CA2481754C - Antibiotic/benzoyl peroxide dispenser - Google Patents
Antibiotic/benzoyl peroxide dispenser Download PDFInfo
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- CA2481754C CA2481754C CA2481754A CA2481754A CA2481754C CA 2481754 C CA2481754 C CA 2481754C CA 2481754 A CA2481754 A CA 2481754A CA 2481754 A CA2481754 A CA 2481754A CA 2481754 C CA2481754 C CA 2481754C
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M35/00—Devices for applying media, e.g. remedies, on the human body
- A61M35/003—Portable hand-held applicators having means for dispensing or spreading integral media
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
-
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/40—Peroxides
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/31—Hydrocarbons
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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- A61K8/35—Ketones, e.g. benzophenone
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
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- A61K8/67—Vitamins
- A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
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- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- A61K8/8147—Homopolymers or copolymers of acids; Metal or ammonium salts thereof, e.g. crotonic acid, (meth)acrylic acid; Compositions of derivatives of such polymers
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- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- A61K8/8152—Homopolymers or copolymers of esters, e.g. (meth)acrylic acid esters; Compositions of derivatives of such polymers
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- A61K8/8158—Homopolymers or copolymers of amides or imides, e.g. (meth) acrylamide; Compositions of derivatives of such polymers
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/86—Polyethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
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- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/88—Two- or multipart kits
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
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- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61Q19/04—Preparations for care of the skin for chemically tanning the skin
Abstract
Two separate compositions, one containing an effective anti-acne treating amount of a first active ingredient and one containing a second active ingredient that is incompatible with the first active ingredient are packaged within and dispensed from a common dispenser. By packaging these two active ingredients in this manner, long shelflife and convenient dispensing and application are provided.
Description
ANTIBIOTIC/BENZOYL PEROXIDE DISPENSER
BACKGROUND
Related Applications This application is a continuation-in-part of U.S. Application Serial No.
09/734,74 filed on December 12, 2000 which is hereby incorporated by reference.
Technical Field This disclosure relates to compositions and apparatus for dispensing two distinct substances. More specifically, this disclosure relates to compositions and apparatus which allow long-term storage and subsequent dispensing of two compositions, to wit, a first composition containing a first active ingredient for treating acne and a second composition containing a second active ingredient that is incompatible with the first active ingredient.
Background of Related Art Acne is a common inflammatory disease of human skin, and concentrates in skin areas where sebaceous glands are largest, most numerous, and most active. In its milder types, it is a more or less superficial disorder which is evidenced by slight, spotty irritations and ordinary skin hygiene is a satisfactory treatment. However, in the more inflammatory types of acne, bacterial invasion of or about the pilosebaceous follicles occurs and pustules, infected cysts and, in extreme cases, canalizing inflamed and infected sacs appear. These lesions may become extensive and leave permanent, disfiguring scars.
Acne is very common by puberty and at least 80% of teenagers are afflicted.
The facial eruptions are known to cause such psychic trauma in many adolescents that they find it difficult to make personal adjustments and consequently, withdraw and self pity occur.
The sufferer may be constantly aware of the obvious facial blemishes. For these reasons a medicinal preparation and treatment are of definite benefit and may eliminate the need for psychotherapy.
To reduce the severity of acne, various forms of medication have previously been topically applied to the skin. Antibacterial soaps have been used as well as bactericidal agents such as sulfur and resorcinol. Other topical compositions have separately contained benzoyl peroxide, hexachlorophene, erythromycin or neomycin sulfate. None of these prior preparations has been completely effective. .
As disclosed by I~lein et al. (U.S. Pat. No. 4,497,794), it was discovered that a mixture on the skin of a peroxide, especially benzoyl peroxide and an antibiotic or antibacterial such as clindamycin, neomycin, sodium sulfacetamide, sulfur, tetracycline or erythromycin is particularly beneficial as they can exert a statistically significant synergistic effect.
Peroxides inhibit the formation of free fatty acids in the skin, primarily through inactivation of extracellular lipase (via oxidation) necessary to cleave triglycerides into free fatty acids and glycerol. The antibiotic or antibacterial component reduces the concentration of Corynebacterium acnes (i.e., P. acnes), a normal anaerobic bacteria which is the prime source of the lipase. Instead of the benzoyl peroxide, which is preferred, peroxides such as stabilized hydrogen peroxide and peroxides of organic acids, such as a lauroyl peroxide, may be used.
As disclosed by Klein et al., erythromycin and benzoyl peroxide may be applied to the skin in combination in a preformulated aqueous-alcoholic gel. However, if a mixture is first made up and then applied to the skin, it is best that the mixture be made at the time of application or that the mixture be used within twenty four hours. The prompt use of a premix is necessary due to the chemical incompatibility of the two active agents. Because of this, it is advisable that the two agents be put in separate vials, bottles or other containers. For example, the Klein et al.
patent discloses a kit containing, separately bottled liquid compositions comprising 5% benzoyl peroxide and a solution of erythromycin in ethanol or acetone.
However, separately packaging multiple dosages of the two active ingredients presents a number of disadvantages to the end-user. For example, a unit application dosage of each active must be removed sequentially from each container and absorbed onto an applicator, such as a cotton swab, so that it can be coated onto the skin of the user. This provides opportunities for spillage or over- or under-dosing, which can lead to skin irntation and other side effects.
Furthermore, such a multidose system necessarily adds to the costs of packaging, shipping and storage.
A dispensing and applicator system intended to overcome these difficulties is disclosed in U.S. Patent No. 5,562,642. A dual-pad package is disclosed therein that purportedly can contain, preserve and deliver single unit doses of two or more chemically- or physically-incompatible active ingredients. For example, an antibiotic in combination with a liquid, semi-liquid (cream) or gelled aqueous or non-aqueous vehicle can be absorbed by and retained by the first pad and a second ingredient which is physically- or chemically-incompatible with the antibiotic, such as a peroxide, can be absorbed and retained by the second pad, preferably in combination with the appropriate vehicle.
BACKGROUND
Related Applications This application is a continuation-in-part of U.S. Application Serial No.
09/734,74 filed on December 12, 2000 which is hereby incorporated by reference.
Technical Field This disclosure relates to compositions and apparatus for dispensing two distinct substances. More specifically, this disclosure relates to compositions and apparatus which allow long-term storage and subsequent dispensing of two compositions, to wit, a first composition containing a first active ingredient for treating acne and a second composition containing a second active ingredient that is incompatible with the first active ingredient.
Background of Related Art Acne is a common inflammatory disease of human skin, and concentrates in skin areas where sebaceous glands are largest, most numerous, and most active. In its milder types, it is a more or less superficial disorder which is evidenced by slight, spotty irritations and ordinary skin hygiene is a satisfactory treatment. However, in the more inflammatory types of acne, bacterial invasion of or about the pilosebaceous follicles occurs and pustules, infected cysts and, in extreme cases, canalizing inflamed and infected sacs appear. These lesions may become extensive and leave permanent, disfiguring scars.
Acne is very common by puberty and at least 80% of teenagers are afflicted.
The facial eruptions are known to cause such psychic trauma in many adolescents that they find it difficult to make personal adjustments and consequently, withdraw and self pity occur.
The sufferer may be constantly aware of the obvious facial blemishes. For these reasons a medicinal preparation and treatment are of definite benefit and may eliminate the need for psychotherapy.
To reduce the severity of acne, various forms of medication have previously been topically applied to the skin. Antibacterial soaps have been used as well as bactericidal agents such as sulfur and resorcinol. Other topical compositions have separately contained benzoyl peroxide, hexachlorophene, erythromycin or neomycin sulfate. None of these prior preparations has been completely effective. .
As disclosed by I~lein et al. (U.S. Pat. No. 4,497,794), it was discovered that a mixture on the skin of a peroxide, especially benzoyl peroxide and an antibiotic or antibacterial such as clindamycin, neomycin, sodium sulfacetamide, sulfur, tetracycline or erythromycin is particularly beneficial as they can exert a statistically significant synergistic effect.
Peroxides inhibit the formation of free fatty acids in the skin, primarily through inactivation of extracellular lipase (via oxidation) necessary to cleave triglycerides into free fatty acids and glycerol. The antibiotic or antibacterial component reduces the concentration of Corynebacterium acnes (i.e., P. acnes), a normal anaerobic bacteria which is the prime source of the lipase. Instead of the benzoyl peroxide, which is preferred, peroxides such as stabilized hydrogen peroxide and peroxides of organic acids, such as a lauroyl peroxide, may be used.
As disclosed by Klein et al., erythromycin and benzoyl peroxide may be applied to the skin in combination in a preformulated aqueous-alcoholic gel. However, if a mixture is first made up and then applied to the skin, it is best that the mixture be made at the time of application or that the mixture be used within twenty four hours. The prompt use of a premix is necessary due to the chemical incompatibility of the two active agents. Because of this, it is advisable that the two agents be put in separate vials, bottles or other containers. For example, the Klein et al.
patent discloses a kit containing, separately bottled liquid compositions comprising 5% benzoyl peroxide and a solution of erythromycin in ethanol or acetone.
However, separately packaging multiple dosages of the two active ingredients presents a number of disadvantages to the end-user. For example, a unit application dosage of each active must be removed sequentially from each container and absorbed onto an applicator, such as a cotton swab, so that it can be coated onto the skin of the user. This provides opportunities for spillage or over- or under-dosing, which can lead to skin irntation and other side effects.
Furthermore, such a multidose system necessarily adds to the costs of packaging, shipping and storage.
A dispensing and applicator system intended to overcome these difficulties is disclosed in U.S. Patent No. 5,562,642. A dual-pad package is disclosed therein that purportedly can contain, preserve and deliver single unit doses of two or more chemically- or physically-incompatible active ingredients. For example, an antibiotic in combination with a liquid, semi-liquid (cream) or gelled aqueous or non-aqueous vehicle can be absorbed by and retained by the first pad and a second ingredient which is physically- or chemically-incompatible with the antibiotic, such as a peroxide, can be absorbed and retained by the second pad, preferably in combination with the appropriate vehicle.
It would be desirable to provide a means for simultaneously dispensing two active acne treating compounds in aesthetically acceptable vehicles which allow prolonged shelf life for both active compounds and easy mixing just prior to application to the skin.
