US20100279988A1 - Transdermal delivery system for hormones and steroids - Google Patents

Transdermal delivery system for hormones and steroids Download PDF

Info

Publication number
US20100279988A1
US20100279988A1 US12/740,666 US74066608A US2010279988A1 US 20100279988 A1 US20100279988 A1 US 20100279988A1 US 74066608 A US74066608 A US 74066608A US 2010279988 A1 US2010279988 A1 US 2010279988A1
Authority
US
United States
Prior art keywords
acetate
delivery system
transdermal delivery
skin
composition
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
US12/740,666
Other languages
English (en)
Inventor
Kerrie Setiawan
Adam Watkinson
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.)
Acrux DDS Pty Ltd
Original Assignee
Acrux DDS Pty Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Acrux DDS Pty Ltd filed Critical Acrux DDS Pty Ltd
Priority to US12/740,666 priority Critical patent/US20100279988A1/en
Assigned to ACRUX DDS PTY LTD. reassignment ACRUX DDS PTY LTD. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: WATKINSON, ADAM, SETIAWAN, KERRIE
Publication of US20100279988A1 publication Critical patent/US20100279988A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M35/00—Devices for applying media, e.g. remedies, on the human body
    • A61M35/003—Portable hand-held applicators having means for dispensing or spreading integral media
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/16—Masculine contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/18—Feminine contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/26—Androgens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/30—Oestrogens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • A61P5/44—Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone

