WO1988001863A1 - Foams for delivery of minoxidil - Google Patents

Foams for delivery of minoxidil Download PDF

Info

Publication number
WO1988001863A1
WO1988001863A1 PCT/US1987/002265 US8702265W WO8801863A1 WO 1988001863 A1 WO1988001863 A1 WO 1988001863A1 US 8702265 W US8702265 W US 8702265W WO 8801863 A1 WO8801863 A1 WO 8801863A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
minoxidil
components
alcohol
propylene glycol
Prior art date
Application number
PCT/US1987/002265
Other languages
French (fr)
Inventor
Susanne M. Peck
Shri C. Valvani
Lorraine Elisabeth Pena
Connie J. Thoennes
Original Assignee
The Upjohn Company
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The Upjohn Company filed Critical The Upjohn Company
Publication of WO1988001863A1 publication Critical patent/WO1988001863A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A61K9/122—Foams; Dry foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • the present application provides a new composition for ad ⁇ ministration of known pharmaceutical compounds.
  • the present invention provides: aerosol and non-aerosol quick-breaking and slow-breaking foams for the topical delivery of minoxidil and related compounds.
  • Minoxidil or 2,4-pyrimidinediamine, 6-(l-piperidinyl)3-oxide, is a potent vasodilator sold under the trademark LONITEN ® Tablets for use in the treatment of hypertension. It is also useful as a topically applied hair growth agent for the treatment of baldness.
  • Topical minoxidil is administered in a topical composition containing propylene glycol, ethanol and water.
  • U.S. Patent 4,139,619 claims topical compositions of minoxidil and related 6-amino-4-(substituted amino)-1,2-dihydro-l-hydroxy-2- iminopyrimidines as well as the use of such compositions for (a) increasing the rate of growth of terminal hair, and (b) converting growth of vellus hair to growth as terminal hair.
  • U.S. Patent 4,596,812 also discloses certain topical minoxidil compositions as well as their use as therapeutic agents to treat human alopecia and arrest and reverse male pattern alopecia.
  • hair loss There are many different types of hair loss, the most common being “alopecia” wherein human males begin losing scalp hair at the temples and on the crown of the head as they get older. While this type of hair loss is largely confined to males, hence its common name “male pattern baldness”, it is not unknown in women. Hair loss can be seen as gradual hair conversion.
  • Terminal hairs are coarse, pigmented, long hairs in which the bulb of the hair follicle is seated deep in the dermis.
  • Vellus hairs are fine, thin, non-pigmented short hairs in which the hair bulb is located superficially in the dermis. As alopecia progresses, a transition takes place in the area of approaching baldness wherein the hairs themselves are changing from the terminal to the vellus type.
  • U.S. Patent 4,139,619 discloses topical minoxidil compositions containing carriers selected from ointments, lotions, pastes, jellies, sprays, and aerosols.
  • U.S. Patent 4,596,812 also discloses topical compositions of minoxidil. SUMMARY OF THE INVENTION
  • the present invention particularly provides
  • a topical composition for application to mammalian skin comprising:
  • an emulsifier and/or surfactant in an amount from about 0.5 to about 10% w/w;
  • composition wherein composition is actuated using a propellant
  • composition wherein the composition is actuated using a hydrocarbon, chlorofluorocarbon P-12 or an approximately 40:60 mixture of chlorofluorocarbon P-12 and P-114 in a range of about 2.5 to about 25% w/w;
  • a topical composition for application to mammalian skin comprising the following components, in a range on a weight to weight basis (% w/w) :
  • a surfactant and/or emulsifier and/or fatty alcohol and/or fatty alkanolamide in an amount from about 0.1 to about 15% w/w
  • film former in an amount up to about 5% w/w; with the remainder of the composition being water
  • composition a skin penetrant in an amount up to about 20%; with the proviso that the composition contain at least 10% of components b-c, at least 15% of components b-d and at least 0.1% of components e-g;
  • composition wherein the composition is actuated by a propellant
  • composition having the following components: Components % • w/w Minoxidil 2 . ⁇ 0 Propylene glycol 25 . 0 1,3 Butylene glycol 30 . 0 Alcohol USP 2 . 15 Polyvinyl pyrollidone and vinyl 4 . 5 acetate Cocamidopropyl betaine 1 . . 0 Polyoxyethylene 23 lauryl ether 5 . , 0 Purified water 56 . . 65 ;
  • compositions selected from the following compositions, comprising the following components:
  • the novel foam compositions provided herein provide a pharmaceutically elegant means of topically administering minoxidil.
  • certain of the compositions provided herein greatly increase skin penetration as compared to the propylene glycol/ethanol/water compositions of the prior art.
  • topical minoxidil compositions including the compositions of the present invention in the treatment and prevention of baldness is well known to an ordinarily skilled physician or dermatologist.
  • this use is set forth in U.S. Patents 4,139,619 and 4,596,812, which patents are expressly incorporated by reference herein.
  • the aerosolized formulation is a homogeneous, aqueous-alcoholic emulsion system.
  • the aerosolized formulation upon actuation produces a stabilized, homogeneous, expandable foam which breaks easily with shear.
  • a composition of this type is sometimes referred to as a "mousse" .
  • minoxidil is meant the compound named 2,4-pyrimidine- diamine, 6-(1-piperidinyl)-3-oxide, as well as analogs salts thereof, as described in U.S. Patents 4,139,619 and 4,596,812, which patents are incorporated by reference herein.
  • Suitable glycols include propylene glycol, 1,3-butylene glycol, propylene glycol 200 (PEG 200), polyethylene glycol 400 (PEG 400) hexylene glycol, and dipropylene glycol.
  • Suitable skin penetrants include alcohols such as dodecanol and oleyl alcohol; amines, such as isopropyl a ine, diisopropyl amine, triethyl amine, triethanol amine, diisopropanolamine and ethylene diamine; carboxylic acids, such as oleic acid, linoleic acid and linolenic acid; esters, such as dibutyl sebacate, dibutyl phthalate, butyl benzoate and ethyl caprate; and others, such as Azone ® , N methyl pyrollidone, bile salts and urea.
  • alcohols such as dodecanol and oleyl alcohol
  • amines such as isopropyl a ine, diisopropyl amine, triethyl amine, triethanol amine, diisopropanolamine and ethylene diamine
  • carboxylic acids such as oleic acid,
  • compositions herein may be actuated using propellants known to those of ordinary skill in pharmaceutical or cosmetic formulations.
  • propellants include hydrocarbons such as propane, isobutane or dimethyl ether and chlorofluorocarbons such as P-12,
  • alcohol any of the common alcohols used in conven ⁇ tional pharmaceutical or cosmetic foam compositions including ethanol, isopropanol, and the like.
  • e ulsi ier and/or surfactant is meant any of the known agents for modifying the surface tension of a composition and making an emulsion more stable, such as Polawax regular, Polawax A-31, cocami ⁇ dopropyl betaine, polyoxy ethylene (POE) 23 lauryl ether, and polyoxyethylene (POE) 2 stearyl ether. Included in the class of emulsion stabilizers are the long chain fatty alcohols and fatty alkanolamides such as lauryl alcohol, isostearyl alcohol, and cocamide DEA.
  • film former is meant a high molecular weight polymer such as a cellulose derivative or resin. Hydroxypropyl methylcellulose and polyvinyl pyrollidone and vinylacetate are typical examples.
  • Span 60 and Tween 80 in ranges of 0.5 to 10% w/w, preferably 3% w/w, is desirable to improve the physical stability of the formulation.
  • Example 1 Alcohol and propylene glycol are heated to 50-60°C and minoxidil is added and mixed until dissolved. In a separate container Polawax is heated until melted (approximately 50-60°C). To a third container of water, heated to 50-60°C, is added hydroxypropylmethyl cellulose, and mixing is continued until the dispersion is complete. The alcohol and Polawax mixtures, are homogenized using a homogenizer, and the aqueous phase is added and this total mixture is homogenized.
  • All three mixtures are maintained at about 50-60°C during this mixing process. After mixing, the mixture is cooled to about 40°C and added to an aerosol vial to which a propellant is added.
  • Minoxidil is dissolved in a glycol mixture.
  • POE (23) lauryl ether and POE (2) stearyl ether, lauryl alcohol, and purified water are added to a separate container.
  • the two mixtures are combined with agitation and cooled to room temperature.
  • a composition containing the following percentages of components is prepared: Components % w/w Propylene glycol 10.0
  • composition upon actuation, is a stiff, slow- breaking foam.
  • Procedure B Oleyl alcohol is heated to about 60°C.
  • POE (2) stearyl ether, and POE (23) lauryl ether are combined and heated to about 60°C, with stirring.
  • Minoxidil is added to butylene glycol and water and the mixture is stirred until the minoxidil is dissolved. The two mixtures are combined and the resulting mixture stirred until cooled to room temperature.
  • Minoxidil is dissolved in propylene glycol and heated with mixing to 72°C. Dissolve the POE (23) lauryl ether in the purified water and heat to 72°C with mixing. In a separate container, combine and mix the POE (2) stearyl ether and the isostearyl alcohol while heating to 70°C. Combine the minoxidil and POE (23) lauryl ether solutions with mixing while maintaining at 72°C. Add the POE (2) stearyl ether-isostearyl alcohol mixture to the minoxidil solution with rapid agitation. Continue mixing until cooled to room temperature. Add the alcohol and mix until uniform.
  • composition containing the following amounts of components is prepared.
  • Minoxidil is dissolved in propylene glycol and heated with mixing to 72°C.
  • the oleth-10 is combined with the purified water and heated with mixing to 72°C.
  • the oleth-10 solution is added to the minoxidil solution with continued mixing while cooling to room temperature. Add the alcohol and mix until uniform.
  • Example 5 Using the procedure described in Example 3, and the appropriate amount of starting materials, a composition containing the following amounts of components is prepared:
  • cocamidopropyl betaine is added to the POE (23) lauryl ether and purified water, then heated to 72°C with mixing.
  • the propylene glycol, butylene glycol, POE (23) lauryl ether, minoxidil and purified water are combined and heated with mixing to 72°C.
  • the POE (23) stearyl ether and isostearyl alcohol are combined and heated with mixing to 70°C, then added to the aqueous solution with rapid agitation. Mixing is continued while cooling to room temperature. Add the alcohol and mix until uniform.
  • compositions prepared as in Example 1 were also tested which contain 25% and 30% water.
  • a comparison study was run utilizing a formulation contain ⁇ ing 30% water applied as the aerosolized foam and also as the non- aerosolized gel.
  • radiolabelled formulations of minoxidil were applied to the surface of 5 hairless mouse skins (Franz cell apparatus) and transport through the stratum was corneum monitored.
  • the minoxidil foams of Example 1 greatly increased the transport of minoxidil through the skin 10 fold as compared to the propylene glycol-ethanol-water formulations of the prior art.

