CA1156558A - Stable benzoyl peroxide composition - Google Patents
Stable benzoyl peroxide compositionInfo
- Publication number
- CA1156558A CA1156558A CA000357119A CA357119A CA1156558A CA 1156558 A CA1156558 A CA 1156558A CA 000357119 A CA000357119 A CA 000357119A CA 357119 A CA357119 A CA 357119A CA 1156558 A CA1156558 A CA 1156558A
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- benzoyl peroxide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/38—Percompounds, e.g. peracids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
- A61K8/466—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur containing sulfonic acid derivatives; Salts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/008—Preparations for oily skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
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- Medicinal Chemistry (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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- Medicinal Preparation (AREA)
Abstract
ABSTRACT
Therapeutic alcoholic gel compositions for treating acne containing micronized benzoyl peroxide and dioctyl sodium sulfosuccinate having greater shelf life and stability.
Therapeutic alcoholic gel compositions for treating acne containing micronized benzoyl peroxide and dioctyl sodium sulfosuccinate having greater shelf life and stability.
Description
..
ST~BLE BEMZOYL PER~IDE COMPOSITION
Field of the Invention This invention relates to aqueous gel compositions which contain henzoyl peroxide that are useful in connection with the treatment of acne and sebhorreic conditions.
Prior Art Acne and sebhorrea are conditions of tlle human skin characterized hy an excessive flow of sebum or skin oil, from the sebaceous glands which are located in the pilosebaceous apparatus. The channel through which sebum reaches the skin 1~ surface is the duct of the hair follicle. The presence of excess amounts of sehum in the duct and on the skin acts to block or stagnate the continuous flow of sebum from the follicle duct, thus producing a thickening of sehum which becomes a solid plug known as a comedone. When this occurs, hyperkeratinization of the follicular opening is stimulated, thus completely closing the duct. The usual result is a papule, pustule or a cyst, which are often contaminated with bacteria that cause secondary infections. These occurrences characterize the ~isease today known as acne, and in lesser severity, sebhorrea.
Many topical therapeutical agents are employed in the treatment of acne and sebhorrea to prevent the blocking of the follicular ducts, to reopen the duct once it has become blocked, to act against the infecting bacteria or the thickened sebum, or to provide combinations of each of these actions. It is well known to use sulfur as a mild cutaneous irritant to remove the horny layer of the skin, and with it the debris clogging the follicular openings. Benzoyl peroxide gel compositions have 1162-7~
11~6~8 been found to be effective in the treatment of acne, sebhorrea, and the associated secondary infections.
U.S. Patent Number 3,535,422 discloses a therapeutic composition for the treatment of acne comprising a uniform dispersion of benzoyl peroxide in a fluid medium containing water and at least one organic emollient.
U.S. Patent Number 4,056,611 discloses a therapeutic composition for the treatment of acne comprising a stable dispersion of finely divided particles of benzoyl peroxide in an aqueous alcohol vehicle having a single phase. The single phase of the composition is non-lipid and contains a non-ionic surface active agent that is soluble in the aqeuous alcohol vehicle.
Prior art benzoyl peroxide compositions which contain merely finely divided benzoyl peroxide particles in an emulsion of water and certain select emollients provides the disadvantage that when the water content of the emulsion evaporates there remains most of the organic emollients and the large benzoyl peroxide particles on the surface of the skin near and in contact with the acne sites which may cause irritation.
Additionally, the use of large amounts of non-ionic surface active agents in such compositions, unless extremely fine particles of benzoyl peroxide are utilized, would cause a likelihood of irritation from the benzoyl peroxide.
Also, because of the powerful oxidizing properties of benzoyl peroxide, the inclusion of this substance in a conventional ointment or emulsion results in unstable compositions that soon display an unacceptable loss in keratolytic potency.
. 1162-78 Summary of the Invention The present invention relates to novel therapeutic composition~s containing micronized particles of benzoyl peroxide in an aclueous alcoholic gel vehicle having greater stability and shelf life.
It has been surprisingly found that in an aqu~ous alcoholic gel vehicle the u-tilization of micronized benzoyl peroxide having a particular size of less than 150 microns in combination with clioctyl sodium sulfosuccinate as the surface active agent results in a composition which displays full stahility with respect to the benzoyl peroxide component even when suhjected to temperatures higher than those normally expected in the ordinary use of the product. ~lso, the alcoholic gel of the present invention upon evaporation allows a uniform release of the mieronizecl henzoyl peroxide so as to obviate the burning and erythema experienced with other harsh gel formulations.
The aqueous alcoholic gel composition of the present invention contains from about 1 to ahout 30%, and preferahly
ST~BLE BEMZOYL PER~IDE COMPOSITION
Field of the Invention This invention relates to aqueous gel compositions which contain henzoyl peroxide that are useful in connection with the treatment of acne and sebhorreic conditions.
