gillette CompanyShaving compositions
US5286475 *8 Nov 199115 Feb 1994L'orealAnhydrous cosmetic composition in the aerosol form forming a foam
US5378451 *27 Sep 19933 Ene 1995Dow B. Hickam, Inc.Topical medicinal pressurized aerosol compositions and method of preparation, method of use and article of manufacture thereof
US5378730 *3 Dic 19923 Ene 1995Alza CorporationPermeation enhancer comprising ethanol and monoglycerides
US5380761 *20 Oct 199310 Ene 1995Chinoin Gyogyszer- Es Vegyeszeti Termekek Gyara Rt.Transdermal compositions
US5384308 *14 Jun 199324 Ene 1995Henkin; R. I.Composition and method for enhancing wound healing
US5385943 *7 Abr 199331 Ene 1995Schering AktiengesellschaftUse of topically applicable preparations for treatment of presbyderma
US5389676 *13 Sep 199314 Feb 1995E. B. Michaels Research Associates, Inc.Viscous surfactant emulsion compositions
US5482965 *3 Sep 19939 Ene 1996Rajadhyaksha; Vithal J.Compositions and method comprising aminoalcohol derivatives as membrane penetration enhancers for physiological active agents
US5491245 *15 Mar 199413 Feb 1996Th. Goldschmidt AgMethod for the synthesis of amphoteric surfactants
US5597560 *10 Abr 199528 Ene 1997Laboratorios Cusi, S.A.Diclofenac and tobramycin formulations for ophthalmic and otic topicaluse
US5603940 *27 Sep 199418 Feb 1997L'orealOil-in-water emulsion which may be used for obtaining a cream
US5605679 *5 Jun 199525 Feb 1997L'orealPhotoprotective/cosmetic compositions comprising at least one solid organic sunscreen compound and diphenylacrylate solvent therefor
US5705472 *18 Jul 19956 Ene 1998Petroferm Inc.Neutral aqueous cleaning composition
US5716611 *2 Ene 199610 Feb 1998Euro-Celtique, S.A.Emollient antimicrobial formulations containing povidone iodine
US5716621 *3 Jul 199610 Feb 1998Pharmadyn, Inc.Nonocclusive drug delivery device and process for its manufacture
US5719122 *15 Oct 199317 Feb 1998Smithkline Beecham Farmaceutici S.P.A.Pharmaceutical compositions containing a calcitonin
US5719197 *7 Jun 199517 Feb 1998Noven Pharmaceuticals, Inc.Compositions and methods for topical administration of pharmaceutically active agents
US5856452 *16 Dic 19965 Ene 1999Sembiosys Genetics Inc.Oil bodies and associated proteins as affinity matrices
US5858371 *21 Abr 199712 Ene 1999Panacea Biotech LimitedPharmaceutical composition for the control and treatment of anorectal and colonic diseases
US5865347 *27 Oct 19972 Feb 1999William T. WilkinsonMulti-chamber dispenser for flowable materials
US5866040 *27 Jul 19942 Feb 1999Shiseido Company, Ltd.Complex and emulsified composition
US5869529 *6 Feb 19969 Feb 1999Agis Industries (1983) Ltd.Topical preparation for the prevention and treatment of lesions and sores associated with a herpes virus
US5871720 *20 Nov 199716 Feb 1999Colgate-Palmolive CompanyCosmetic compositions with DBS and functionalized silicones
US6019967 *26 Ene 19961 Feb 2000Societe L'oreal S.A.Therapeutic/cosmetic compositions comprising CGRP antagonists for treating sensitive human skin
US6024942 *8 Dic 199715 Feb 2000The Procter & Gamble CompanyPhotoprotective compositions
US6030630 *27 Dic 199629 Feb 2000Rhodia ChimieCosmetic compositions for the hair or skin based on sulfone copolyesters with polyorganosiloxane units
US6168576 *24 May 19992 Ene 2001Irene N. ReynoldsDevice for dispensing vaginal medication