Definitions

  • This invention relates to a transdermal delivery system and to a method of transdermal delivery of hormones and steroids.
  • Steroids and hormones include sex hormones and certain adrenocortical hormones (corticosteroids).
  • the corticosteroids have numerous and diversified physiological functions and pharmacological effects. They influence carbohydrate, protein, fat, and purine metabolism; electrolyte and water balance; and the functions of the cardiovascular system, the kidney, skeletal muscle, nervous system, and other organs and tissues.
  • the corticosteroids are used for treating hormonal insufficiencies, inflammation, and other conditions, whereas the sex hormones are widely used for contraception and hormonal insufficiencies, as well as for treating other conditions.
  • sex steroids The two main classes of sex steroids are androgens and estrogens, of which the most important human derivatives are testosterone and estradiol (17 ⁇ -estradiol), respectively.
  • Other contexts will include progestagen as a third class of sex steroids, distinct from androgens and estrogens.
  • Progesterone is the only naturally-occurring human progestagen.
  • Progestins are synthetic sex hormones used in contraception either alone or with estradiol. Androgens are often referred to as “male sex hormones”, since they have masculinizing effects, while estrogens and progestagens are considered “female sex hormones” although all types are present in each gender, albeit at different levels. Androgens may be used in treatment of reduced libido or in treatment of depression in both men and women.
  • transdermal delivery has received increased attention because it not only provides a potentially simple dosage regime but it also provides a relatively controlled route for release of a hormone into the systemic circulation.
  • transdermal drug delivery is complicated by the fact that the skin behaves as a natural barrier and therefore transport of agents through the skin is a complex mechanism.
  • the skin consists of two principle parts, a relatively thin outermost layer (the ‘epidermis’) and a thicker inner region (the ‘dermis’).
  • the outermost layer of the epidermis (the ‘stratum corneum’) consists of flattened dead cells which are filled with keratin.
  • the region between the flattened dead cells of the stratum corneum is filled with lipids which form lamellar phases that are responsible for the natural barrier properties of the skin.
  • the agent For effective transdermal delivery of a pharmacological agent that is applied to the surface of the skin (‘topical application’), the agent must partition firstly from the vehicle into the stratum corneum, it must typically then diffuse within the stratum corneum before partitioning from the stratum corneum to the viable epidermis.
  • a transdermal “patch” typically consists of a matrix or reservoir containing the drug to be administered, together with a backing layer, an adhesive and a protective release liner. Release membranes may also be incorporated.
  • the delivery of drugs through these systems is either through passive diffusion, controlled by a semi-permeable release membrane, or is controlled by the adhesive/adhesive matrix.
  • the system may also incorporate drug penetration enhancers to increase the flux of the drug through the skin.
  • the rate of drug delivery across a dermal surface can be increased by dermal penetration enhancers.
  • dermal penetration enhancers are often toxic, irritating or allergenic. These enhancers tend to be proton accepting solvents such as dimethylsulfoxide and dimethylacetamide.
  • 2-pyrrolidine, N,N-diethyl-m-toluamide (Deet), 1-dodecal-azacycloheptane-2-one (Azone), N,N dimethylformamide, N-methyl-2-pyrrolidine and calcium thioglycolate have been reported as effective enhancers.
  • difficulties remain with because the problem of irritation at the site of application. and/or difficulty in providing sufficient enhancement of transdermel absorption.
  • the invention provides a transdermal delivery system comprising a composition comprising at least one agent selected from hormones and steroids, and a penetration enhancer comprising a polyethylene glycol of average molecular weight no more than 300.
  • the invention provides a method of transdermal administration of an active agent to an animal subject, including a human, comprising application to a dermal surface of the animal of the above described transdermal delivery system.
  • the invention provides use of (i) polyethylene glycol of average molecular weight no more than 300 and (ii) at least one agent selected from hormones and steroids in manufacture of a medicament for transdermal administration to a subject by application of the medicament to an area of the skin surface of the subject.
  • the medicament may be for treatment of an insufficient level of a hormone such as a sex hormone or for contraception.
  • the invention comprises a composition comprising a pharmacological agent selected from steroids and hormones and a penetration enhance for application to an area of skin of a subject.
  • the composition may be for treatment of an insufficient level of a hormone such as a sex hormone, for hormone replacement therapy or contraception.
  • the invention provides a method of preparing a transdermal delivery system for administration to an area of dermal surface of an animal the method comprising combining at least one pharmacological agent selected from hormones and steroids and a penetration enhancer comprising polyethylene glycol of average molecular weight no more than 300.
  • the invention comprises a transdermal delivery system comprising a spray apparatus comprising a container for a transdermal composition a spray nozzle and an actuator for delivering a metered dose of spray from the container via the nozzle, wherein the transdermal composition comprises at least one pharmacological agent selected from hormones and steroids and a penetration enhancer component comprising polyethylene glycol of average molecular weight no more than 300.
  • the transdermal delivery system will preferably be applied in a dose sufficient to provide an effective amount of at least one pharmacological agent in the bloodstream of the animal.
  • the animal is a human but the invention also extends to the treatment of non-human animals.
  • polyethylene glycol does not include diethylene glycol (although diethylene glycol may if desired be present as an additional component).
  • Polyethylene glycol of average molecular weight no more than 300 includes polyethylene glycol of nominal average molecular weight 200 and 300 wherein the average molecular weight is not more than 110% and not less than 90% (preferably not more than 105% and not less than 95%) of the nominated value.
  • Polyethylene glycol is of formula H—[OCH 2 CH 2 ] n —OH.
