US20110124736A1 - Compositions and methods for stimulating hair growth - Google Patents

Compositions and methods for stimulating hair growth Download PDF

Info

Publication number
US20110124736A1
US20110124736A1 US12940711 US94071110A US2011124736A1 US 20110124736 A1 US20110124736 A1 US 20110124736A1 US 12940711 US12940711 US 12940711 US 94071110 A US94071110 A US 94071110A US 2011124736 A1 US2011124736 A1 US 2011124736A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
composition
bimatoprost
carbon atoms
radical
group consisting
Prior art date
Legal status (The legal status 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 status listed.)
Abandoned
Application number
US12940711
Inventor
John T. Trogden
Adnan K. Salameh
Chetan P. Pujara
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Allergan Inc
Original Assignee
Allergan Inc
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

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/557Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/5575Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/02Cosmetics or similar toilet preparations characterised by special physical form
    • A61K8/0216Solid or semisolid forms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/02Cosmetics or similar toilet preparations characterised by special physical form
    • A61K8/0216Solid or semisolid forms
    • A61K8/022Powders; Compacted Powders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/02Cosmetics or similar toilet preparations characterised by special physical form
    • A61K8/04Dispersions; Emulsions
    • A61K8/042Gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/02Cosmetics or similar toilet preparations characterised by special physical form
    • A61K8/04Dispersions; Emulsions
    • A61K8/046Aerosols; Foams
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • A61K8/345Alcohols containing more than one hydroxy group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37Esters of carboxylic acids
    • A61K8/375Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/39Derivatives containing from 2 to 10 oxyalkylene groups
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/40Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/41Amines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/40Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42Amides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/72Cosmetics or similar toilet preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81Cosmetics or similar toilet preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8141Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • A61K8/8147Homopolymers or copolymers of acids; Metal or ammonium salts thereof, e.g. crotonic acid, (meth)acrylic acid; Compositions of derivatives of such polymers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/72Cosmetics or similar toilet preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84Cosmetics or similar toilet preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/86Polyethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/12Aerosols; Foams
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/12Aerosols; Foams
    • A61K9/122Foams; Dry foams
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILET PREPARATIONS
    • A61Q7/00Preparations for affecting hair growth
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59Mixtures
    • A61K2800/592Mixtures of compounds complementing their respective functions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74Biological properties of particular ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/87Application Devices; Containers; Packaging

Abstract

Methods and compositions for stimulating the growth of hair are disclosed wherein said compositions include a cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compound represented by the formula I
Figure US20110124736A1-20110526-C00001
    • wherein the dashed bonds represent the presence or absence of a double bond which can be in the cis or trans configuration and A, B, Z, X, R1 and R2 are as defined in the specification and a penetration enhancer. Such compositions are used in stimulating hair growth of human or non-human animals.