US6171347 *29 Ago 19979 Ene 2001Wella AktiengesellschaftCompositions, methods and kits for reductively removing color from dyed hair
US6180669 *5 Abr 199930 Ene 2001Tamarkin Pharmaceutical Innovation Ltd.Method for treatment of dermatological disorders
US6183762 *24 Nov 19996 Feb 2001Sembiosys Genetics Inc.Oil body based personal care products
US6186367 *19 Oct 199913 Feb 2001Valley Design Inc.Metered liquid squeeze dispenser
US6187290 *5 Dic 199513 Feb 2001Giltech LimitedPhysiologically acceptable foamable formulation and foam
US6189810 *22 Sep 199920 Feb 2001Sergei Alexeevich NerushaiMethod for aerosol spraying liquid perfume products
US6190365 *21 Jun 199920 Feb 2001Chun Lim AbbottVaginal douche applicator and method of vaginal deodorization using the same
US6335022 *13 Dic 19991 Ene 2002L'orealNanoemulsion based on oxyethylenated or non-oxyethylenated sorbitan fatty esters, and its uses in the cosmetics, dermatological and/or ophthalmological fields
US6341717 *28 Mar 200129 Ene 2002Megaplast Gmbh & Co. KgMetering pump dispenser with at least two metering pumps
US6511655 *11 Ago 200028 Ene 2003Beiersdorf AgCosmetic or dermatological preparations of the oil-in-water type
US6672483 *3 Feb 20006 Ene 2004Rexam SofabDispenser for chemically unstable products
US6682726 *30 Abr 200127 Ene 2004The Gillette CompanySelf-foaming shaving lotion
US6843390 *17 Mar 200318 Ene 2005Joe G. BristorMultiple fluid closed system dispensing device
US7645803 *9 May 200612 Ene 2010Foamix Ltd.Saccharide foamable compositions
US20020002151 *21 May 20013 Ene 2002Showa Yakuhin Kako Co., Ltd.Minocycline-containing compositions
US20020004063 *28 Sep 199910 Ene 2002Jie ZhangMethods and apparatus for drug delivery involving phase changing formulations
US20020013481 *3 Feb 199931 Ene 2002Uwe SchonrockUse of flavones flavanones and flavonoids for protecting ascorbic acid and/or ascorbyl compounds from oxidation
US20030003193 *28 Jun 20012 Ene 2003Crosswind Industries, Inc.Multi-layer food product, system and process
US20040018228 *7 May 200329 Ene 2004Afmedica, Inc.Compositions and methods for reducing scar tissue formation
US20050002976 *14 Jun 20046 Ene 2005The Procter & Gamble CompanyPolyol-in-silicone emulsions
US20050013853 *10 Feb 200420 Ene 2005Irit Gil-AdAnti-proliferative drugs
US20060008432 *7 Jul 200412 Ene 2006Sebastiano ScarampiGilsonite derived pharmaceutical delivery compositions and methods: nail applications
US20060018938 *14 Jul 200526 Ene 2006Stephanie NeubourgFoam skin cream, use of the foam skin protection cream and a process of its preparation
US20070009607 *11 Jul 200511 Ene 2007George JonesAntibacterial/anti-infalmmatory composition and method
US20070017696 *18 Jul 200625 Ene 2007Hon Hai Precision Industry Co., Ltd.Multi-layer printed circuit board
US20070020213 *19 Jul 200625 Ene 2007Foamix Ltd.Foamable composition combining a polar solvent and a hydrophobic carrier
US20070020304 *6 Jul 200625 Ene 2007Foamix Ltd.Non-flammable insecticide composition and uses thereof
US20080008397 *4 Jul 200610 Ene 2008Pavel KisilevFeature-aware image defect removal
US20080015263 *21 Jun 200717 Ene 2008Bolotin Elijah MCompositions for delivery of therapeutics and other materials
US20080015271 *12 Jul 200717 Ene 2008Stiefel Research Austrialia Pty LtdFatty acid pharmaceutical foam
US20110002857 *14 Sep 20106 Ene 2011Foamix Ltd.Oleaginous pharmaceutical and cosmetic foam