  • An average molecular weight of no more than 300 means the average value of n is at least 3 and is generally from 3 to 6 such as 3, 4, 5 or 6 (although the average need not be an integer) and more preferably 3 to 5.
  • Polyethylene glycol is widely available from commercial suppliers in pharmaceutical grades and is sold in specified nominal molecular weights which generally signify that the average molecular weight is not more than 105% and not less than 95% of the nominated value.
  • the viscosities and methods for molecular weight determination are disclosed in USP NF Official Compendium of Standards Volume 11180-1182 [2007 Edition].
  • pharmacological agent is used herein to refer to a broad class of useful chemical and therapeutic agents.
  • pharmacological agent in describing the agents contemplated herein is used in a broad sense to comprehend not only agents having a direct pharmacological effect on the host, but also those having an indirect or observable effect which is useful in the medical arts.
  • pharmacological agent includes prodrugs of the agent which in vivo exerts the physiological effect.
  • Steroids encompass compounds having the general cyclopentanoperhydrophenanthrene ring system of formula:
  • Steroids vary by the functional groups attached to these rings and the oxidation tate of the rings.
  • the steroid may be in the form of the active drug or may be a prodrug steroid which in vivo provides a more active form of the steroid.
  • the steroids include drugs and prodrugs which provide eutrogenic, androgenic glucocorticoid, adrenocortoid, anabolic or birth control activity.
  • steroids examples include, for example, dexamethasone, dexamethasone acetate, dexamethasone sodium phosphate, cortisone, cortisone acetate, hydrocortisone, hydrocortisone acetate, hydrocortisone cypionate, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, prednisone, prednisolone, prednisolone acetate, prednisolone sodium phosphate, prednisolone tebutate, prednisolone pivalate, triamcinolone, triamcinolone acetonide, triamcinolone hexacetonide, triamcinolone diacetate, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, flunsolide, beclomethasone dipropionate, betamethasone sodium phosphate, betamethasone, vetamethas
  • prodrug is a pharmacological drug which is administered in an inactive or less active form and is metabilised into an active form.
  • the prodrug itself may have little or none of the desired activity until it interacts with the systems of the body such as the skin or circulatory systems. Nonetheless hormones and steroids used in the transdermal delivery system of the invention include hormones and steroids which are prodrugs which on administration form a more active hormone or steroid in vivo during or after the process of transdermal administration.
  • a prodrug or a composition of prodrug mixed with the parent composition has a permeation rate that is faster or slower than an identical composition having a pharmacologically equivalent amount of the parent drug.
  • the composition has a duration of the therapeutic effect that is longer or shorter than a composition having a pharmacologically equivalent amount of the parent drug alone.
  • the prodrug is more lipophilic than the parent drug and the prodrug has a greater permeation rate through the skin.
  • the Prohormones and prosteroids are variations or derivatives of the parent hormones or steroids which have groups cleavable under metabolic conditions.
  • Prodrugs become the parent drugs which are pharmaceutically active in vivo, when they undergo solvolysis under physiological conditions or undergo enzymatic degradation.
  • Prodrugs commonly known in the art include acid esters prepared by reaction of the parent acids or alcohol with a suitable alcohol or acid respectively, or amides prepared by reaction of the parent acid or amine compound with an amine or acid respectively, or basic groups reacted to form an acylated base derivative. Examples of prodrugs are discussed in, Bundgard, Design of Prodrugs, pp. 7-9, 21-24, Elsevier, Amsterdam 1985; Silverman, The Organic Chemistry of Drug Design and Drug Action, pp. 352-401, Academic Press, San Diego, Calif., 1992 and Burger's Medicinal Chemistry and Drug Chemistry, Fifth Ed., Vol. 1, pp.
  • the other method for controlling the blood plasma profile of subject is in the selection of the prodrug, such as based on its molecular weight or polarity.
  • the molecular weight of the prodrug By increasing the molecular weight of the prodrug, the time to the onset of permeation of effective amounts of the prodrug will increase relatives to the parent drug.
  • This effect is in the use of norethindrone and norethindrone acetate. The permeation rate of norethindrone rapidly peaks after application, whereas norethindrone acetate having a higher molecular weight reaches a maximum after the norethindrone permeation rate begins to decline.
  • steroids having a free hydroxy group at a position on the steroid ring, such as the 17-position, the 3-position, or at the 11-position on the fused ring.
  • steroidal hormones such as estrogens, progestins, and androgens.
  • the corresponding steroid prodrug is defined as a corresponding structure to the steroid where the free hydroxy at the 3, 11 or 17 position has been reacted with an alcohol reactive moiety.
  • each provides a source of steroid in the bloodstream to achieve the intended physiological effect which, in the case of the corresponding prosteroid, occurs through metabolic conversion of the derivative.
  • a steroid ester is the corresponding structure to the steroid where the free hydroxy group on the ring has been esterified.
  • Examples of a steroid and its corresponding ester include estradiol and estradiol benzoate, estradiol 17-beta cypionate, estradiol 17 propionate, estradiol hemisuccinate (eutocol), estradiol enanthate, estradiol undecylate, estradiol acetate, and estradiol proprionate, etc.
  • Another example is testosterone and its corresponding ester of testosterone such as 17 beta-cypionate, testosterone enanthate, testosterone nicotinate, testosterone phenylacetate, testosterone proprionate, etc.
  • non-esters that have groups on the 17 position such as testosterone 17-chloral hemiacetal, or ethers that have groups on the 3-position such as estradiol 3-methyl ether.
  • percutaneous and “transdermal” are used herein in the broadest sense to refer to being able to pass through unbroken skin.
  • skin penetration enhancer is used herein in its broadest sense to refer to an agent which improves the rate of percutaneous transport of active agents across the skin for use and delivery of active agents to organisms such as animals, whether it be for local application or systemic delivery.
  • non-occlusive is used herein in its broadest sense to refer to not trapping or closing the skin to the atmosphere by means of a patch device, fixed reservoir, application chamber, tape, bandage, sticking plaster, or the like which remains on the skin at the site of application for a prolonged length of time. It is particularly preferred that the transdermal delivery system of the invention is non-occlusive.