STJMMARY
It has now been discovered that two separate compositions, one containing a first active ingredient which is effective in treating acne and one containing a second active ingredient that is incompatible with the first active ingredient can be packaged within and dispensed from a common dispenser. More particularly, a dual dispenser and has two chambers and a pump means for removing first and second compositions from the chambers through one or more outlets. The first chamber contains a first composition that includes a first active ingredient that is effective in treating acne; and the second chamber contains a second composition containing a second active ingredient that is incompatible with the first active ingredient. Preferably, both the first and second active ingredients are effective against acne. By packaging the two active ingredients in this manner, long shelflife and convenient dispensing and application are provided.
In one embodiment, the frst active ingredient is an antibiotic and the second active ingredient is benzoyl peroxide. In an alternate embodiment, the first active ingredient is an antibiotic and the second active ingredient is a retinoid . In yet another embodiment, the first active ingredient is benzoyl peroxide and the second active ingredient is a retinoid .
In one particularly useful embodiment, a dual dispenser contains i) a first composition that is substantially anhydrous and includes a polar solvent, an antibiotic and a thickening agent selected from the group consisting of acrylic acid polymers and polyacrylamides; and ii) a second composition containing benzoyl peroxide. In another particularly useful embodiment, a dual dispenser contains i) a first composition that is substantially anhydrous and includes a polar solvent, an antibiotic and a thickening agent selected from the group consisting of acrylic acid polymers and polyacrylamides; and ii) a second composition that is substantially anhydrous, and includes a polar solvent, a retinoid, and a thickening agent selected from the group consisting of acrylic acid polymers and polyacrylamides. Preferably, in each embodiment the first and second compositions have viscosities that differ by no greater than 25%.
Brief Description of the Drawi ~s Various embodiments are described herein with reference to the drawing wherein:
FIG. 1 is an schematic view of a container suitable for dispensing the first and second compositions in accordance with this disclosure, Detailed Description of Preferred Embodiments The dual dispensers described herein include a first chamber containing a first composition, a second chamber containing a second composition and pump means for simultaneously dispensing the first and second compositions. The first and second compositions I S can be any cream, lotion, gel emulsion or suspension that is of an appropriate consistency to be pumped out of the chambers by pump means. The first and second compositions can thus have a viscosity greater than about 1000 centipoise (cps) when measured using a Brookfield viscometer (model LVT) at room temperature using spindle number 3 or 4 at 0.3 to 30 rpm.
It should be understood that all viscosities referred to herein are measured in this manner. Preferably, the first and second compositions have a viscosity greater than 5,000 cps. In particularly useful embodiments, the compositions have a viscosity in the range of from about 1000 to about two million centipoise. Most preferably, the first and second compositions have a viscosity in the range of about 10,000 cps to about 1,000,000 cps. For purposes of presenting a composition with a good feel to the user, the first and second compositions advantageously have viscosities that differ by no greater than 25%.
The first composition contains a first active ingredient effective in treating acne. The first composition can be substantially anhydrous or aqueous. The first composition should be formulated to provide stability for the first active ingredient. If the first active ingredient is susceptible to deterioration from contact with water, then the first composition should be substantially anhydrous. By the term "substantially anhydrous" it is meant that, other than water of hydration contained in the various components used to formulate the composition, no free water is added to the composition. Typically, the water content of the composition will be less than 5% by weight. Preferably the water content of the composition is less than 3% and most preferably less than about 1 % by weight of the composition. However, where the first active ingredient is not sensitive to water, then aqueous formulations are acceptable for the first composition, including solutions, suspensions and water-in-oil emulsions.
One class of active ingredients known to be effective in treating acne is antibiotics.
Preferably the antibiotic is one currently known to be useful in treating acne, such as, for example, erythromycin, tetracyclin, clindamycin, their derivatives or pharmaceutically acceptable salts. The antibiotic is present in the first composition in an effective acne-treating amount, preferably an amount from about 0.001 wt. % to about 5 wt. %, more preferably about 0.1 wt.
to about 1.0 wt. %.
In a particularly useful embodiment, the first composition is substantially anhydrous and contains a polar solvent, a thickening agent and an antibiotic.
STJMMARY
It has now been discovered that two separate compositions, one containing a first active ingredient which is effective in treating acne and one containing a second active ingredient that is incompatible with the first active ingredient can be packaged within and dispensed from a common dispenser. More particularly, a dual dispenser and has two chambers and a pump means for removing first and second compositions from the chambers through one or more outlets. The first chamber contains a first composition that includes a first active ingredient that is effective in treating acne; and the second chamber contains a second composition containing a second active ingredient that is incompatible with the first active ingredient. Preferably, both the first and second active ingredients are effective against acne. By packaging the two active ingredients in this manner, long shelflife and convenient dispensing and application are provided.
In one embodiment, the frst active ingredient is an antibiotic and the second active ingredient is benzoyl peroxide. In an alternate embodiment, the first active ingredient is an antibiotic and the second active ingredient is a retinoid . In yet another embodiment, the first active ingredient is benzoyl peroxide and the second active ingredient is a retinoid .
In one particularly useful embodiment, a dual dispenser contains i) a first composition that is substantially anhydrous and includes a polar solvent, an antibiotic and a thickening agent selected from the group consisting of acrylic acid polymers and polyacrylamides; and ii) a second composition containing benzoyl peroxide. In another particularly useful embodiment, a dual dispenser contains i) a first composition that is substantially anhydrous and includes a polar solvent, an antibiotic and a thickening agent selected from the group consisting of acrylic acid polymers and polyacrylamides; and ii) a second composition that is substantially anhydrous, and includes a polar solvent, a retinoid, and a thickening agent selected from the group consisting of acrylic acid polymers and polyacrylamides. Preferably, in each embodiment the first and second compositions have viscosities that differ by no greater than 25%.
Brief Description of the Drawi ~s Various embodiments are described herein with reference to the drawing wherein:
FIG. 1 is an schematic view of a container suitable for dispensing the first and second compositions in accordance with this disclosure, Detailed Description of Preferred Embodiments The dual dispensers described herein include a first chamber containing a first composition, a second chamber containing a second composition and pump means for simultaneously dispensing the first and second compositions. The first and second compositions I S can be any cream, lotion, gel emulsion or suspension that is of an appropriate consistency to be pumped out of the chambers by pump means. The first and second compositions can thus have a viscosity greater than about 1000 centipoise (cps) when measured using a Brookfield viscometer (model LVT) at room temperature using spindle number 3 or 4 at 0.3 to 30 rpm.
It should be understood that all viscosities referred to herein are measured in this manner. Preferably, the first and second compositions have a viscosity greater than 5,000 cps. In particularly useful embodiments, the compositions have a viscosity in the range of from about 1000 to about two million centipoise. Most preferably, the first and second compositions have a viscosity in the range of about 10,000 cps to about 1,000,000 cps. For purposes of presenting a composition with a good feel to the user, the first and second compositions advantageously have viscosities that differ by no greater than 25%.
The first composition contains a first active ingredient effective in treating acne. The first composition can be substantially anhydrous or aqueous. The first composition should be formulated to provide stability for the first active ingredient. If the first active ingredient is susceptible to deterioration from contact with water, then the first composition should be substantially anhydrous. By the term "substantially anhydrous" it is meant that, other than water of hydration contained in the various components used to formulate the composition, no free water is added to the composition. Typically, the water content of the composition will be less than 5% by weight. Preferably the water content of the composition is less than 3% and most preferably less than about 1 % by weight of the composition. However, where the first active ingredient is not sensitive to water, then aqueous formulations are acceptable for the first composition, including solutions, suspensions and water-in-oil emulsions.
One class of active ingredients known to be effective in treating acne is antibiotics.
Preferably the antibiotic is one currently known to be useful in treating acne, such as, for example, erythromycin, tetracyclin, clindamycin, their derivatives or pharmaceutically acceptable salts. The antibiotic is present in the first composition in an effective acne-treating amount, preferably an amount from about 0.001 wt. % to about 5 wt. %, more preferably about 0.1 wt.
to about 1.0 wt. %.
In a particularly useful embodiment, the first composition is substantially anhydrous and contains a polar solvent, a thickening agent and an antibiotic.
Polar solvents useful in this embodiment of the first composition include polyols. A
polyol is a compound with at Least two hydroxyl groups per molecule, i.e., a compound having multiple hydroxyl groups as part of its molecular structure. Among the useful polyols are polyhydric alcohols. Propylene glycol, dipropylene glycol, polyethylene glycol and glycerine are particularly preferred polar solvents for use in the first composition.
The thickening agent used in this embodiment of the first composition is selected from the group consisting of acrylic acid polymers and polyacrylamides. The thickening agent are used in an amount sufficient to obtain a composition of viscosity in the desired range.
Useful acrylic acid polymers include copolymers of (meth)acrylic acid and of monomers containing at least one fatty chain; these monomers are chosen from hydrophobic monomers with a fatty chain, amphiphilic monomers containing a hydrophobic part with a fatty chain and a hydrophilic part, or alternatively their mixtures. Suitable materials include, for example, copolymers of Clo-3o alkyl acrylates with one or more monomers of acrylic acid, methacrylic acid, or one of their short chain (i.e., Cl~ alcohol) esters, wherein the crosslinking agent is an allyl ether of sucrose or pentaerythritol. These copolymers are commoniy.referred to as acrylates/Clo-3o alkyl acrylate crosspolymers and are commercially available under the tradename CARBOPOL~ from B.F. Goodrich, Cleveland, Ohio U.S.A. Other polymers useful in the preparation of the present compositions are polymers of polyacrylic acid crosslinked with from about 0.75% to about 2.0% of polyalkyl sucrose or polyalkyl pentaerythritol often with molecular weights of 4 to S million or more that are commercially available, for example, under the trade designation CARBOPOL~ 934, 940 and 941 from B.F. Goodrich, Cleveland, Ohio U.S.A.
Anionic amphiphilic polymers which comprise 95% to 60% by weight of acrylic recurring structural units, 4% to 40% by weight of acrylate recurring structural units and 0.1 % to 6% by weight of crosslinking monomer, or (ii) which comprise 98% to 96% by weight of acrylic recurnng structural units, 1% to 4% by weight of acrylate recurring structural units and 0.1% to 0.6% by weight of crosslinking monomer are also useful as the thickening agent in the present compositions. Such polymers include, for example, those hydrophobically-modified cross-linked polymers of acrylic acid having amphipathic properties marketed by B.F.