US20110002969 *27 Feb 20096 Ene 2011Lipotec, S.A.Cosmetic or pharmaceutical compositions comprising metalloproteinase inhibitors
USRE38964 *30 Nov 199931 Ene 2006Becton Dickinson And CompanyOne hand needle release system
Otras citas
Referencia
1 *WIKIPIDEA (http://en.wikipedia.org/wiki/Alcohol downloaded on 04/27/2014)
Citada por
Patente citante Fecha de presentación Fecha de publicación Solicitante Título
US770007620 Ago 200420 Abr 2010Foamix, Ltd.Penetrating pharmaceutical foam
US77045189 May 200627 Abr 2010Foamix, Ltd.Foamable vehicle and pharmaceutical compositions thereof
US782014528 Abr 200426 Oct 2010Foamix Ltd.Oleaginous pharmaceutical and cosmetic foam
US7846888 *7 Feb 20067 Dic 2010Battelle Energy Alliance, LlcLong lasting decontamination foam
US79154727 Feb 200629 Mar 2011Battelle Energy Alliance, LlcSurface decontamination compositions and methods
US8042544 *2 Sep 200525 Oct 2011Virginia Commonwealth UniversityPrevention of ventilator associated pneumonia (VAP)
US80583032 Oct 200615 Nov 2011Nihon Nohyaku Co, LtdPharmaceutical composition for external use
US811438526 Dic 200614 Feb 2012Foamix Ltd.Oleaginous pharmaceutical and cosmetic foam
US81191068 Jul 200921 Feb 2012Foamix LtdFoamable iodine compositions
US811910913 Mar 200721 Feb 2012Foamix Ltd.Foamable compositions, kits and methods for hyperhidrosis
US81191506 Jul 200621 Feb 2012Foamix Ltd.Non-flammable insecticide composition and uses thereof
US815810929 Mar 200717 Abr 2012Stiefel Research Australia Pty LtdFoamable suspension gel
US8206688 *12 Ene 200726 Jun 2012Disphar International B.V.Foam-forming composition
US826358026 May 200611 Sep 2012Stiefel Research Australia Pty LtdVitamin formulation
US82688762 Oct 200618 Sep 2012Nihon Nohyaku Co., Ltd.Pharmaceutical composition for external use
US829851528 Sep 201030 Oct 2012Stiefel Research Australia Pty Ltd.Vitamin formulation
US83439457 Jun 20101 Ene 2013Foamix Ltd.Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof
US83498822 Oct 20068 Ene 2013Nihon Nohyaku Co., Ltd.Pharmaceutical composition for external use
US836209126 Abr 201029 Ene 2013Foamix Ltd.Foamable vehicle and pharmaceutical compositions thereof
US841994822 Nov 200916 Abr 2013United Laboratories International, LlcWastewater treatment
US84354981 Abr 20107 May 2013Foamix Ltd.Penetrating pharmaceutical foam
US84757702 Sep 20112 Jul 2013Stiefel Research Australia Pty LtdFoamable suspension gel
US848637414 Ene 200816 Jul 2013Foamix Ltd.Hydrophilic, non-aqueous pharmaceutical carriers and compositions and uses
US8486375 *20 Feb 201216 Jul 2013Foamix Ltd.Foamable compositions
US84863766 Abr 200516 Jul 2013Foamix Ltd.Moisturizing foam containing lanolin
US851271812 Feb 201020 Ago 2013Foamix Ltd.Pharmaceutical composition for topical application
US85132964 Sep 201220 Ago 2013Pola Pharma Inc.Pharmaceutical composition
US85183766 Oct 200927 Ago 2013Foamix Ltd.Oil-based foamable carriers and formulations
US851837814 Sep 201027 Ago 2013Foamix Ltd.Oleaginous pharmaceutical and cosmetic foam
US86180814 May 201131 Dic 2013Foamix Ltd.Compositions, gels and foams with rheology modulators and uses thereof
US862912820 Sep 201214 Ene 2014Stiefel West Coast, LlcVitamin formulation
US86369827 Ago 200828 Ene 2014Foamix Ltd.Wax foamable vehicle and pharmaceutical compositions thereof