Abstract

Novel, slow- and quick-breaking foams containing minoxidil. These foams provide a pharmaceutically elegant means for the topical delivery of this compound.

Description

FOAMS FOR DELIVERY OF MINOXIDIL DESCRIPTION
The present application provides a new composition for ad¬ ministration of known pharmaceutical compounds. In particular, the present invention provides: aerosol and non-aerosol quick-breaking and slow-breaking foams for the topical delivery of minoxidil and related compounds.
Minoxidil, or 2,4-pyrimidinediamine, 6-(l-piperidinyl)3-oxide, is a potent vasodilator sold under the trademark LONITEN® Tablets for use in the treatment of hypertension. It is also useful as a topically applied hair growth agent for the treatment of baldness. Topical minoxidil is administered in a topical composition containing propylene glycol, ethanol and water.
U.S. Patent 4,139,619 claims topical compositions of minoxidil and related 6-amino-4-(substituted amino)-1,2-dihydro-l-hydroxy-2- iminopyrimidines as well as the use of such compositions for (a) increasing the rate of growth of terminal hair, and (b) converting growth of vellus hair to growth as terminal hair. U.S. Patent 4,596,812 also discloses certain topical minoxidil compositions as well as their use as therapeutic agents to treat human alopecia and arrest and reverse male pattern alopecia.
There are many different types of hair loss, the most common being "alopecia" wherein human males begin losing scalp hair at the temples and on the crown of the head as they get older. While this type of hair loss is largely confined to males, hence its common name "male pattern baldness", it is not unknown in women. Hair loss can be seen as gradual hair conversion.
Terminal hairs are coarse, pigmented, long hairs in which the bulb of the hair follicle is seated deep in the dermis. Vellus hairs are fine, thin, non-pigmented short hairs in which the hair bulb is located superficially in the dermis. As alopecia progresses, a transition takes place in the area of approaching baldness wherein the hairs themselves are changing from the terminal to the vellus type. INFORMATION DISCLOSURE
U.S. Patent 4,139,619 discloses topical minoxidil compositions containing carriers selected from ointments, lotions, pastes, jellies, sprays, and aerosols. U.S. Patent 4,596,812 also discloses topical compositions of minoxidil. SUMMARY OF THE INVENTION
The present invention particularly provides
(1) a topical composition for application to mammalian skin comprising:
(a) minoxidil in an amount from about 1 to about 5% on a weight to weight basis (%w/w) ;
(b) propylene glycol in an amount from about 10 to about 50% w/w; (c) alcohol in an amount from about 30 to about 75% w/w;
(d.) an emulsifier and/or surfactant in an amount from about 0.5 to about 10% w/w;
(e) hydroxypropyl methylcellulose in an amount from about 0.1 to 0.5% w/w; and (f) water in an amount from about 10 to about 50% w/w;
(2) the above composition wherein composition is actuated using a propellant;
(3) the above composition wherein the composition is actuated using a hydrocarbon, chlorofluorocarbon P-12 or an approximately 40:60 mixture of chlorofluorocarbon P-12 and P-114 in a range of about 2.5 to about 25% w/w;
(4) the above composition wherein the following amounts are employed:
Components % w/w Minoxidil 2
Propylene glycol USP 20
Alcohol USP 53
Polawax 4
Hydroxypropyl methylcellulose USP 0.1 Purified water USP 20;
(5) a topical composition for application to mammalian skin comprising the following components, in a range on a weight to weight basis (% w/w) :
(a) minoxidil in an amount from about 1 to about 3% on a weight to weight basis (%w/w) ;
(b) 1,3 butylene glycol in an amount from about one to about 30% w/w;
(c) a glycol in an amount up to about 50% w/w; (d) alcohol in an amount up to about 20% w/w;
(e) a surfactant and/or emulsifier and/or fatty alcohol and/or fatty alkanolamide in an amount from about 0.1 to about 15% w/w; (f) film former in an amount up to about 5% w/w; with the remainder of the composition being water; and
(g) a skin penetrant in an amount up to about 20%; with the proviso that the composition contain at least 10% of components b-c, at least 15% of components b-d and at least 0.1% of components e-g;
(6) the above composition wherein the composition is actuated by a propellant;
(7) the above composition wherein the propellant is chlorofluo¬ rocarbon P-12 or a suitable hydrocarbon in the range of about 1-15% w/w;
(8) the above composition having the following components: Components % • w/w Minoxidil 2 . ι 0 Propylene glycol 25 . 0 1,3 Butylene glycol 30 . 0 Alcohol USP 2 . 15 Polyvinyl pyrollidone and vinyl 4 . 5 acetate Cocamidopropyl betaine 1 . . 0 Polyoxyethylene 23 lauryl ether 5 . , 0 Purified water 56 . . 65 ;
(9) a composition selected from the following compositions, comprising the following components:
(a) Components % w/w Polawax A.31 (emulsifying wax NF ethoxylated stearyl alcohol with emulsifying agents) 2.0
Alcohol USP 15.0
Propylene glycol 10.0 1,3 Butylene glycol 30.0
Hydroxypropylmethylcellulose 0.2
Minoxidil 2.0
Purified water 42.8; (b) Components % w/w
Propylene glycol 25.0
Alcohol USP 20.0
Polyoxyethylene 23 lauryl ether 5.0
Minoxidil 2.0
Purified water 48.0;
(c) Components % w/w
Propylene glycol 30.0
Alcohol USP 20.0
Minoxidil 2.0
POE (23) lauryl ether 0.5
POE (2) stearyl ether 0.5
Cocamidopropyl betaine 0.5
Isostearyl alcohol 0.5
Purified water 46.0;
(d) Components % w/w
Propylene glycol 30.0
Alcohol USP 20.0
Minoxidil 2.0
Oleth-10 2.0
Purified water 46.0;
(e) Components % w/w
Propylene glycol 50.0
Alcohol USP 20.0
Minoxidil 5.0
POE (23) lauryl ether 0.5
POE (2) stearyl ether 0.5
Cocamidopropyl betaine 0.5
Isostearyl alcohol 0.5
Purified water 23.0;
(f) Components % w/w
Propylene glycol 50.0
Alcohol USP 20.0
Minoxidil 5.0
Oleth-10 3.0
Cocamidopropylbetaine 1.0
Purified water 21.0; and (g) Components % w/w