Goodrich under the trademarks CARBOPOL~ 1342 and CARBOPOL~ 1382. Also useful is ULTREZ~ 10 (available from B. F. Goodrich), an oil in water emulsion of a modified acrylic copolymer comprising of a major portion of a monoolefinically unsaturated carboxylic acid monomer or its anhydride having a length of from about 3 to 6 carbon atoms and a minor portion of a C$_3o chain acrylate or methacrylate ester monomer wherein the carboxylic acid or its anhydride is from about 80 to about 99% by weight and the C$_3o chain acrylate or methacrylate ester monomer is from about 1% to about 20% by weight. The polymer is described in U.S. Pat.
No. 5,004,598, hereby incorporated by reference in its entirety.
When used, these acrylic acid polymers are present in the first composition at a level from about 0.05% to about 20%, preferably from about 0.5% to 10% and most preferably from about I% to about I0%.
Where the first composition is an anhydrous antibiotic composition, the first composition can alternatively contain polyacrylamide polymers as the thickening agent, especially nonionic ,polyacrylamide polymers. Useful non-ionic polymers are branched or unbranched polyacrylamides and substituted polyacrylamides. These polymers are non-ionic polymers which can be formed from a variety of monomers including acrylamide and methacrylamide which are unsubstituted or substituted with one or two alkyl groups (preferably Cl.s).
Preferred acrylate amides and methacrylate amides in which the amide nitrogen is unsubstituted, or substituted with one or two Ct_5 alkyl groups (preferably: methyl, ethyl or propyl), for example, acrylamide, methacrylamide, N-methylacrylamide, N-methylmethacrylamide, N,N-dimethylmethacrylamide, N-isopropylacrylamide, N-isopropylmethacrylamide and N,N-dirnethylacrylamide.
These monomers are generally disclosed in U.S. Pat. No. 4,963,348 which is incorporated by reference herein in its entirety. These copolymers may optionally be formed using conventional neutral crosslinking agents such as dialkenyl compounds. The use of such crosslinking agents for cationic polymers is disclosed in U.S. Pat. Nos. 4,628,078 and 4,599,379 both of which are I 0 incorporated by reference herein. These non-ionic copolymers may have a molecular weight greater than about 1,000,000 preferably greater than about 1,500,000 and range up to about 30,000,000. Most preferred among these polyacrylamide polymers is the nonionic polymer given the CTFA designation polyacrylamide and isoparaffin and laureth-7, available under the tradename SEPIGEL~ 305 from Seppic Corporation (Fairfield, N.J.). Other polyacrylamide 15 polymers useful herein include mufti-block copolymers of acrylamides and substituted acrylamides with acrylic acids and substituted acrylic acids. Commercially available examples of these mufti-block copolymers include Hypan SR150H, SSSOOV, SSSOOW, SSSAIOOH, from Lipo Chemicals; Inc., (Patterson, N.J.).
When used, these non-ionic polyacrylamides are present in the first composition at a level 20 from about 0.05% to about 20%, preferably from about 0.5% to 10% and most preferably from about I % to about 10%.
Quite surprisingly, it has been found that contrary to product literature relating to the commercially available acrylic acid polymers and polyacrylamides, when used to formulate the first composition as a substantially anhydrous composition, the thickening agents need not be dispersed in an aqueous medium or neutralized to provide the desired thickening.
Benzoyl peroxide is another active ingredient known to be an effective anti-acne treatment that can be incorporated into the first composition. Where benzoyl peroxide is the first active ingredient, the first composition can be either substantially anhydrous or may contain water and can be any benzoyl peroxide-containing cream, lotion, gel or suspension. Examples of benzoyl peroxide compositions that are suitable for use in.accordance with this disclosure include, but are not limited to the compositions disclosed in U.S. Patent No.
5,632,996, the disclosure of which is incorporated herein by reference. In particularly useful embodiments, the benzoyl peroxide composition is also substantially anhydrous. Among these embodiments are compositions containing a) a polar solvent, b) a thickening agent selected from the group consisting of acrylic acid polymers, polyacrylamides and combinations thereof (as described above), c) benzoyl peroxide, d) alkyl benzoate and, optionally e) a synthetic cleanser. Suitable synthetic cleansers include, but are not limited to sodium cocoyl isethionate, alpha olefin sulfonate sarcosynates and acyl glutamates.
The amount of benzoyl peroxide in the composition can be from about 0.1 to about 20 percent by weight based on the total weight of the composition, preferably from about 1.0 to about 15 weight percent, most preferably from about 1.5 to about 10 weight percent. In this embodiment, the benzoyl peroxide-containing composition can have a viscosity greater than about 1000 centipoise (cps) when measured using a Brookfield viscometer (model LVT) at room temperature using spindle number 3 or 4 at 0.3 to 30 rpm. Preferably, the benzoyl peroxide-containing composition has a viscosity greater than 5,000 cps. In particularly useful embodiments, the benzoyl peroxide-containing composition has a viscosity in the range of from about 1000 to about two million centipoise. Most preferably, the benzoyl peroxide-containing composition has a viscosity in the range of about 10,000 cps to about 1,000,000 cps.
In an alternative embodiment, the first composition contains a retinoid.
Suitable retinoids, include, for example, retinol, retinoic acid, retinyl paliuitate, retinyl propionate or retinyl acetate as well as synthetic retinoid mimics. The retinoid is preferably present in the second composition in an amount from about 0.001 wt. % to about S wt. %, more preferably about 0.1 wt. % to about 2.0 wt. %.
In a particularly useful embodiments, the retinoid-containing compositions are also substantially anhydrous and contains a polar solvent, a thickening agent and a retinoid. Suitable polar solvents and thickening agents for the second composition are the same as described above for the antibiotic and benzoyl peroxide compositions described above. In this alternative embodiment, the retinoid-containing composition can have a viscosity greater than about 1000 centipoise (cps) when measured using a Brookfield viscometer (model LVT) at room temperature using spindle number 3 or 4 at 0.3 to 30 rpm. Preferably, the retinoid-containing composition has a viscosity greater than 5,000 cps. In particularly useful embodiments, the second, retinoid-containing composition has a viscosity in the range of from about 1000 to about two million centipoise. Most preferably, the second, retinoid-containing composition has a viscosity in the range of about 10,000 cps to about 1,000,000 cps.
The second composition contains a second active ingredient that is incompatible with the first active ingredient. The second active ingredient may be effective in treating acne or may provide some other beneficial effect upon topical administration to a user's skin (such as, for example, alpha-hydroxy acids or anti-irritants The second composition can be substantially anhydrous or aqueous. The second composition is formulated to provide stability for the second active ingredient. If the second active ingredient is susceptible to deterioration from contact with water, then the second composition should be substantially anhydrous. However, where the second active ingredient is not sensitive to water, then aqueous formulations are acceptable for the second composition, including solutions, suspensions and water-in-oil emulsions.
Combinations of first and second active ingredients for use in the first and second compositions include but are mot limited to: a) anibiotic in the first composition and benzoyl peroxide in the second composition; b) antibiotic in the first composition and a retinoid in the second composition; and c) benzoyl peroxide in the first composition and a retinoid in the second composition.
The first and second compositions preferably have viscosities that are similar to provide a cosmetically elegant product when the first and second compositions are simultaneously dispensed. In particularly useful embodiments the difference in viscosity between the first and second compositions is no more than about 25%.
In addition to the above-listed ingredients, one or both of the first and second compositions may also contain a variety of non-essential ingredients such as, for example, co-solvents, preservatives, emollients, humectants, anti-inflammatory agents, antioxidants, insect repellents or skin cooling compounds, etc. For example, either of the first or second composition may contain one or more co-solvents, such as ethanol, acetone or propylene carbonate.
A preservative can also be used in either or both of the first or second compositions.
Preservatives suitable for use in connection with the present compositions include parabens, sorbates, benzyl alcohol, diazolidinyl urea and isothiazolinones.
Preservatives can be present in an amount from about 0,001 wt. % to about 15 wt. % of the total composition.
One or both of the first or second compositions can also be formulated to contain about 0.01 wt. % to about 30 wt. %, preferably about 1.0 wt. % to about 15 wt. % of the total composition, skin cooling compounds, such as menthol, methyl glycerol, asymmetrical carbonates, thiocarbonates and urethanes, substituted carboxamides, areas or phosphine oxides as described in J. Cosmet. Chem., vol. 29, page 185 (1978) and incorporated herein by reference, methyl lactate and menthone glycerin acetal.
The first substantially and second compositions are stored in and dispensed from a multi-chamber dispenser. Dispensing systems that include pump means suited for simultaneously dosing two separately contained incompatible compounds 'are well known. As such, the.
dispensing system schematically depicted in FIG. 1 (dispenser from Maplast, Tradate, Italy) is just one example out of a number of products which range from small, two-chambered single use pouches to tubes using different product compartments or tubes compartmentalized using extrudable, viscous and relatively inert materials to separate the incompatible compounds.
The dispenser shown in FIG. 1 is able to simultaneously dose two compounds separately contained in A and B by pressing dosing head C. Pressing dosing head C
activates two small pumps which subsequently dispense the two compounds in approximately equal volumes.
Depending on the design of the dosing head, the compounds can be dosed in two separate streams or in just one stream. If desired, a dispensing unit that is able to deliver The first and second substantially anhydrous compositions in a ratio, such as, for example, 1:2 can be used.
Translated to the dispenser depicted in FIG. 1, this would mean that one of the two pumps is able to dose at least twice the volume of the other pump in just one stroke of dosing head C.
Translated to a two-chambered single use pouch, this would mean that the chamber containing the first substantially anhydrous composition contains at least half as much product volume as the other chamber. Translated to a two-compartment tube, this would mean that under equal pressure the discharge orifice for the compartment containing the first substantially anhydrous composition allows the passage of at least twice as much product as the discharge orifice of the ~ other compartment. Translated to a tube which is compartmentalized using extrudable material, this would mean that first substantially anhydrous composition is present inside the tube in at least double the volume of the second substantially anhydrous composition.
Other suitable dispensers are disclosed in U. S. Patent Nos. 5,356,040;
5,823,391, and 4,826,048 the disclosures of which are incorporated herein by this reference.