Prior Art Acne and sebhorrea are conditions of tlle human skin characterized hy an excessive flow of sebum or skin oil, from the sebaceous glands which are located in the pilosebaceous apparatus. The channel through which sebum reaches the skin 1~ surface is the duct of the hair follicle. The presence of excess amounts of sehum in the duct and on the skin acts to block or stagnate the continuous flow of sebum from the follicle duct, thus producing a thickening of sehum which becomes a solid plug known as a comedone. When this occurs, hyperkeratinization of the follicular opening is stimulated, thus completely closing the duct. The usual result is a papule, pustule or a cyst, which are often contaminated with bacteria that cause secondary infections. These occurrences characterize the ~isease today known as acne, and in lesser severity, sebhorrea.
Many topical therapeutical agents are employed in the treatment of acne and sebhorrea to prevent the blocking of the follicular ducts, to reopen the duct once it has become blocked, to act against the infecting bacteria or the thickened sebum, or to provide combinations of each of these actions. It is well known to use sulfur as a mild cutaneous irritant to remove the horny layer of the skin, and with it the debris clogging the follicular openings. Benzoyl peroxide gel compositions have 1162-7~
11~6~8 been found to be effective in the treatment of acne, sebhorrea, and the associated secondary infections.
U.S. Patent Number 3,535,422 discloses a therapeutic composition for the treatment of acne comprising a uniform dispersion of benzoyl peroxide in a fluid medium containing water and at least one organic emollient.
U.S. Patent Number 4,056,611 discloses a therapeutic composition for the treatment of acne comprising a stable dispersion of finely divided particles of benzoyl peroxide in an aqueous alcohol vehicle having a single phase. The single phase of the composition is non-lipid and contains a non-ionic surface active agent that is soluble in the aqeuous alcohol vehicle.
Prior art benzoyl peroxide compositions which contain merely finely divided benzoyl peroxide particles in an emulsion of water and certain select emollients provides the disadvantage that when the water content of the emulsion evaporates there remains most of the organic emollients and the large benzoyl peroxide particles on the surface of the skin near and in contact with the acne sites which may cause irritation.
Additionally, the use of large amounts of non-ionic surface active agents in such compositions, unless extremely fine particles of benzoyl peroxide are utilized, would cause a likelihood of irritation from the benzoyl peroxide.
Also, because of the powerful oxidizing properties of benzoyl peroxide, the inclusion of this substance in a conventional ointment or emulsion results in unstable compositions that soon display an unacceptable loss in keratolytic potency.
. 1162-78 Summary of the Invention The present invention relates to novel therapeutic composition~s containing micronized particles of benzoyl peroxide in an aclueous alcoholic gel vehicle having greater stability and shelf life.
It has been surprisingly found that in an aqu~ous alcoholic gel vehicle the u-tilization of micronized benzoyl peroxide having a particular size of less than 150 microns in combination with clioctyl sodium sulfosuccinate as the surface active agent results in a composition which displays full stahility with respect to the benzoyl peroxide component even when suhjected to temperatures higher than those normally expected in the ordinary use of the product. ~lso, the alcoholic gel of the present invention upon evaporation allows a uniform release of the mieronizecl henzoyl peroxide so as to obviate the burning and erythema experienced with other harsh gel formulations.
The aqueous alcoholic gel composition of the present invention contains from about 1 to ahout 30%, and preferahly
2~ from about 5 - 15%, by weight, of micronized benzoyl peroxide having a particle size of less than 150 microns Witl the mean average partic].e size being less than 35 microns. Dioctyl sodium sulfosuccinate which serves as a surface active agént as well as provicling for the increasecl stability of the composition is present in the amount of about 0.1 to about 3%, by weight, preferably about ~.1 to 1%, by weight of composition.
The composition also acdvantageously contains a wetting agent in an amount of about 1.0 to about 6.0~ by weight and preferably ahout 3~6% by weight.
netailed nescription The therapeutic gel composition of the present invention must contain sufficient ben70yl peroxide to be tllerapeutically effective, and should not contain more peroxide than can ke uniformly dispersed in the vehicle to form a smoothly spreada~le composition. Such considerations dictate that the composition contain at least 1% and not more than 30% by weight of benzoyl peroxide, and preferably that the composition contain from about 5 to about 15%, by weight benzoyl peroxide. The benzoyl peroxide constituent of the composition should be high purity and in the form of micronized finely divided crystalline particles having a mean average particle siæe of less than 35 microns. The aqueous gel composition of the present invention advantageously includes a wetting agent such as t'ne esters o~
polyols and sugars, the products o~ the condensation of ethylene oxide with fatty acids, fatty alcohols, long-chain al]:yl phenols, long-chain mercaptans, long-chain amides, polye-thers of poly-hydroxylated fatty alcohols and alkyl polyglycol ethers in an amount of from 3 to 6%, by weight. Alkyl polyglycol ether when utiliæed in about the same amounts as the dioctyl sodium sulfosuccinate has been found to provide the composition with extraordinary shelf life.
Another important component of the present composition is the gelling agent. These may be selected both as to type and quantity to give products of various viscosities. In the preferred form of this invention, the gelling agent is selected so as to produce an elegantly formed and stal~le gel.
A variety of gelling agents may be used for the present purposes.