Propylene glycol 10.0
Butylene glycol 15.0
Alcohol USP 20.0 POE (23) lauryl ether 0.5
POE (2) stearyl ether 0.5
Isostearyl alcohol 0.5
Minoxidil 2.0
Purified water 50.0. Surprisingly and unexpectedly, the novel foam compositions provided herein provide a pharmaceutically elegant means of topically administering minoxidil. In addition, certain of the compositions provided herein greatly increase skin penetration as compared to the propylene glycol/ethanol/water compositions of the prior art. The use of topical minoxidil compositions, including the compositions of the present invention in the treatment and prevention of baldness is well known to an ordinarily skilled physician or dermatologist. In addition, this use is set forth in U.S. Patents 4,139,619 and 4,596,812, which patents are expressly incorporated by reference herein.
The aerosolized formulation is a homogeneous, aqueous-alcoholic emulsion system. The aerosolized formulation upon actuation produces a stabilized, homogeneous, expandable foam which breaks easily with shear. A composition of this type is sometimes referred to as a "mousse" .
By "minoxidil" is meant the compound named 2,4-pyrimidine- diamine, 6-(1-piperidinyl)-3-oxide, as well as analogs salts thereof, as described in U.S. Patents 4,139,619 and 4,596,812, which patents are incorporated by reference herein. Suitable glycols include propylene glycol, 1,3-butylene glycol, propylene glycol 200 (PEG 200), polyethylene glycol 400 (PEG 400) hexylene glycol, and dipropylene glycol.
Suitable skin penetrants include alcohols such as dodecanol and oleyl alcohol; amines, such as isopropyl a ine, diisopropyl amine, triethyl amine, triethanol amine, diisopropanolamine and ethylene diamine; carboxylic acids, such as oleic acid, linoleic acid and linolenic acid; esters, such as dibutyl sebacate, dibutyl phthalate, butyl benzoate and ethyl caprate; and others, such as Azone®, N methyl pyrollidone, bile salts and urea.
All of the compositions herein may be actuated using propellants known to those of ordinary skill in pharmaceutical or cosmetic formulations. Such propellants include hydrocarbons such as propane, isobutane or dimethyl ether and chlorofluorocarbons such as P-12,
P114, and a 40:60 mixture thereof.
By alcohol is meant any of the common alcohols used in conven¬ tional pharmaceutical or cosmetic foam compositions including ethanol, isopropanol, and the like. By e ulsi ier and/or surfactant is meant any of the known agents for modifying the surface tension of a composition and making an emulsion more stable, such as Polawax regular, Polawax A-31, cocami¬ dopropyl betaine, polyoxy ethylene (POE) 23 lauryl ether, and polyoxyethylene (POE) 2 stearyl ether. Included in the class of emulsion stabilizers are the long chain fatty alcohols and fatty alkanolamides such as lauryl alcohol, isostearyl alcohol, and cocamide DEA.
By film former is meant a high molecular weight polymer such as a cellulose derivative or resin. Hydroxypropyl methylcellulose and polyvinyl pyrollidone and vinylacetate are typical examples.
Small amounts of other components may be added to the composi¬ tion, e.g., perfumes, color additives, and the like. In particular, the addition of surfactants Span 60 and Tween 80, in ranges of 0.5 to 10% w/w, preferably 3% w/w, is desirable to improve the physical stability of the formulation.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention is seen more fully by the Examples given below. Example 1 Alcohol and propylene glycol are heated to 50-60°C and minoxidil is added and mixed until dissolved. In a separate container Polawax is heated until melted (approximately 50-60°C). To a third container of water, heated to 50-60°C, is added hydroxypropylmethyl cellulose, and mixing is continued until the dispersion is complete. The alcohol and Polawax mixtures, are homogenized using a homogenizer, and the aqueous phase is added and this total mixture is homogenized.
All three mixtures are maintained at about 50-60°C during this mixing process. After mixing, the mixture is cooled to about 40°C and added to an aerosol vial to which a propellant is added.
Using this procedure, and the appropriate amounts of starting materials, a composition containing the following percentages of components is prepared: Components % w/w
Minoxidil 2
Propylene glycol USP 20
Alcohol USP 53
Polawax Regular 4 Hydroxypropyl methylcellulose USP 1 Purified water USP 20
The resulting foam is quick-breaking and pharmaceutically elegant. Using analogous procedures, and the appropriate starting materials, all of the compositions of Claim 1 are prepared. Example 2
Procedure A
Minoxidil is dissolved in a glycol mixture. To a separate container is added POE (23) lauryl ether and POE (2) stearyl ether, lauryl alcohol, and purified water, and the mixture is heated to a temperature to dissolve the waxes. The two mixtures are combined with agitation and cooled to room temperature. Using this procedure, and the appropriate amounts of starting materials, a composition containing the following percentages of components is prepared: Components % w/w Propylene glycol 10.0
Butylene glycol 30.0
POE (23) lauryl ether 1.8
POE (2) stearyl ether 1.2
Lauryl alcohol 0.9 Minoxidil 2.0
Purified water 53.5
The resulting composition, upon actuation, is a stiff, slow- breaking foam.
Procedure B Oleyl alcohol is heated to about 60°C. In a separate container water, POE (2) stearyl ether, and POE (23) lauryl ether are combined and heated to about 60°C, with stirring. Minoxidil is added to butylene glycol and water and the mixture is stirred until the minoxidil is dissolved. The two mixtures are combined and the resulting mixture stirred until cooled to room temperature.
Using this procedure, and the appropriate amount of starting materials, a composition containing the following amounts of com- ponents is prepared:
Components % w/w
Oleyl alcohol 15.0
POE (2) Stearyl ether 8.0