The following examples are presented to illustrate specific embodiments of the present compositions and methods. These examples should not be interpreted as limitations upon the scope of the invention.
EXAMPLES I - IV
The following formulations are exemplary of substantially anhydrous antibiotic compositions suitable for use as the first composition:
I _II III
erythromycin 2 2 propylene glycol 96 71.5 96.0 ULTREZ 10 2 1.5 2.0 polyethylene glycol- 25.0 -clindamycin - - 1.0 I_V
erythromycin 2.0 propylene glycol 96.0 LTLTREZ 10 1.0 SEPIGEL 305 1.0 ELES V - VI
The following exemplary benzoyl peroxide-containing formulations are suitable for use as the second composition to be dispensed simultaneously with any of the anhydrous formulations of Examples I-IV:
V_ Petrotalium 15.50 Sodium Cocoyl Isethionate 5.00 Alfa olefin Sulfonate . 2.00 Titaniam Dioxide 0.30 Lucidol 75% (Benzoyl Peroxide)15.80 Cra-is Alkyl Benzoate 7.00 Triethanolamine 0.60 Carbopol 1382 0.80 Glycerin S 8.0 VI - Gel Composition Water 56.4 Glycerine 5.0 SEPIGEL 305 2.0 Sodium Hydroxide 1.60 Steareth S-20 2.0 Steareth S-2 2.0 Cetyl Stearyl Alcohol 3.0 Silicone Cupoydoyl 5.0 Lucidol 75% (Benzoyl Peroxide)16.0 C1z_15 Benzoate Ester 7.00 VII - Benzovl Peroxide Gel propylene glycol 88.5 ULTREZ 10 1.5 Benzoyl Peroxide S.0 Fin Solv TN S.0 VIII - Benzovl Peroxide Gel Cleanser glycerin 66.0 ULTR.EZ 10 2.0 Benzoyl Peroxide 5.0 Fin Solv TN 5.0 Sodium Cocoyl Isethionate 20.0 It will be understood that various modifications may be made to the embodiments disclosed herein. Therefore, the above description should not be construed as limiting, but merely as exemplifications of preferred embodiments. Those skilled in art will envision other modifications within the scope and spirit of the claims appended hereto.
polyol is a compound with at Least two hydroxyl groups per molecule, i.e., a compound having multiple hydroxyl groups as part of its molecular structure. Among the useful polyols are polyhydric alcohols. Propylene glycol, dipropylene glycol, polyethylene glycol and glycerine are particularly preferred polar solvents for use in the first composition.
The thickening agent used in this embodiment of the first composition is selected from the group consisting of acrylic acid polymers and polyacrylamides. The thickening agent are used in an amount sufficient to obtain a composition of viscosity in the desired range.
Useful acrylic acid polymers include copolymers of (meth)acrylic acid and of monomers containing at least one fatty chain; these monomers are chosen from hydrophobic monomers with a fatty chain, amphiphilic monomers containing a hydrophobic part with a fatty chain and a hydrophilic part, or alternatively their mixtures. Suitable materials include, for example, copolymers of Clo-3o alkyl acrylates with one or more monomers of acrylic acid, methacrylic acid, or one of their short chain (i.e., Cl~ alcohol) esters, wherein the crosslinking agent is an allyl ether of sucrose or pentaerythritol. These copolymers are commoniy.referred to as acrylates/Clo-3o alkyl acrylate crosspolymers and are commercially available under the tradename CARBOPOL~ from B.F. Goodrich, Cleveland, Ohio U.S.A. Other polymers useful in the preparation of the present compositions are polymers of polyacrylic acid crosslinked with from about 0.75% to about 2.0% of polyalkyl sucrose or polyalkyl pentaerythritol often with molecular weights of 4 to S million or more that are commercially available, for example, under the trade designation CARBOPOL~ 934, 940 and 941 from B.F. Goodrich, Cleveland, Ohio U.S.A.
Anionic amphiphilic polymers which comprise 95% to 60% by weight of acrylic recurring structural units, 4% to 40% by weight of acrylate recurring structural units and 0.1 % to 6% by weight of crosslinking monomer, or (ii) which comprise 98% to 96% by weight of acrylic recurnng structural units, 1% to 4% by weight of acrylate recurring structural units and 0.1% to 0.6% by weight of crosslinking monomer are also useful as the thickening agent in the present compositions. Such polymers include, for example, those hydrophobically-modified cross-linked polymers of acrylic acid having amphipathic properties marketed by B.F.
Goodrich under the trademarks CARBOPOL~ 1342 and CARBOPOL~ 1382. Also useful is ULTREZ~ 10 (available from B. F. Goodrich), an oil in water emulsion of a modified acrylic copolymer comprising of a major portion of a monoolefinically unsaturated carboxylic acid monomer or its anhydride having a length of from about 3 to 6 carbon atoms and a minor portion of a C$_3o chain acrylate or methacrylate ester monomer wherein the carboxylic acid or its anhydride is from about 80 to about 99% by weight and the C$_3o chain acrylate or methacrylate ester monomer is from about 1% to about 20% by weight. The polymer is described in U.S. Pat.
No. 5,004,598, hereby incorporated by reference in its entirety.
When used, these acrylic acid polymers are present in the first composition at a level from about 0.05% to about 20%, preferably from about 0.5% to 10% and most preferably from about I% to about I0%.
Where the first composition is an anhydrous antibiotic composition, the first composition can alternatively contain polyacrylamide polymers as the thickening agent, especially nonionic ,polyacrylamide polymers. Useful non-ionic polymers are branched or unbranched polyacrylamides and substituted polyacrylamides. These polymers are non-ionic polymers which can be formed from a variety of monomers including acrylamide and methacrylamide which are unsubstituted or substituted with one or two alkyl groups (preferably Cl.s).
Preferred acrylate amides and methacrylate amides in which the amide nitrogen is unsubstituted, or substituted with one or two Ct_5 alkyl groups (preferably: methyl, ethyl or propyl), for example, acrylamide, methacrylamide, N-methylacrylamide, N-methylmethacrylamide, N,N-dimethylmethacrylamide, N-isopropylacrylamide, N-isopropylmethacrylamide and N,N-dirnethylacrylamide.
These monomers are generally disclosed in U.S. Pat. No. 4,963,348 which is incorporated by reference herein in its entirety. These copolymers may optionally be formed using conventional neutral crosslinking agents such as dialkenyl compounds. The use of such crosslinking agents for cationic polymers is disclosed in U.S. Pat. Nos. 4,628,078 and 4,599,379 both of which are I 0 incorporated by reference herein. These non-ionic copolymers may have a molecular weight greater than about 1,000,000 preferably greater than about 1,500,000 and range up to about 30,000,000. Most preferred among these polyacrylamide polymers is the nonionic polymer given the CTFA designation polyacrylamide and isoparaffin and laureth-7, available under the tradename SEPIGEL~ 305 from Seppic Corporation (Fairfield, N.J.). Other polyacrylamide 15 polymers useful herein include mufti-block copolymers of acrylamides and substituted acrylamides with acrylic acids and substituted acrylic acids. Commercially available examples of these mufti-block copolymers include Hypan SR150H, SSSOOV, SSSOOW, SSSAIOOH, from Lipo Chemicals; Inc., (Patterson, N.J.).
When used, these non-ionic polyacrylamides are present in the first composition at a level 20 from about 0.05% to about 20%, preferably from about 0.5% to 10% and most preferably from about I % to about 10%.
Quite surprisingly, it has been found that contrary to product literature relating to the commercially available acrylic acid polymers and polyacrylamides, when used to formulate the first composition as a substantially anhydrous composition, the thickening agents need not be dispersed in an aqueous medium or neutralized to provide the desired thickening.
Benzoyl peroxide is another active ingredient known to be an effective anti-acne treatment that can be incorporated into the first composition. Where benzoyl peroxide is the first active ingredient, the first composition can be either substantially anhydrous or may contain water and can be any benzoyl peroxide-containing cream, lotion, gel or suspension. Examples of benzoyl peroxide compositions that are suitable for use in.accordance with this disclosure include, but are not limited to the compositions disclosed in U.S. Patent No.
5,632,996, the disclosure of which is incorporated herein by reference. In particularly useful embodiments, the benzoyl peroxide composition is also substantially anhydrous. Among these embodiments are compositions containing a) a polar solvent, b) a thickening agent selected from the group consisting of acrylic acid polymers, polyacrylamides and combinations thereof (as described above), c) benzoyl peroxide, d) alkyl benzoate and, optionally e) a synthetic cleanser. Suitable synthetic cleansers include, but are not limited to sodium cocoyl isethionate, alpha olefin sulfonate sarcosynates and acyl glutamates.
The amount of benzoyl peroxide in the composition can be from about 0.1 to about 20 percent by weight based on the total weight of the composition, preferably from about 1.0 to about 15 weight percent, most preferably from about 1.5 to about 10 weight percent. In this embodiment, the benzoyl peroxide-containing composition can have a viscosity greater than about 1000 centipoise (cps) when measured using a Brookfield viscometer (model LVT) at room temperature using spindle number 3 or 4 at 0.3 to 30 rpm. Preferably, the benzoyl peroxide-containing composition has a viscosity greater than 5,000 cps. In particularly useful embodiments, the benzoyl peroxide-containing composition has a viscosity in the range of from about 1000 to about two million centipoise. Most preferably, the benzoyl peroxide-containing composition has a viscosity in the range of about 10,000 cps to about 1,000,000 cps.
In an alternative embodiment, the first composition contains a retinoid.
Suitable retinoids, include, for example, retinol, retinoic acid, retinyl paliuitate, retinyl propionate or retinyl acetate as well as synthetic retinoid mimics. The retinoid is preferably present in the second composition in an amount from about 0.001 wt. % to about S wt. %, more preferably about 0.1 wt. % to about 2.0 wt. %.
In a particularly useful embodiments, the retinoid-containing compositions are also substantially anhydrous and contains a polar solvent, a thickening agent and a retinoid. Suitable polar solvents and thickening agents for the second composition are the same as described above for the antibiotic and benzoyl peroxide compositions described above. In this alternative embodiment, the retinoid-containing composition can have a viscosity greater than about 1000 centipoise (cps) when measured using a Brookfield viscometer (model LVT) at room temperature using spindle number 3 or 4 at 0.3 to 30 rpm. Preferably, the retinoid-containing composition has a viscosity greater than 5,000 cps. In particularly useful embodiments, the second, retinoid-containing composition has a viscosity in the range of from about 1000 to about two million centipoise. Most preferably, the second, retinoid-containing composition has a viscosity in the range of about 10,000 cps to about 1,000,000 cps.