However, preferred gelling agents are pure micro-crystalline cellulose, colloidal magnesium aluminum silicate, hydro-xypropyl methyl cellulose and the so-called hydroxylated vinylic polymers, particularly, those disclosed in U.S. Patent No. 2,798,053. Among those hydroxylated vinylic polymers of special interest herein are described generally as interpolymers of a monomeric monoolefinic acrylic acid, and from about 0.1 to about 10% by weight based on the total monomer of a monomeric polyether of an oligosaccharide in which the hydroxyl groups which are modified are esterified with allyl groups with said polyether containing at least two allyl ether groups per oligosaccharide molecule. Commercially available interpolymers of this type are marketed under the trade name "Carbopol". These are described as being polymers of acrylic acid cross-lined with about 1% of a polyallyl ether of sucrose having an average of about 5.8 allyl groups for each sucrose molecule. These polymers have molecular weight in~the order of magnitude of l,000,000.
Such polymers are available from the B.F. Goodrich Chemical Company and are sold under the trademark "Carbopol 934", "Carbopol 940" and "Carbopol 941".
The various Carbopols are distinguished from each other by the manufacturer on the basis of their viscosity. The polymers are gelled by neutralizing them with an alkaline material. Suitable neutralizing agents are the organic amines among which may be mentioned triethanolamine, triethylamine, isopropylamine, diisopropylamine, etc. and inorganic bases, among which may be NaOH, KOH, Ca(OH)2, etc.
The quantity of gelling agent that may be contained in the present compositions may also vary somewhat. Ordinarily, this will constitute about 0.5% to about 15% by weight, and . 1156~58 preferably ahout 1% to ahout 5~ hy weight, hased on the total weight of the finished composition.
The compositions of the present invention will also ordinarily contain substantial aqueous components. When water is present, it may also vary dependent on the nature of the product desired. Usually this will constitute between about 30-70%, based on the total weight of the finis~ed procluct.
It is also preferred to use demineralized water.
The alcohol employed in the aqueous alcohol gel vehicle must be soluble in water, serve as a coso]vent for the surface active agent and wetting agent in the vehicle and also as an antiseptic and drying agent when applied to the skin.
Alkyl alcohols having from 1-6 carbon atoms meet the foregoing criteria and are used in the formulation of the composition of the invention. The compositions with from 10-80% ~y weight of one or more of these alcohols is sufficient to insure that the surface active agents and wetting agents will dissolve therein.
It is sometimes advantageous to add additional therapeutically active ingredients to the present compositions which may serve to augment the activity of the benzoyl peroxide or to supplement them. A variety of materials may ~e used for this purpose. Of special interest as an auxiliary skin treating agent is the keratolytic agents and especially salicylic acid. When these are used, they may be employed over a range of concentrations which may vary from about 0.2% toabout 8go ~y weight.
The composition may also advantageously contain from 1-25% by weight of finely divided, micronized or colloidal sulfur. Sulfur is an antimicrobial and keralytic agent that has long been used in the treatment of acne. Although it is not known precisely how sulfur exerts its keratolytic effect on the skin, it is believed that the hydrogen sulfide, which is formed when sulfur is in contact with animal tissue, reacts with alkali in tissue fluids to produce active sulfides, which in turn, promote keratosis. The col~bination of sulfur with benzoyl peroxide produces significantly greater keratosis than either sub-tance will when used alone.
If desired, minute amounts of a compatible acid base may be added to the composition to adjust the relative acidity or alkalinity thereof, the pH of the composition usually being adjusted to within the range 3.5 and 7.5, preferably 5-6.5.
In addition, for purposes of formulating more elegant products, additional additives may be incorporated into the present composition. Typical among these may be emulsifying agents, emollients, preservatives, etc.
The yel composition of the present invention is applied topically to the skin of the patient by rubbing the gel in one or more times daily depending on the skin condition to provide drying, desquamative and antiseptic effects. Almost all persons who use the compositions of the present invention show a definite suppression of the acne eruption within the first few weeks of treatment. Moreover, the compositions of this invention have been demonstrated to be markedly more effective and faster acting than benzoyl peroxide containing emulsions or gel formulations of comparative strength previously known in the art.
The following examples are representative but not limited of therapeutic compositions prepared in accordance with the invention:
llS65S8 ..
EX~MPLE I
495.0 mg~ of purified water was mixed and 15.0 mg.
of Carbopol 940 (a carboxy vinyl polymer, acid form, of B. F. Goodrich Co.) were added to the water while stirring.
Stirring of the mixture was continued for 45 minutes. Then 4.095 mg. of sodium hydroxide in 4.91 ml. of purified water was added thereto. Stirring of the mixture was continued for lO minutes, whereupon 150.0 mg. of ethyl alcohol, 0.50 mg. of perfume and 0.50 mg. of methyl salicylate was added. To the stirred mixture was then added a mixture comprising 210.0 mg.
of wet pack micronized benzoyl peroxide (50% benzoyl peroxide -50% water), 2.0 mg. of dioctyl sodium sulfosuccinate, 41.0 mg.
of alkyl polyglycol ether and 41.0 mg. of purified water.
The mixture was stirred for 30 more minutes until a smooth and elegant gel mixture was obtained.