Description

    RELATED APPLICATION
  • This application claims the benefit of U.S. Provisional Application Ser. No. 61/259,368, filed Nov. 9, 2009, the disclosure of which is hereby incorporated in its entirety herein by reference.
  • FIELD OF THE INVENTION
  • Disclosed herein are compositions and methods for stimulating the growth of hair and treating disorders resulting in hair loss wherein said compositions include a cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compound represented by the formula I:
  • Figure US20110124736A1-20110526-C00002
  • wherein the dashed bonds represent the presence or absence of a double bond which can be in the cis or trans configuration and A, B, Z, X, R1 and R2 are as defined in the specification and a penetration enhancer. Such compositions are used in stimulating hair growth of human or non-human animals.
  • BACKGROUND OF THE INVENTION
  • Dermatologists recognize many different types of hair loss, the most common being “alopecia” or “baldness” wherein humans (mostly males) begin losing scalp hair at the temples and on the crown of their head. However, hair loss may be due to many other disorders.
  • Hair loss is often accompanied by a change in the hair growth cycle. All mammalian hair passes through a life cycle that includes the anagen phase, the catagen phase and the telogen phase. The anagen phase is the period of active hair growth. In the scalp, this phase lasts from 3-5 years. The catagen phase is a short 1-2 week transitional phase between the anagen phase and the telogen phase. The final telogen phase is considered a “resting phase” where all growth ceases. This phase is also relatively short-lived lasting about 3-4 months before the hair is shed and a new one begins to grow. With the onset of baldness, a successively greater proportion of hairs are in the telogen phase with correspondingly fewer in the active growth anagen phase.
  • Additionally, different types of hair exist including terminal hairs, vellus hairs and modified terminal hairs. Terminal hairs are coarse, pigmented, long hairs in which the bulb of the hair follicle is seated deep in the dermis. Vellus hairs, on the other hand, are fine, thin, non-pigmented short hairs in which the hair bulb is located superficially in the dermis. Modified terminal hairs are seen in eye lashes and eye brows. As alopecia progresses, a transition takes place wherein the hairs themselves change from the terminal to the vellus type. Accordingly, alopecia (baldness) also includes a deficiency in terminal hairs.
  • One non-drug treatment for alopecia is hair transplantation. Plugs of skin containing hair are transplanted from areas of the scalp where hair is growing to bald areas. This approach can be reasonably successful, however it is costly, time-consuming and painful. Other non-drug related approaches to treating alopecia include ultra-violet radiation, massage, psychiatric treatment and exercise therapy. None of these approaches, however, have been generally accepted as effective. Even such things as revascularization surgery or acupuncture have shown little, if any, effect.
  • SUMMARY OF THE INVENTION
  • Compositions and methods are disclosed herein for topical application of an effective amount of at least one penetration enhancer and cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compound represented by the formula I:
  • Figure US20110124736A1-20110526-C00003
  • wherein the dashed bonds represent the presence or absence of a double bond which can be in the cis or trans configuration, A is an alkylene or alkenylene radical having from two to six carbon atoms, which radical can be interrupted by one or more oxo radicals and substituted with one or more hydroxy, oxo, alkyloxy or alkylcarboxy groups wherein the alkyl radical comprises from one to six carbon atoms; B is a cycloalkyl radical having from three to seven carbon atoms, or an aryl radical, selected from the group consisting of hydrogen, a lower alkyl radical having from four to ten carbon atoms wherein the heteroatom is selected from the group consisting of nitrogen, oxygen and sulfur atoms; X is —N(R4)2 wherein R4 is selected from the group consisting of hydrogen, a lower alkyl radical having from one to six carbon atoms,
  • Figure US20110124736A1-20110526-C00004
  • wherein R5 is a lower alkyl radical having from one to six carbon atoms; Z is =0; one of R1 and R2 is ═O, —OH or a—O(CO)R6 group, and the other one is —OH or —O(CO)R6, or R1 is ═O and R2 is H, wherein R6 is a saturated or unsaturated acyclic hydrocarbon group having from 1 to about 20 carbon atoms, or
    —(CH2)mR7 wherein m is 0 or an integer of from 1 to 10, and R7 is cycloalkyl radical, having from three to seven carbon atoms, or a hydrocarbyl aryl or heteroaryl radical, as defined above in free form or a pharmaceutically acceptable salt thereof, in association with a penetration enhancer in particular formulations adapted for topical application to mammalian skin.
  • In one embodiment, the cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compound represented by the formula I is the compound bimatoprost.
  • Another embodiment includes a composition comprising bimatoprost at a concentration of about 0.001-1.5% w/w, from 0.01-1.0% w/w, from 0.02-1.0% w/w, 0.03 to about 1.0% w/w, 0.03 to 0.9% w/w, 0.04 to 0.8% w/w, 0.05-0.7% w/w, 0.06%-0.6% w/w, 0.07%-0.5% w/w, 0.08-0.4% w/w, 0.09-0.3% w/w, 0.1% w/w, 0.2% w/w, 0.3% w/w, 0.4% w/w, 0.5% w/w, 0.6% w/w, 0.7% w/w, 0.8% w/w, 0.9% w/w and 1.0% w/w. The following excipients maybe also be included: Carbomer at a concentration of about 0.05-1.0% w/w; base at a concentration of about 0.01 to about 2.0% w/w; ethanol at a concentration of about 10 to about 90% w/w; glycerin at a concentration of about 1.0 to about 20% w/w; diethylene glycol monoethyl ether at a concentration of about 1.0 to about 50% w/w; polysorbate 20 at a concentration of about 0.1 to about 5.0% w/w; polysorbate 40 at a concentration of about 0.1 to about 5.0% w/w; polysorbate 60 at a concentration of about 0.1 to about 5.0% w/w; polysorbate 80 at a concentration of about 0.1 to about 5.0% w/w; PPG-5 ceteth-20 at a concentration of about 0.1 to about 5.0% w/w; oleic acid at a concentration of about 0.1 to about 5.0% w/w; isostearyl isostearate at a concentration of about 0.1 to about 10% w/w; isopropyl myristate at a concentration of about 0.1 to about 10% w/w; dipropylene glycol dimethyl ether at a concentration of about 1 to about 50% w/w; diethylene glycol at a concentration of about 1 to about 50% w/w; dipropylene glycol at a concentration of about 1 to about 50% w/w; caprylic/capric at a concentration of about 0.1 to about 10% w/w; benzyl alcohol at a concentration of about 0.1 to about 2.0% w/w; silicone at a concentration of about 0.1 to about 10% w/w; and/or water at a concentration of about 0 to about 90% w/w.
  • Another embodiment includes a composition comprising bimatoprost at about 0.1% w/w; carbomer at about 0.10% w/w; NaOH at about 0.035% w/w; ethanol at about 15.0% w/w; diethylene glycol monoethyl ether at about 10.0% w/w; and water at about 74.8% w/w.
  • Another embodiment includes a composition comprising bimatoprost at about 0.1% w/w; carbomer at about 0.15% w/w; triethylamine (TEA) at about 0.22% w/w; ethanol at about 15.0% w/w; diethylene glycol monoethyl ether at about 10.0% w/w; polysorbate 20 at about 4.0% w/w; and water at about 70.5% w/w.
  • Another embodiment includes a composition comprising bimatoprost at about 0.1% w/w; carbomer at about 0.125% w/w; TEA at about 0.18% w/w; ethanol at about 30.0% w/w; diethylene glycol monoethyl ether at about 20.0% w/w; and water at about 49.59% w/w.
  • Another embodiment includes a composition comprising bimatoprost at about 0.1% w/w; carbomer at about 0.10% w/w; TEA at about 0.15% w/w; ethanol at about 30.0% w/w; propylene glycol at about 20% w/w; and water at about 49.7% w/w.
  • Another embodiment includes a composition comprising bimatoprost at about 0.1% w/w; carbomer at about 0.20% w/w; TEA at about 0.22% w/w; ethanol at about 60.0% w/w; glycerin at about 5.0% w/w; and water at about 34.48% w/w.
  • Another embodiment includes a composition comprising bimatoprost at about 0.1% w/w; carbomer at about 0.25% w/w; TEA at about 0.38% w/w; ethanol at about 60.0% w/w; polysorbate 20 at about 4.0% w/w; and water at about 35.27% w/w.
  • Another embodiment includes a composition comprising bimatoprost at about 0.1% w/w; carbomer at about 0.25% w/w; TEA at about 0.38% w/w; ethanol at about 50.0% w/w; diethylene glycol monoethyl ether at about 10% w/w; polysorbate 20 at about 4.0% w/w; and water at about 35.27% w/w.
  • The compositions were manufactured using the following general procedure. Non-aqueous components (e.g. bimatoprost, ethanol, glycols) were combined in a beaker and stirred using a propeller type overhead mixer until the solution was clear. Water was added to the non-aqueous mixture followed by the addition of the thickening agent. Upon dispersion of the thickening agent, a base was added to neutralize the polymer and thicken the solution into a gel other desired composition.
  • DETAILED DESCRIPTION
  • Bimatoprost is a moderately soluble compound intended for topical delivery to the skin to stimulate hair growth. Hair growth includes, without limitation, stimulating the conversion of vellus hair to growth as terminal hair as well as increasing the rate of growth of terminal hair. Embodiments disclosed herein provide formulations of bimatoprost and similar compounds with penetration enhancers. These penetration enhancers facilitate active component penetration and/or maintenance at their site of action in the skin. Formulations disclosed herein can be self-preserved or contain an antimicrobial agent such as benzyl alcohol.
  • In accordance with embodiments disclosed herein, active components are represented by
  • Figure US20110124736A1-20110526-C00005
  • The active components are provided in particular formulations that include penetration enhancers. Some examples of representative compounds useful in the practice of embodiments disclosed herein include the compounds shown in Table 1:
  • TABLE 1
    Representative Compounds
    cyclopentane heptenamide-5-cis-2-(3α-hydroxy-5-phenyl-1-trans-
    pentenyl)-3,5-dihydroxy, [1α,2β,3α,5α] cyclopentane N,N-dimethyl-
    heptenamide-5-cis-2-(3α-hydroxy-5-phenyl-1-trans-penten-yl)-3,5-
    dihydroxy, [1α,2β,3α,5α]
    cyclopentane heptenylamide-5-cis-2-(3α-hydroxy-4-meta-chlorophenoxy-
    1-trans-pent-enyl)-3,5-dihydroxy, [1α,2β,3α,5α]
    cyclopentane heptenylamide-5-cis-2-(3α-hydroxy-4-trifluoromethylphen-
    oxy-1-trans--pentenyl)-3,5-dihydroxy, [1α,2β,3α,5α]
    cyclopentane N-isopropyl heptenamide-5-cis-2-(3α-hydroxy-5-phenyl-1-
    trans-pentenyl)-3,5-dihydroxy, [1α,2β,3α,5α]
    cyclopentane N-ethyl heptenamide-5-cis-2-(3α-hydroxy-5-phenyl-1-
    trans-pentenyl)-3,5-dihydroxy, [1α,2β,3α,5α]
    cyclopentane N-methyl heptenamide-5-cis-2-(3α-hydroxy-5-phenyl-1-
    trans-pentenyl)-3,5-dihydroxy, [1α,2β,3α,5α]
    cyclopentane heptenamide-5-cis-2-(3α-hydroxy-4-meta-chlorophenoxy-1-
    trans-buteny-l)-3,5-dihydroxy, [1α,2β,3α,5α]
  • In one embodiment, the compound is a cyclopentane heptanoic acid, 2-(phenyl alkyl or phenyloxyalkyl) represented by the formula II:
  • Figure US20110124736A1-20110526-C00006
  • wherein y is 0 or 1, x is 0 or 1 and x and y are not both 1, Y is selected from the group consisting of alkyl, halo, e.g. fluoro, chloro, etc., nitro, amino, thiol, hydroxy, alkyloxy, alkylcarboxy, halo substituted alkyl wherein said alkyl radical comprises from one to six carbon atoms, etc. and n is 0 or an integer of from 1 to 3 and R3 is ═O, —OH or —O(CO)R6 wherein R6 is as defined above or a pharmaceutically acceptable salt thereof.
  • In another embodiment, the compound is a compound of formula III:
  • Figure US20110124736A1-20110526-C00007
  • wherein hatched lines indicate a configuration, solid triangles are used to indicate 13 configuration. In another embodiment, y is 1 and x is 0 and R1, R2 and R3 are hydroxy.
  • One exemplary compound is cyclopentane N-ethyl heptanamide-5-cis-2-(3α-hydroxy-5-phenyl-1-trans-pentenyl)-3,5-dihy-droxy, [1α,2β,3α,5α], also known as bimatoprost and sold under the name of LUMIGAN® by Allergan, Inc., California, USA. This compound has the following structure:
  • Figure US20110124736A1-20110526-C00008
  • The synthesis of the above compounds has been disclosed in U.S. Pat. No. 5,607,978 which is incorporated by reference in its entirety.
  • Effective amounts of the active compounds can be determined by one of ordinary skill in the art but will vary depending on the compound employed, frequency of application and desired result. The compound will generally range from about 1×10-7 to about 50% w/w of the composition, in one embodiment from about 0.001 to about 50% w/w of the composition and in another embodiment from about 0.1 to about 30% w/w of the composition. Ranges of within about 10-50% w/w; about 20-50% w/w; about 30-40% w/w and about 35% are also included.
  • The pharmaceutical formulations disclosed herein can include one or more penetration enhancers. The phrase “penetration enhancers” includes any agent that facilitates the transfer of active components to their site of action or maintains them at their site of action. Non-limiting examples of classes of appropriate penetration enhancers include alcohols, glycols, fatty acids, ethers, esters, occlusive agents and surface active agents. Representative examples of these classes are provided below.
  • Alcohols include, without limitation, ethanol, propanol, N-propanol, isopropanol, butyl alcohol, octanol, benzyl alcohol and acetyl alcohol, in one embodiment, as described in U.S. Pat. No. 5,789,244, the entire contents of which are incorporated by reference herein. Fatty alcohols include, for example, stearyl alcohol and oleyl alcohol.
  • Glycols include, without limitation, glycerine, propyleneglycol, polyethyleneglycol and other low molecular weight glycols such as glycerol and thioglycerol.
  • Fatty acids, esters and ethers include, without limitation, oleic acid, palmitoleic acid, straight chain C4-C20 saturated monocarboxylic and dicarboxylic acids, octanoic and decanoic acids, methyl laurate, ethyl oleate, polyethylene glycol monolaurate, propylene glycol monolaurate, propylene glycerol dilaurate, glycerol monolaurate, glycerol monooleate, isopropyl n-decanoate, octyldodecyl myristate, diethylene glycol monoethyl ether, diethylene glycol monomethyl ether and compounds wherein a C2-C4 alkane diol or triol is substituted with one or two fatty ether substituents.
  • Occlusive agents include, without limitation, silicones, mineral oils and greases, long chain acids, animal fats and greases, vegetable fats and greases, water insoluble polymers, paraffin, paraffin oil, liquid paraffin, petrolatum, liquid petrolatum, white petrolatum, yellow petrolatum, microcrystalline wax and ceresin.
  • Surface active agents include without limitation, polysorbate 20, 40, 60 and 80, TWEEN® (20, 40, 60, 80), POLOXAMER® (231, 182, 184), sodium dodecyl sulfate (SDS), lecithin, lysolecithin, nonylphenoxypolyoxyethylene, lysophosphatidylcholine, polyethylenglycol 400, polyoxyethylene ethers, polyglycol ether surfactants, DMSO, sodium laurate, sodium lauryl sulfate, cetyltrimethylammonium bromide, and benzalkonium chloride.
  • Additional penetration enhancers will be known to those of ordinary skill in the art of topical drug delivery, and/or are described in the pertinent texts and literature.
  • Embodiments disclosed herein can also include viscosity increasing agents. Appropriate agents include, without limitation, methylcellulose, polyvinyl alcohol, polyvinyl pyrrolidone, hyaluronic acid and chondroitin sulfate.
  • Certain embodiments disclosed herein can include preservatives including, without limitation, benzyl alcohol, benzalkonium chloride, chlorhexidine, chlorobutanol, methyl-, propyl-, or butyl-parahydroxybenzoic acids, phenylmercuric salts including, without limitation, nitrate, chloride, acetate, and borate and betain.
  • Various other additives may be included in the compositions of the present invention in addition to those identified above. These include, but are not limited to, antioxidants, astringents, perfumes, emollients, pigments, dyes, humectants, propellants, and sunscreen agents, as well as other classes of materials whose presence may be cosmetically, medicinally or otherwise desirable. The compositions and formulations may also be taken in conjunction with minoxidil and propecia.
  • Compositions can also be formulated as “slow-releasing” formulations so that the activity of active components is sustained for a longer period of time between treatments.
  • While particular embodiments disclosed herein can include each of the components discussed above, other particular embodiments can be required to be “substantially free” of one or more of these components in various combinations. “Substantially free”, as used herein, means that the component is not added to a formulation and cannot be present in any amount greater than about 1% w/w.
  • While not limiting the scope of express exclusion of the preceding paragraph, particular embodiments disclosed herein can be substantially free of one or more of bimatoprost, carbomer, NaOH (s), TEA, ethanol, glycerin, diethylene glycol, monoethyl ether, propylene glycol, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, PPG-5 ceteth-20, oleic acid, isostearyl isostearate, isopropyl myristate, dipropylene glycol dimethyl ether, diethylene glycol, dipropylene glycol, triglycerides, caprylic/capric, benzyl alcohol, silicone and water.