POE (23) Lauryl ether 2.0 Purified water 30.0
Butylene glycol 15.0
Minoxidil 1.0
Purified water q.s. 100
The resulting composition, upon actuation, produces a stiff, creamy, slow-breaking foam. Example 3
Minoxidil is dissolved in propylene glycol and heated with mixing to 72°C. Dissolve the POE (23) lauryl ether in the purified water and heat to 72°C with mixing. In a separate container, combine and mix the POE (2) stearyl ether and the isostearyl alcohol while heating to 70°C. Combine the minoxidil and POE (23) lauryl ether solutions with mixing while maintaining at 72°C. Add the POE (2) stearyl ether-isostearyl alcohol mixture to the minoxidil solution with rapid agitation. Continue mixing until cooled to room temperature. Add the alcohol and mix until uniform.
Using this procedure, and the appropriate amount of starting materials, a composition containing the following amounts of components is prepared.
Components % w/w Propylene glycol 30.0
Alcohol USP 20.0
Minoxidil 2.0
POE (23) lauryl ether 0.5
POE (2) stearyl ether 0.5 Cocamidopropyl betaine 0.5
Isostearyl alcohol 0.5
Purified water 46.0
The resulting foam is pressure-sensitive, slow breaking and pharmaceutically elegant. Example 4
Minoxidil is dissolved in propylene glycol and heated with mixing to 72°C. The oleth-10 is combined with the purified water and heated with mixing to 72°C. The oleth-10 solution is added to the minoxidil solution with continued mixing while cooling to room temperature. Add the alcohol and mix until uniform.
Using the procedure and the appropriate amount of starting materials, a composition containing the following amounts of components is prepared:
Components % w/w
Propylene glycol 30.0
Alcohol USP 20.0
Minoxidil 2.0 Oleth-10 2.0
Purified water 46.0
The resulting foam is pressure-sensitive, slow-breaking and pharmaceutically elegant. Example 5 Using the procedure described in Example 3, and the appropriate amount of starting materials, a composition containing the following amounts of components is prepared:
Components % w/w
Propylene glycol 50.0 Alcohol USP 20.0
Minoxidil 5.0
POE (23) lauryl ether 0.5
POE (2) stearyl ether 0.5
Cocamidopropyl betaine 0.5 Isostearyl alcohol 0.5
Purified water 23.0
Note: The cocamidopropyl betaine is added to the POE (23) lauryl ether and purified water, then heated to 72°C with mixing.
The resultant foam is pressure-sensitive, slow-breaking and pharmaceutically elegant. Example 6
Using the procedure described in Example 4,and the appropriate amount of starting materials, a composition containing the following its of components is prepared:
Components % w/w
Propylene glycol 50.0
Alcohol USP 20.0
Minoxidil 5.0
Oleth-10 3.0
Cocamidopropyl betaine 1.0
Purified water 21.0
Note: The cocamidopropyl betaine is added to the purified water with the oleth-10, then heated with mixing to 72°C. Example 7
The propylene glycol, butylene glycol, POE (23) lauryl ether, minoxidil and purified water are combined and heated with mixing to 72°C. The POE (23) stearyl ether and isostearyl alcohol are combined and heated with mixing to 70°C, then added to the aqueous solution with rapid agitation. Mixing is continued while cooling to room temperature. Add the alcohol and mix until uniform.
Using this procedure, and the appropriate amount of starting materials, a composition containing the following amounts of components is prepared:
Components % w/w
Propylene glycol 10.0
Butylene glycol 15.0
Alcohol USP 20.0 POE (23) lauryl ether 0.5
POE (2) Stearyl ether 0.5
Isostearyl alcohol 0.5
Minoxidil 2.0
Purified water 50.0 Using these and analogous procedures, all of the compositions of Claim 5 are prepared. Example 8
The following hairless mouse skin transport studies were conducted on compositions prepared as in Example 1. For comparison, formulations were also tested which contain 25% and 30% water. In addition, a comparison study was run utilizing a formulation contain¬ ing 30% water applied as the aerosolized foam and also as the non- aerosolized gel. For each composition, radiolabelled formulations of minoxidil were applied to the surface of 5 hairless mouse skins (Franz cell apparatus) and transport through the stratum was corneum monitored.
Permeability coefficients and lag times for the absorption of minoxidil through the skin were calculated.
Minoxidil Topical Foam 2% (25% water)
Cell# Pe (cm/sec) T (lag) (hr)
1 1.187 x 10-7 2.146
2 101.922 x 10-7 1.895 3 2.470 x 10-7 2.107
4 2.332 x 10-7 1.658
5 1.494 x 10-7 1.825 Ave: 1.881 x 10-7 1.926
Minoxidil Topical Solution 2% Cell# Pe (cm/sec) T (lag) (hr)
1 2.164 x 10-8 3.521
2 3.141 . 10-8 4.745
3 2.267 x 10-8 2.782
4 1.503 x 10-8 4.421 5 2.703 x 10-8 4.254
Ave: 2.355 x 10-8 3.944
Minoxidil Topical Foam 2% (30% Water)
Cell# Pe (cm/sec) T (lag) (hr)
1 1.590 x 10-8 1.001 2 2.730 x 10-8 1.258
3 2.840 x 10-8 1.675
4 2.114 x 10-8 3.611
5 3.440 x 10-8 3.120 Ave: 2.543 x 10-8 2.133 Minoxidil Topical Foam 2% (20% Water)
Cell# Pe (cm/sec) T dag) (hr)
1 5.908 x 10-8* 1.504
2 2.373 x 10-7 2.142
3 1.209 x 10-7 3.109 4 1.384 x 10-7 1.881
5 1.130 x 10-7 2.618 Ave: 1.524 x 10-7 Ave (4): 2.251 * Data excluded from average Minoxidil Topical Solution 2%. (20% Water)
Cell# Pe (cm/sec) T (lag) (hr)
1 1.425 x 10-8 3.120
2 1.575 x 10-8 2.514
3 1.760 x 10-8 3.383
4 1.244 x 10-8 3.029
5 1.511 x 10-8 2.191
Ave: 1.511 x 10-8 2.847
Minoxidil Topical Foam 2% (30% Water)
Cell# Pe (cm/sec) T (la -) (hr)
1 1.012 x 10-7* 4.021
2 6.400 x 10-8 3.261
3 5.297 x 10-8 4.144
4 3.500 x 10-8 3.952
5 3.240 x 10-8 4.899 Ave: 4.608 x 10-8 Ave (4) 4.055 * Data excluded from average
Minoxidil Topical Gel 2% (30% Water)
Cell# Pe (cm/sec) T (lag) (hr)
1 1.034 x 10-7 4.129
2 1.325 x 10-7 3.611
3 2.180 x 10-7 3.217
4 1.653 x 10-7 3.217
5 1.686 x 10-7 3.034 Ave: 1.576 x 10-7 3.361
As can be seen, the minoxidil foams of Example 1 greatly increased the transport of minoxidil through the skin 10 fold as compared to the propylene glycol-ethanol-water formulations of the prior art.