The second composition contains a second active ingredient that is incompatible with the first active ingredient. The second active ingredient may be effective in treating acne or may provide some other beneficial effect upon topical administration to a user's skin (such as, for example, alpha-hydroxy acids or anti-irritants The second composition can be substantially anhydrous or aqueous. The second composition is formulated to provide stability for the second active ingredient. If the second active ingredient is susceptible to deterioration from contact with water, then the second composition should be substantially anhydrous. However, where the second active ingredient is not sensitive to water, then aqueous formulations are acceptable for the second composition, including solutions, suspensions and water-in-oil emulsions.
Combinations of first and second active ingredients for use in the first and second compositions include but are mot limited to: a) anibiotic in the first composition and benzoyl peroxide in the second composition; b) antibiotic in the first composition and a retinoid in the second composition; and c) benzoyl peroxide in the first composition and a retinoid in the second composition.
The first and second compositions preferably have viscosities that are similar to provide a cosmetically elegant product when the first and second compositions are simultaneously dispensed. In particularly useful embodiments the difference in viscosity between the first and second compositions is no more than about 25%.
In addition to the above-listed ingredients, one or both of the first and second compositions may also contain a variety of non-essential ingredients such as, for example, co-solvents, preservatives, emollients, humectants, anti-inflammatory agents, antioxidants, insect repellents or skin cooling compounds, etc. For example, either of the first or second composition may contain one or more co-solvents, such as ethanol, acetone or propylene carbonate.
A preservative can also be used in either or both of the first or second compositions.
Preservatives suitable for use in connection with the present compositions include parabens, sorbates, benzyl alcohol, diazolidinyl urea and isothiazolinones.
Preservatives can be present in an amount from about 0,001 wt. % to about 15 wt. % of the total composition.
One or both of the first or second compositions can also be formulated to contain about 0.01 wt. % to about 30 wt. %, preferably about 1.0 wt. % to about 15 wt. % of the total composition, skin cooling compounds, such as menthol, methyl glycerol, asymmetrical carbonates, thiocarbonates and urethanes, substituted carboxamides, areas or phosphine oxides as described in J. Cosmet. Chem., vol. 29, page 185 (1978) and incorporated herein by reference, methyl lactate and menthone glycerin acetal.
The first substantially and second compositions are stored in and dispensed from a multi-chamber dispenser. Dispensing systems that include pump means suited for simultaneously dosing two separately contained incompatible compounds 'are well known. As such, the.
dispensing system schematically depicted in FIG. 1 (dispenser from Maplast, Tradate, Italy) is just one example out of a number of products which range from small, two-chambered single use pouches to tubes using different product compartments or tubes compartmentalized using extrudable, viscous and relatively inert materials to separate the incompatible compounds.
The dispenser shown in FIG. 1 is able to simultaneously dose two compounds separately contained in A and B by pressing dosing head C. Pressing dosing head C
activates two small pumps which subsequently dispense the two compounds in approximately equal volumes.
Depending on the design of the dosing head, the compounds can be dosed in two separate streams or in just one stream. If desired, a dispensing unit that is able to deliver The first and second substantially anhydrous compositions in a ratio, such as, for example, 1:2 can be used.
Translated to the dispenser depicted in FIG. 1, this would mean that one of the two pumps is able to dose at least twice the volume of the other pump in just one stroke of dosing head C.
Translated to a two-chambered single use pouch, this would mean that the chamber containing the first substantially anhydrous composition contains at least half as much product volume as the other chamber. Translated to a two-compartment tube, this would mean that under equal pressure the discharge orifice for the compartment containing the first substantially anhydrous composition allows the passage of at least twice as much product as the discharge orifice of the ~ other compartment. Translated to a tube which is compartmentalized using extrudable material, this would mean that first substantially anhydrous composition is present inside the tube in at least double the volume of the second substantially anhydrous composition.
Other suitable dispensers are disclosed in U. S. Patent Nos. 5,356,040;
5,823,391, and 4,826,048 the disclosures of which are incorporated herein by this reference.
The following examples are presented to illustrate specific embodiments of the present compositions and methods. These examples should not be interpreted as limitations upon the scope of the invention.
EXAMPLES I - IV
The following formulations are exemplary of substantially anhydrous antibiotic compositions suitable for use as the first composition:
I _II III
erythromycin 2 2 propylene glycol 96 71.5 96.0 ULTREZ 10 2 1.5 2.0 polyethylene glycol- 25.0 -clindamycin - - 1.0 I_V
erythromycin 2.0 propylene glycol 96.0 LTLTREZ 10 1.0 SEPIGEL 305 1.0 ELES V - VI
The following exemplary benzoyl peroxide-containing formulations are suitable for use as the second composition to be dispensed simultaneously with any of the anhydrous formulations of Examples I-IV:
V_ Petrotalium 15.50 Sodium Cocoyl Isethionate 5.00 Alfa olefin Sulfonate . 2.00 Titaniam Dioxide 0.30 Lucidol 75% (Benzoyl Peroxide)15.80 Cra-is Alkyl Benzoate 7.00 Triethanolamine 0.60 Carbopol 1382 0.80 Glycerin S 8.0 VI - Gel Composition Water 56.4 Glycerine 5.0 SEPIGEL 305 2.0 Sodium Hydroxide 1.60 Steareth S-20 2.0 Steareth S-2 2.0 Cetyl Stearyl Alcohol 3.0 Silicone Cupoydoyl 5.0 Lucidol 75% (Benzoyl Peroxide)16.0 C1z_15 Benzoate Ester 7.00 VII - Benzovl Peroxide Gel propylene glycol 88.5 ULTREZ 10 1.5 Benzoyl Peroxide S.0 Fin Solv TN S.0 VIII - Benzovl Peroxide Gel Cleanser glycerin 66.0 ULTR.EZ 10 2.0 Benzoyl Peroxide 5.0 Fin Solv TN 5.0 Sodium Cocoyl Isethionate 20.0 It will be understood that various modifications may be made to the embodiments disclosed herein. Therefore, the above description should not be construed as limiting, but merely as exemplifications of preferred embodiments. Those skilled in art will envision other modifications within the scope and spirit of the claims appended hereto.
Claims (48)
1. An apparatus comprising:
a first chamber containing a first composition, the first composition comprising a first active ingredient effective in treating acne;
a second chamber containing a second composition comprising a second active ingredient that is incompatible with the first active ingredient;
pump means for moving the first and second compositions out of the first and second chambers, respectively; and one or more outlets for dispensing the first and second compositions.
a first chamber containing a first composition, the first composition comprising a first active ingredient effective in treating acne;
a second chamber containing a second composition comprising a second active ingredient that is incompatible with the first active ingredient;
pump means for moving the first and second compositions out of the first and second chambers, respectively; and one or more outlets for dispensing the first and second compositions.
2. An apparatus as in claim 1 wherein the first composition comprises an active ingredient selected from the group consisting of antibiotics, retinoids and benzoyl peroxide.
3. An apparatus as in claim 1 wherein the first active ingredient is an antibiotic.
4. An apparatus as in claim 3 wherein the antibiotic is selected from the group consisting of erythromycin, clindamycin, tetracycline, derivatives of erythromycin, clindamycin or tetracycline and pharmaceutically acceptable salts of erythromycin, clindamycin or tetracycline.
5. An apparatus as in claim 3 wherein the second active ingredient is benzoyl peroxide.
6. An apparatus as in claim 5 wherein benzoyl peroxide comprises from about 0.1 to about 25 weight percent of the second composition.
7. An apparatus as in claim 3 wherein the second composition comprises a retinoid.
8. An apparatus as in claim 7 wherein the retinoid is selected from the group consisting of retinol, retinoic acid, retinyl palmitate, retinyl propionate, retinyl acetate and synthetic retinoid mimetics.
9. An apparatus as in claim 1 wherein the first active ingredient is benzoyl peroxide.
10. An apparatus as in claim 9 wherein benzoyl peroxide comprises from about 0.1 to about 25 weight percent of the second composition.
11. An apparatus as in claim 9 wherein the second composition comprises a retinoid.
12. An apparatus as in claim 11 wherein the retinoid is selected from the group consisting of retinol, retinoic acid, retinyl palmitate, retinyl propionate, retinyl acetate and synthetic retinoid mimetics.
13. An apparatus as in claim 1 wherein the first composition is substantially anhydrous.
14. An apparatus as in claim 13 wherein the first composition comprises i) a polar solvent;
ii) an antibiotic; and iii) a thickening agent in an amount sufficient to impart to the first composition a viscosity of at least 1000 cenetipoise measured at room temperature, the thickening agent being selected from the group consisting of acrylic acid polymers, polyacrylamides and combinations thereof.
ii) an antibiotic; and iii) a thickening agent in an amount sufficient to impart to the first composition a viscosity of at least 1000 cenetipoise measured at room temperature, the thickening agent being selected from the group consisting of acrylic acid polymers, polyacrylamides and combinations thereof.
15. An apparatus as in claim 14 wherein the first composition contains a thickening agent selected from the group consisting of copolymers of C10-30 alkyl acrylates with one or more monomers of acrylic acid, methacrylic acid, or one of their short chain (i.e., C1-4 alcohol) esters, crosslinked with an allyl ether of sucrose or pentaerythritol, polymers of polyacrylic acid crosslinked with from about 0.75% to about 2.0% of polyalkyl sucrose or polyalkyl pentaerythritol, anionic amphiphilic polymers which comprise 95% to 60% by weight of acrylic recurring structural units, 4% to 40% by weight of acrylate recurring structural units and 0.1% to 6% by weight of a crosslinking monomer, polymers which comprise 98% to 96% by weight of acrylic recurring structural units, 1% to 4% by weight of acrylate recurring structural units and 0.1% to 0.6% by weight of a crosslinking monomer, and copolymers of (meth)acrylic acid and of monomers containing at least one fatty chain, the monomers being selected from the group consisting of hydrophobic monomers with a fatty chain, amphiphilic monomers containing a hydrophobic part with a fatty chain and a hydrophilic part and mixtures thereof.