EXAMPLE II
Benxoyl peroxide (micronized) 5.46% by weight Water 40.69% by weight Ethyl alcohol 44.10% by weight Polyoxyethylene lauryl ether 6.00% by weight Colloidal magnesium aluminum silicate 2.50% by weight Hydroxypropylmethylcellulose 1.00% by weight Citric acid 0.05% by weight Dioctyl sodium sulfosuccinate 0.2 % by weight -1 1565$8 E~1PLE III
Benzoyl peroxide (micronized) 2.50% by weight Water ll.35% bY weight Ethyl alcohol70.00~O by weigh-t Polyoxyethylene (8) stearate 5.00% by weight Carboxy vinyl polymer (Carbopol 934)lO.50% by weig'1t ~1ydroxypropylcellulose0.45% by weight Dioctyl sodium sulfosuccinate 0.20% by weight EX~MPLE IV
Benzoyl peroxide (micronized) 2.8 % by weight Water 16.~ 9O hy weight Ethyl alcohol70.0 9~, by weight Polyoxyethylene lauryl ether 5.0 % by weight Carhoxy vinyl polymer (Carbopol 94l)5.0 % by weight Potassium hydroxiden. 2 % by weight nioctyl sodium sulfosuccinate 0.2 % by weight EXAMPLE V
Benzoyl peroxide (micronized) 15. OOQo by weight 1~1ater 49.35% by wei.ght Ethyl alcohol25.00~o hy weight Polyoxyethylene (40) stearate 5.50% ~y weight Colloidal magnesium aluminum silicate4.50% by weight Sodium carboxymethylcellulose 0.60% by weight Citric acid0.059O by weight Dioctyl sodium sulfosuccinate 0.50% hy weight EX~MPLE VI
Benzoyl peroxide (micronized) 5.00O by weight ~1ater 76.47o ]-y wcight Isopropyl alcohollO.00~ by weight Polyoxyethylene (20) sorbitan monolaurate5.009~ by weight Hydroxypropylmethylcellulose l.50% hy weight Xanthan guml.509~ by weight Phosphoric acid0.0396 hy weight Dioctyl sodium sulfosuccinate 0.50~ ~y weight ll~a-7~
-` 1 1~6~58 EX~PLE VII
Benzoyl peroxide (micronized) ~.00% hy weight Water 68.74g~ by weight Ethyl alcohol15.09% by weight Polyoxypropylenepolyoxyethylene polymer 5.09% by weight ~Iydroxypropylmethylcellulose 1.50% by weight Guar gum ~ 1.50% by weight Tartaric-acid0.06~ by weight Dioctyl sodium sulfosuccinate 0.20% by weight .. . .. .. . .
EXAMPLE VIII
Benzoyl peroxide (micronized) 15.0ng5 by weigllt Water 52.73o by weight Ethyl alcohol24.00% by weigllt Polyethylene glycol 400 laurate 5.00% by weight Microcrystalline cellulose2.50% by weight Sodium carboxymethylcellulose 0.50% by weight Citric acid 0.07% by weight Dioctyl sodium sulfosuccinate 9.20% by weight EXAMPLE IX
Benzoyl peroxide (micronized) 15.0 gs by weight ~la~er 45~ g~ ly weight Isopropyl alcohol20. n % by weight Alkyl polyglycol ether6.0 % by weight Sodium carboxymethylcellulose 11.5 ~ by weight Sodium naphthalene sulfonic acid-formaldehyde condensate1.0 % ~y weight Citric acid 0.2 % by weight Dioctyl sodium sulfosuccinate 1.0 % by weight Sulfur (micronized)10.0 % by weight .
EX~MPLR Y
.
Benzoyl peroxide (micronized) 7.50~ by weight Water 62.75% by weight Isopropyl alcohol15.00% by weight Polyoxyethylene (20) oleyl ether 3.00% by weight Collodial magnesium aluminum silicate 10.03% by weight Polyethylene gylcol polymer 1.50% by weight Citric acid Ø05% by weight ~ioctyl sodium sulfosuccinate 0.20~ by weight E~AMPLE ~I
Benzoyl peroxide (micronized) 10. 99Q by weight ~7ater 24.36% by weight Ethyl alcohol44.10% by weight Alkyl polyglycol ether6.00% by weight Collo~lial magnesium aluminum silicate 12.50~ by weight Hydroxypropylmethylcellulose 1.00% by weight Citric acid 0.05~ by weight Dioctyl sodium su~lfosuccinate 1.03% by weight
The composition also acdvantageously contains a wetting agent in an amount of about 1.0 to about 6.0~ by weight and preferably ahout 3~6% by weight.
netailed nescription The therapeutic gel composition of the present invention must contain sufficient ben70yl peroxide to be tllerapeutically effective, and should not contain more peroxide than can ke uniformly dispersed in the vehicle to form a smoothly spreada~le composition. Such considerations dictate that the composition contain at least 1% and not more than 30% by weight of benzoyl peroxide, and preferably that the composition contain from about 5 to about 15%, by weight benzoyl peroxide. The benzoyl peroxide constituent of the composition should be high purity and in the form of micronized finely divided crystalline particles having a mean average particle siæe of less than 35 microns. The aqueous gel composition of the present invention advantageously includes a wetting agent such as t'ne esters o~
polyols and sugars, the products o~ the condensation of ethylene oxide with fatty acids, fatty alcohols, long-chain al]:yl phenols, long-chain mercaptans, long-chain amides, polye-thers of poly-hydroxylated fatty alcohols and alkyl polyglycol ethers in an amount of from 3 to 6%, by weight. Alkyl polyglycol ether when utiliæed in about the same amounts as the dioctyl sodium sulfosuccinate has been found to provide the composition with extraordinary shelf life.