US865244313 Feb 200918 Feb 2014Precision Dermatology, Inc.Foamable microemulsion compositions for topical administration
US869763913 Abr 200915 Abr 2014Biosynexus IncorporatedCompositions and methods for treating bacteria
US870310511 Mar 201322 Abr 2014Foamix Ltd.Oleaginous pharmaceutical and cosmetic foam
US870938514 Jul 201029 Abr 2014Foamix Ltd.Poloxamer foamable pharmaceutical compositions with active agents and/or therapeutic cells and uses
US87220216 Mar 201313 May 2014Foamix Ltd.Foamable carriers
US8741265 *4 Mar 20133 Jun 2014Foamix Ltd.Penetrating pharmaceutical foam
US875872831 May 201324 Jun 2014Stiefel Research Australia Pty LtdFoamable suspension gel
US879563512 May 20105 Ago 2014Foamix Ltd.Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses
US879569329 Nov 20075 Ago 2014Foamix Ltd.Compositions with modulating agents
US884086928 Abr 200523 Sep 2014Foamix Ltd.Body cavity foams
US88651399 Jul 201421 Oct 2014Foamix Pharmaceuticals Ltd.Topical tetracycline compositions
US88711841 Oct 201028 Oct 2014Foamix Ltd.Topical tetracycline compositions
US89005537 Jun 20102 Dic 2014Foamix Pharmaceuticals Ltd.Oil and liquid silicone foamable carriers and formulations
US890055420 Feb 20122 Dic 2014Foamix Pharmaceuticals Ltd.Foamable composition and uses thereof
US89455161 Oct 20103 Feb 2015Foamix Pharmaceuticals Ltd.Surfactant-free water-free foamable compositions, breakable foams and gels and their uses
US895204429 Jul 201010 Feb 2015Pola Pharma Inc.Antimycotic pharmaceutical composition
US899289627 Ago 201431 Mar 2015Foamix Pharmaceuticals Ltd.Topical tetracycline compositions
US90502537 Abr 20149 Jun 2015Foamix Pharmaceuticals Ltd.Oleaginous pharmaceutical and cosmetic foam
US90502719 Abr 20109 Jun 2015Pola Pharma Inc.Antimycotic pharmaceutical composition
US907266727 Ene 20127 Jul 2015Foamix Pharmaceuticals Ltd.Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses
US91016623 Oct 201311 Ago 2015Foamix Pharmaceuticals Ltd.Compositions with modulating agents
US9107823 *6 Sep 201218 Ago 2015Nuvo Research Inc.Foamable formulation
US916191631 Dic 201220 Oct 2015Foamix Pharmaceuticals Ltd.Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof
US916781327 Ene 201227 Oct 2015Foamix Pharmaceuticals Ltd.Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses
US92112597 Jun 200615 Dic 2015Foamix Pharmaceuticals Ltd.Antibiotic kit and composition and uses thereof
US92657255 Jul 200723 Feb 2016Foamix Pharmaceuticals Ltd.Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US926572612 May 201423 Feb 2016Stiefel Research Australia Pty LtdFoamable suspension gel
US9277746 *2 May 20068 Mar 2016Nippon Soda Co., Ltd.Liquid composition, process for producing the liquid composition, and ectoparasite controlling agent for use in mammals and avians
US927806621 Ene 20148 Mar 2016Precision Dermatology, Inc.Topical pharmaceutical foam composition
US93207058 Ene 200926 Abr 2016Foamix Pharmaceuticals Ltd.Sensation modifying topical composition foam
US9358209 *5 Ago 20117 Jun 2016Exeltis Usa Dermatology, Inc.Econazole composition and methods of treatment therewith
US94398571 Dic 200813 Sep 2016Foamix Pharmaceuticals Ltd.Foam containing benzoyl peroxide
US9445982 *21 May 200820 Sep 2016Schwan-Stabilo Cosmetics Gmbh & Co. KgPolymer-based pigment-bearing ink
US945716313 Jul 20114 Oct 2016Virginia Commonwealth UniversityPrevention of ventilator associated pneumonia (VAP)