16. An apparatus as in claim 14 wherein the first composition contains a thickening agent selected from the group consisting of polyacrylamides and substituted polyacrylamides, branched or unbranched.
17. An apparatus as in claim 14 wherein the first composition contains as the thickening agent a mixture of polyacrylamide, C13-C14 isoparaffin and Laureth 7.
18. An apparatus as in claim 14 wherein the first composition contains a polar solvent selected from the group consisting of polyols and polyhydric alcohols.
19. An apparatus as in claim 1 wherein the second composition is substantially anhydrous.
20. An apparatus as in claim 1 wherein the second composition comprises (i) a polar solvent;
(ii) a thickening agent selected from the group consisting of acrylic acid polymers, polyacrylamides and combinations thereof;
(iii) benzoyl peroxide;
(iv) alkyl benzoate; and optionally (v) a synthetic cleanser.
(ii) a thickening agent selected from the group consisting of acrylic acid polymers, polyacrylamides and combinations thereof;
(iii) benzoyl peroxide;
(iv) alkyl benzoate; and optionally (v) a synthetic cleanser.
21. An apparatus comprising:
a first chamber containing a first composition, the first composition comprising an effective acne-treating amount of an antibiotic;
a second chamber containing a second composition comprising an active ingredient that is incompatible with the antibiotic;
pump means for moving the first and second compositions out of the first and second chambers; and one or more outlets for dispensing the first and second compositions.
a first chamber containing a first composition, the first composition comprising an effective acne-treating amount of an antibiotic;
a second chamber containing a second composition comprising an active ingredient that is incompatible with the antibiotic;
pump means for moving the first and second compositions out of the first and second chambers; and one or more outlets for dispensing the first and second compositions.
22. An apparatus as in claim 21 wherein the second composition comprises benzoyl peroxide.
23. An apparatus as in claim 21 wherein the second composition comprises a retinoid.
24. An apparatus as in claim 23 wherein the retinoid is selected from the group consisting of retinol, retinoic acid, retinyl palmitate, retinyl propionate, retinyl acetate and synthetic retinoid mimetics.
25. An apparatus as in claim 21 wherein the antibiotic is selected from the group consisting of erythromycin, clindamycin, tetracycline, derivatives of erythromycin, clindamycin or tetracycline and pharmaceutically acceptable salts of erythromycin, clindamycin or tetracycline.
26. ~An apparatus comprising:
a first chamber containing a first composition, the first composition comprising an effective acne-treating amount of benzoyl peroxide;
a second chamber containing a second composition comprising an active ingredient that is incompatible with benzoyl peroxide;
pump means for moving the first and second compositions out of the first and second chambers; and one or more outlets for dispensing the first and second compositions.
a first chamber containing a first composition, the first composition comprising an effective acne-treating amount of benzoyl peroxide;
a second chamber containing a second composition comprising an active ingredient that is incompatible with benzoyl peroxide;
pump means for moving the first and second compositions out of the first and second chambers; and one or more outlets for dispensing the first and second compositions.
27. ~An apparatus as in claim 26 wherein the second composition comprises an antibiotic.
28. ~An apparatus as in claim 27 wherein the antibiotic is selected from the group consisting of erythromycin, clindamycin, tetracycline, derivatives of erythromycin, clindamycin or tetracycline and pharmaceutically acceptable salts of erythromycin, clindamycin or tetracycline.
29. ~An apparatus as in claim 26 wherein the second composition comprises a retinoid.
30. ~An apparatus as in claim 29 wherein the retinoid is selected from the group consisting of retinol, retinoic acid, retinyl palmitate, retinyl propionate, retinyl acetate and synthetic retinoid mimetics.
31. An apparatus comprising:
a first chamber containing a first composition, the first composition comprising a retinoid;
a second chamber containing a second composition comprising an active ingredient that is incompatible with the retinoid;
pump means for moving the first and second compositions out of the first and second chambers; and one or more outlets for dispensing the first and second compositions.
a first chamber containing a first composition, the first composition comprising a retinoid;
a second chamber containing a second composition comprising an active ingredient that is incompatible with the retinoid;
pump means for moving the first and second compositions out of the first and second chambers; and one or more outlets for dispensing the first and second compositions.
32. An apparatus as in claim 31 wherein the second composition comprises an antibiotic.
33. An apparatus as in claim 32 wherein the antibiotic is selected from the group consisting of erythromycin, clindamycin, tetracycline, derivatives of erythromycin, clindamycin or tetracycline and pharmaceutically acceptable salts of erythromycin, clindamycin or tetracycline.
34. An apparatus as in claim 31 wherein the second composition comprises benzoyl peroxide.
35. A method of treating acne comprising simultaneously pumping a first composition and a second composition from first and second chambers, respectively, the first composition comprising an effective acne-treating amount of a first active ingredient, the second composition comprising a second active ingredient which is incompatible with the first active ingredient; and contacting the first composition and second composition with the skin of a person afflicted with acne.
36. A method as in claim 35 wherein the first composition comprises an active ingredient selected from the group consisting of antibiotics, retinoids and benzoyl peroxide.
37. A method as in claim 35 wherein the first active ingredient is an antibiotic.
38. A method as in claim 37 wherein the antibiotic is selected from the group consisting of erythromycin, clindamycin, tetracycline, derivatives of erythromycin, clindamycin or tetracycline and pharmaceutically acceptable salts of erythromycin, clindamycin or tetracycline.
39. A method as in claim 35 wherein the second active ingredient is benzoyl peroxide.
40. A method as in claim 39 wherein benzoyl peroxide comprises from about 0.1 to about 25 weight percent of the second composition.
41. A method as in claim 35 wherein the second composition comprises a retinoid.
42. A method as in claim 41 wherein the retinoid is selected from the group consisting of retinol, retinoic acid, retinyl palmitate, retinyl propionate, retinyl acetate and synthetic retinoid mimetics.
43. A method as in claim 35 wherein the first active ingredient is benzoyl peroxide.
44. A method as in claim 43 wherein benzoyl peroxide comprises from about 0.1 to about 25 weight percent of the second composition.
45. A method as in claim 43 wherein the second composition comprises a retinoid.
46. A method as in claim 45 wherein the retinoid is selected from the group consisting of retinol, retinoic acid, retinyl palmitate, retinyl propionate, retinyl acetate and synthetic retinoid mimetics.
47. A method as in claim 35 wherein the first composition is substantially anhydrous.
48. A method as in claim 35 wherein the second composition is substantially anhydrous.
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US10/121,839 | 2002-04-12 | ||
US10/121,839 US7060732B2 (en) | 2000-12-12 | 2002-04-12 | Antibiotic/benzoyl peroxide dispenser |
PCT/US2003/011363 WO2003086419A1 (en) | 2002-04-12 | 2003-04-14 | Antibiotic/benzoyl peroxide dispenser |
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CA2481754C true CA2481754C (en) | 2011-01-04 |
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EP (1) | EP1503769A4 (en) |
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Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030044432A1 (en) * | 2000-09-29 | 2003-03-06 | Manetta Vincent E. | Acne treating composition |
US20020193321A1 (en) * | 2000-12-12 | 2002-12-19 | Mohan Vishnupad | Dual dispenser for aesthitically acceptable delivery of anhydrous skin treatment compositions |
US7060732B2 (en) * | 2000-12-12 | 2006-06-13 | Imaginative Research Associates, Inc. | Antibiotic/benzoyl peroxide dispenser |
US20060189552A1 (en) * | 2000-12-12 | 2006-08-24 | Mohan Vishnupad | Dispenser for dispensing three or more actives |
US7820186B2 (en) * | 2001-12-21 | 2010-10-26 | Galderma Research & Development | Gel composition for once-daily treatment of common acne comprising a combination of benzoyl peroxide and adapalene and/or adapalene salt |
DE10342211A1 (en) * | 2003-09-12 | 2005-04-07 | Beiersdorf Ag | cosmetic |
US7662855B2 (en) * | 2004-05-11 | 2010-02-16 | Imaginative Research Associates, Inc. | Retinoid solutions and formulations made therefrom |