  • All components of formulations described herein will be included in amounts that are dermatologically-acceptable. As used herein, “dermatologically-acceptable” means that the compositions or components thereof are suitable for use in contact with human skin without undue toxicity, incompatibility, instability, allergic response, and the like. As used in herein as applied to active agents and excipients, the term “about” refers to variations in concentrations which are considered to be bioequivalent.
  • Embodiments disclosed herein find application in mammalian species, including both humans and animals. In humans, the compounds of embodiments disclosed herein can be applied without limitation, to the scalp, face, beard, head, pubic area, upper lip, eyebrows, and eyelids. The compositions of the present inventions may be used for treating various hair loss disorders including but not limited to alopecia greata, telogen effluvium, anagen effluvium, cicatricial alopecia and scarring alopecia; hair shaft abnormalities such as trichorrexis nodosa, loose anagen syndrome, trichotillomania and traction alopecia; infectious hair disorders such as tiniea capitis, sebohorreic dermatitis, and follicullitus of the scalp; genetic disorders such as androgenetic alopecia and patients undergoing hair loss due to chemotherapy, hormonal imbalance (e.g., thyroid conditions such as hypothyroidism and hyperthyroidism, pregnancy, child birth, discontinuation of birth control pills and changes in menstrual cycle), fungal infection of the scalp such as ringworm, medicines which cause hair loss such as anti-coagulants, medicine for gout, depression, high blood pressure and certain heart medications. The formulations of the present invention may be used to treat hair loss related to other disease such as diabetes, lupus, and poor nutrition, mental and physical stress such as due to surgery, illness and high fever. Environmental factors and chemicals used in hair treatment (dying, tinting and bleaching).
  • In animals raised for their pelts, e.g., mink, the formulations can be applied over the entire surface of the body to improve the overall pelt for commercial reasons. The process can also be used for cosmetic reasons in animals, e.g., applied to the skin of dogs and cats having bald patches due to mange or other diseases causing a degree of alopecia.
  • The compositions and methods of the present invention may be applied to patients suffering from hair loss or in healthy patients simply wanting to increase hair growth in any part of the body.
  • The compositions disclosed herein are formulated for topical administration. The term “topical administration” as used herein includes applying a formulation as described herein to the outer skin or hair. The application will generally occur at or near the area of desired hair growth.
  • Accordingly, appropriate formulation or composition types include, without limitation, solutions, gels, ointments, foams, films, liniments, creams, shampoos, lotions, pastes, jellies, sprays and aerosols. Such formulation types can be applied in swaths, patches, applicators or through the use of impregnated dressings depending on the situation and part of the body to be treated.
  • Typically, the formulations described herein will be applied repeatedly for a sustained period of time to the part of the body to be treated. In particular embodiments, formulations disclosed herein can include one or more applications daily, one or more applications weekly, one or more applications monthly or one or more applications yearly for a period of treatment of at least one day, at least one week, at least one month, at least one year or until the treatment has achieved or achieved and maintained a desired result.
  • Formulations described herein will be administered in safe and effective amounts. As used herein, “safe and effective amounts” include an amount sufficient so that the composition provides the desired hair growth stimulation effect at a reasonable benefit/risk ratio attendant with any medical treatment. Within the scope of sound medical judgment, the amount of active components used can vary with the particular condition being treated, the severity of the condition, the cause of the condition, the duration of the treatment, the specific active component employed, its concentration, the specific vehicle utilized, the general health of the patient, the tolerance of the patient to various effects of the administration, other drugs being administered to the patient, and like factors within the specific knowledge and expertise of the patient or attending physician.
  • For daily administration, an appropriate dose can include, without limitation, about 0.1 ng to about 100 mg, about 1 ng to about 10 mg per day or in another embodiment about 10 ng to about 1 mg per day.
  • Non-limiting examples of some components with their appropriate concentration ranges and function are provided in Table 1 below. Particular examples of non-limiting formulations or compositions are provided in Table 2.
  • TABLE 1
    Example Components with Function and Concentration Ranges
    Ingredient Function Composition (% w/w)
    bimatoprost Active 0.03-1.0 
    carbomer Thickener 0.05-1.0 
    base Neutralizing Agent 0.01-2.0 
    ethanol Penetration 10-90
    glycerin enhancers 1.0-20 
    diethylene glycol 1.0-50 
    monoethyl ether
    propylene glycol  1-50
    polysorbate 20 0.1-5.0
    polysorbate 40 0.1-5.0
    polysorbate 60 0.1-5.0
    polysorbate 80 0.1-5.0
    PPG-5 ceteth-20 0.1-5.0
    oleic acid 0.1-5.0
    isostearyl isostearate 0.1-10 
    isopropyl myristate 0.1-10 
    dipropylene glycol  1-50
    dimethyl ether
    diethylene glycol  1-50
    dipropylene glycol  1-50
    caprylic/capric triglycerides 0.1-10 
    benzyl alcohol Preservative 0.1-2.0
    silicone Occlusive Agent 0.1-10 
    water Vehicle  0-90
  • TABLE 2
    Example Compositions
    Ingredient Function Composition (% w/w)
    bimatoprost Active 0.1 0.1 0.1 0.1 0.1 0.1 0.1
    carbomer Thickener 0.10 0.15 0.125 0.10 0.20 0.25 0.25
    NaOH (s) Neutralizing 0.035
    Agent
    TEA Neutralizing 0.22 0.18 0.15 0.22 0.38 0.38
    Agent
    ethanol Penetration 15.0 15.0 30.0 30.0 60.0 60.0 50.0
    glycerin enhancers 5.0
    diethylene glycol 10.0 10.0 20.0 10
    monoethyl ether
    propylene glycol 20
    polysorbate 20 4.0 4.0 4.0
    water Vehicle 74.8 70.5 49.595 49.7 34.48 35.27 35.27
  • Example I Preparations of Bimatoprost Scalp Hair Growth Gel Compositions
  • Ethyl alcohol is weighed into a suitable media jar equipped for mixing, bimatoprost is then added to the ethyl alcohol and stirred at moderate speed until bimatoprost is dissolved. Into separate mixing tank water for injection, glycerin, diethylene glycol monoethyl ether, and propylene glycol are added and mixed until the solvents are dispersed. Ethyl alcohol/bimatoprost solution is then added into the water mixture and mixed until the components are homogenously mixed (about 5 minutes of mixing). To the above mixture the carbomer thickener is added and mixed until well dispersed, once dispersed a base is added to thicken the solution into a gel. Representative formulations made according to the method above are shown in Table 3 below.
  • TABLE 3
    Bimatoprost Scalp Hair Growth Topical Gel Formulations
    Bimatoprost 0.03% Bimatoprost 0.1% Bimatoprost 0.3% Bimatoprost 0.2%
    (Propylene Glycol) (Propylene Glycol) (Propylene Glycol) (Propylene Glycol)
    Ingredient (% w/w) Function Solution Solution Solution Solution
    Bimatoprost Active 0.03 0.1 0.3 0.2
    Propylene glycol Penetration 10.0 10.0 10.0 10.0
    Diethylene glycol enhancer 10.0 10.0 10.0 10.0
    monoethyl ether
    Ethyl alcohol 30.0 30.0 30.0 30.0
    Glycerin 2.0 2.0 2.0 2.0
    Carbomer (Ultrez 10) Thickener 0.15 0.15 0.15 0.15
    Triethanolamine Neutralizing 0.16 0.16 0.16 0.16
    agent
    Purified water Vehicle 47.66 47.59 47.39 47.49
  • Example II In Vivo Treatment
  • A study is initiated to systematically evaluate the appearance of hair on the scalp and eyebrows who are administered bimatoprost gel formulations as in Table 3. The study involves 10 subjects, 5 male, 5 female, average age 70 years, (ranging from 50-94 years). Each subject is treated daily by the topical application of bimatoprost by the 0.3% w/w bimatoprost formulation of Table 3.
  • The study is limited to subjects who have administered bimatoprost for more than 3 months. The mean duration of exposure to the 0.3% w/w bimatoprost gel formulation prior to assessing the parameter of hair or eyebrow growth between the control and study eye is 129 days (range 90-254 days). Observations are made under high magnification at a slit lamp biomicroscope. Documentation of differences between the control and treatment areas is accomplished using a camera specially adapted for use with a slit lamp biomicroscope.
  • The Results of the Observations Will be as Follows:
  • Length of hair and eyebrows: Increased length of hair in both groups is regularly observed. The difference in length varies from approximately 10% to as much as 30%.
  • Number of hairs and eyebrows: Increased numbers of hairs are observed on the scalp and eyebrows of each patient. The difference in number of hair and eyebrows varies from approximately 5% to as much as 30%. Whether statistically significant or not, bimatoprost with a penetration enhancer will provide better and/or faster results than bimatoprost without a penetration enhancer.
  • The foregoing observations will establish that 0.03% w/w bimatoprost composition penetrates skin and grows hair.
  • Example III Topical Cream
  • A topical 0.2% w/w bimatoprost cream is prepared as follows: Tegacid and spermaceti are melted together at a temperature of 70-80° C. Methylparaben is dissolved in about 500 gm of water and propylene glycol, polysorbate 80, bimatoprost and a penetration enhancer are added in turn, maintaining a temperature of 75-80° C. The methylparaben mixture is added slowly to the Tegacid and spermaceti melt, with constant stirring. The addition is continued for at least 30 minutes with additional stirring until the temperature has dropped to 40-45° C. Finally, sufficient water is added to bring the final weight to 1000 gm and the preparation stirred to maintain homogeneity until cooled and congealed.
  • Example IV Topical Cream
  • A 0.1% w/w bimatoprost topical cream is prepared as follows: Tegacid and spermaceti are melted together at a temperature of 70-80° C. Methylparaben is dissolved in water and propylene glycol, polysorbate 80, bimatoprost and a penetration enhancer are added in turn, maintaining a temperature of 75-80° C. The methylparaben mixture is added slowly to the Tegacid and spermaceti melt, with constant stirring. The addition is continued for at least 30 minutes with additional stirring until the temperature has dropped to 40-45° C. Finally, sufficient water is added to bring the final weight to 1000 gm and the preparation stirred to maintain homogeneity until cooled and congealed.
  • Example V Topical Ointment
  • An Ointment Containing 2.0% w/w Bimatoprost is Prepared as Follows:
  • White petrolatum and wool fat are melted, strained and liquid petrolatum is added thereto. Bimatoprost, a penetration enhancer, zinc oxide, and calamine are added to the remaining liquid petrolatum and the mixture milled until the powders are finely divided and uniformly dispersed. The mixture is stirred into the white petrolatum, melted and cooled with stirring until the ointment congeals. In other variants, the zinc oxide and/or calamine can be omitted such that the formulation is substantially free of the zinc oxide or calamine.
  • Example VI Ointment
  • An ointment containing 5% w/w bimatoprost and a penetration enhancer is prepared by adding the active compound to light liquid petrolatum. White petrolatum is melted together with wool fat, strained, and the temperature adjusted to 45-50° C. The liquid petrolatum slurry is added and the ointment stirred until congealed. The ointment can be packaged in 30 gm tubes.
  • Example VII Spray Formulation
  • An aqueous spray formulation containing 0.03%, w/w bimatoprost and a penetration enhancer are prepared as follows. Bimatoprost and a penetration enhancer are dissolved in water and the resulting solution is sterilized by filtration. The solution is aseptically filled into sterile containers with a spray nozzle for application on top of the head. The formulation is as follows:
  • TABLE 4
    Bimatoprost Spray Formulation of Example VII
    Ingredient (% w/w) Function Spray formulation
    Bimatoprost Active 0.03
    Propylene glycol Penetration 5
    Diethylene glycol enhancer 5
    monoethyl ether
    Ethyl alcohol 15
    Light mineral oil
    Ceteareth 12
    Glycerin 1
    Carbomer (Ultrez 10) Thickener
    Triethanolamine Neutralizing agent
    Purified water Vehicle 24
    Hydrofluoro carbon, hydro- Propellant 49.97
    carbon propellant, CO2,
    or, Nitrogen
  • Example VIII Lotion
  • A sample of bimatoprost and a penetration enhancer is dissolved in the vehicle of N-methylpyrrolidone and propylene glycol to make a 0.5% w/w bimatoprost lotion for application to the scalp or other parts of the body for growing hair.
  • Example IX Aerosol
  • An aerosol containing approximately 0.1% w/w bimatoprost and a penetration enhancer is prepared by dissolving the bimatoprost and a penetration enhancer in absolute alcohol. The resulting solution is filtered to remove particles and lint. This solution is chilled to about −30° C. A chilled mixture of dichlorodifluoromethane and dichlorotetrafluoroethane is then added to the solution. Thirteen ml plastic-coated amber bottles can be cold filled with 11.5 gm each of the resulting solution and capped. The aerosol may be sprayed onto the scalp or other parts of the body to grow hair.
  • Example X Topical Foam Formulation
  • A 0.1% w/w bimatoprost topical foam formulation is prepared as follows: Methylparaben is dissolved in about 500 gm of water and propylene glycol, polysorbate 80, bimatoprost and a penetration enhancer are added in turn, maintaining a temperature of 75-80° C. The methylparaben mixture is added slowly to Tegacid and spermaceti, with constant stirring. The addition is continued for at least 30 minutes with additional stirring until the temperature has dropped to 40-45° C. Finally, sufficient water is added to bring the final weight to 1000 gm and the preparation stirred to maintain homogeneity until cooled and congealed.
  • An alternative foam formulation prepared in a similar manner as taught in Example X in Table V is as follows:
  • Ingredient (% w/w) Function Foam formulation
    Bimatoprost Active 0.03
    Propylene glycol Penetration
    Diethylene glycol enhancer 5
    monoethyl ether
    Ethyl alcohol 10
    Light mineral oil 6
    Ceteareth 12 5
    Glycerin
    Carbomer (Ultrez 10) Thickener
  • Example XI Dusting Powder
  • A powder of the compound bimatoprost and a penetration enhancer is prepared by mixing in dry form with talcum powder at a weight/weight ratio of 1:1:10.
  • Example XII Related Compounds
  • Following the procedures of the preceding Examples, compositions are similarly prepared substituting an equimolar amount of a compound of Table 1 for the bimatoprost disclosed in the preceding Examples.
  • Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, etc. used in the specification and claims are to be understood as being modified in all instances by the term “about.” “About” refers to variations in concentrations of excipients and types of excipients which are considered to be bioequivalent according to the FDA and other regulatory authorities.
  • Example XIII
  • A 44 year old Caucasian male undergoing hair loss due to alopecia greata applies once daily before sleeping the 0.1% w/w bimatoprost composition of Table 3 for a period of 6 months. After 3 months of application, the subject will notice new hair growth where there previously had been none and darkening of the follicles of old hair. Observations of new hair growth are made under high magnification at the slit lamp biomicroscope and by computer assisted image analysis. Documentation of differences between the control and treatment areas is accomplished using a camera specially adapted for use with the slit lamp biomicroscope.
  • Example XIV
  • A 37 year old Hispanic male suffering from male pattern baldness due to androgenetic alopecia applies the 0.2% w/w bimatoprost composition of Table 3 twice daily in areas where hair is noticeably thinning. After 63 days of application, increased growth of hair will be noticed as will be new hair growth as measured by high magnification at the slit lamp biomicroscope and by computer assisted image analysis. After satisfactory levels of hair growth are observed, the patient applies the 0.2% w/w bimatoprost composition only twice a week.
  • Example XV
  • A 29 year old Caucasian healthy female wishes to have fuller hair and more hair growth even though no disease or hair loss condition has been diagnosed by doctors. The patient will apply the 0.3% w/w bimatoprost composition of Table 3 once daily until more hair growth is observed after approximately three months of use. The patient continues to apply the composition once a week to maintain the increased hair growth.
  • Example XVI
  • A 35 year old African American male diagnosed with follicular degeneration syndrome and associated hair loss will apply the 0.03% w/w bimatoprost composition of Table 3. The composition will be applied twice daily, once in the morning after showering and once in the evening. After 46 days of application, increased hair growth will be noticed and easing of the symptoms of follicular degeneration syndrome. The patient continues application for another 6 months.