Claims

CLAIMS 1. A topical composition for application to mammalian skin compris¬ ing:
(a) minoxidil in an amount from about 1 to about 5% on a weight to weight basis (%w/w) ;
(b) propylene glycol in an amount from about 10 to about 50% w/w;
(c) alcohol in an amount from about 30 to about 75% w/w;
(d) an emulsifier and/or surfactant in an amount from about 0.5 to about 10% w/w;
(e) hydroxypropyl methylcellulose in an amount from about 0.1 to 5% w/w; and
(f) water in an amount from about 10 to about 50% w/w.
2. A composition of Claim 1, wherein the composition is actuated using a propellant.
3. A composition of Claim 1, wherein the chlorofluorocarbon P-12 or an approximately 40:60 mixture of chlorofluorocarbon P-12 and P-114 in a range of about 10 to about 20% w/w, or a hydrocarbon in the range of 10 to 30% w/w.
4. A composition of Claim 3, wherein the following amounts are employed: Components % w/w
Minoxidil 2
Propylene glycol USP 20
Alcohol USP 53
Polawax 4 Hydroxypropyl methylcellulose USP 1
Purified water USP 20
5. A topical composition for application to mammalian skin compris¬ ing the following components, in a range on a weight to weight basis (% w/w) :
(a) minoxidil in an amount from about 1 to about 5% on a weight to weight basis (%w/w) ;
(b) 1,3 butylene glycol in an amount up to about 30% w/w; (c) propylene glycol in an amount up to about 50% w/w;
(d) alcohol in an amount up to about 25% w/w;
(e) surfactant and/or emulsifier and/or fatty alcohol and/or fatty alkanolamide in an amount up to about 15% w/w; (f) film former in an amount up to about 5% w/w; and (g) skin penetrant in an amount up to about 20% w/w; with the remainder of the composition being water; with the provisos that the composition contain at least 5% of components b-c, at least 15% of components b-d and, at least 0.1% of components e-g.
6. A composition of Claim 5, wherein the composition is actuated using a propellant.
7. A composition of Claim 5, wherein the propellant is a hydrocarbon or chlorofluorocarbon in the range of about 1 to 20% w/w.
8. A composition of Claim 5 comprising the following components:
Components % w/w
Minoxidil 2.0%
Propylene glycol 25.0%
1,3 Butylene glycol 30.0%
Alcohol USP 2.15
Polyvinyl pyrollidone and vinyl 4.5% acetate
Cocamidopropyl betaine 1.0%
Polyoxyethylene 23 lauryl ether 5.0%
Purified water 56.65%
9. A composition of Claim 5 comprising the following components:
Components % w/w Polawax A.31 (emulsifying wax NF ethoxylated stearyl alcohol with emulsifying agents) 2.0% Alcohol USP 15.0%
Propylene glycol 10.0%
1,3 Butylene glycol 30.0%
Hydroxypropylmethylcellulose 0.2% Minoxidil 2.0% Purified water 42.8%
10. A composition of Claim 5 comprising the following components:
Components % w/w
Propylene glycol 25.0%
Alcohol USP 20.0%
Polyoxyethylene 23 lauryl ether 5.0%
Minoxidil 2.0%
Purified water 48.0%
11. A composition of Claim 5 comprising the following components:
Components % w/w
Propylene glycol 30.0 Alcohol USP 20.0 Minoxidil 2.0
POE (23) lauryl ether 0.5
POE (2) stearyl ether 0.5
Cocamidopropyl betaine 0.5 Isostearyl alcohol 0.5
Purified water 46.0
12. A composition of Claim 5 comprising the following components: Components % w/w Propylene glycol 30.0
Alcohol USP 20.0
Minoxidil 2.0
Oleth-10 2.0
Purified water 46.0
13. A composition of Claim 5 comprising the following components: Components % w/w
Propylene glycol 50.0
Alcohol USP 20.0 Minoxidil 5.0
POE (23) lauryl ether 0.5
POE (2) stearyl ether 0.5
Cocamidopropyl betaine 0.5 Isostearyl alcohol 0.5
Purified water 23.0
14. A composition of Claim 5 comprising the following components: Components % w/w
Propylene glycol 50.0
Alcohol USP 20.0
Minoxidil 5.0
Oleth-10 3.0 Coca idopropylbetaine 1.0
Purified water 21.0
15. A composition of CLaim 5 comprising the following components: Components % w/w Propylene glycol 10.0
Butylene glycol 15.0
Alcohol USP 20.0
POE (23) lauryl ether 0.5
POE (2) stearyl ether 0.5 Isostearyl alcohol 0.5
Minoxidil 2.0
Purified water 50.0
16. A composition of Claim 1, comprising the following components:
Components % w/w
Minoxidil 2%
Propylene glycol 20%
Alcohol USP 46.5%
Polawax A-31 or Reg 4%
Span 60 3%
Tween 80 3%
Hydroxypropyl methylcellulose USP 1.5%
Purified Water USP 20%
PCT/US1987/002265 1986-09-12 1987-09-10 Foams for delivery of minoxidil WO1988001863A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US90704186A 1986-09-12 1986-09-12
US907,041 1986-09-12