  • stratum corneum is used herein in its broadest sense to refer to the outer layer of the skin, which is comprised of (approximately 15) layers of terminally differentiated keratinocytes made primarily of the proteinaceous material keratin arranged in a ‘brick and mortar’ fashion with the mortar being comprised of a lipid matrix made primarily from cholesterol, ceramides and long chain fatty acids.
  • the stratum corneum creates the rate limiting barrier for diffusion of the active agent across the skin.
  • skin-depot is used herein in its broadest sense to refer to a reservoir or deposit of active agent and dermal penetration enhancer within the stratum corneum, whether it be intra-cellular (within keratinocytes) or inter-cellular.
  • volatile:non-volatile liquid vehicle is used in the art to refer to a liquid pharmaceutical vehicle comprising a volatile liquid mixed with a non-volatile liquid vehicle, such as a dermal penetration enhancer.
  • a system or vehicle comprising a volatile liquid mixed with a non-volatile dermal penetration enhancer when described herein is used in its broadest sense to include those systems known as volatile: non-volatile liquid vehicles.
  • aliphatic includes straight chain, branched chain and cyclic aliphatic and may be saturated alkyl groups or unsaturated aliphatic containing from 1 to 3 unsaturated groups particularly 1 to 3 double bonds.
  • the transdermal drug delivery system of the present invention enables a wide range of pharmacological agents selected from hormones and steroids to be delivered through the skin to achieve a desired systemic effect.
  • the drug delivery system preferably comprises at least one active agent intimately mixed with a non-volatile dermal penetration enhancer and a volatile liquid. Where the drug delivery system is applied to the skin, at least one active agent selected from hormones and steroids and non-volatile liquid are thermodynamically driven into the skin as the volatile liquid evaporates. Once within the skin the non-volatile liquid may either disrupt the lipid matrix and/or act as a solubilizer to allow an enhanced penetration rate of the at least one active agent through the skin and into the subject being treated. In this way, the dermal penetration enhancer acts as a vehicle and many systemic active agents are able to be transdermally administered to an animal.
  • the subject to be treated with the transdermal delivery system is generally a mammal, preferably a human being, male or female.
  • the term “therapeutically effective amount” means the amount of the subject compound that will elicit the biological or medical response of a tissue, system, animal or human that is being sought.
  • polyethylene glycol of molecular weight no more than 300
  • a penetration enhancer shows a significant improvement in penetration enhancement of the active agent.
  • the PEG of average molecular weight less than 300 will be present in an amount in the range of from 0.5 to 20% such as 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%.
  • the PEG of average molecular weight less than 300 is present in an amount in the range of from 0.5 to 15% and most preferably from 0.5 to 10% by weight of the composition.
  • the composition of the invention preferably comprises PEG 200 in an amount in the range of from 0.1 to 40% by weight of the total composition and preferably from 0.5 to 20% such as 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%.
  • the composition of the invention may and preferably will contain a volatile solvent.
  • the volatile solvent has a vapour pressure above 35 mm Hg at atmospheric pressure and normal skin temperature of 32 degrees Celsius.
  • the solvent preferably is a C 2 to C 4 alkanol and more preferably is ethanol or isopropanol, or a mixture thereof.
  • the volatile solvent is preferably present in the composition of the invention in an amount in the range of from 40 to 95% by weight of the composition and preferably from 50 to 95%, more preferably from 60 to 95% by weight such as 65% to 95% by weight, 70% to 95%, 70 to 90% or 75 to 90% by weight of the total composition.
  • composition of the invention may if desired contain one or more additional adjuvants such as those selected from the group consisting of penetration enhancers, surfactants, thickeners and solvents.
  • additional adjuvants such as those selected from the group consisting of penetration enhancers, surfactants, thickeners and solvents.
  • suitable thickeners include polyacrylic acids; and acylic acid copolymers, agor, carrageenan, food starch, gelatins, germ Arabic, guorgem, hydroxyethyl cellulose hydroxypropymethyl cellulose, protein and polyvinyl pyrrolidone.
  • the content of thickener may be from 0 to 5%.
  • the penetration enhancer component of the composition may comprise one or more additional penetration enhancers.
  • esters of salicylic acid preferably selected from the C 6 to C 30 aliphatic ester of salicylic acid and more preferably C 8 to C 12 alkyl salicylate and most preferably octyl salicylate particularly 2-ethylhexyl saliclate.
  • the weight ratio of the ester of salicylic acid to the polyethylene glycol is preferably in the range of from 95:5 to 5:95 and preferably from to 1:10 to 10:1 such as 1:10 to 5:1 and 1:5 to 2:1. The optimal ratio may vary depending on the nature and concentration of the active agent and the concentration of the penetration enhancer combination.
  • Known dermal penetration enhancers may be included in addition to PEG of molecular weight no more than 300.
  • Examples of known penetration enhancers are laurocapram and laurocapram derivatives, such as those 1-alkylazacycloheptan-2-ones specified in U.S. Pat. No. 5,196,410, and oleic acid and its ester derivatives, such as methyl, ethyl, propyl, isopropyl, butyl, vinyl and glycerylmonooleate, and those given in U.S. Pat. No.
  • the composition will comprise no more than 5% by weight of the other non-volatile penetration enhancer more preferably no more than 1% and most preferably no more than 0.5% by weight of the composition of non-volatile penetration enhancers other than PEG of molecular weight of no more than 300.
  • alcohols and polyols contain a certain amount of water.
  • the total water content of the composition is less than 20% by weight and preferably less than 10% by weight of the total composition.
  • composition of the invention may be in a range of forms such as a liquid, cream, paste, gel, lotion, patch (matrix and reservoir), tape, plaster or film former.
  • transdermal delivery system is in the form of a liquid for application to a defined area of skin.
  • compositions of the present invention may be in any form suitable for topical application to the skin. Suitable forms include sprayable liquids; gels; liquids that may be applied using a roll-on device; lacquers; and sustained release matrices of transdermal delivery devices such as patches.