Claims (20)

  1. 1. A composition for growing hair by topical application comprising:
    at least one penetration enhancer; and
    0.01% to 0.3% w/w cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compound represented by the formula I:
    Figure US20110124736A1-20110526-C00009
    wherein the dashed bonds represent the presence or absence of a double bond which can be in the cis or trans configuration, A is an alkylene or alkenylene radical having from two to six carbon atoms, which radical can be interrupted by one or more oxa radicals and substituted with one or more hydroxy, oxo, alkyloxy or alkylcarboxy groups wherein the alkyl radical comprises from one to six carbon atoms; B is a cycloalkyl radical having from three to seven carbon atoms, or an aryl radical, selected from the group consisting of hydrogen, a lower alkyl radical having from four to ten carbon atoms wherein the heteroatom is selected from the group consisting of nitrogen, oxygen and sulfur atoms; X is —N(R4)2 wherein R4 is selected from the group consisting of hydrogen, a lower alkyl radical having from one to six carbon atoms,
    Figure US20110124736A1-20110526-C00010
    wherein R5 is a lower alkyl radical having from one to six carbon atoms; Z is ═O; one of R1 and R2 is ═O, —OH or a—O(CO)R6 group, and the other one is —OH or —O(CO)R6, or R1 is ═O and R2 is H, wherein R6 is a saturated or unsaturated acyclic hydrocarbon group having from 1 to about 20 carbon atoms, or —(CH2)mR7 wherein m is 0 or an integer of from 1 to 10, and R7 is cycloalkyl radical, having from three to seven carbon atoms, or a hydrocarbyl aryl or heteroaryl radical, as defined above in free form or a pharmaceutically acceptable salt thereof, in association with a penetration enhancer in particular formulations adapted for topical application to mammalian skin;
    wherein said composition is formulated for topical administration to the skin.
  2. 2. The composition according to claim 1 wherein said cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compound represented by the formula I is bimatoprost.
  3. 3. The composition according to claim 1 wherein the penetrating enhancer is selected from the group consisting of propylene glycol, diethylene glycol monoether, ethyl alcohol and glycerin.
  4. 4. The composition according to claim 1 wherein the penetrating enhancer is selected from the group consisting of at least two compounds selected from the group consisting of propylene glycol, diethylene glycol monoether, ethyl alcohol and glycerin.
  5. 5. A composition according to claim 1 wherein the penetrating enhancer consists of the following compounds: propylene glycol, diethylene glycol monoether, ethyl alcohol and glycerin.
  6. 6. A composition according to claim 1 comprising from 0.03-0.3% w/w bimatoprost, about 10% w/w propylene glycol, about 10% w/w diethylene glycol monoether, about 30% w/w ethyl alcohol, about 2% w/w glycerin, about 0.15% w/w carbomer, about 0.16% w/w triethanolamine, and purified water.
  7. 7. The composition according to claim 6 comprising 0.03% w/w bimatoprost.
  8. 8. The composition of claim 6 wherein the composition comprises 0.1% w/w bimatoprost.
  9. 9. The composition of claim 6 wherein the composition comprises 0.2% bimatoprost.
  10. 10. The composition of claim 6 wherein the composition consists of 0.3% w/w bimatoprost.
  11. 11. The composition according to claim 6 wherein the composition is in the form of one selected from the group consisting of solutions, gels, ointments, foams, films, liniments, creams, shampoos, lotions, pastes, jellies, sprays and aerosols.
  12. 12. The composition of claim 11 wherein the composition is packaged in a kit with an applicator for application to the skin.
  13. 13. A method for stimulating hair growth comprising topically administering a composition comprising:
    at least one penetration enhancer; and
    a cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compound represented by the formula I:
    Figure US20110124736A1-20110526-C00011
    wherein the dashed bonds represent the presence or absence of a double bond which can be in the cis or trans configuration, A is an alkylene or alkenylene radical having from two to six carbon atoms, which radical can be interrupted by one or more oxa radicals and substituted with one or more hydroxy, oxo, alkyloxy or alkylcarboxy groups wherein the alkyl radical comprises from one to six carbon atoms; B is a cycloalkyl radical having from three to seven carbon atoms, or an aryl radical, selected from the group consisting of hydrogen, a lower alkyl radical having from four to ten carbon atoms wherein the heteroatom is selected from the group consisting of nitrogen, oxygen and sulfur atoms; X is —N(R4)2 wherein R4 is selected from the group consisting of hydrogen, a lower alkyl radical having from one to six carbon atoms,
    Figure US20110124736A1-20110526-C00012
    wherein R5 is a lower alkyl radical having from one to six carbon atoms; Z is ═O; one of R1 and R2 is ═O, —OH or a—O(CO)R6 group, and the other one is —OH or —O(CO)R6, or R1 is ═O and R2 is H, wherein R6 is a saturated or unsaturated acyclic hydrocarbon group having from 1 to about 20 carbon atoms, or —(CH2)mR7 wherein m is 0 or an integer of from 1 to 10, and R7 is cycloalkyl radical, having from three to seven carbon atoms, or a hydrocarbyl aryl or heteroaryl radical, as defined above in free form or a pharmaceutically acceptable salt thereof, in association with a penetration enhancer in particular formulations adapted for topical application to mammalian skin;
    wherein said composition is formulated for topical administration to the skin.
  14. 14. The method according to claim 13 wherein said cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compound represented by the formula I is bimatoprost.
  15. 15. The method according to claim 14 comprising bimatoprost at a concentration of about 0.03% w/w to about 0.3% w/w.
  16. 16. The method according to claim 14 comprising bimatoprost at about 0.1% w/w; about 10% w/w propylene glycol, about 10% w/w diethylene glycol monoether, about 30% w/w ethyl alcohol, about 2% w/w glycerin, about 0.15% w/w carbomer, about 0.16% w/w triethanolamine, and purified water.
  17. 17. The method according to according to claim 14 comprising bimatoprost at about 0.3% w/w; about 10% w/w propylene glycol, about 10% w/w diethylene glycol monoether, about 30% w/w ethyl alcohol, about 2% w/w glycerin, about 0.15% w/w carbomer, about 0.16% w/w triethanolamine, and purified water.
  18. 18. The method according to claim 14, wherein the composition is applied at least once daily to the scalp.
  19. 19. The method according to claim 14, wherein the composition is applied at least once daily to the scalp for treatment of one of the following conditions selected from the group consisting of alopecia greata, telogen effluvium, anagen effluvium, cicatricial alopecia, scarring alopecia; hair shaft abnormalities, trichorrexis nodosa, loose anagen syndrome, trichotillomania, traction alopecia; infectious hair disorders, tiniea capitis, sebohorreic dermatitis, follicullitus of the scalp, and androgenetic alopecia.
  20. 20. The method according to claim 14 wherein the composition is applied at least once a day to both the scalp and the eyebrows for patients experiencing hair loss due to chemotherapy, hormonal imbalance, fungal infection of the scalp, anti-coagulants, medicine for gout, depression, high blood pressure and heart disease.
US12940711 2009-11-09 2010-11-05 Compositions and methods for stimulating hair growth Abandoned US20110124736A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US25936809 true 2009-11-09 2009-11-09
US12940711 US20110124736A1 (en) 2009-11-09 2010-11-05 Compositions and methods for stimulating hair growth

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US12940711 US20110124736A1 (en) 2009-11-09 2010-11-05 Compositions and methods for stimulating hair growth
US14163954 US9138480B2 (en) 2009-11-09 2014-01-24 Compositions and methods for stimulating hair growth
US14175972 US9149484B2 (en) 2009-11-09 2014-02-07 Compositions and methods for stimulating hair growth
US14829273 US9763959B2 (en) 2009-11-09 2015-08-18 Compositions and methods for stimulating hair growth
US14829957 US9849140B2 (en) 2009-11-09 2015-08-19 Topical compositions comprising bimatoprost and methods for stimulating hair growth therewith
US15675210 US20180177798A1 (en) 2009-11-09 2017-08-11 Compositions and methods for stimulating hair growth

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US14163954 Continuation US9138480B2 (en) 2009-11-09 2014-01-24 Compositions and methods for stimulating hair growth

Publications (1)

Publication Number Publication Date
US20110124736A1 true true US20110124736A1 (en) 2011-05-26

Family

ID=43827484

Family Applications (7)

Application Number Title Priority Date Filing Date
US13508260 Abandoned US20120322882A1 (en) 2009-11-09 2010-11-05 Compositions And Methods For Stimulating Hair Growth
US12940711 Abandoned US20110124736A1 (en) 2009-11-09 2010-11-05 Compositions and methods for stimulating hair growth
US14163954 Active US9138480B2 (en) 2009-11-09 2014-01-24 Compositions and methods for stimulating hair growth
US14727104 Active US9750750B2 (en) 2009-11-09 2015-06-01 Compositions and methods for stimulating hair growth
US14829273 Active US9763959B2 (en) 2009-11-09 2015-08-18 Compositions and methods for stimulating hair growth
US14829957 Active US9849140B2 (en) 2009-11-09 2015-08-19 Topical compositions comprising bimatoprost and methods for stimulating hair growth therewith
US15675210 Pending US20180177798A1 (en) 2009-11-09 2017-08-11 Compositions and methods for stimulating hair growth

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US13508260 Abandoned US20120322882A1 (en) 2009-11-09 2010-11-05 Compositions And Methods For Stimulating Hair Growth

Family Applications After (5)

Application Number Title Priority Date Filing Date
US14163954 Active US9138480B2 (en) 2009-11-09 2014-01-24 Compositions and methods for stimulating hair growth
US14727104 Active US9750750B2 (en) 2009-11-09 2015-06-01 Compositions and methods for stimulating hair growth
US14829273 Active US9763959B2 (en) 2009-11-09 2015-08-18 Compositions and methods for stimulating hair growth
US14829957 Active US9849140B2 (en) 2009-11-09 2015-08-19 Topical compositions comprising bimatoprost and methods for stimulating hair growth therewith
US15675210 Pending US20180177798A1 (en) 2009-11-09 2017-08-11 Compositions and methods for stimulating hair growth

Country Status (8)

Country Link
US (7) US20120322882A1 (en)
EP (1) EP2498783A2 (en)
JP (2) JP5982287B2 (en)
KR (3) KR20170095402A (en)
CN (2) CN106176261A (en)
CA (1) CA2780267A1 (en)
RU (1) RU2567792C2 (en)
WO (1) WO2011057129A3 (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012112451A1 (en) 2011-02-14 2012-08-23 Allergan, Inc. Ester derivatives of bimatoprost compositions and methods
WO2014035827A1 (en) 2012-08-27 2014-03-06 Allergan, Inc. Reduced central corneal thickening by use of hydrophilic ester prodrugs of beta-chlorocyclopentanes
US9090595B2 (en) 2012-08-27 2015-07-28 Allergan, Inc. Reduced central corneal thickening by use of hydrophilic ester prodrugs of beta-chlorocyclopentanes
WO2015175075A1 (en) 2014-02-20 2015-11-19 Allergan, Inc. Reduced central corneal thickening by use of hydrophilic ester prodrugs of beta-chlorocyclopentanes
US20160067263A1 (en) * 2013-05-15 2016-03-10 Topokine Therapeutics, Inc. Methods and compositions for topical delivery of prostaglandins to subcutaneous fat
WO2016054596A1 (en) 2014-10-02 2016-04-07 Allergan, Inc. Ester prodrugs of gamma-lactams and their use
US9849179B2 (en) 2013-05-10 2017-12-26 Topokine Therapeutics, Inc. Methods for topical delivery of prostaglandins to subcutaneous fat
US9861641B2 (en) 2011-12-19 2018-01-09 Topokine Therapeutics, Inc. Methods for reducing body fat using tafluprost and analogs thereof

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2780267A1 (en) 2009-11-09 2011-05-12 Allergan, Inc. Compositions and methods for stimulating hair growth
US9149484B2 (en) 2009-11-09 2015-10-06 Allergan, Inc. Compositions and methods for stimulating hair growth
EP2968093A1 (en) * 2013-03-14 2016-01-20 Allergan, Inc. Topical compositions comprising bimatoprost and methods for stimulating hair growth therewith
EP2640350A2 (en) * 2010-11-18 2013-09-25 Steven Yoelin Compositions and methods for hair growth
WO2012099942A3 (en) 2011-01-19 2013-06-27 Terakine Therapeutics, Inc. Methods and compositions for treating metabolic syndrome
US8783451B2 (en) 2011-02-18 2014-07-22 Allergan, Inc. Unit dose breakable vial with integrated brush applicator
US20150164765A1 (en) * 2012-05-17 2015-06-18 Steven G. Yoelin Compositions and methods for hair growth
US9173921B1 (en) 2015-03-23 2015-11-03 Jaehyun Lim Method of promoting hair growth by administration of bFGF
US9937117B2 (en) * 2015-07-09 2018-04-10 Galderma S.A. Method of reducing hair loss associated with chemotherapy