Publications (1)

Publication Number Publication Date
WO1988001863A1 true WO1988001863A1 (en) 1988-03-24

Family

ID=25423423

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1987/002265 WO1988001863A1 (en) 1986-09-12 1987-09-10 Foams for delivery of minoxidil

Country Status (2)

Country Link
AU (1) AU8025787A (en)
WO (1) WO1988001863A1 (en)

Cited By (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0319027A1 (en) * 1987-12-04 1989-06-07 L'oreal Composition to induce and stimulate the hair growth and/or to reduce the hair loss containing a non-ionic surfactant and a pyrimidine derivative
EP0347328A1 (en) * 1988-06-17 1989-12-20 L'oreal Composition containing an amphoteric surfactant and a pyrimidine derivative to induce and stimulate the hair growth and/or to reduce hair loss
EP0354553A2 (en) * 1988-08-09 1990-02-14 E.R. SQUIBB & SONS, INC. Aryl cyanoguanidines: potassium channel activators and method of making same
EP0362655A1 (en) * 1988-10-01 1990-04-11 CASSELLA Aktiengesellschaft Foamable medicinal mixture
US5278169A (en) * 1988-08-09 1994-01-11 E. R. Squibb & Sons, Inc. Method of treating or prevention of fibrillation of the heart
EP0510561B1 (en) * 1991-04-24 1996-07-24 POLI INDUSTRIA CHIMICA S.p.A. Oral, cutaneous and intravaginal pharmaceutical compositions in the form of foam
WO2000007627A2 (en) * 1998-08-04 2000-02-17 Johnson & Johnson Consumer Companies, Inc. Topical delivery systems for active agents
WO2003055454A1 (en) * 2001-12-21 2003-07-10 Ponsus Pharma Ab New composition
GB2406791A (en) * 2003-10-11 2005-04-13 Nupharm Lab Ltd Foam formulation of minoxidil
US6946120B2 (en) 1998-04-22 2005-09-20 Connetics Australia Pty. Ltd. Pharmaceutical composition
WO2008110872A2 (en) * 2006-06-23 2008-09-18 Foamix Ltd. Foamable compositions and kits comprising one or more of a channel agent, a cholinergic agent, a nitric oxide donor, and related agents and their uses
US8263580B2 (en) 1998-09-11 2012-09-11 Stiefel Research Australia Pty Ltd Vitamin formulation
US8840869B2 (en) 2002-10-25 2014-09-23 Foamix Ltd. Body cavity foams
US8865139B1 (en) 2009-10-02 2014-10-21 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US8900553B2 (en) 2007-12-07 2014-12-02 Foamix Pharmaceuticals Ltd. Oil and liquid silicone foamable carriers and formulations
US8900554B2 (en) 2002-10-25 2014-12-02 Foamix Pharmaceuticals Ltd. Foamable composition and uses thereof
US9050253B2 (en) 2003-08-04 2015-06-09 Foamix Pharmaceuticals Ltd. Oleaginous pharmaceutical and cosmetic foam
US9072667B2 (en) 2009-07-29 2015-07-07 Foamix Pharmaceuticals Ltd. Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses
US9101662B2 (en) 2003-08-04 2015-08-11 Foamix Pharmaceuticals Ltd. Compositions with modulating agents
US9167813B2 (en) 2009-07-29 2015-10-27 Foamix Pharmaceuticals Ltd. Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses
US9211259B2 (en) 2002-11-29 2015-12-15 Foamix Pharmaceuticals Ltd. Antibiotic kit and composition and uses thereof
US9265725B2 (en) 2002-10-25 2016-02-23 Foamix Pharmaceuticals Ltd. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
CN105434352A (en) * 2015-12-31 2016-03-30 浙江万晟药业有限公司 Minoxidil foaming agent as well as preparation method and application thereof
US9320705B2 (en) 2002-10-25 2016-04-26 Foamix Pharmaceuticals Ltd. Sensation modifying topical composition foam
US9439857B2 (en) 2007-11-30 2016-09-13 Foamix Pharmaceuticals Ltd. Foam containing benzoyl peroxide
US9492412B2 (en) 2002-10-25 2016-11-15 Foamix Pharmaceuticals Ltd. Penetrating pharmaceutical foam
US9539208B2 (en) 2002-10-25 2017-01-10 Foamix Pharmaceuticals Ltd. Foam prepared from nanoemulsions and uses
US9622947B2 (en) 2002-10-25 2017-04-18 Foamix Pharmaceuticals Ltd. Foamable composition combining a polar solvent and a hydrophobic carrier
US9636405B2 (en) 2003-08-04 2017-05-02 Foamix Pharmaceuticals Ltd. Foamable vehicle and pharmaceutical compositions thereof
US9662298B2 (en) 2007-08-07 2017-05-30 Foamix Pharmaceuticals Ltd. Wax foamable vehicle and pharmaceutical compositions thereof
US9668972B2 (en) 2002-10-25 2017-06-06 Foamix Pharmaceuticals Ltd. Nonsteroidal immunomodulating kit and composition and uses thereof
US9682021B2 (en) 2006-11-14 2017-06-20 Foamix Pharmaceuticals Ltd. Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses
US9849142B2 (en) 2009-10-02 2017-12-26 Foamix Pharmaceuticals Ltd. Methods for accelerated return of skin integrity and for the treatment of impetigo
US9884017B2 (en) 2009-04-28 2018-02-06 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
US10398641B2 (en) 2016-09-08 2019-09-03 Foamix Pharmaceuticals Ltd. Compositions and methods for treating rosacea and acne
JP2019210268A (en) * 2018-05-30 2019-12-12 ダイヤ製薬株式会社 External preparation and method for producing external preparation

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0315648B1 (en) * 1986-09-05 1992-04-01 The Upjohn Company Sebum-dissolving nonaqueous minoxidil formulation
AUPO983897A0 (en) 1997-10-17 1997-11-06 Soltec Research Pty Ltd Topical antifungal composition
PL1917072T3 (en) 2005-06-01 2014-01-31 Glaxosmithkline Ip Dev Ltd Vitamin formulation