Another important component of the present composition is the gelling agent. These may be selected both as to type and quantity to give products of various viscosities. In the preferred form of this invention, the gelling agent is selected so as to produce an elegantly formed and stal~le gel.
A variety of gelling agents may be used for the present purposes.
However, preferred gelling agents are pure micro-crystalline cellulose, colloidal magnesium aluminum silicate, hydro-xypropyl methyl cellulose and the so-called hydroxylated vinylic polymers, particularly, those disclosed in U.S. Patent No. 2,798,053. Among those hydroxylated vinylic polymers of special interest herein are described generally as interpolymers of a monomeric monoolefinic acrylic acid, and from about 0.1 to about 10% by weight based on the total monomer of a monomeric polyether of an oligosaccharide in which the hydroxyl groups which are modified are esterified with allyl groups with said polyether containing at least two allyl ether groups per oligosaccharide molecule. Commercially available interpolymers of this type are marketed under the trade name "Carbopol". These are described as being polymers of acrylic acid cross-lined with about 1% of a polyallyl ether of sucrose having an average of about 5.8 allyl groups for each sucrose molecule. These polymers have molecular weight in~the order of magnitude of l,000,000.
Such polymers are available from the B.F. Goodrich Chemical Company and are sold under the trademark "Carbopol 934", "Carbopol 940" and "Carbopol 941".
The various Carbopols are distinguished from each other by the manufacturer on the basis of their viscosity. The polymers are gelled by neutralizing them with an alkaline material. Suitable neutralizing agents are the organic amines among which may be mentioned triethanolamine, triethylamine, isopropylamine, diisopropylamine, etc. and inorganic bases, among which may be NaOH, KOH, Ca(OH)2, etc.
The quantity of gelling agent that may be contained in the present compositions may also vary somewhat. Ordinarily, this will constitute about 0.5% to about 15% by weight, and . 1156~58 preferably ahout 1% to ahout 5~ hy weight, hased on the total weight of the finished composition.
The compositions of the present invention will also ordinarily contain substantial aqueous components. When water is present, it may also vary dependent on the nature of the product desired. Usually this will constitute between about 30-70%, based on the total weight of the finis~ed procluct.
It is also preferred to use demineralized water.
The alcohol employed in the aqueous alcohol gel vehicle must be soluble in water, serve as a coso]vent for the surface active agent and wetting agent in the vehicle and also as an antiseptic and drying agent when applied to the skin.
Alkyl alcohols having from 1-6 carbon atoms meet the foregoing criteria and are used in the formulation of the composition of the invention. The compositions with from 10-80% ~y weight of one or more of these alcohols is sufficient to insure that the surface active agents and wetting agents will dissolve therein.
It is sometimes advantageous to add additional therapeutically active ingredients to the present compositions which may serve to augment the activity of the benzoyl peroxide or to supplement them. A variety of materials may ~e used for this purpose. Of special interest as an auxiliary skin treating agent is the keratolytic agents and especially salicylic acid. When these are used, they may be employed over a range of concentrations which may vary from about 0.2% toabout 8go ~y weight.
The composition may also advantageously contain from 1-25% by weight of finely divided, micronized or colloidal sulfur. Sulfur is an antimicrobial and keralytic agent that has long been used in the treatment of acne. Although it is not known precisely how sulfur exerts its keratolytic effect on the skin, it is believed that the hydrogen sulfide, which is formed when sulfur is in contact with animal tissue, reacts with alkali in tissue fluids to produce active sulfides, which in turn, promote keratosis. The col~bination of sulfur with benzoyl peroxide produces significantly greater keratosis than either sub-tance will when used alone.
If desired, minute amounts of a compatible acid base may be added to the composition to adjust the relative acidity or alkalinity thereof, the pH of the composition usually being adjusted to within the range 3.5 and 7.5, preferably 5-6.5.
In addition, for purposes of formulating more elegant products, additional additives may be incorporated into the present composition. Typical among these may be emulsifying agents, emollients, preservatives, etc.
The yel composition of the present invention is applied topically to the skin of the patient by rubbing the gel in one or more times daily depending on the skin condition to provide drying, desquamative and antiseptic effects. Almost all persons who use the compositions of the present invention show a definite suppression of the acne eruption within the first few weeks of treatment. Moreover, the compositions of this invention have been demonstrated to be markedly more effective and faster acting than benzoyl peroxide containing emulsions or gel formulations of comparative strength previously known in the art.
The following examples are representative but not limited of therapeutic compositions prepared in accordance with the invention:
llS65S8 ..