Citations (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3382247A (en) * 1965-11-01 1968-05-07 Upjohn Co 6-amino-1, 2-dihydro-1-hydroxy-2-imino-4-phenoxypyrimidines
US3644363A (en) * 1969-09-02 1972-02-22 Richardson Merrell Inc 1 4-dioxidoquinoxalinyl nitrones
US4128577A (en) * 1975-12-29 1978-12-05 The Upjohn Company 15-Methyl- and 16-phenoxy-PGF2 α, amides
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
US4311707A (en) * 1979-02-12 1982-01-19 American Cyanamid Company Process for topically producing cutaneous vasodilation for the treatment of vasospastic or ischemic conditions
US4543353A (en) * 1981-11-27 1985-09-24 Farmitalia Carlo Erba S.P.A. Ester and amide derivatives of 13,14-didehydro prostaglandins
US4596812A (en) * 1976-05-24 1986-06-24 The Upjohn Company Methods and solutions for treating male pattern alopecia
US4599353A (en) * 1982-05-03 1986-07-08 The Trustees Of Columbia University In The City Of New York Use of eicosanoids and their derivatives for treatment of ocular hypertension and glaucoma
US4812457A (en) * 1984-11-21 1989-03-14 Research Development Corporation Prostaglandin derivatives
US4883581A (en) * 1986-10-03 1989-11-28 Exxon Chemical Patents Inc. Pretreatment for reducing oxidative reactivity of baseoils
US4889845A (en) * 1986-06-09 1989-12-26 American Cyanamid Company Vehicle for topical application of pharmaceuticals
US4952581A (en) * 1987-04-03 1990-08-28 The Trustees Of Columbia University In The City Of New York Use of a prostaglandin in combination with an adrenergic blocking agent for reduction of intraocular pressure
US4968812A (en) * 1989-06-23 1990-11-06 Shell Oil Company Spirolactonelactams
US5001153A (en) * 1987-09-18 1991-03-19 K.K. Ueno Seiyaku Oyo Kenkyujo Ocular hypotensive agents
US5194429A (en) * 1988-10-01 1993-03-16 K.K. Ueno Seiyaku Oyo Kenkyujo Ocular hypotensive agents
US5288754A (en) * 1992-02-04 1994-02-22 Allergan, Inc. Polar C-1 esters of prostaglandins
US5296504A (en) * 1988-09-06 1994-03-22 Kabi Pharmacia Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension
US5321128A (en) * 1988-09-06 1994-06-14 Kabi Pharmacia Ab Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension
US5352708A (en) * 1992-09-21 1994-10-04 Allergan, Inc. Non-acidic cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents
US5422368A (en) * 1988-09-06 1995-06-06 Kabi Pharmacia Ab Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension
US5431881A (en) * 1993-12-10 1995-07-11 Palacios; Henry J. Treatment of hair loss and dermatological problems
US5480900A (en) * 1992-10-13 1996-01-02 Alcon Laboratories, Inc. Combinations of prostaglandins and clonidine derivatives for the treatment of glaucoma
US5508303A (en) * 1992-05-29 1996-04-16 Toray Industries, Inc. Hair-growing composition
US5510383A (en) * 1993-08-03 1996-04-23 Alcon Laboratories, Inc. Use of cloprostenol, fluprostenol and their salts and esters to treat glaucoma and ocular hypertension
US5545655A (en) * 1985-09-19 1996-08-13 Uniroyal Chemical Company, Inc. Substituted oxathiolanes
US5578643A (en) * 1992-05-20 1996-11-26 Loyola University Of Chicago Protective prostaglandins for use in conjunction with chemotherapeutic agents
US5688819A (en) * 1992-09-21 1997-11-18 Allergan Cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents
US5698733A (en) * 1994-09-30 1997-12-16 Alcon Laboratories, Inc. Use of 9-deoxy prostaglandin derivatives to treat glaucoma
US5773472A (en) * 1993-11-03 1998-06-30 Pharmacia Ab Method and means for prevention of cataract
US5789244A (en) * 1996-01-08 1998-08-04 Canji, Inc. Compositions and methods for the treatment of cancer using recombinant viral vector delivery systems
US6025392A (en) * 1995-12-22 2000-02-15 Alcon Laboratories, Inc. substituted tetrahydrofuran analogs of prostaglandins as ocular hypotensives
US6124344A (en) * 1993-12-28 2000-09-26 Allergan Sales, Inc. Cyclopentane heptan(ene)oic acid, 2-heteroarylalkenyl derivatives as therapeutic agents
US6232344B1 (en) * 1997-12-22 2001-05-15 Alcon Laboratories, Inc. 13-Oxa prostaglandins for the treatment of glaucoma and ocular hypertension
US6258844B1 (en) * 1996-05-28 2001-07-10 Allergan Sales, Inc. Cyclopentane (ene) oic acid, 2-alkenyl derivatives as therapeutic agents
US6262105B1 (en) * 1997-02-04 2001-07-17 Murray A. Johnstone Method of enhancing hair growth
US20020044953A1 (en) * 2000-07-28 2002-04-18 Michelet Jean Francois Use of non-prostanoic agonists of prostaglandin EP-2 and/or EP-4 receptors as cosmetic agents for attenuating, reducing or stopping the loss of head hair and other hairs
US6403649B1 (en) * 1992-09-21 2002-06-11 Allergan Sales, Inc. Non-acidic cyclopentane heptanoic acid,2-cycloalkyl or arylalkyl derivatives as therapeutic agents
US20020103255A1 (en) * 1997-12-19 2002-08-01 Hellberg Mark R. Use of non-steroidal anti-inflammatory agents in combination with prostaglandin FP receptor agonists to treat glaucoma and ocular hypertension
US6441047B2 (en) * 1995-11-17 2002-08-27 Alcon Manufacturing Ltd.. Combination therapy for treating glaucoma
US20020172693A1 (en) * 2000-03-31 2002-11-21 Delong Michell Anthony Compositions and methods for treating hair loss using non-naturally occurring prostaglandins
US20030083381A1 (en) * 2000-03-31 2003-05-01 Hiroki Kumagai Hair growth or hair formation controlling agents
US20030147823A1 (en) * 2002-02-04 2003-08-07 Allergan, Inc. Method of enhancing hair growth
US20030199590A1 (en) * 2002-07-25 2003-10-23 Cagle Gerald D Prostaglandin analogues for promotion of hair growth
US20070160562A1 (en) * 2006-01-06 2007-07-12 Brinkenhoff Michael C Delivery devices for hair-promoting cosmetic agent
US20080275118A1 (en) * 2008-06-12 2008-11-06 Shaw Mari M Health and cosmetic composition and regime for stimulating hair growth and thickening on the head, including the scalp, eyelashes, and eyebrows, and which discourages hair loss
US20090018204A1 (en) * 2007-07-13 2009-01-15 Brinkenhoff Michael C Composition and method for enhancing hair growth
US7514474B1 (en) * 2007-10-31 2009-04-07 Meta Cosmetics, Llc Prostaglandin analog compositions and methods to treat epithelial-related conditions
US20090270392A1 (en) * 2008-04-24 2009-10-29 Allergan, Inc. Substituted gamma lactams as therapeutic agents
US20110002866A1 (en) * 2007-10-31 2011-01-06 Lubit Beverly W Methods to prevent a hair-related side effect of treatment with a chemotherapeutic agent
US20110112198A1 (en) * 2009-11-09 2011-05-12 Allergan, Inc. Compositions for enhancing hair growth
US20120322882A1 (en) * 2009-11-09 2012-12-20 Allergan, Inc. Compositions And Methods For Stimulating Hair Growth
US20130030055A1 (en) * 2010-03-24 2013-01-31 Allergan, Inc. Compositions and methods for treating hair loss, hair thinning, and hair color loss
US20130131097A1 (en) * 2002-02-04 2013-05-23 Allergan, Inc. Topical treatment for chemotherapy induced eyelash loss or hypotrichosis using prostamide f2 alpha agonists
US9009430B2 (en) * 2010-12-02 2015-04-14 International Business Machines Corporation Restoration of data from a backup storage volume
US9009431B2 (en) * 2012-05-29 2015-04-14 Compellent Technologies Virtual snapshot system and method