US20060014834A1 (en) * | 2004-05-11 | 2006-01-19 | Mohan Vishnupad | Retinoid solutions and formulations made therefrom |
DE602005021238D1 (en) * | 2004-11-09 | 2010-06-24 | Imaginative Res Associates Inc | RETINOID SOLUTIONS AND FORMULATIONS THEREFROM |
PL1871433T3 (en) | 2005-03-24 | 2009-09-30 | Nolabs Ab | Cosmetic treatment with nitric oxide, device for performing said treatment and manufacturing method therefor |
AR054805A1 (en) * | 2005-06-29 | 2007-07-18 | Stiefel Laboratories | TOPICAL COMPOSITIONS FOR SKIN TREATMENT |
EP2431088A1 (en) | 2005-08-02 | 2012-03-21 | Sol-Gel Technologies Ltd. | Metal oxide coating of water insoluble ingredients |
US9107844B2 (en) * | 2006-02-03 | 2015-08-18 | Stiefel Laboratories Inc. | Topical skin treating compositions |
MX2008012526A (en) | 2006-03-31 | 2008-10-14 | Stiefel Res Australia Pyt Ltd | Foamable suspension gel. |
FR2910320B1 (en) * | 2006-12-21 | 2009-02-13 | Galderma Res & Dev S N C Snc | EMULSION COMPRISING AT LEAST ONE RETINOID AND BENZOLE PEROXIDE |
FR2910321B1 (en) | 2006-12-21 | 2009-07-10 | Galderma Res & Dev S N C Snc | CREAM GEL COMPRISING AT LEAST ONE RETINOID AND BENZOLE PEROXIDE |
EA200970724A1 (en) * | 2007-02-01 | 2010-02-26 | Сол-Джел Текнолоджиз Лтд. | COMPOSITIONS FOR LOCAL APPLICATION CONTAINING PEROXIDE AND RETINOID |
CA2824842C (en) * | 2007-02-01 | 2016-10-11 | Sol-Gel Technologies Ltd. | Method for preparing particles comprising metal oxide coating and particles with metal oxide coating |
US20080188445A1 (en) * | 2007-02-02 | 2008-08-07 | Warner Chilcott Company Inc. | Tetracycline compositions for topical administration |
WO2008097851A1 (en) * | 2007-02-02 | 2008-08-14 | Warner Chilcott Company, Inc. | Tetracycline compositions for topical administration |
US20080287373A1 (en) * | 2007-05-17 | 2008-11-20 | Popp Karl F | Topical skin treating kits |
US7875001B2 (en) * | 2008-02-25 | 2011-01-25 | Americo Michael Minotti | Multi medication nasal spray device and method |
WO2010080438A2 (en) * | 2008-12-18 | 2010-07-15 | Minntech Corporation | Sporicidal hand sanitizing lotion |
CA2742360C (en) * | 2009-01-05 | 2018-05-22 | Sol-Gel Technologies Ltd. | Topical compositions containing coated active agents |
EP2729131B1 (en) | 2011-07-05 | 2020-04-15 | Novan, Inc. | Topical compositions |
US9687465B2 (en) | 2012-11-27 | 2017-06-27 | Sol-Gel Technologies Ltd. | Compositions for the treatment of rosacea |
US9855211B2 (en) | 2013-02-28 | 2018-01-02 | Novan, Inc. | Topical compositions and methods of using the same |
KR102321169B1 (en) | 2013-08-08 | 2021-11-02 | 노반, 인크. | Topical compositions and methods of using the same |
US10206947B2 (en) | 2013-08-08 | 2019-02-19 | Novan, Inc. | Topical compositions and methods of using the same |
JP7090549B2 (en) | 2016-03-02 | 2022-06-24 | ノヴァン,インコーポレイテッド | Therapeutic compositions for inflammation and their treatment methods |
KR102426006B1 (en) | 2016-04-13 | 2022-07-29 | 노반, 인크. | Compositions, systems, kits, and methods for treating infections |
Family Cites Families (102)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3535422A (en) | 1968-03-11 | 1970-10-20 | Stiefel Laboratories | Stable benzoyl peroxide composition |
US3729568A (en) * | 1969-09-23 | 1973-04-24 | Johnson & Johnson | Acne treatment |
US3969518A (en) * | 1972-05-24 | 1976-07-13 | Merck & Co., Inc. | Inhibiting xanthine oxidase with 3-haloalkyl substituted benzothiadiazine-1,1-dioxides |
US3906108A (en) * | 1973-10-12 | 1975-09-16 | Johnson & Johnson | Stabilized tretinoin cream emulsion |
US3969516A (en) | 1974-12-19 | 1976-07-13 | Nelson Research & Development Company | Composition and method for treatment of acne |
DE2526938C2 (en) | 1975-02-14 | 1982-04-22 | F. Hoffmann-La Roche & Co. AG, 4002 Basel | Vitamin preparations |
US4000263A (en) | 1975-05-02 | 1976-12-28 | Westwood Pharmaceuticals, Inc. | Erythromycin solution |
GB1485207A (en) | 1975-05-28 | 1977-09-08 | Ucb Sa | Anti-fungal agent lucknomycine |
US4497794A (en) * | 1980-12-08 | 1985-02-05 | Dermik Laboratories, Inc. | Erythromycin/benzoyl peroxide composition for the treatment of acne |
US4330531A (en) | 1976-03-26 | 1982-05-18 | Howard Alliger | Germ-killing materials |
US4124707A (en) | 1976-12-22 | 1978-11-07 | Schering Corporation | 7α-Halogeno-3,20-dioxo-1,4-pregnadienes, methods for their manufacture, their use as anti-inflammatory agents, and pharmaceutical formulations useful therefor |
US4187287A (en) * | 1977-08-24 | 1980-02-05 | Colgate Palmolive Company | Warm two tone flavored dentifrice |
US4132771A (en) * | 1977-08-24 | 1979-01-02 | Schreiber Ronald S | Warm two tone flavored dentifrice |
US4140656A (en) | 1977-10-07 | 1979-02-20 | Armour-Dial, Inc. | Anhydrous clear gel facial cleanser |
US4606913A (en) | 1978-09-25 | 1986-08-19 | Lever Brothers Company | High internal phase emulsions |
US4247547A (en) * | 1979-03-19 | 1981-01-27 | Johnson & Johnson | Tretinoin in a gel vehicle for acne treatment |
US4387107A (en) | 1979-07-25 | 1983-06-07 | Dermik Laboratories, Inc. | Stable benzoyl peroxide composition |
IT1210608B (en) * | 1980-12-08 | 1989-09-14 | Rorer Int Overseas | COMPOSITION FOR TOPICAL ACNE TREATMENT |
US4692329A (en) | 1980-12-08 | 1987-09-08 | William H. Rorer, Inc. | Erythromycin/benzoyl peroxide antiacne compositions |
AU548845B2 (en) | 1981-06-12 | 1986-01-02 | Rorer International (Overseas) Inc. | Method and composition for treating acne |
US4603146A (en) * | 1984-05-16 | 1986-07-29 | Kligman Albert M | Methods for retarding the effects of aging of the skin |
JPS5855411A (en) * | 1981-09-28 | 1983-04-01 | Nitto Electric Ind Co Ltd | Base material composition and medicinal composition for external use |
ZA837627B (en) | 1982-10-15 | 1984-06-27 | Procter & Gamble | Storage stable topical pharmaceutical composition containing low dielectric solvents |
US4532133A (en) | 1983-05-24 | 1985-07-30 | Basf Wyandotte Corporation | Low temperature stable, emulsifiable vitamin A concentrates |
JPS6025918A (en) | 1983-07-25 | 1985-02-08 | Ajinomoto Co Inc | Aqueous solution containing fat-soluble drug |
LU85111A1 (en) | 1983-12-01 | 1985-09-12 | Oreal | ANTI-ACNETIC COMPOSITION BASED ON BENZOYL PEROXIDE AND AT LEAST ONE SOLAR FILTER |
GB8401206D0 (en) | 1984-01-17 | 1984-02-22 | Allied Colloids Ltd | Polymers and aqueous solutions |
GB8414950D0 (en) | 1984-06-12 | 1984-07-18 | Allied Colloids Ltd | Cationic polyelectrolytes |
US4826828A (en) * | 1985-04-22 | 1989-05-02 | Avon Products, Inc. | Composition and method for reducing wrinkles |
FR2591105B1 (en) * | 1985-12-11 | 1989-03-24 | Moet Hennessy Rech | PHARMACEUTICAL COMPOSITION, IN PARTICULAR DERMATOLOGICAL, OR COSMETIC, BASED ON HYDRATED LIPID LAMELLAR PHASES OR LIPOSOMES CONTAINING A RETINOIDE OR A STRUCTURAL ANALOG OF SUCH A RETINOID AS A CAROTENOID. |
US5446028A (en) | 1985-12-12 | 1995-08-29 | Dermik Laboratories, Inc. | Anti-acne method and composition |
US5879716A (en) | 1985-12-18 | 1999-03-09 | Advanced Polymer Systems, Inc. | Methods and compositions for topical delivery of benzoyl peroxide |
DE3614515A1 (en) | 1986-04-29 | 1987-11-05 | Pfeiffer Erich Gmbh & Co Kg | DISCHARGE DEVICE FOR MEDIA |
JP2622955B2 (en) * | 1986-07-29 | 1997-06-25 | エイボン プロダクツ インコ−ポレイテツド | Anhydrous cosmetics |
US5004598A (en) | 1986-11-10 | 1991-04-02 | The B. F. Goodrich Company | Stable and quick-breaking topical skin compositions |
US5389677B1 (en) * | 1986-12-23 | 1997-07-15 | Tristrata Inc | Method of treating wrinkles using glycalic acid |
US4885161A (en) * | 1987-03-11 | 1989-12-05 | Medi-Tech International Corporation | Wound dressings in gelled paste form |
FR2623395B1 (en) | 1987-11-24 | 1990-04-20 | Oreal | PHARMACEUTICAL AND COSMETIC COMPOSITIONS BASED ON BENZOYL PEROXIDE AND QUATERNARY AMMONIUM LIPOPHILIC SALICYLATES AND THEIR USE, ESPECIALLY IN THE TREATMENT OF ACNE |
US4963348A (en) | 1987-12-11 | 1990-10-16 | The Procter & Gamble Company | Styling agents and compositions containing the same |
DE3905050A1 (en) | 1989-02-18 | 1990-08-30 | Lohmann Therapie Syst Lts | THERAPEUTIC SYSTEM FOR DELAYED AND CONTROLLED TRANSDERMAL OR TRANSMUCOSAL ADMINISTRATION OF ACTIVE SUBSTANCES (II) |
CA2063576C (en) * | 1989-06-07 | 1994-01-25 | Gail S. Bazzano | Slow release vehicles for minimizing skin irritancy of topical compositions |
US4966779A (en) | 1989-12-21 | 1990-10-30 | Basf Corporation | Stable, water miscible emulsion comprising a fat-soluble vitamin |
US5559149A (en) * | 1990-01-29 | 1996-09-24 | Johnson & Johnson Consumer Products, Inc. | Skin care compositions containing retinoids |
CA2015111A1 (en) | 1990-04-23 | 1991-10-23 | Tom Y. Woo | New binary dispensor for the application of fluids, semi-fluids or semi-solids |
JP3256997B2 (en) | 1990-08-30 | 2002-02-18 | 千寿製薬株式会社 | Stable aqueous formulation |
FR2677650B1 (en) | 1991-06-14 | 1993-09-24 | Oreal | RETINOUIDES SUBSTITUTED BY A DITHIAN CYCLE AND THEIR USE, PROCESS FOR PREPARING THE SAME, COSMETIC AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND THERAPEUTIC USE THEREOF. |
US6117843A (en) | 1992-02-18 | 2000-09-12 | Lloyd J. Baroody | Compositions for the treatment of acne containing clindamycin and benzoyl peroxide |
TW203552B (en) | 1992-02-18 | 1993-04-11 | J Baroody Lloyd | Compositions of clindamycin and benzoyl peroxide for acne treatment |