US94806785 Sep 20081 Nov 2016Pola Pharma Inc.Antifungal pharmaceutical composition
US949241222 Abr 201415 Nov 2016Foamix Pharmaceuticals Ltd.Penetrating pharmaceutical foam
US949977213 Mar 201322 Nov 2016Battelle Energy Alliance, LlcMethods of decontaminating surfaces and related compositions
US95392084 Feb 201410 Ene 2017Foamix Pharmaceuticals Ltd.Foam prepared from nanoemulsions and uses
US95498982 Oct 201424 Ene 2017Foamix Pharmaceuticals Ltd.Oil and liquid silicone foamable carriers and formulations
US957277517 Sep 201521 Feb 2017Foamix Pharmaceuticals Ltd.Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses
US96229478 Ene 200918 Abr 2017Foamix Pharmaceuticals Ltd.Foamable composition combining a polar solvent and a hydrophobic carrier
US963640511 Mar 20132 May 2017Foamix Pharmaceuticals Ltd.Foamable vehicle and pharmaceutical compositions thereof
US966229822 Ene 201430 May 2017Foamix Pharmaceuticals Ltd.Wax foamable vehicle and pharmaceutical compositions thereof
US966897211 Mar 20056 Jun 2017Foamix Pharmaceuticals Ltd.Nonsteroidal immunomodulating kit and composition and uses thereof
US967570013 Ene 201513 Jun 2017Foamix Pharmaceuticals Ltd.Topical tetracycline compositions
US968202125 Feb 201420 Jun 2017Foamix Pharmaceuticals Ltd.Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses
US97136438 May 201425 Jul 2017Foamix Pharmaceuticals Ltd.Foamable carriers
US979556415 Ago 201324 Oct 2017Foamix Pharmaceuticals Ltd.Oil-based foamable carriers and formulations
US20050123484 *1 Oct 20049 Jun 2005Collegium Pharmaceutical, Inc.Non-flammable topical anesthetic liquid aerosols
US20060107962 *2 Sep 200525 May 2006Ward Kevin RPrevention of ventilator associated pneumonia (VAP)
US20060188449 *4 Oct 200424 Ago 2006Jane HirshTopical aerosol foams
US20060292080 *26 May 200628 Dic 2006Connetics Australia Pty LtdVitamin formulation
US20070154402 *24 Oct 20065 Jul 2007Collegium Pharmaceutical, Inc.Topical Pharmaceutical Foam Composition
US20070185002 *7 Feb 20069 Ago 2007Demmer Ricky LLong lasting decontamination foam
US20070185365 *7 Feb 20069 Ago 2007Wright Karen ESurface decontamination compositions and methods
US20080292570 *21 May 200827 Nov 2008Schwan-Stabilo Cosmetics Gmbh & Co. KgPolymer-based pigment-bearing ink
US20090030059 *2 Oct 200629 Ene 2009Nihon Nohyaku Co., Ltd.Pharmaceutical composition for external use
US20090069386 *2 May 200612 Mar 2009Hiroshi DairikiLiquid Composition, Process for Producing the Liquid Composition,and Ectoparasite Controlling Agent for Use in Mammals and Avians
US20090076109 *2 Oct 200619 Mar 2009Nihon Nohyaku Co., Ltd.Pharmaceutical Composition for External Use
US20090137651 *2 Oct 200628 May 2009Hirokazu KobayashiPharmaceutical composition for external use
US20090196945 *13 Abr 20096 Ago 2009Biosynexus IncorporatedCompositions and methods for treating bacteria
US20090232743 *13 Feb 200917 Sep 2009Collegium Pharmaceutical, Inc.Foamable Microemulsion Compositions for Topical Administration
US20090304783 *17 Ago 200910 Dic 2009Biosynexus IncorporatedCompositions and methods for treating bacteria
US20090324727 *21 Dic 200731 Dic 2009Biofrontera Bioscience GmbhNanoemulsion
US20100041704 *11 Ene 200818 Feb 2010Aberg A K GunnarDermal compositions of substituted amides and the use thereof as medication for pain and pruritus