Family Cites Families (197)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4052505A (en) 1975-05-30 1977-10-04 Alza Corporation Ocular therapeutic system manufactured from copolymer
US4144317A (en) 1975-05-30 1979-03-13 Alza Corporation Device consisting of copolymer having acetoxy groups for delivering drugs
US3845770A (en) 1972-06-05 1974-11-05 Alza Corp Osmatic dispensing device for releasing beneficial agent
JPS4969636A (en) 1972-11-07 1974-07-05
US3916899A (en) 1973-04-25 1975-11-04 Alza Corp Osmotic dispensing device with maximum and minimum sizes for the passageway
FR2239458B3 (en) 1973-07-31 1976-07-16 Aries Robert
US4008864A (en) 1974-02-18 1977-02-22 Nils Gustav Yngve Torphammar Locking mechanism for a safety belt
US4014335A (en) 1975-04-21 1977-03-29 Alza Corporation Ocular drug delivery device
US4063064A (en) 1976-02-23 1977-12-13 Coherent Radiation Apparatus for tracking moving workpiece by a laser beam
GB1478759A (en) 1974-11-18 1977-07-06 Alza Corp Process for forming outlet passageways in pills using a laser
US3966749A (en) 1975-02-10 1976-06-29 Interx Research Corporation Novel synthesis of optically active m-acyloxy-α-[(methylamino)methyl]benzyl alcohols, the pharmaceutically acceptable acid addition salts thereof and intermediate useful in the preparation thereof
US4057619A (en) 1975-06-30 1977-11-08 Alza Corporation Ocular therapeutic system with selected membranes for administering ophthalmic drug
US4968619A (en) 1976-09-27 1990-11-06 Research Corporation Modified microorganisms and method of preparing and using same
US4186184A (en) 1977-12-27 1980-01-29 Alza Corporation Selective administration of drug with ocular therapeutic system
US4190642A (en) 1978-04-17 1980-02-26 Alza Corporation Ocular therapeutic system for dispensing a medication formulation
US4200098A (en) 1978-10-23 1980-04-29 Alza Corporation Osmotic system with distribution zone for dispensing beneficial agent
US4285987A (en) 1978-10-23 1981-08-25 Alza Corporation Process for manufacturing device with dispersion zone
US4303637A (en) 1980-04-04 1981-12-01 Alza Corporation Medication indicated for ocular hypertension
US4281654A (en) 1980-04-07 1981-08-04 Alza Corporation Drug delivery system for controlled ocular therapy
US4396625A (en) 1980-05-13 1983-08-02 Sumitomo Chemical Company, Limited Treatment of glaucoma or ocular hypertension and ophthalmic composition
US4425346A (en) 1980-08-01 1984-01-10 Smith And Nephew Associated Companies Limited Pharmaceutical compositions
US4304765A (en) 1980-10-14 1981-12-08 Alza Corporation Ocular insert housing steroid in two different therapeutic forms
US4327725A (en) 1980-11-25 1982-05-04 Alza Corporation Osmotic device with hydrogel driving member
US4478818A (en) 1982-12-27 1984-10-23 Alza Corporation Ocular preparation housing steroid in two different therapeutic forms
JPS58126435U (en) 1982-02-19 1983-08-27
DE3220156C2 (en) 1982-05-28 1990-01-25 Heida Houston Tex. Us Thurlow
US5543154A (en) 1991-12-27 1996-08-06 Merck & Co., Inc. Controlled release nifedipine delivery device
US4649151A (en) 1982-09-27 1987-03-10 Health Research, Inc. Drugs comprising porphyrins
US4521210A (en) 1982-12-27 1985-06-04 Wong Vernon G Eye implant for relieving glaucoma, and device and method for use therewith
US6309669B1 (en) 1984-03-16 2001-10-30 The United States Of America As Represented By The Secretary Of The Army Therapeutic treatment and prevention of infections with a bioactive materials encapsulated within a biodegradable-biocompatible polymeric matrix
US6447796B1 (en) 1994-05-16 2002-09-10 The United States Of America As Represented By The Secretary Of The Army Sustained release hydrophobic bioactive PLGA microspheres
US4693885A (en) 1984-07-18 1987-09-15 Nippon Petrochemicals Co., Ltd. Tetrapyrrole therapeutic agents
US4675338A (en) 1984-07-18 1987-06-23 Nippon Petrochemicals Co., Ltd. Tetrapyrrole therapeutic agents
ES545700A0 (en) 1984-07-31 1986-06-16 Syntex Inc Process for preparing derivatives of acids 11-subbed-2-16-phenoxy and 16-substituted phenoxy-prostatrienoicos
FR2577509B1 (en) 1985-02-21 1987-05-07 Nirvana Espar Systems Sa Mast sailing boat
JPH0473406B2 (en) 1985-03-22 1992-11-20 Kenichi Katsu
US4656186A (en) 1985-04-30 1987-04-07 Nippon Petrochemicals Co., Ltd. Tetrapyrrole therapeutic agents
US4668506A (en) 1985-08-16 1987-05-26 Bausch & Lomb Incorporated Sustained-release formulation containing and amino acid polymer
FR2594438B1 (en) 1986-02-14 1990-01-26 Labaz Sanofi Nv Derivatives indolizine, their method of preparing and compositions containing
US4959217A (en) 1986-05-22 1990-09-25 Syntex (U.S.A.) Inc. Delayed/sustained release of macromolecules
FI872552A (en) 1986-06-09 1987-12-10 American Cyanamid Co Prostaglandinkomposition Foer lokalt bruk.
US4863457A (en) 1986-11-24 1989-09-05 Lee David A Drug delivery device
US4981871A (en) 1987-05-15 1991-01-01 Abelson Mark B Treatment of ocular hypertension with class I calcium channel blocking agents
US4839342A (en) 1987-09-03 1989-06-13 University Of Georgia Research Foundation, Inc. Method of increasing tear production by topical administration of cyclosporin
DE3872701T2 (en) 1987-10-07 1992-12-03 Kabi Pharmacia Ab Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension.
DE3734223A1 (en) 1987-10-09 1989-04-20 Boehringer Ingelheim Kg An implantable, biodegradable drug-release system
US4888354A (en) 1987-12-21 1989-12-19 Theratech, Inc. Skin penetration enhancement using free base and acid addition salt combinations of active agents
US4997652A (en) 1987-12-22 1991-03-05 Visionex Biodegradable ocular implants
US4853224A (en) 1987-12-22 1989-08-01 Visionex Biodegradable ocular implants
US4865846A (en) 1988-06-03 1989-09-12 Kaufman Herbert E Drug delivery system
US4968715A (en) 1988-07-06 1990-11-06 Health Research, Inc. Use of purified hematoporphyrin trimers in photodynamic therapy
US5190966A (en) 1988-07-06 1993-03-02 Health Research, Inc. Purified hematoporphyrin dimers and trimers useful in photodynamic therapy
US5002962A (en) 1988-07-20 1991-03-26 Health Research, Inc. Photosensitizing agents
US5198460A (en) 1988-07-20 1993-03-30 Health Research Inc. Pyropheophorbides and their use in photodynamic therapy
US5093349A (en) 1988-07-20 1992-03-03 Health Research Inc. Photosensitizing agents
US5089509A (en) 1988-09-15 1992-02-18 Allergan, Inc. Disubstituted acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity
US4935498A (en) 1989-03-06 1990-06-19 Board Of Regents, The University Of Texas System Expanded porphyrins: large porphyrin-like tripyrroledimethine-derived macrocycles
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
US5173504A (en) 1989-04-21 1992-12-22 Health Research, Inc. Bacteriochlorophyll-a derivatives useful in photodynamic therapy
US5171741A (en) 1989-04-21 1992-12-15 Health Research, Inc. Bacteriochlorophyll-a derivatives useful in photodynamic therapy
US5019400A (en) 1989-05-01 1991-05-28 Enzytech, Inc. Very low temperature casting of controlled release microspheres
US5034413A (en) 1989-07-27 1991-07-23 Allergan, Inc. Intraocular pressure reducing 9,11-diacyl prostaglandins
CA1339132C (en) 1989-09-12 1997-07-29 Johan W. Stjernschantz Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension
US5268178A (en) 1989-09-25 1993-12-07 The Board Of Regents, The University Of Texas System Biodegradable antibiotic implants and methods of their use in treating and preventing infections
US5164188A (en) 1989-11-22 1992-11-17 Visionex, Inc. Biodegradable ocular implants
US6203782B1 (en) 1990-03-02 2001-03-20 Universal Biologics, Inc. Method and product for promoting hair growth and treating skin conditions
US5075115A (en) 1990-04-02 1991-12-24 Fmc Corporation Process for polymerizing poly(lactic acid)
US5232844A (en) 1990-05-15 1993-08-03 New York Blood Center Photodynamic inactivation of viruses in cell-containing compositions
US5100431A (en) 1990-09-27 1992-03-31 Allergan, Inc. Single stitch suture needle and method
JP3116489B2 (en) 1990-11-30 2000-12-11 千寿製薬株式会社 The sustained release intraocular embedded preparations
US5378475A (en) 1991-02-21 1995-01-03 University Of Kentucky Research Foundation Sustained release drug delivery devices
CA2111199C (en) 1991-06-21 2008-08-05 Eyal Ron Pharmaceutical formulations of osteogenic proteins
US5356629A (en) 1991-07-12 1994-10-18 United States Surgical Corporation Composition for effecting bone repair
US5503721A (en) 1991-07-18 1996-04-02 Hri Research, Inc. Method for photoactivation
US5169638A (en) 1991-10-23 1992-12-08 E. R. Squibb & Sons, Inc. Buoyant controlled release powder formulation
US5656297A (en) 1992-03-12 1997-08-12 Alkermes Controlled Therapeutics, Incorporated Modulated release from biocompatible polymers
WO1993021172A1 (en) 1992-04-09 1993-10-28 Rotta Research Laboratorium S.P.A. Basic derivatives of glutamic acid and aspartic acid as gastrin or cholecystokinin antagonists
US5655832A (en) 1992-04-16 1997-08-12 Tir Technologies, Inc. Multiple wavelength light processor
US5244914A (en) 1992-04-27 1993-09-14 American Cyanamid Company Stable porfimer sodium compositions and methods for their manufacture
US5178635A (en) 1992-05-04 1993-01-12 Allergan, Inc. Method for determining amount of medication in an implantable device
US6217869B1 (en) 1992-06-09 2001-04-17 Neorx Corporation Pretargeting methods and compounds
US5922773A (en) 1992-12-04 1999-07-13 The Children's Medical Center Corp. Glaucoma treatment
US5707643A (en) 1993-02-26 1998-01-13 Santen Pharmaceutical Co., Ltd. Biodegradable scleral plug
WO1995003009A1 (en) 1993-07-22 1995-02-02 Oculex Pharmaceuticals, Inc. Method of treatment of macular degeneration
US5770589A (en) 1993-07-27 1998-06-23 The University Of Sydney Treatment of macular degeneration
US5504074A (en) 1993-08-06 1996-04-02 Children's Medical Center Corporation Estrogenic compounds as anti-angiogenic agents
US5385887A (en) 1993-09-10 1995-01-31 Genetics Institute, Inc. Formulations for delivery of osteogenic proteins
WO1995011003A1 (en) 1993-10-20 1995-04-27 Pharmacia Ab New use of prostaglandins
US5443505A (en) 1993-11-15 1995-08-22 Oculex Pharmaceuticals, Inc. Biocompatible ocular implants
US6051576A (en) 1994-01-28 2000-04-18 University Of Kentucky Research Foundation Means to achieve sustained release of synergistic drugs by conjugation
DE4403326C1 (en) 1994-02-03 1995-06-22 Hans Reinhard Prof Dr Koch An intraocular lens assembly for astigmatism
US5798349A (en) 1994-03-14 1998-08-25 The General Hospital Corporation Use of green porphyrins to treat neovasculature in the eye
US5466233A (en) 1994-04-25 1995-11-14 Escalon Ophthalmics, Inc. Tack for intraocular drug delivery and method for inserting and removing same
US5474979A (en) 1994-05-17 1995-12-12 Allergan, Inc. Nonirritating emulsions for sensitive tissue
US6270492B1 (en) 1994-09-09 2001-08-07 Cardiofocus, Inc. Phototherapeutic apparatus with diffusive tip assembly
US6294563B1 (en) 1994-10-27 2001-09-25 Allergan Sales, Inc. Combinations of prostaglandins and brimonidine or derivatives thereof
US6290991B1 (en) 1994-12-02 2001-09-18 Quandrant Holdings Cambridge Limited Solid dose delivery vehicle and methods of making same
US5869079A (en) 1995-06-02 1999-02-09 Oculex Pharmaceuticals, Inc. Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents
US6369116B1 (en) 1995-06-02 2002-04-09 Oculex Pharmaceuticals, Inc. Composition and method for treating glaucoma
EP0778768B1 (en) 1995-06-09 2004-05-26 Euroceltique S.A. Formulations and methods for providing prolonged local anesthesia
US6194415B1 (en) 1995-06-28 2001-02-27 Allergan Sales, Inc. Method of using (2-imidazolin-2-ylamino) quinoxoalines in treating neural injury
US5856329A (en) 1995-06-28 1999-01-05 Allergan Method of using (2-imidazolin-2-ylamino) quinoxalines in treating ocular neural injury
US5906920A (en) 1995-08-29 1999-05-25 The Salk Institute For Biological Studies Methods for the detection of ligands for retinoid X receptors
US5776699A (en) 1995-09-01 1998-07-07 Allergan, Inc. Method of identifying negative hormone and/or antagonist activities
US5958954A (en) 1995-09-01 1999-09-28 Allergan Sales, Inc. Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities
US5877207A (en) 1996-03-11 1999-03-02 Allergan Sales, Inc. Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities
US5741810A (en) 1996-02-29 1998-04-21 Allergan Cyclopentane heptan(ene)oic acid, 2- heteroarylalkenyl derivatives as therapeutic agents
JP3049593B2 (en) 1996-05-01 2000-06-05 日本ソシア株式会社 Hair growth tonic
US6066675A (en) 1996-09-13 2000-05-23 The Regents Of The University Of California Method for treatment of retinal diseases
US5913884A (en) 1996-09-19 1999-06-22 The General Hospital Corporation Inhibition of fibrosis by photodynamic therapy
US6270749B1 (en) 1996-12-11 2001-08-07 Pharmacyclics, Inc. Use of Texaphyrin in ocular diagnosis and therapy
US6274614B1 (en) 1997-02-11 2001-08-14 Qlt Inc. Methods, compositions and articles for reducing or preventing the effects of inflammation
US6271220B1 (en) 1998-03-11 2001-08-07 Allergan Sales, Inc. Anti-angiogenic agents
JP3217293B2 (en) 1997-04-17 2001-10-09 株式会社アールテック・ウエノ Hair growth and hair tonic
US5919970A (en) 1997-04-24 1999-07-06 Allergan Sales, Inc. Substituted diaryl or diheteroaryl methanes, ethers and amines having retinoid agonist, antagonist or inverse agonist type biological activity
EP0994709A4 (en) 1997-06-30 2006-02-01 Allergan Inc Calcium blockers to treat proliferative vitreoretinopathy
WO1999001156A1 (en) 1997-07-02 1999-01-14 Santen Pharmaceutical Co., Ltd. Polylactic acid scleral plugs
US6306426B1 (en) 1997-08-11 2001-10-23 Allergan Sales, Inc. Implant device with a retinoid for improved biocompatibility
EP1003569B1 (en) 1997-08-11 2004-10-20 Allergan, Inc. Sterile bioerodible implant device containing retinoid with improved biocompatability and method of manufacture
EP1012136B1 (en) 1997-09-09 2004-07-07 Duke University Aromatic c 16?-c 20?-substituted tetrahydro prostaglandins useful as fp agonists
EP1100366B1 (en) 1998-07-09 2009-04-15 Curelight Medical Ltd Apparatus and method for efficient high energy photodynamic therapy of acne vulgaris and seborrhea
WO2000030532A1 (en) 1998-11-20 2000-06-02 University Of Connecticut Generic integrated implantable potentiostat telemetry unit for electrochemical sensors
ES2147538B1 (en) * 1999-01-29 2001-04-01 Revlon Consumer Prod Corp A hair lotion with improved hair in its protective and preventive action their fall properties, and reduction of external effects of androgenetic alopecia and thus the hair loss.
US6410045B1 (en) 1999-02-22 2002-06-25 Clyde Lewis Schultz Drug delivery system for antiglaucomatous medication
CA2371814C (en) 1999-02-26 2014-05-27 The University Of British Columbia Trpm-2 antisense therapy
EP1169061A1 (en) 1999-03-12 2002-01-09 Alcon Laboratories, Inc. Combination therapy for treating glaucoma
US6217895B1 (en) 1999-03-22 2001-04-17 Control Delivery Systems Method for treating and/or preventing retinal diseases with sustained release corticosteroids
US6482854B1 (en) 1999-03-25 2002-11-19 Massachusetts Eye And Ear Infirmary Glaucoma treatment
US6254860B1 (en) 1999-04-13 2001-07-03 Allergan Sales, Inc. Ocular treatment using cyclosporin-A derivatives
US6290713B1 (en) 1999-08-24 2001-09-18 Thomas A. Russell Flexible illuminators for phototherapy
US6317616B1 (en) 1999-09-15 2001-11-13 Neil David Glossop Method and system to facilitate image guided surgery
US6331313B1 (en) 1999-10-22 2001-12-18 Oculex Pharmaceticals, Inc. Controlled-release biocompatible ocular drug delivery implant devices and methods
US6319273B1 (en) 1999-12-16 2001-11-20 Light Sciences Corporation Illuminating device for treating eye disease
US20010049369A1 (en) 2000-02-10 2001-12-06 Jablonski Monica M. Brimonidine compositions and methods for retinal degeneration
CA2398901C (en) 2000-02-10 2010-11-16 Massachusetts Eye And Ear Infirmary Methods and compositions for treating conditions of the eye
JP2003527423A (en) 2000-03-17 2003-09-16 アルコン、インコーポレイテッド Compounds having 5-ht2 and 5-HT1A agonist activity for glaucoma treatment
US20020037914A1 (en) 2000-03-31 2002-03-28 Delong Mitchell Anthony Compositions and methods for treating hair loss using C16-C20 aromatic tetrahydro prostaglandins
US20020146439A1 (en) 2000-03-31 2002-10-10 Delong Mitchell Anthony Compositions and methods for treating hair loss using oximyl and hydroxylamino prostaglandins
US20040208910A1 (en) 2000-04-26 2004-10-21 Control Delivery Systems, Inc. Sustained release device and method for ocular delivery of adrenergic agents
US20040170665A1 (en) 2000-06-02 2004-09-02 Allergan, Inc. Intravitreal botulinum toxin implant
US6692759B1 (en) 2000-06-28 2004-02-17 The Regents Of The University Of California Methods for preparing and using implantable substance delivery devices
US6726918B1 (en) 2000-07-05 2004-04-27 Oculex Pharmaceuticals, Inc. Methods for treating inflammation-mediated conditions of the eye
CN100569291C (en) 2000-07-14 2009-12-16 阿勒根公司 Compositions containing alpha-2-adrenergic agonist components
US6357568B1 (en) 2000-09-27 2002-03-19 Shou Mao Chen Structure for protecting a luggage shell
WO2002058730A3 (en) 2000-11-01 2003-05-15 Allergan Inc Compositions for treatment of ocular neovascularization
DK1339438T3 (en) 2000-11-29 2006-02-13 Allergan Inc Preventing transplant rejection in the eye
US6595945B2 (en) 2001-01-09 2003-07-22 J. David Brown Glaucoma treatment device and method
US6713081B2 (en) 2001-03-15 2004-03-30 The United States Of America As Represented By The Department Of Health And Human Services Ocular therapeutic agent delivery devices and methods for making and using such devices
EP1418903A2 (en) 2001-04-23 2004-05-19 The Board of Regents of the University of Texas System Prostanoids augment ocular drug penetration
US7563255B2 (en) 2001-05-03 2009-07-21 Massachusetts Eye And Ear Infirmary Implantable drug delivery device and use thereof
US8629140B2 (en) 2001-05-31 2014-01-14 Allergan, Inc. Hypotensive lipid and timolol compositions and methods of using same
US6713268B2 (en) 2001-06-26 2004-03-30 Allergan, Inc. Methods of identifying ocular hypotensive compounds having reduced hyperpigmentation
JP2005508336A (en) 2001-09-27 2005-03-31 アラーガン、インコーポレイテッドAllergan,Incorporated Kinase inhibitors as a 3- (aryl) methylene-1,3-dihydro -2h- indol-2-ones
JP5170935B2 (en) 2001-11-14 2013-03-27 デュレクト コーポレーション Injectable depot composition
WO2003048190A3 (en) 2001-12-04 2003-11-13 Ashim K Mitra Acyclovir-peptide analogs
US9216183B2 (en) * 2002-02-04 2015-12-22 Allergan, Inc. Topical treatment for chemotherapy induced eyelash loss or hypotrichosis using prostamide F2 alpha agonists
CN1313155C (en) 2002-03-18 2007-05-02 诺瓦提斯公司 Topical composition comprising a cyclofructan, a carrier and a drug
US7320967B2 (en) 2002-04-23 2008-01-22 L'oreal Cosmetic composition, method of cosmetic treatment and preparation of a composition for promoting the growth and/or preventing or delaying the loss of hair
US7091232B2 (en) 2002-05-21 2006-08-15 Allergan, Inc. 4-(substituted cycloalkylmethyl) imidazole-2-thiones, 4-(substituted cycloalkenylmethyl) imidazole-2-thiones, 4-(substituted cycloalkylmethyl) imidazol-2-ones and 4-(substituted cycloalkenylmethyl) imidazol-2-ones and related compounds
US20040001889A1 (en) 2002-06-25 2004-01-01 Guohua Chen Short duration depot formulations
CN100355455C (en) 2002-07-15 2007-12-19 爱尔康公司 Non-polymeric lipophilic pharmaceutical implant compositions for intraocular use
US7468065B2 (en) 2002-09-18 2008-12-23 Allergan, Inc. Apparatus for delivery of ocular implants
US6899717B2 (en) 2002-09-18 2005-05-31 Allergan, Inc. Methods and apparatus for delivery of ocular implants
JP2006508127A (en) 2002-11-06 2006-03-09 アルザ・コーポレーション Controlled-release depot formulation
US20050048099A1 (en) 2003-01-09 2005-03-03 Allergan, Inc. Ocular implant made by a double extrusion process
DK1592408T3 (en) 2003-01-24 2010-01-04 Psivida Inc Sustained release device and method for ocular administration of adrenergic agents
US20040266776A1 (en) 2003-06-25 2004-12-30 Gil Daniel W. Methods of preventing and reducing the severity of stress-associated conditions
WO2005009510A3 (en) 2003-07-23 2005-04-07 Univ California Penetration enhancer combinations for transdermal delivery
KR101091461B1 (en) 2003-11-07 2011-12-07 센주 세이야꾸 가부시키가이샤 Pharmaceutical composition containing prostaglandin
US20050244463A1 (en) 2004-04-30 2005-11-03 Allergan, Inc. Sustained release intraocular implants and methods for treating ocular vasculopathies
US8685435B2 (en) 2004-04-30 2014-04-01 Allergan, Inc. Extended release biodegradable ocular implants
US8425929B2 (en) 2004-04-30 2013-04-23 Allergan, Inc. Sustained release intraocular implants and methods for preventing retinal dysfunction
US20050244458A1 (en) 2004-04-30 2005-11-03 Allergan, Inc. Sustained release intraocular implants and methods for treating ocular neuropathies
US7589057B2 (en) 2004-04-30 2009-09-15 Allergan, Inc. Oil-in-water method for making alpha-2 agonist polymeric drug delivery systems
US20050244469A1 (en) 2004-04-30 2005-11-03 Allergan, Inc. Extended therapeutic effect ocular implant treatments
US8529927B2 (en) 2004-04-30 2013-09-10 Allergan, Inc. Alpha-2 agonist polymeric drug delivery systems
RU2355691C2 (en) 2004-09-22 2009-05-20 Пфайзер Инк. Polymorphous and amorphous forms of 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6h-azepine[5,4,3-cd]indol-6-on phosphate
JP2007191396A (en) * 2005-01-07 2007-08-02 Rohto Pharmaceut Co Ltd Skin preparation for external use
JP2007045808A (en) * 2005-01-07 2007-02-22 Rohto Pharmaceut Co Ltd Skin care preparation
US20080207560A1 (en) 2005-01-07 2008-08-28 Ayako Harada Composition For External Use
US7931909B2 (en) 2005-05-10 2011-04-26 Allergan, Inc. Ocular therapy using alpha-2 adrenergic receptor compounds having enhanced anterior clearance rates
CA2850858A1 (en) 2005-09-16 2007-04-05 Allergan, Inc. Compositions and methods for the intraocular transport of therapeutic agents
US20070078175A1 (en) 2005-10-05 2007-04-05 L'oreal Administration of novel phenylfurylmethylthiazolidine-2,4-dione and phenylthienylmethylthiazolidine-2,4-dione compounds for stimulating or inducing the growth of keratinous fibers and/or slowing loss thereof
WO2007074602A1 (en) * 2005-12-26 2007-07-05 Lion Corporation Cosmetic for scalp and hair
CA2645073A1 (en) 2006-03-08 2007-09-13 Nuviance, Inc. Transdermal drug delivery compositions and topical compositions for application on the skin
CA2681668C (en) 2006-03-23 2014-04-01 Michael S. Singer Compositions comprising prostaglandin f2-alpha analogs and methods for reducing body fat
US20070286890A1 (en) * 2006-06-07 2007-12-13 John Garnett Walt Eyelash applicator and method
US8802128B2 (en) 2006-06-23 2014-08-12 Allergan, Inc. Steroid-containing sustained release intraocular implants and related methods
US8969415B2 (en) 2006-12-01 2015-03-03 Allergan, Inc. Intraocular drug delivery systems
US9095506B2 (en) 2008-11-17 2015-08-04 Allergan, Inc. Biodegradable alpha-2 agonist polymeric implants and therapeutic uses thereof
US20100204335A1 (en) 2008-12-01 2010-08-12 Allergan, Inc. Kit and composition for eyelash growth
US9149484B2 (en) * 2009-11-09 2015-10-06 Allergan, Inc. Compositions and methods for stimulating hair growth
EP2640350A2 (en) 2010-11-18 2013-09-25 Steven Yoelin Compositions and methods for hair growth
WO2012099942A3 (en) 2011-01-19 2013-06-27 Terakine Therapeutics, Inc. Methods and compositions for treating metabolic syndrome
KR20140015364A (en) 2011-02-14 2014-02-06 알러간, 인코포레이티드 Ester derivatives of bimatoprost compositions and methods
US20120251613A1 (en) 2011-03-29 2012-10-04 Agila Specialities Pvt. Ltd. Method for treating vitiligo with a prostaglandin analogue
RU2635864C2 (en) 2013-05-10 2017-11-16 Топокине Терапеутикс Инк. Compositions and methods for topical prostaglandins delivery to subcutaneous fat