EX~MPLE I
495.0 mg~ of purified water was mixed and 15.0 mg.
of Carbopol 940 (a carboxy vinyl polymer, acid form, of B. F. Goodrich Co.) were added to the water while stirring.
Stirring of the mixture was continued for 45 minutes. Then 4.095 mg. of sodium hydroxide in 4.91 ml. of purified water was added thereto. Stirring of the mixture was continued for lO minutes, whereupon 150.0 mg. of ethyl alcohol, 0.50 mg. of perfume and 0.50 mg. of methyl salicylate was added. To the stirred mixture was then added a mixture comprising 210.0 mg.
of wet pack micronized benzoyl peroxide (50% benzoyl peroxide -50% water), 2.0 mg. of dioctyl sodium sulfosuccinate, 41.0 mg.
of alkyl polyglycol ether and 41.0 mg. of purified water.
The mixture was stirred for 30 more minutes until a smooth and elegant gel mixture was obtained.
EXAMPLE II
Benxoyl peroxide (micronized) 5.46% by weight Water 40.69% by weight Ethyl alcohol 44.10% by weight Polyoxyethylene lauryl ether 6.00% by weight Colloidal magnesium aluminum silicate 2.50% by weight Hydroxypropylmethylcellulose 1.00% by weight Citric acid 0.05% by weight Dioctyl sodium sulfosuccinate 0.2 % by weight -1 1565$8 E~1PLE III
Benzoyl peroxide (micronized) 2.50% by weight Water ll.35% bY weight Ethyl alcohol70.00~O by weigh-t Polyoxyethylene (8) stearate 5.00% by weight Carboxy vinyl polymer (Carbopol 934)lO.50% by weig'1t ~1ydroxypropylcellulose0.45% by weight Dioctyl sodium sulfosuccinate 0.20% by weight EX~MPLE IV
Benzoyl peroxide (micronized) 2.8 % by weight Water 16.~ 9O hy weight Ethyl alcohol70.0 9~, by weight Polyoxyethylene lauryl ether 5.0 % by weight Carhoxy vinyl polymer (Carbopol 94l)5.0 % by weight Potassium hydroxiden. 2 % by weight nioctyl sodium sulfosuccinate 0.2 % by weight EXAMPLE V
Benzoyl peroxide (micronized) 15. OOQo by weight 1~1ater 49.35% by wei.ght Ethyl alcohol25.00~o hy weight Polyoxyethylene (40) stearate 5.50% ~y weight Colloidal magnesium aluminum silicate4.50% by weight Sodium carboxymethylcellulose 0.60% by weight Citric acid0.059O by weight Dioctyl sodium sulfosuccinate 0.50% hy weight EX~MPLE VI
Benzoyl peroxide (micronized) 5.00O by weight ~1ater 76.47o ]-y wcight Isopropyl alcohollO.00~ by weight Polyoxyethylene (20) sorbitan monolaurate5.009~ by weight Hydroxypropylmethylcellulose l.50% hy weight Xanthan guml.509~ by weight Phosphoric acid0.0396 hy weight Dioctyl sodium sulfosuccinate 0.50~ ~y weight ll~a-7~
-` 1 1~6~58 EX~PLE VII
Benzoyl peroxide (micronized) ~.00% hy weight Water 68.74g~ by weight Ethyl alcohol15.09% by weight Polyoxypropylenepolyoxyethylene polymer 5.09% by weight ~Iydroxypropylmethylcellulose 1.50% by weight Guar gum ~ 1.50% by weight Tartaric-acid0.06~ by weight Dioctyl sodium sulfosuccinate 0.20% by weight .. . .. .. . .
EXAMPLE VIII
Benzoyl peroxide (micronized) 15.0ng5 by weigllt Water 52.73o by weight Ethyl alcohol24.00% by weigllt Polyethylene glycol 400 laurate 5.00% by weight Microcrystalline cellulose2.50% by weight Sodium carboxymethylcellulose 0.50% by weight Citric acid 0.07% by weight Dioctyl sodium sulfosuccinate 9.20% by weight EXAMPLE IX
Benzoyl peroxide (micronized) 15.0 gs by weight ~la~er 45~ g~ ly weight Isopropyl alcohol20. n % by weight Alkyl polyglycol ether6.0 % by weight Sodium carboxymethylcellulose 11.5 ~ by weight Sodium naphthalene sulfonic acid-formaldehyde condensate1.0 % ~y weight Citric acid 0.2 % by weight Dioctyl sodium sulfosuccinate 1.0 % by weight Sulfur (micronized)10.0 % by weight .
EX~MPLR Y
.
Benzoyl peroxide (micronized) 7.50~ by weight Water 62.75% by weight Isopropyl alcohol15.00% by weight Polyoxyethylene (20) oleyl ether 3.00% by weight Collodial magnesium aluminum silicate 10.03% by weight Polyethylene gylcol polymer 1.50% by weight Citric acid Ø05% by weight ~ioctyl sodium sulfosuccinate 0.20~ by weight E~AMPLE ~I
Benzoyl peroxide (micronized) 10. 99Q by weight ~7ater 24.36% by weight Ethyl alcohol44.10% by weight Alkyl polyglycol ether6.00% by weight Collo~lial magnesium aluminum silicate 12.50~ by weight Hydroxypropylmethylcellulose 1.00% by weight Citric acid 0.05~ by weight Dioctyl sodium su~lfosuccinate 1.03% by weight
Claims (13)
1. A stable aqueous benzoyl peroxide composition characterized by having from about 1% to about 30% by weight of benzoyl peroxide, having a particle size of less than 150 microns with a mean average particle size in said composition of less than 35 microns, and an effective amount of dioctyl sodium sulfosuccinate as a stabilizing and surface active agent.