  • the compositions are usually administered alone but, under some circumstances, administration may be further modified by using other delivery mechanisms such as iontophoresism, ultrasound and microneedles to enhance penetration. Non-occlusive application and in particular spray application is preferred.
  • Suitable pharmacologically active hormones and steroids may be selected from:
  • Estrogens such as estradiol, estriol, estradiol benzoate, estradiol 17 . beta.-cypionate, estradiol enanthate, estradiol propionate, estrone, ethinylestradiol, Fosfestrol, Dienestrol mestranol, stilboestrol, dienoestrol, epioestriol, estropipate Diethylstilbestrol, Chlorotrianisene, conjugated estrogenic hormones, Polyestradiol phosphate and zeranol and mixtures thereof;
  • Progesterone and progestins such as norethisterone, norethisterone acetate, gestodene, levonorgestrel, allylestrenol, anagestone, desogestrel, dimethisterone, dydrogesterone, ethisterone, ethynodiol, Ethynodiol diacetate, Etonogestrel, gestodene, ethinylestradiol, haloprogesterone, 17-hydroxy-16-methylene-progesterone, 17.
  • Selective progesterone receptor modulators such as Asoprisnil, CDB-4124 and mixtures thereof;
  • Selective estrogen receptor modulators such as Bazedoxifene, Clomifene, Fulvestrant, Lasofoxifene, Raloxifene, Tamoxifen, Toremifene and mixtures thereof;
  • Antiprogestogen such as Mifepristone and mixtures thereof.
  • Antigonadotropins such as Danazol and Gestrinone and mixtures thereof;
  • Antiandrogens such as cyproterone acetate and danazol and mixtures thereof;
  • Antiestrogens such as tamoxifen and epitiostanol and the aromatase inhibitors, exemestane and 4-hydroxy-androstenedione and its derivatives and mixtures thereof.
  • Androgens and anabolic agents such as androisoxazole, androstenediol, bolandiol, bolasterone, clostebol, ethylestrenol. formyldienolone, 4-hydroxy-19-nortestosterone, methandriol, methenolone, methyltrienolone, nandrolone, norbolethone, oxymesterone, stenbolone and trenbolone.
  • Androgenic steroids can include boldenone, fluoxymesterone, mestanolone, mesterolone, methandrostenolone, 17-methyltestosterone, 17.
  • 5-alpha reductase inhibitors such as finasteride, turosteride, LY-191704 and MK-306 and mixtures thereof;
  • Corticosteroids such as betamethasone, betamethasone valerate, cortisone, dexamethasone, dexamethasone 21-phosphate, fludrocortisone, flumethasone, fluocinonide, fluocinonide desonide, fluocinolone, fluocinolone acetonide, fluocortolone, halcinonide, halopredone, hydrocortisone, hydrocortisone 17-valerate, hydrocortisone 17-butyrate, hydrocortisone 21-acetate methylprednisolone, prednisolone, prednisolone 21-phosphate, prednisone, triamcinolone, triamcinolone acetonide and mixtures thereof;
  • Aromatase inhibitor such as Aminogluthetimide, Anastrozole, Exemestane, Formestane, Letrozole and Vorozole;
  • Gonadotropins such as Clomifene and Urofollitropin;
  • GnRH (receptor) agonists such as Buserelin, Goserelin, Histrelin, Leuprorelin, Nafarelin and Triptorelin;
  • GnRH antagonist Abarelix, Cetrorelix and Ganirelix
  • Pituitary hormones and their active derivatives or analogs such as corticotrophin, thyrotropin, follicle stimulating hormone (FSH), luteinising hormone (LH) and gonadotrophin releasing hormone (GnRH);
  • FSH follicle stimulating hormone
  • LH luteinising hormone
  • GnRH gonadotrophin releasing hormone
  • Thyroid hormones such as calcitonin, thyroxine and liothyronine and antithyroid agents such as carbimazole and propylthiouracil; and
  • miscellaneous hormone agents such asoctreotide; and mixtures from two or more of the groups.
  • the optimal ratio of penetration enhancer to active will differ depending on the nature of the active and the penetration enhancer.
  • the weight ratio of penetration enhancer to active will be in the range of from 1000:1 to 1:1000 and preferably from 500:1 to 1:10 and most preferably from 20:1 to 1:1.
  • the penetration enhancer of the invention is particularly useful in transdermal administration of hormones.
  • Hormones that may be used in the drug delivery system of the present invention include systemically active hormones which can be delivered through the skin with the assistance of the dermal penetration enhancer to achieve a desired effect.
  • compositions of the invention may include a plurality of hormones from one or more of these groups.
  • hormones from one or more of these groups.
  • contraceptive formulations may comprise one or more estrogens and one or more progestins.
  • the transdermal delivery system may be used to deliver a therapeutically effective amount of the hormone and/or steroid to a local area or to the systemic circulation.
  • the system provides a pharmaceutically effective level of the pharmacological agent in the systemic circulation, for example a pharmaceutically effective blood level.
  • the drug delivery system comprises on a weight basis from about 0.1 to about 10% of at least one pharmacological agent selected from hormone and steroids in an amount of from about 0.1 to 12% of the dermal penetration enhancer and from about 78 to 99.8% ethanol, isopropanol or mixture thereof.
  • the drug delivery system comprises, on a weight basis, from about 1 to 3% of at least one pharmacological agent selected from hormone and steroids in an amount of from about 1 to 15% of the dermal penetration enhancer combination, from about 45 to 90% ethanol, isopropanol or mixture thereof, and 5 to 45% water.
  • Diseases or conditions that may be treated by using the drug delivery system and methods of the present invention include, but are not limited to, male hormone replacement in testosterone deficient hypogonadal men, female hormone replacement therapy for postmenopausal women using for example estradiol, androgen replacement therapy for females lacking libido using an androgen such as testosterone, male contraception (for example using a progestin such etonogestrel optionally with testosterone) and female contraception (for example using a progestin optionally in combination with an estrogen).
  • the transdermal delivery system comprises a spray apparatus comprising a container for a transdermal composition, a spray nozzle and an actuator for delivering a metered dose of spray from the container via the nozzle, wherein the transdermal composition comprises at least one pharmacological agent and a first penetration enhancer component of polyethylene glycol of average molecular weight no more than 300; and optionally a second penetration enhancer component of an ester of salicylic acid.
  • the transdermal delivery system will preferably be applied in a dose sufficient to provide an effective amount of the at least one pharmacological agent in the bloodstream of the animal.
  • the applicator provides a metered dose application such as a metered dose aerosol, a stored-energy metered dose pump or a manual metered dose pump.