Patent Citations (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3382247A (en) * 1965-11-01 1968-05-07 Upjohn Co 6-amino-1, 2-dihydro-1-hydroxy-2-imino-4-phenoxypyrimidines
US3644363A (en) * 1969-09-02 1972-02-22 Richardson Merrell Inc 1 4-dioxidoquinoxalinyl nitrones
US4128577A (en) * 1975-12-29 1978-12-05 The Upjohn Company 15-Methyl- and 16-phenoxy-PGF2 α, amides
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
US4596812A (en) * 1976-05-24 1986-06-24 The Upjohn Company Methods and solutions for treating male pattern alopecia
US4311707A (en) * 1979-02-12 1982-01-19 American Cyanamid Company Process for topically producing cutaneous vasodilation for the treatment of vasospastic or ischemic conditions
US4543353A (en) * 1981-11-27 1985-09-24 Farmitalia Carlo Erba S.P.A. Ester and amide derivatives of 13,14-didehydro prostaglandins
US4599353A (en) * 1982-05-03 1986-07-08 The Trustees Of Columbia University In The City Of New York Use of eicosanoids and their derivatives for treatment of ocular hypertension and glaucoma
US4812457A (en) * 1984-11-21 1989-03-14 Research Development Corporation Prostaglandin derivatives
US5545655A (en) * 1985-09-19 1996-08-13 Uniroyal Chemical Company, Inc. Substituted oxathiolanes
US4889845A (en) * 1986-06-09 1989-12-26 American Cyanamid Company Vehicle for topical application of pharmaceuticals
US5280018A (en) * 1986-06-09 1994-01-18 American Cyanamid Company Vehicle for optical application of pharmaceuticals
US4883581A (en) * 1986-10-03 1989-11-28 Exxon Chemical Patents Inc. Pretreatment for reducing oxidative reactivity of baseoils
US4952581A (en) * 1987-04-03 1990-08-28 The Trustees Of Columbia University In The City Of New York Use of a prostaglandin in combination with an adrenergic blocking agent for reduction of intraocular pressure
US5001153A (en) * 1987-09-18 1991-03-19 K.K. Ueno Seiyaku Oyo Kenkyujo Ocular hypotensive agents
US5422368A (en) * 1988-09-06 1995-06-06 Kabi Pharmacia Ab Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension
US5578618A (en) * 1988-09-06 1996-11-26 Pharmacia Aktiebolag Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension
US5296504A (en) * 1988-09-06 1994-03-22 Kabi Pharmacia Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension
US5321128A (en) * 1988-09-06 1994-06-14 Kabi Pharmacia Ab Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension
US5422369A (en) * 1988-09-06 1995-06-06 Kabi Pharmacia Ab Prostaglanddin derivatives for the treatment of glaucoma or ocular hypertension
US5194429A (en) * 1988-10-01 1993-03-16 K.K. Ueno Seiyaku Oyo Kenkyujo Ocular hypotensive agents
US4968812A (en) * 1989-06-23 1990-11-06 Shell Oil Company Spirolactonelactams
US5288754A (en) * 1992-02-04 1994-02-22 Allergan, Inc. Polar C-1 esters of prostaglandins
US5578643A (en) * 1992-05-20 1996-11-26 Loyola University Of Chicago Protective prostaglandins for use in conjunction with chemotherapeutic agents
US5508303A (en) * 1992-05-29 1996-04-16 Toray Industries, Inc. Hair-growing composition
US5688819A (en) * 1992-09-21 1997-11-18 Allergan Cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents
US6403649B1 (en) * 1992-09-21 2002-06-11 Allergan Sales, Inc. Non-acidic cyclopentane heptanoic acid,2-cycloalkyl or arylalkyl derivatives as therapeutic agents
US5352708A (en) * 1992-09-21 1994-10-04 Allergan, Inc. Non-acidic cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents
US5607978A (en) * 1992-09-21 1997-03-04 Allergan Non-acidic cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents
US5480900A (en) * 1992-10-13 1996-01-02 Alcon Laboratories, Inc. Combinations of prostaglandins and clonidine derivatives for the treatment of glaucoma
US5510383A (en) * 1993-08-03 1996-04-23 Alcon Laboratories, Inc. Use of cloprostenol, fluprostenol and their salts and esters to treat glaucoma and ocular hypertension
US5773472A (en) * 1993-11-03 1998-06-30 Pharmacia Ab Method and means for prevention of cataract
US5431881A (en) * 1993-12-10 1995-07-11 Palacios; Henry J. Treatment of hair loss and dermatological problems
US6124344A (en) * 1993-12-28 2000-09-26 Allergan Sales, Inc. Cyclopentane heptan(ene)oic acid, 2-heteroarylalkenyl derivatives as therapeutic agents
US6160129A (en) * 1993-12-28 2000-12-12 Allergan Sales, Inc. Cyclopentane heptan(ene)oic acid, 2-heteroarylalkenyl derivatives as therapeutic agents
US5698733A (en) * 1994-09-30 1997-12-16 Alcon Laboratories, Inc. Use of 9-deoxy prostaglandin derivatives to treat glaucoma
US6441047B2 (en) * 1995-11-17 2002-08-27 Alcon Manufacturing Ltd.. Combination therapy for treating glaucoma
US6025392A (en) * 1995-12-22 2000-02-15 Alcon Laboratories, Inc. substituted tetrahydrofuran analogs of prostaglandins as ocular hypotensives
US5789244A (en) * 1996-01-08 1998-08-04 Canji, Inc. Compositions and methods for the treatment of cancer using recombinant viral vector delivery systems
US6258844B1 (en) * 1996-05-28 2001-07-10 Allergan Sales, Inc. Cyclopentane (ene) oic acid, 2-alkenyl derivatives as therapeutic agents
US6262105B1 (en) * 1997-02-04 2001-07-17 Murray A. Johnstone Method of enhancing hair growth
US20020103255A1 (en) * 1997-12-19 2002-08-01 Hellberg Mark R. Use of non-steroidal anti-inflammatory agents in combination with prostaglandin FP receptor agonists to treat glaucoma and ocular hypertension
US6232344B1 (en) * 1997-12-22 2001-05-15 Alcon Laboratories, Inc. 13-Oxa prostaglandins for the treatment of glaucoma and ocular hypertension
US20050222232A1 (en) * 2000-03-31 2005-10-06 Duke University Compositions and methods for treating hair loss using non-naturally occurring prostaglandins
US20020172693A1 (en) * 2000-03-31 2002-11-21 Delong Michell Anthony Compositions and methods for treating hair loss using non-naturally occurring prostaglandins
US20030083381A1 (en) * 2000-03-31 2003-05-01 Hiroki Kumagai Hair growth or hair formation controlling agents
US7388029B2 (en) * 2000-03-31 2008-06-17 Duke University Compositions and methods for treating hair loss using non-naturally occurring prostaglandins
US20020044953A1 (en) * 2000-07-28 2002-04-18 Michelet Jean Francois Use of non-prostanoic agonists of prostaglandin EP-2 and/or EP-4 receptors as cosmetic agents for attenuating, reducing or stopping the loss of head hair and other hairs
US20080070988A1 (en) * 2002-02-04 2008-03-20 Allergan, Inc. Method of Enhancing Hair Growth
US8101161B2 (en) * 2002-02-04 2012-01-24 Allergan, Inc. Method of enhancing hair growth
US20130131097A1 (en) * 2002-02-04 2013-05-23 Allergan, Inc. Topical treatment for chemotherapy induced eyelash loss or hypotrichosis using prostamide f2 alpha agonists
US7351404B2 (en) * 2002-02-04 2008-04-01 Allergan, Inc. Method of enhancing hair growth
US20030147823A1 (en) * 2002-02-04 2003-08-07 Allergan, Inc. Method of enhancing hair growth
US20130041025A1 (en) * 2002-02-04 2013-02-14 Allergan, Inc. Compositions and methods for treating hair loss, hair thinning, and hair color loss
US8038988B2 (en) * 2002-02-04 2011-10-18 Allergan, Inc. Method of enhancing hair growth
US20030199590A1 (en) * 2002-07-25 2003-10-23 Cagle Gerald D Prostaglandin analogues for promotion of hair growth
US20070160562A1 (en) * 2006-01-06 2007-07-12 Brinkenhoff Michael C Delivery devices for hair-promoting cosmetic agent
US20090018204A1 (en) * 2007-07-13 2009-01-15 Brinkenhoff Michael C Composition and method for enhancing hair growth
US20110002866A1 (en) * 2007-10-31 2011-01-06 Lubit Beverly W Methods to prevent a hair-related side effect of treatment with a chemotherapeutic agent
US7514474B1 (en) * 2007-10-31 2009-04-07 Meta Cosmetics, Llc Prostaglandin analog compositions and methods to treat epithelial-related conditions
US20090270392A1 (en) * 2008-04-24 2009-10-29 Allergan, Inc. Substituted gamma lactams as therapeutic agents
US20080275118A1 (en) * 2008-06-12 2008-11-06 Shaw Mari M Health and cosmetic composition and regime for stimulating hair growth and thickening on the head, including the scalp, eyelashes, and eyebrows, and which discourages hair loss
US20120322882A1 (en) * 2009-11-09 2012-12-20 Allergan, Inc. Compositions And Methods For Stimulating Hair Growth
US20110112198A1 (en) * 2009-11-09 2011-05-12 Allergan, Inc. Compositions for enhancing hair growth
US20130030055A1 (en) * 2010-03-24 2013-01-31 Allergan, Inc. Compositions and methods for treating hair loss, hair thinning, and hair color loss
US9009430B2 (en) * 2010-12-02 2015-04-14 International Business Machines Corporation Restoration of data from a backup storage volume
US9009431B2 (en) * 2012-05-29 2015-04-14 Compellent Technologies Virtual snapshot system and method