2. The composition according to Claim 1 characterized by said dioctyl sodium sulfosuccinate being present in an amount of 0.1 to 3.0% by weight composition.
3. The composition according to Claim 1, characterized by having 0.5% to 15% by weight of a gelling agent.
4. The composition according to Claim 3, characterized by said gelling agent being colloidal magnesium aluminum silicate, hydroxypropylmethylcellulose, microcrystalline cellulose or hydroxylated vinylic polymers.
5. The composition according to Claim 1 characterized by including a keratolytic agent.
6. The composition according to Claim 5, characterized by said keratolytic agent being salicylic acid.
7. The composition according to Claim 1, characterized by including sulfur.
8. The composition according to Claim 1 characterized by including a further wetting agent.
9. The composition according to Claim 8 characterized by said additional wetting agent being an alkyl polyglycol ether.
10. The composition according to Claims 1-3 characterized by said composition containing about 10% by weight of micronized benzoyl peroxide, about 0.2% weight of dioctyl sodium sulfo-succinate, about 4.1% by weight of alkyl polyglycol ether, about 1% to about 5% of a hydroxylated vinylic polymer gelling agent, about 15% by weight of an alkanol, about 0.4% by weight of sodium hydroxide and the balance water.
11. The composition according to Claims 1-3 characterized by said composition containing about 5% by weight of micronized benzoyl peroxide, about 0.2% by weight of dioctyl sodium sulfo-succinate, about 4.1% by weight of alkyl polyglycol ether, about 1% to about 5% of a hydroxylated vinylic polymer gelling agent, about 15% by weight of an alkanol, about 0.4% by weight of sodium hydroxide and the balance water.
12. A method for stabilizing aqueous benzoyl peroxide compositions containing 1% to about 30% by weight of benzoyl peroxide having a particle size of less than 150 microns with a mean average particle size in said composition of less than 35 microns characterized by including in said composition an effective amount of dioctyl sodium sulfosuccinate as a stabilizing agent.
13. The method according to Claim 12 characterized by said dioctyl sodium sulfosuccinate being present in an amount of 0.1 to 3.0% of total composition.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6039279A | 1979-07-25 | 1979-07-25 | |
| US060,392 | 1979-07-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1156558A true CA1156558A (en) | 1983-11-08 |
Family
ID=22029179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000357119A Expired CA1156558A (en) | 1979-07-25 | 1980-07-24 | Stable benzoyl peroxide composition |
Country Status (20)
| Country | Link |
|---|---|
| JP (1) | JPH0327532B2 (en) |
| AR (1) | AR221949A1 (en) |
| AT (1) | AT379309B (en) |
| AU (1) | AU540640B2 (en) |
| BE (1) | BE884455A (en) |
| CA (1) | CA1156558A (en) |
| CH (1) | CH644758A5 (en) |
| DE (1) | DE3049722C2 (en) |
| DK (1) | DK132081A (en) |
| ES (1) | ES494336A0 (en) |
| FR (1) | FR2462424A1 (en) |
| GB (1) | GB2054375B (en) |
| IE (1) | IE51097B1 (en) |
| IT (1) | IT1141612B (en) |
| NL (1) | NL8020303A (en) |
| NZ (1) | NZ194326A (en) |
| PH (1) | PH16734A (en) |
| SE (1) | SE451666B (en) |
| WO (1) | WO1981000206A1 (en) |
| ZA (1) | ZA804349B (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6251666A (en) * | 1985-08-29 | 1987-03-06 | Nippon Oil & Fats Co Ltd | Dibenzoyl peroxide-containing composition |
| 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 |
| EP1988974B1 (en) * | 2006-02-28 | 2011-12-21 | Swissdent Cosmetics AG | Toothpaste |
| WO2008006848A1 (en) * | 2006-07-13 | 2008-01-17 | Galderma Research & Development | Composition comprising a retinoid and benzoyl peroxide |
| FR2903604B1 (en) * | 2006-07-13 | 2008-09-05 | Galderma Res & Dev S N C Snc | COMPOSITION COMPRISING A RETINOID AND BENZOYL PEROXIDE |
| FR2909000B1 (en) * | 2006-11-28 | 2009-02-06 | Galderma Res & Dev S N C Snc | COMPOSITIONS COMPRISING BENZOYL PEROXIDE, AT LEAST ONE NAPHTHOIC ACID DERIVATIVE AND AT LEAST ONE POLYURETHANE POLYMER COMPOUND OR DERIVATIVES THEREOF, AND USES THEREOF. |