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4139619A (en) * 1976-05-24 1979-02-13 The Upjohn Company 6-Amino-4-(substituted amino)-1,2-dihydro-1-hydroxy-2-iminopyrimidine, topical compositions and process for hair growth
EP0188793A1 (en) * 1984-12-21 1986-07-30 Richardson-Vicks, Inc. Improved topical minoxidil composition

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4139619A (en) * 1976-05-24 1979-02-13 The Upjohn Company 6-Amino-4-(substituted amino)-1,2-dihydro-1-hydroxy-2-iminopyrimidine, topical compositions and process for hair growth
EP0188793A1 (en) * 1984-12-21 1986-07-30 Richardson-Vicks, Inc. Improved topical minoxidil composition

Cited By (81)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0319027A1 (en) * 1987-12-04 1989-06-07 L'oreal Composition to induce and stimulate the hair growth and/or to reduce the hair loss containing a non-ionic surfactant and a pyrimidine derivative
US5006332A (en) * 1988-06-17 1991-04-09 L'oreal Composition for inducing and stimulating the growth of hair and/or retarding its loss, based on an amphoteric surface-active agent and on a pyrimidine derivative
EP0347328A1 (en) * 1988-06-17 1989-12-20 L'oreal Composition containing an amphoteric surfactant and a pyrimidine derivative to induce and stimulate the hair growth and/or to reduce hair loss
US5278169A (en) * 1988-08-09 1994-01-11 E. R. Squibb & Sons, Inc. Method of treating or prevention of fibrillation of the heart
EP0354553A3 (en) * 1988-08-09 1990-04-11 E.R. SQUIBB & SONS, INC. Aryl cyanoguanidines: potassium channel activators and method of making same
EP0354553A2 (en) * 1988-08-09 1990-02-14 E.R. SQUIBB & SONS, INC. Aryl cyanoguanidines: potassium channel activators and method of making same
EP0362655A1 (en) * 1988-10-01 1990-04-11 CASSELLA Aktiengesellschaft Foamable medicinal mixture
EP0510561B1 (en) * 1991-04-24 1996-07-24 POLI INDUSTRIA CHIMICA S.p.A. Oral, cutaneous and intravaginal pharmaceutical compositions in the form of foam
US6946120B2 (en) 1998-04-22 2005-09-20 Connetics Australia Pty. Ltd. Pharmaceutical composition
WO2000007627A2 (en) * 1998-08-04 2000-02-17 Johnson & Johnson Consumer Companies, Inc. Topical delivery systems for active agents
WO2000007627A3 (en) * 1998-08-04 2000-08-17 Johnson & Johnson Consumer Topical delivery systems for active agents
US6284234B1 (en) 1998-08-04 2001-09-04 Johnson & Johnson Consumer Companies, Inc. Topical delivery systems for active agents
US6419913B1 (en) 1998-08-04 2002-07-16 Johnson & Johnson Consumer Companies, Inc. Topical delivery systems for active agents
US8263580B2 (en) 1998-09-11 2012-09-11 Stiefel Research Australia Pty Ltd Vitamin formulation
WO2003055454A1 (en) * 2001-12-21 2003-07-10 Ponsus Pharma Ab New composition
US11033491B2 (en) 2002-10-25 2021-06-15 Vyne Therapeutics Inc. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US9265725B2 (en) 2002-10-25 2016-02-23 Foamix Pharmaceuticals Ltd. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US9713643B2 (en) 2002-10-25 2017-07-25 Foamix Pharmaceuticals Ltd. Foamable carriers
US10322085B2 (en) 2002-10-25 2019-06-18 Foamix Pharmaceuticals Ltd. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US8840869B2 (en) 2002-10-25 2014-09-23 Foamix Ltd. Body cavity foams
US9668972B2 (en) 2002-10-25 2017-06-06 Foamix Pharmaceuticals Ltd. Nonsteroidal immunomodulating kit and composition and uses thereof
US9622947B2 (en) 2002-10-25 2017-04-18 Foamix Pharmaceuticals Ltd. Foamable composition combining a polar solvent and a hydrophobic carrier
US9539208B2 (en) 2002-10-25 2017-01-10 Foamix Pharmaceuticals Ltd. Foam prepared from nanoemulsions and uses
US8900554B2 (en) 2002-10-25 2014-12-02 Foamix Pharmaceuticals Ltd. Foamable composition and uses thereof
US10117812B2 (en) 2002-10-25 2018-11-06 Foamix Pharmaceuticals Ltd. Foamable composition combining a polar solvent and a hydrophobic carrier
US10821077B2 (en) 2002-10-25 2020-11-03 Foamix Pharmaceuticals Ltd. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US9492412B2 (en) 2002-10-25 2016-11-15 Foamix Pharmaceuticals Ltd. Penetrating pharmaceutical foam
US9320705B2 (en) 2002-10-25 2016-04-26 Foamix Pharmaceuticals Ltd. Sensation modifying topical composition foam
US9211259B2 (en) 2002-11-29 2015-12-15 Foamix Pharmaceuticals Ltd. Antibiotic kit and composition and uses thereof
US9101662B2 (en) 2003-08-04 2015-08-11 Foamix Pharmaceuticals Ltd. Compositions with modulating agents
US9050253B2 (en) 2003-08-04 2015-06-09 Foamix Pharmaceuticals Ltd. Oleaginous pharmaceutical and cosmetic foam
US9636405B2 (en) 2003-08-04 2017-05-02 Foamix Pharmaceuticals Ltd. Foamable vehicle and pharmaceutical compositions thereof
GB2406791B (en) * 2003-10-11 2008-02-06 Nupharm Lab Ltd Minoxidil pharmaceutical foam formulation
GB2406791A (en) * 2003-10-11 2005-04-13 Nupharm Lab Ltd Foam formulation of minoxidil
WO2008110872A3 (en) * 2006-06-23 2009-06-25 Foamix Ltd Foamable compositions and kits comprising one or more of a channel agent, a cholinergic agent, a nitric oxide donor, and related agents and their uses
WO2008110872A2 (en) * 2006-06-23 2008-09-18 Foamix Ltd. Foamable compositions and kits comprising one or more of a channel agent, a cholinergic agent, a nitric oxide donor, and related agents and their uses
US9682021B2 (en) 2006-11-14 2017-06-20 Foamix Pharmaceuticals Ltd. Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses
US10369102B2 (en) 2007-08-07 2019-08-06 Foamix Pharmaceuticals Ltd. Wax foamable vehicle and pharmaceutical compositions thereof
US9662298B2 (en) 2007-08-07 2017-05-30 Foamix Pharmaceuticals Ltd. Wax foamable vehicle and pharmaceutical compositions thereof
US11103454B2 (en) 2007-08-07 2021-08-31 Vyne Therapeutics Inc. Wax foamable vehicle and pharmaceutical compositions thereof
US9439857B2 (en) 2007-11-30 2016-09-13 Foamix Pharmaceuticals Ltd. Foam containing benzoyl peroxide
US11433025B2 (en) 2007-12-07 2022-09-06 Vyne Therapeutics Inc. Oil foamable carriers and formulations
US9549898B2 (en) 2007-12-07 2017-01-24 Foamix Pharmaceuticals Ltd. Oil and liquid silicone foamable carriers and formulations
US8900553B2 (en) 2007-12-07 2014-12-02 Foamix Pharmaceuticals Ltd. Oil and liquid silicone foamable carriers and formulations
US9161916B2 (en) 2007-12-07 2015-10-20 Foamix Pharmaceuticals Ltd. Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof
US9795564B2 (en) 2007-12-07 2017-10-24 Foamix Pharmaceuticals Ltd. Oil-based foamable carriers and formulations
US10588858B2 (en) 2009-04-28 2020-03-17 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
US10363216B2 (en) 2009-04-28 2019-07-30 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
US10213384B2 (en) 2009-04-28 2019-02-26 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
US9884017B2 (en) 2009-04-28 2018-02-06 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
US10350166B2 (en) 2009-07-29 2019-07-16 Foamix Pharmaceuticals Ltd. Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses
US9572775B2 (en) 2009-07-29 2017-02-21 Foamix Pharmaceuticals Ltd. Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses
US10092588B2 (en) 2009-07-29 2018-10-09 Foamix Pharmaceuticals Ltd. Foamable compositions, breakable foams and their uses
US11219631B2 (en) 2009-07-29 2022-01-11 Vyne Pharmaceuticals Inc. Foamable compositions, breakable foams and their uses
US9072667B2 (en) 2009-07-29 2015-07-07 Foamix Pharmaceuticals Ltd. Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses
US9167813B2 (en) 2009-07-29 2015-10-27 Foamix Pharmaceuticals Ltd. Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses
US10463742B2 (en) 2009-10-02 2019-11-05 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US10610599B2 (en) 2009-10-02 2020-04-07 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US10265404B2 (en) 2009-10-02 2019-04-23 Foamix Pharmaceuticals Ltd. Compositions, gels and foams with rheology modulators and uses thereof
US10322186B2 (en) 2009-10-02 2019-06-18 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US9675700B2 (en) 2009-10-02 2017-06-13 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US9849142B2 (en) 2009-10-02 2017-12-26 Foamix Pharmaceuticals Ltd. Methods for accelerated return of skin integrity and for the treatment of impetigo
US8865139B1 (en) 2009-10-02 2014-10-21 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US10213512B2 (en) 2009-10-02 2019-02-26 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US10029013B2 (en) 2009-10-02 2018-07-24 Foamix Pharmaceuticals Ltd. Surfactant-free, water-free formable composition and breakable foams and their uses
US10086080B2 (en) 2009-10-02 2018-10-02 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US8871184B2 (en) 2009-10-02 2014-10-28 Foamix Ltd. Topical tetracycline compositions
US10517882B2 (en) 2009-10-02 2019-12-31 Foamix Pharmaceuticals Ltd. Method for healing of an infected acne lesion without scarring
US10137200B2 (en) 2009-10-02 2018-11-27 Foamix Pharmaceuticals Ltd. Surfactant-free water-free foamable compositions, breakable foams and gels and their uses
US10238746B2 (en) 2009-10-02 2019-03-26 Foamix Pharmaceuticals Ltd Surfactant-free water-free foamable compositions, breakable foams and gels and their uses
US10821187B2 (en) 2009-10-02 2020-11-03 Foamix Pharmaceuticals Ltd. Compositions, gels and foams with rheology modulators and uses thereof
US8992896B2 (en) 2009-10-02 2015-03-31 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US10835613B2 (en) 2009-10-02 2020-11-17 Foamix Pharmaceuticals Ltd. Compositions, gels and foams with rheology modulators and uses thereof
US8945516B2 (en) 2009-10-02 2015-02-03 Foamix Pharmaceuticals Ltd. Surfactant-free water-free foamable compositions, breakable foams and gels and their uses
US10946101B2 (en) 2009-10-02 2021-03-16 Vyne Therapeutics Inc. Surfactant-free water-free foamable compositions, breakable foams and gels and their uses
US10967063B2 (en) 2009-10-02 2021-04-06 Vyne Therapeutics Inc. Surfactant-free, water-free formable composition and breakable foams and their uses
CN105434352A (en) * 2015-12-31 2016-03-30 浙江万晟药业有限公司 Minoxidil foaming agent as well as preparation method and application thereof
US10849847B2 (en) 2016-09-08 2020-12-01 Foamix Pharamaceuticals Ltd. Compositions and methods for treating rosacea and acne
US10398641B2 (en) 2016-09-08 2019-09-03 Foamix Pharmaceuticals Ltd. Compositions and methods for treating rosacea and acne
US11324691B2 (en) 2016-09-08 2022-05-10 Journey Medical Corporation Compositions and methods for treating rosacea and acne
JP2019210268A (en) * 2018-05-30 2019-12-12 ダイヤ製薬株式会社 External preparation and method for producing external preparation