ATE156042T1 (en) * | 1992-03-30 | 1997-08-15 | Immuno France S A R L | DEVICE FOR APPLYING A PHARMACEUTICAL OR COSMETIC COMPOSITION |
US5356040A (en) | 1992-03-31 | 1994-10-18 | Maplast S.R.L. | Container particulary for multicomponent products |
GB9207988D0 (en) * | 1992-04-10 | 1992-05-27 | Smithkline Beecham Plc | Topical composition |
US5409706A (en) | 1992-05-04 | 1995-04-25 | Imaginative Research Associates, Inc. | Anhydrous foaming composition containing low concentrations of detergents and high levels of glycerin and emollients such as oils and esters |
US5254334A (en) | 1992-05-04 | 1993-10-19 | Imaginative Research Associates, Inc. | Anhydrous foaming composition containing low concentrations of detergents and high levels of glycerin amd emollients such as oils and esters |
US5242433A (en) | 1992-12-07 | 1993-09-07 | Creative Products Resource Associates, Ltd. | Packaging system with in-tandem applicator pads for topical drug delivery |
US5460620A (en) | 1992-07-31 | 1995-10-24 | Creative Products Resource, Inc. | Method of applying in-tandem applicator pads for transdermal delivery of a therapeutic agent |
US5254109A (en) * | 1992-12-07 | 1993-10-19 | Creative Products Resource Associates, Ltd. | Separately packaged applicator pads for topical delivery of incompatable drugs |
US5645822A (en) | 1992-12-16 | 1997-07-08 | Schering-Plough Healthcare Products, Inc. | Method and apparatus for sunless tanning |
US5902600A (en) * | 1992-12-21 | 1999-05-11 | Healthpoint, Ltd. | Hydrogel polymer wound dressing |
US6387363B1 (en) * | 1992-12-31 | 2002-05-14 | United States Surgical Corporation | Biocompatible medical devices |
US5460062A (en) * | 1993-03-03 | 1995-10-24 | Dynamic Aerospace Tools Company | Reaction unit for threaded connector manipulating device and combination thereof |
CA2166062C (en) * | 1993-07-01 | 2008-09-16 | Tom De Vringer | The use of non-ionic surfactants in stable topical retinoid compositions |
FR2710841B1 (en) * | 1993-10-05 | 1995-11-17 | Oreal | Cosmetic or pharmaceutical composition for the skin, anhydrous and stable, based on retinol and its use for the treatment of skin diseases. |
AUPM294993A0 (en) | 1993-12-13 | 1994-01-13 | HADDON, Bruce Alexander | A deodorizer |
US5621066A (en) * | 1994-08-10 | 1997-04-15 | General Electric Company | Environmentally friendly method for poly(phenylene ether) polymerization and catalyst recycle |
US6461622B2 (en) * | 1994-09-07 | 2002-10-08 | Johnson & Johnson Consumer Companies, Inc. | Topical compositions |
US5558874A (en) * | 1994-12-12 | 1996-09-24 | Habley Medical Technology Corporation | Multi-compartment applicator for packaging, reconstituting and applying a dehydrated multi-constituent medication |
EP0729746A1 (en) * | 1995-02-28 | 1996-09-04 | Unilever Plc | Vitamin C delivery system |
DE19513164A1 (en) * | 1995-04-07 | 1996-10-10 | Bayer Ag | Hydroxy-terminated polycarbonates based on high mol. cyclic dimer diols with and use in prodn. of polyurethanes stable against hydrolysis and oxidn. |
US5632996A (en) | 1995-04-14 | 1997-05-27 | Imaginative Research Associates, Inc. | Benzoyl peroxide and benzoate ester containing compositions suitable for contact with skin |
EP0738510A3 (en) * | 1995-04-20 | 2005-12-21 | L'oreal | Use of a HMG-CoA reductase inhibitor as an anti-ageing agent and as an anti-acne agent. Composition comprising at least one HMG-CoA reductase inhibitor and at least one active substance with scaling properties. |
US5750092A (en) | 1996-03-14 | 1998-05-12 | Schering-Plough Healthcare Products, Inc. | Sunless tanning composition and method |
US5998392A (en) | 1996-04-10 | 1999-12-07 | Gattefosse S.A. | Benzoyl peroxide flocculent materials and methods of their preparation |
US6331291B1 (en) * | 1996-05-30 | 2001-12-18 | William R. Glace | Dentifrice gel/paste compositions |
FR2752734B1 (en) * | 1996-09-02 | 1998-11-06 | Cird Galderma | USE OF RETINOIDS FOR THE PREPARATION OF A MEDICAMENT FOR TREATING CONDITIONS RELATED TO VEGF OVEREXPRESSION |
US5823391A (en) | 1996-09-04 | 1998-10-20 | Owens-Brockway Plastic Products Inc. | Dual chamber flexible tube dispensing package and method of making |
US5744148A (en) * | 1996-09-20 | 1998-04-28 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Stabilization of an unstable retinoid in oil-in-water emulsions for skin care compositions |
US6082588A (en) | 1997-01-10 | 2000-07-04 | Lever Brothers Company, Division Of Conopco, Inc. | Dual compartment package and pumps |
CN1133422C (en) | 1997-07-08 | 2004-01-07 | 科斯莫弗姆有限公司 | Topical application of combination of benzoyl peroxide and second active ingredient |
FR2769299B1 (en) * | 1997-10-03 | 1999-12-31 | Oreal | BI-PRODUCTS PACKAGING AND DISTRIBUTION SET |
US6020367A (en) | 1997-12-02 | 2000-02-01 | Avon Products, Inc. | Supersaturated ascorbic acid solutions |
US6013637A (en) | 1998-06-12 | 2000-01-11 | Dermik Laboratories Inc. | Anti-acne method and composition |
US6458340B1 (en) * | 1998-09-10 | 2002-10-01 | Den-Mat Corporation | Desensitizing bleaching gel |
JP2000297018A (en) * | 1999-04-13 | 2000-10-24 | Hoyu Co Ltd | Hair make-up agent, hair cosmetic and method for using hair make-up agent |
US6428799B1 (en) * | 1999-08-02 | 2002-08-06 | The Procter & Gamble Company | Personal care articles |
US6268322B1 (en) | 1999-10-22 | 2001-07-31 | Unilever Home & Personal Care Usa, A Division Of Conopco, Inc. | Dual chamber cleansing system, comprising multiple emulsion |
EP1166225A1 (en) * | 2000-01-31 | 2002-01-02 | Collaborative Technologies, Inc. | Method and system for producing customized cosmetic and pharmaceutical formulations on demand |
US6585984B1 (en) * | 2000-03-03 | 2003-07-01 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Dual composition cosmetic product with a concentration sensitive and an incompatible active respectively placed within first and second compositions |
US6531141B1 (en) * | 2000-03-07 | 2003-03-11 | Ortho-Mcneil Pharmaceutical, Inc. | Oil-in-water emulsion containing tretinoin |
ES2366886T1 (en) * | 2000-04-21 | 2011-10-26 | Sol-Gel Technologies Ltd. | COMPOSITION THAT PRESENTS STABILITY OF POTENTIAL FORMULATION AND ADMINISTRATION OF POTENTIAL ACTIVE ACTIVE INGREDIENTS. |
US6207179B1 (en) * | 2000-05-18 | 2001-03-27 | Phoenix Scientific, Inc. | Parasiticidal formulation for animals and a method of making this formulation |
AU2001275201A1 (en) | 2000-06-02 | 2001-12-11 | Dermik International Holding Inc. | Acne-treating composition |
US6387383B1 (en) * | 2000-08-03 | 2002-05-14 | Dow Pharmaceutical Sciences | Topical low-viscosity gel composition |
US20030044432A1 (en) | 2000-09-29 | 2003-03-06 | Manetta Vincent E. | Acne treating composition |
US6467622B1 (en) * | 2000-10-12 | 2002-10-22 | Rubbermaid Incorporated | Adjustable organizer |
US6774100B2 (en) * | 2000-12-06 | 2004-08-10 | Imaginative Research Associates, Inc. | Anhydrous creams, lotions and gels |
US20020193321A1 (en) * | 2000-12-12 | 2002-12-19 | Mohan Vishnupad | Dual dispenser for aesthitically acceptable delivery of anhydrous skin treatment compositions |
US6462025B2 (en) * | 2000-12-12 | 2002-10-08 | Imaginative Research Associates, Inc. | Antibiotic/benzoyl peroxide dispenser |
US7060732B2 (en) * | 2000-12-12 | 2006-06-13 | Imaginative Research Associates, Inc. | Antibiotic/benzoyl peroxide dispenser |
US6399092B1 (en) * | 2000-12-27 | 2002-06-04 | Healthpoint, Ltd. | Anhydrous, hydrophilic absorbent wound dressing (tube) with antimicrobials or other pharmaceutically active agents |
US6899890B2 (en) * | 2002-03-20 | 2005-05-31 | Kv Pharmaceutical Company | Bioadhesive drug delivery system |
US20030215493A1 (en) * | 2002-04-30 | 2003-11-20 | Patel Pravin M. | Composition and method for dermatological treatment |
US20050255131A1 (en) * | 2004-05-11 | 2005-11-17 | Mohan Vishnupad | Clindamycin compositions and delivery system therefor |
-
2002
- 2002-04-12 US US10/121,839 patent/US7060732B2/en not_active Expired - Fee Related
-
2003
- 2003-04-14 CA CA2481754A patent/CA2481754C/en not_active Expired - Fee Related
- 2003-04-14 MX MXPA04009941A patent/MXPA04009941A/en active IP Right Grant
- 2003-04-14 WO PCT/US2003/011363 patent/WO2003086419A1/en active Application Filing
- 2003-04-14 EP EP03746745A patent/EP1503769A4/en not_active Withdrawn
- 2003-04-14 JP JP2003583438A patent/JP2005529636A/en active Pending
- 2003-04-14 AU AU2003226363A patent/AU2003226363A1/en not_active Abandoned
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2006
- 2006-03-31 US US11/395,802 patent/US20060172955A1/en not_active Abandoned
- 2006-03-31 US US11/395,505 patent/US20060173076A1/en not_active Abandoned
Also Published As
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MXPA04009941A (en) | 2004-12-13 |
EP1503769A1 (en) | 2005-02-09 |
US20030004118A1 (en) | 2003-01-02 |
EP1503769A4 (en) | 2009-07-15 |
JP2005529636A (en) | 2005-10-06 |
AU2003226363A1 (en) | 2003-10-27 |
WO2003086419A1 (en) | 2003-10-23 |
US20060172955A1 (en) | 2006-08-03 |
US20060173076A1 (en) | 2006-08-03 |
US7060732B2 (en) | 2006-06-13 |
CA2481754A1 (en) | 2003-10-23 |
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