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Block, L. H. Medicated Applications, in Remington's Pharmaceutical Sciences; Gennaro, A., Ed., 17th Edition, Mack Publishing Company, Easton PA, 1985; Chapter 88, pages 1567-1578 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012112451A1 (en) 2011-02-14 2012-08-23 Allergan, Inc. Ester derivatives of bimatoprost compositions and methods
US9499478B2 (en) 2011-02-14 2016-11-22 Allergan, Inc. Substituted cyclopentanes for inducing hair growth
US8865766B2 (en) 2011-02-14 2014-10-21 Allergan, Inc. Ester derivatives of bimatoprost compositions and methods
US9861641B2 (en) 2011-12-19 2018-01-09 Topokine Therapeutics, Inc. Methods for reducing body fat using tafluprost and analogs thereof
US9090595B2 (en) 2012-08-27 2015-07-28 Allergan, Inc. Reduced central corneal thickening by use of hydrophilic ester prodrugs of beta-chlorocyclopentanes
US9024042B2 (en) 2012-08-27 2015-05-05 Allergan, Inc. Reduced central corneal thickening by use of hydrophilic ester prodrugs of beta-chlorocyclopentanes
US9427401B2 (en) 2012-08-27 2016-08-30 Allergan, Inc. Reduced central corneal thickening by use of hydrophilic ester prodrugs of beta-chlorocyclopentanes
WO2014035827A1 (en) 2012-08-27 2014-03-06 Allergan, Inc. Reduced central corneal thickening by use of hydrophilic ester prodrugs of beta-chlorocyclopentanes
US9849179B2 (en) 2013-05-10 2017-12-26 Topokine Therapeutics, Inc. Methods for topical delivery of prostaglandins to subcutaneous fat
US9820993B2 (en) * 2013-05-15 2017-11-21 Topokine Therapeutics, Inc. Methods and compositions for topical delivery of prostaglandins to subcutaneous fat
US20160067263A1 (en) * 2013-05-15 2016-03-10 Topokine Therapeutics, Inc. Methods and compositions for topical delivery of prostaglandins to subcutaneous fat
WO2015175075A1 (en) 2014-02-20 2015-11-19 Allergan, Inc. Reduced central corneal thickening by use of hydrophilic ester prodrugs of beta-chlorocyclopentanes
WO2016054596A1 (en) 2014-10-02 2016-04-07 Allergan, Inc. Ester prodrugs of gamma-lactams and their use

Also Published As

Publication number Publication date Type
KR20180021919A (en) 2018-03-05 application
EP2498783A2 (en) 2012-09-19 application
WO2011057129A3 (en) 2012-07-26 application
KR101769637B1 (en) 2017-08-18 grant
KR20170095402A (en) 2017-08-22 application
US20180177798A1 (en) 2018-06-28 application
JP5982287B2 (en) 2016-08-31 grant
US9849140B2 (en) 2017-12-26 grant
US9763959B2 (en) 2017-09-19 grant
US20170035779A9 (en) 2017-02-09 application
KR20120099454A (en) 2012-09-10 application
US20160199277A1 (en) 2016-07-14 application
US20120322882A1 (en) 2012-12-20 application
US20140371320A1 (en) 2014-12-18 application
US9138480B2 (en) 2015-09-22 grant
WO2011057129A2 (en) 2011-05-12 application
CN102724951A (en) 2012-10-10 application
JP2016138154A (en) 2016-08-04 application
CN106176261A (en) 2016-12-07 application
RU2567792C2 (en) 2015-11-10 grant
JP2013510174A (en) 2013-03-21 application
US20150328108A1 (en) 2015-11-19 application
RU2012122616A (en) 2013-12-20 application
US9750750B2 (en) 2017-09-05 grant
CA2780267A1 (en) 2011-05-12 application
US20160206626A1 (en) 2016-07-21 application

Similar Documents

Publication Publication Date Title
US6433003B1 (en) Method for treating hyperhidrosis in mammals
US6328987B1 (en) Cosmetic skin care compositions containing alpha interferon
US5656264A (en) Method for promoting hair growth
US20020045659A1 (en) Use, in cosmetic preparations, of prostaglandin EP-3 receptor agonists to attenuate, reduce or stop the growth of head hair and other hairs
US6281203B1 (en) Cosmetic and/or dermatological composition containing salicyclic acid derivative and its use
US5041439A (en) Penetrating topical pharmaceutical compositions
US5425954A (en) Topical amino acid - vitamin complex compositions for pharmaceutical and cosmetic use
US7070768B2 (en) Method for imparting artificial tan to human skin
WO2002015860A1 (en) Topical antioxidant having vitamin c and method of combination with topical agent by user
JP2000095663A (en) Agent for external use containing plant extract
US20120136011A1 (en) Compounds and methods for skin repair
US20050058614A1 (en) Methods for the treatment of gray hair using cyclopentane(ene) heptan(en)oic acid amides
US20060182794A1 (en) Stabilized compositions for topical administration and methods of making same
US7351404B2 (en) Method of enhancing hair growth
US5886038A (en) Composition and method for treatment of psoriasis
US20020052414A1 (en) Use, in cosmetic preparations, of prostaglandin EP-2 and/or EP-4 receptor antagonists to attenuate, reduce or stop the growth of head hair and other hairs
EP0249397A2 (en) Improved penetrating topical pharmaceutical compositions
US6607735B2 (en) Method for reducing the appearance of dark circles under the eyes
US6521222B1 (en) Inorganic/organic complexes for reducing skin irritation
US4189487A (en) Use of pyridine aldehydes for the prevention and treatment of acne vulgaris
US20050137164A1 (en) Diclofenac compositions for the treatment of skin disorders
EP0421333A1 (en) Tretinoin emulsified cream formulations of improved stability
US6977081B1 (en) Facial cream composition containing allantoin
US7056498B2 (en) Composition containing aminophenol derivative, use thereof, and process for dissolving aminophenol derivative
US20040141935A1 (en) Reduction of hair growth

Legal Events

Date Code Title Description
AS Assignment

Owner name: ALLERGAN, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:TROGDEN, JOHN T.;SALAMEH, ADNAN K.;PUJARA, CHETAN P.;SIGNING DATES FROM 20110112 TO 20110202;REEL/FRAME:025733/0049