US20100111920 *28 Sep 20076 May 2010Michael PellicoMethods and compositions for the treatment of vaginal diseases employing peroxide-producing enzymes and peroxidases
US20100166672 *12 Ene 20071 Jul 2010Disphar International B.V.Foam-forming composition
US20100168200 *5 Sep 20081 Jul 2010Pola Pharma Inc.Antifungal pharmaceutical composition
US20100173965 *5 Sep 20088 Jul 2010Pola Pharma Inc.Antifungal composition
US20100204293 *5 Sep 200812 Ago 2010Pola Pharma Inc.Pharmaceutical composition
US20110014135 *28 Sep 201020 Ene 2011Stiefel Research Australia Pty LtdVitamin formulation
US20110076244 *24 Sep 201031 Mar 2011Pharmasol CorporationSurface coatings for skin
US20110120958 *22 Nov 200926 May 2011United Laboratories International, LlcWastewater Treatment
US20110250239 *7 Abr 201113 Oct 2011Biofrontera Bioscience GmbhPharmaceutical and/or cosmetic composition for treating the skin
US20120022178 *16 Jun 201126 Ene 2012Diversified Glogal Technologies, LlcMethods of embedding foam with additives
US20120100080 *5 Ago 201126 Abr 2012Quinnova Pharmaceuticals, Inc.Econazole Composition and Methods of Treatment Therewith
US20120101139 *5 Ago 201126 Abr 2012Quinnova Pharmaceuticals, Inc.Econazole Composition and Methods of Treatment Therewith
US20120128598 *5 Ene 201224 May 2012Precision Dermatology, Inc.Topical Pharmaceutical Foam Composition
US20120195836 *20 Feb 20122 Ago 2012FoamixFoamable Iodine Compositions
US20130243701 *6 Sep 201219 Sep 2013Nuvo Research Inc.Foamable formulation
US20150297518 *2 Jul 201522 Oct 2015Nuvo Research Inc.Foamable formulation
EP1938801A1 *22 Dic 20062 Jul 2008Biofrontera Bioscience GmbHNanoemulsion
EP2191827A1 *5 Sep 20082 Jun 2010Pola Pharma Inc.Antifungal composition
EP2191827A4 *5 Sep 200815 Sep 2010Pola Pharma IncAntifungal composition
WO2008077641A1 *21 Dic 20073 Jul 2008Biofrontera Bioscience GmbhNanoemulsion
WO2008088756A1 *11 Ene 200824 Jul 2008Bridge Pharma, Inc.Dermal compositions of substituted amides and the use thereof as medication for pain and pruritus
Clasificaciones
Clasificación de EE.UU.424/400
Clasificación internacionalA61K9/12, A61K8/04, A61Q17/04, A61Q19/04, A61Q19/02, A61Q7/00, A61Q7/02, A61K8/60, A61Q17/02, A61K9/00
Clasificación cooperativaA61K31/7048, A61K47/14, A61K47/10, A61K47/38, A61K47/34, A61K31/351, A61K9/0007, A61K31/522, A61K31/4164, A61K31/137, A61K31/4174, A61K47/46, A61K31/567, A61K31/535, A61K31/573, A61K47/26, A61K9/107, A61K31/7036, A61K38/12, A61K47/20, A61K38/212, A01N25/16, A61K9/122, A61Q7/00, A61Q7/02, A61K9/12, A61Q17/04, A61K9/0014, A61Q17/02, A61K8/046, A61K2800/75, A61K9/0034, A61Q19/02, A61K8/60, A61Q19/04
Clasificación europeaA61K9/12, A61K8/04F, A61Q7/00, A61K8/60, A61Q17/02, A61Q17/04, A61Q7/02, A61Q19/04, A61K9/00M8, A61Q19/02, A61K9/12B, A61K9/00M3
Eventos legales
FechaCódigoEventoDescripción
20 Dic 2005ASAssignment
Owner name: FOAMIX LTD., ISRAEL
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:TAMARKIN, DOV;FRIEDMAN, DORON;EINI, MEIR;REEL/FRAME:017135/0307
Effective date: 20051214
22 Dic 2005ASAssignment
Owner name: FOAMIX LTD., ISRAEL
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:TAMARKIN, DOV;FRIEDMAN, DORON;EINI, MEIR;REEL/FRAME:017673/0847
Effective date: 20051214
30 Jul 2014ASAssignment
Owner name: FOAMIX PHARMACEUTICALS LTD., ISRAEL
Free format text: CHANGE OF NAME;ASSIGNOR:FOAMIX LTD.;REEL/FRAME:033445/0249
Effective date: 20140601