  • a metered dose application such as a metered dose aerosol, a stored-energy metered dose pump or a manual metered dose pump.
  • the drug delivery system is applied to the skin of the animal covering a delivery surface area between about 10 and 800 cm 2 , more preferably between about 10 and 400 cm 2 , and most preferably between about 10 and 200 cm 2 .
  • the application is most preferably performed by means of a topical metered dose spray combined with an actuator nozzle shroud which together accurately control the amount and/or uniformity of the dose applied.
  • One function of the shroud is to keep the nozzle at a pre-determined height above, and perpendicular to, the skin to which the drug delivery system is being applied.
  • shroud This function may also be achieved by means of a spacer-bar or the like.
  • Another function of the shroud is to enclose the area above the skin in order to prevent or limit bounce-back and/or loss of the drug delivery system to the surrounding environment.
  • the area of application defined by the shroud is substantially circular in shape.
  • FIG. 1 is a column chart comparing the permeation of a progestin+an estrogen from a control with progestin transdermal delivery composition of the invention containing PEG-200 pursuant to Example 1.
  • FIGS. 2 a and 2 b are column charts showing the effect on progestin permeation of comparative transdermal compositions containing different progestins and PEG400 rather than PEG 200 as described in Example 2.
  • FIG. 3 is a column chart which shows the effect of PEG 200 on the permeation of an androgen from transdermal delivery compositions described in Example 3.
  • FIG. 4 and FIG. 5 are column charts which compare the effect of PEG 200 and PEG 400 respectively on permeation of an androgen from transdermal delivery compositions described in Example 4.
  • FIG. 6 is a column chart examining the effect of PEG 200 on permeation of an androgen from compositions of Example 5.
  • FIG. 7 is a column chart examining the effect of PEG 200 on the permeation of an estrogen from transdermal delivery compositions described in Example 6.
  • FIG. 8 is a column chart showing the effect of PEG 200 on the permeation of the androgen testosterone in the presence of another permeation enhancer as described in Example 7.
  • the formulations were applied to the skin at a dose of 3.6 ⁇ L/cm 2 .
  • the applied formulation was spread over the skin area using an Eppendorf positive displacement pipette tip without breaking the skin membrane.
  • the amount of active that permeated the skin was quantified using validated HPLC methods
  • FIG. 1 compares the penetration of comparative composition 1 with compositions 2-5 relating to invention.
  • PEG200 in combination with OS was found to significantly enhance the permeation of both Norethisterone Acetate and estradiol through human epidermis in vitro.
  • Permeation of NETA is compared in FIG. 1 .
  • the diffusion cells were maintained at a flow rate of approximately 0.5 mL/hr by a microcassette peristaltic pump (Watson Marlow 505S UK). The cells were kept at 32 ⁇ 0.5° C. by a heater bar and the samples were collected into appropriately sized glass vials for a period of 24 hr.
  • the receptor solutions Phosphate Buffered Saline pH7.4 maintained sink conditions below the skin.
  • the amount of active that permeated the skin was quantified using validated HPLC methods.
  • FIGS. 2 a and 2 b show The effect of PEG400 on permeation of NES and EE.
  • FIGS. 2 a and 2 b thus show Nestorone and Ethinylestradiol permeation respectively obtained from the application of Composition 2 (not of the invention) compared against application of a control composition 1.
  • PEG200 in combination with OS was found to enhance the permeation of both Nestorone and Ethinylestradiol through human epidermis in vitro.
  • PEG400 did not have a significant effect (enhancing or inhibitory) on the permeation of Nestorone through human epidermis in vitro.
  • PEG400 was found to inhibit the permeation of ethinylestradiol through human epidermis in vitro.
  • the diffusion cells were maintained at a flow rate of approximately 1.0 mL/hr by a microcassette peristaltic pump (Watson Marlow 505S UK). The cells were kept at 32 ⁇ 0.5° C. by a heater bar and the samples were collected into appropriately sized glass vials for a period of 24 hr.
  • the receptor solutions (0.002% w/v NaN 3 ) maintained sink conditions below the skin.
  • the amount of active that permeated the skin was quantified using validated HPLC methods.
  • the stratum corneum surface was dosed with either 15 or 30 ⁇ L/cm 2 of an MD-Lotion formulation using a positive displacement pipette. The formulation was spread evenly over the skin area using the pipette tip. Permeation samples were collected into appropriately sized glass vials for a period of 24 h.
  • results for PEG 200 are shown in FIG. 4 and results for PEG 400 are shown in FIG. 5 .
  • PEG200 significantly enhanced the permeation of TES through human skin in vitro.
  • PEG400 did not have any effect on the permeation of TES through human skin in vitro.
  • the stratum corneum surface was dosed with 3.6 ⁇ L/cm 2 of a Metered Dose Transdermal Spray (MDTS) formulation using a positive displacement pipette. The formulation was spread evenly over the skin area using the pipette tip. Permeation samples were collected into appropriately sized glass vials for a period of 24 h.
  • RS receptor solution
  • MDTS Metered Dose Transdermal Spray
  • the Metered Dose Transdermal Spray formulations contained:
  • the amount of active that permeated the skin was quantified using validated HPLC methods and the results for PEG 200 are shown in FIG. 6 .
  • PEG200 increased the permeation of TES through human skin in vitro.
  • the addition of Adding PEG 400 to the formulation did not result in any significant difference in the permeation of TES when compared with the control formulation.
  • the stratum corneum surface was dosed with 3.6 ⁇ L/cm 2 of an Estradiol Transdermal Spray formulation using a positive displacement pipette. The formulation was spread evenly over the skin area using the pipette tip. Permeation samples were collected into appropriately sized glass vials for a period of 24 h.
  • estradiol Transdermal Spray formulations contained:—
  • the amount of active that permeated the skin was quantified using validated HPLC methods and the results are depicted in FIG. 7 .
  • the diffusion cells were maintained at a flow rate of approximately 1.0 mL/hr by a microcassette peristaltic pump (Watson Marlow 505S UK). The cells were kept at 32 ⁇ 0.5° C. by a heater bar and the samples were collected into appropriately sized glass vials for a period of 24 hr.
  • the receptor solutions (0.002% w/v NaN 3 ) maintained sink conditions below the skin.
  • the amount of active that permeated the skin was quantified using validated HPLC methods