Also Published As

Publication number Publication date
AU8025787A (en) 1988-04-07

Similar Documents

Publication Publication Date Title
WO1988001863A1 (en) Foams for delivery of minoxidil
EP1073439B1 (en) Pharmaceutical composition
EP0315648B1 (en) Sebum-dissolving nonaqueous minoxidil formulation
WO1988006041A1 (en) Percutaneous absorption promoter and dermatologic preparation for external use
US4145413A (en) Artificial skin darkening composition and method of using the same
JPH0317804B2 (en)
JPH08277209A (en) Revitalizing hair tonic
US7056498B2 (en) Composition containing aminophenol derivative, use thereof, and process for dissolving aminophenol derivative
JPH10265343A (en) Sustained release hair growing agent
US20030031639A1 (en) Hair growth promoter
JPH11349451A (en) Hair grower
JP2810040B2 (en) Hair restorer for scalp and hair
JPH07316022A (en) Hair tonic
JP2810041B2 (en) Hair restorer for scalp and hair
WO2003030844A1 (en) Long-acting hair growth stimulant preparations
JPH0971513A (en) Hair tonic
JP3808412B2 (en) Hair nourishing
AU757601B2 (en) Pharmaceutical composition
JPH01139523A (en) Hair tonic agent
JPH082774B2 (en) [Benzo-1,2,4-thiadiazine] -1-dioxide derivative-dissolved composition
JPH08259435A (en) Dermal preparation for external use
JPH05286839A (en) Hair-raising agent
JPH07206646A (en) Hair tonic
JPH0818951B2 (en) [Benzo-1,2,4-thiadiazine] -1-dioxide derivative-dissolved composition

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU DK FI JP KR NO US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LU NL SE