| 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 |
| FR2910320B1 (en) | 2006-12-21 | 2009-02-13 | Galderma Res & Dev S N C Snc | EMULSION COMPRISING AT LEAST ONE RETINOID AND BENZOLE PEROXIDE |
| GB2449973B8 (en) * | 2007-05-31 | 2010-01-06 | Syntopix Group Plc | Antibacterial & anti-acne formulations containing dialkyl sulphosuccinates |
| US8288434B2 (en) | 2008-06-05 | 2012-10-16 | Dow Pharmaceutical Sciences, Inc. | Topical pharmaceutical formulations containing a low concentration of benzoyl peroxide in suspension in water and a water-miscible organic solvent |
| GB0911213D0 (en) | 2009-06-30 | 2009-08-12 | Syntopix Group Plc | Formulation |
| US9744150B2 (en) | 2009-10-21 | 2017-08-29 | Dow Pharmaceutical Sciences Inc. | Suspension containing micronized benzoyl peroxide |
| EP2490528A4 (en) * | 2009-10-21 | 2013-06-12 | Dow Pharmaceutical Sciences | Method for wetting a powder containing benzoyl peroxide |
| USD743637S1 (en) * | 2014-07-07 | 2015-11-17 | Monty L. Ruetenik | Equine ice boot |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4056611A (en) * | 1973-04-16 | 1977-11-01 | Stiefel Laboratories, Inc. | Therapeutic composition |
| US4075353A (en) * | 1976-06-09 | 1978-02-21 | Dermatologics For Veterinary Medicine, Inc. | Process for the treatment of acarid skin infections in animals |
| US4318907A (en) * | 1978-04-04 | 1982-03-09 | Westwood Pharmaceuticals, Inc. | Method for treating acne vulgaris and compositions useful for that purpose |
-
1980
- 1980-07-11 NZ NZ194326A patent/NZ194326A/en unknown
- 1980-07-18 ZA ZA00804349A patent/ZA804349B/en unknown
- 1980-07-21 IT IT68161/80A patent/IT1141612B/en active Protection Beyond IP Right Term
- 1980-07-21 CH CH555980A patent/CH644758A5/en not_active IP Right Cessation
- 1980-07-23 AR AR281860A patent/AR221949A1/en active
- 1980-07-23 ES ES494336A patent/ES494336A0/en active Granted
- 1980-07-23 PH PH24331A patent/PH16734A/en unknown
- 1980-07-24 BE BE0/201513A patent/BE884455A/en not_active IP Right Cessation
- 1980-07-24 JP JP55501909A patent/JPH0327532B2/ja not_active Expired - Lifetime
- 1980-07-24 DE DE3049722T patent/DE3049722C2/en not_active Expired - Lifetime
- 1980-07-24 AU AU60755/80A patent/AU540640B2/en not_active Expired
- 1980-07-24 AT AT0907180A patent/AT379309B/en not_active IP Right Cessation
- 1980-07-24 NL NL8020303A patent/NL8020303A/en not_active Application Discontinuation
- 1980-07-24 CA CA000357119A patent/CA1156558A/en not_active Expired
- 1980-07-24 WO PCT/US1980/000967 patent/WO1981000206A1/en active Application Filing
- 1980-07-24 FR FR8016309A patent/FR2462424A1/en active Granted
- 1980-07-25 GB GB8024458A patent/GB2054375B/en not_active Expired
- 1980-07-25 IE IE1563/80A patent/IE51097B1/en unknown
-
1981
- 1981-03-23 SE SE8101833A patent/SE451666B/en not_active IP Right Cessation
- 1981-03-24 DK DK132081A patent/DK132081A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| FR2462424A1 (en) | 1981-02-13 |
| SE451666B (en) | 1987-10-26 |
| IT1141612B (en) | 1986-10-01 |
| AR221949A1 (en) | 1981-03-31 |
| JPS56500888A (en) | 1981-07-02 |
| DE3049722T1 (en) | 1982-03-04 |
| IE51097B1 (en) | 1986-10-01 |
| AU540640B2 (en) | 1984-11-29 |
| SE8101833L (en) | 1981-03-23 |
| GB2054375B (en) | 1983-08-24 |
| DE3049722C2 (en) | 1994-07-07 |
| ES8105279A1 (en) | 1981-06-16 |
| GB2054375A (en) | 1981-02-18 |
| IT8068161A0 (en) | 1980-07-21 |
| AT379309B (en) | 1985-12-27 |
| NL8020303A (en) | 1981-06-16 |
| ATA907180A (en) | 1985-05-15 |
| BE884455A (en) | 1981-01-26 |
| ZA804349B (en) | 1981-11-25 |
| NZ194326A (en) | 1982-05-31 |
| JPH0327532B2 (en) | 1991-04-16 |
| PH16734A (en) | 1984-02-06 |
| FR2462424B1 (en) | 1984-12-07 |
| AU6075580A (en) | 1981-01-29 |
| DK132081A (en) | 1981-03-24 |
| WO1981000206A1 (en) | 1981-02-05 |
| ES494336A0 (en) | 1981-06-16 |
| IE801563L (en) | 1981-01-25 |
| CH644758A5 (en) | 1984-08-31 |
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