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dispersion Chemistry (AREA)
  • Reproductive Health (AREA)
  • Dermatology (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Gynecology & Obstetrics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Psychiatry (AREA)
  • Rheumatology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
US12/740,666 2007-11-02 2008-10-31 Transdermal delivery system for hormones and steroids Abandoned US20100279988A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/740,666 US20100279988A1 (en) 2007-11-02 2008-10-31 Transdermal delivery system for hormones and steroids

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US98478707P 2007-11-02 2007-11-02
US12/740,666 US20100279988A1 (en) 2007-11-02 2008-10-31 Transdermal delivery system for hormones and steroids
PCT/AU2008/001613 WO2009055859A1 (en) 2007-11-02 2008-10-31 Transdermal delivery system for hormones and steroids

Publications (1)

Publication Number Publication Date
US20100279988A1 true US20100279988A1 (en) 2010-11-04

Family

ID=40590452

Family Applications (5)

Application Number Title Priority Date Filing Date
US12/740,666 Abandoned US20100279988A1 (en) 2007-11-02 2008-10-31 Transdermal delivery system for hormones and steroids
US12/740,663 Abandoned US20100297032A1 (en) 2007-11-02 2008-10-31 Transdermal delivery system
US13/887,719 Abandoned US20130317462A1 (en) 2007-11-02 2013-05-06 Transdermal delivery system for hormones and steroids
US13/887,758 Expired - Fee Related US9078810B2 (en) 2007-11-02 2013-05-06 Transdermal delivery system
US14/735,428 Abandoned US20160022820A1 (en) 2007-11-02 2015-06-10 Transdermal delivery system

Family Applications After (4)

Application Number Title Priority Date Filing Date
US12/740,663 Abandoned US20100297032A1 (en) 2007-11-02 2008-10-31 Transdermal delivery system
US13/887,719 Abandoned US20130317462A1 (en) 2007-11-02 2013-05-06 Transdermal delivery system for hormones and steroids
US13/887,758 Expired - Fee Related US9078810B2 (en) 2007-11-02 2013-05-06 Transdermal delivery system
US14/735,428 Abandoned US20160022820A1 (en) 2007-11-02 2015-06-10 Transdermal delivery system

Country Status (17)

Country Link
US (5) US20100279988A1 (enExample)
EP (2) EP2214643B1 (enExample)
JP (2) JP2011502172A (enExample)
KR (2) KR101662186B1 (enExample)
CN (2) CN101883556B (enExample)
AU (2) AU2008318283B2 (enExample)
BR (2) BRPI0819235A2 (enExample)
CA (2) CA2704116A1 (enExample)
DK (2) DK2219603T3 (enExample)
EA (2) EA201000747A1 (enExample)
ES (2) ES2494853T3 (enExample)
MX (2) MX2010004788A (enExample)
NZ (2) NZ585033A (enExample)
PL (2) PL2214643T3 (enExample)
PT (2) PT2214643E (enExample)
WO (2) WO2009055859A1 (enExample)
ZA (1) ZA201003553B (enExample)

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090075963A1 (en) * 2007-09-14 2009-03-19 Drugtech Corporation Transdermal hormone spray
US20090098069A1 (en) * 2007-09-14 2009-04-16 Drugtech Corporation Transdermal, alcohol-free, pharmaceutical compositions
US20100297032A1 (en) * 2007-11-02 2010-11-25 Acrux Dds Pty Ltd. Transdermal delivery system
US8933059B2 (en) 2012-06-18 2015-01-13 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
WO2015031412A1 (en) * 2013-08-27 2015-03-05 Professional Compounding Centers Of America Testosterone booster transdermal compositions
US8987237B2 (en) 2011-11-23 2015-03-24 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US9180091B2 (en) 2012-12-21 2015-11-10 Therapeuticsmd, Inc. Soluble estradiol capsule for vaginal insertion
US9289382B2 (en) 2012-06-18 2016-03-22 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
WO2018031576A1 (en) * 2016-08-08 2018-02-15 Baucom Karan Y Hormone delivery system and method
US9931349B2 (en) 2016-04-01 2018-04-03 Therapeuticsmd, Inc. Steroid hormone pharmaceutical composition
US10052386B2 (en) 2012-06-18 2018-08-21 Therapeuticsmd, Inc. Progesterone formulations
US10206932B2 (en) 2014-05-22 2019-02-19 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US10258630B2 (en) 2014-10-22 2019-04-16 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10286077B2 (en) 2016-04-01 2019-05-14 Therapeuticsmd, Inc. Steroid hormone compositions in medium chain oils
US10328087B2 (en) 2015-07-23 2019-06-25 Therapeuticsmd, Inc. Formulations for solubilizing hormones
WO2019140087A1 (en) * 2018-01-10 2019-07-18 Celista Pharmaceuticals Llc Testosterone transdermal spray with film
US10471072B2 (en) 2012-12-21 2019-11-12 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10471148B2 (en) 2012-06-18 2019-11-12 Therapeuticsmd, Inc. Progesterone formulations having a desirable PK profile
US10537581B2 (en) 2012-12-21 2020-01-21 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10806740B2 (en) 2012-06-18 2020-10-20 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US11246875B2 (en) 2012-12-21 2022-02-15 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11266661B2 (en) 2012-12-21 2022-03-08 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130253449A1 (en) * 2010-12-07 2013-09-26 Yutoku Pharmaceutical Industries Co., Ltd. Noradrenergic and specific serotonergic antidepressant-containing transdermal patch
JPWO2013183407A1 (ja) * 2012-06-05 2016-01-28 祐徳薬品工業株式会社 ミルタザピン含有経皮吸収型貼付製剤
US10201549B2 (en) * 2013-06-14 2019-02-12 Professional Compounding Centers Of America (Pcca) Testosterone combined with anastrozole injection solutions
CN111840246A (zh) * 2014-05-05 2020-10-30 艾尔建制药国际有限公司 用于抗孕激素的阴道递送的制剂和方法
EP3261645B1 (en) 2015-02-27 2021-04-28 Dechra Limited Stimulation of appetite, management of weight loss, and treatment of anorexia in dogs and cats
WO2016167545A1 (ko) * 2015-04-13 2016-10-20 주식회사 엘지생활건강 신경전달물질의 배출을 조절하는 성분이 포함된 용해성 마이크로니들
CN107427474A (zh) 2015-04-13 2017-12-01 株式会社Lg生活健康 含有调节神经递质释放的成分的可溶性微针
US20180125860A1 (en) * 2015-05-18 2018-05-10 Agile Therapeutics, Inc. Contraceptive Compositions and Methods for Improved Efficacy and Modulation of Side Effects
US10449201B2 (en) * 2015-08-17 2019-10-22 Alpha To Omega Pharmaceutical Consultants, Inc. Transdermal and/or topical delivery system comprising clobazam
GB201604484D0 (en) 2016-03-16 2016-04-27 Antibiotx Aps And Københavns Uni University Of Copenhagen Topical antibacterial compositions
US20200054649A1 (en) * 2016-11-17 2020-02-20 Cytoo Skeletal muscle hypertrophy inducers
KR102436756B1 (ko) * 2017-01-31 2022-08-29 신신제약 주식회사 비스테로이드계 소염진통제와 살리실산 유도체를 포함하는 경피흡수 제제
GB2560365B (en) 2017-03-09 2021-10-20 Brightwake Ltd Improvements relating to apparatus negative pressure wound therapy
CN107929268A (zh) * 2017-12-19 2018-04-20 郑州泰丰制药有限公司 一种含质子泵抑制剂药物的透皮贴剂及其制备方法
US10285998B1 (en) 2018-04-04 2019-05-14 The Menopause Method, Inc. Composition and method to aid in hormone replacement therapy
CN108703942B (zh) * 2018-04-23 2021-04-06 中山大学 载有纳米材料包裹保胎药物的微针给药系统及制备方法
EP3817731B1 (en) 2018-07-05 2025-09-03 Celista Pharmaceuticals Llc Testosterone and estradiol transdermal spray
CN110947088A (zh) * 2019-12-06 2020-04-03 广州新济薇娜生物科技有限公司 护眼组合贴片及其制备方法
KR102592892B1 (ko) 2021-03-12 2023-10-23 충남대학교산학협력단 데속시코르티코스테론 글루코사이드를 포함하는 당뇨병 예방 또는 치료용 조성물

Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6299900B1 (en) * 1996-02-19 2001-10-09 Monash University Dermal penetration enhancers and drug delivery systems involving same
US20020103372A1 (en) * 1999-11-24 2002-08-01 Sumika Fine Chemicals Co., Ltd. Anhydrous mirtazapine crystals and process for preparing the same
US20050002868A1 (en) * 2003-06-23 2005-01-06 Acrux Dds Pty Ltd. Method of treatment of a female suffering from androgen insufficiency
US20050090488A1 (en) * 2000-01-19 2005-04-28 Akzo Nobel N.V. Drug combination for the treatment of depression and related disorders comprising mirtazapine
US6916486B2 (en) * 1996-02-19 2005-07-12 Acrux Dds Pty Ltd Transdermal delivery of analgesics
US6916487B2 (en) * 1996-02-19 2005-07-12 Acrux Dds Pty Ltd Transdermal delivery of antiemetics
US6923983B2 (en) * 1996-02-19 2005-08-02 Acrux Dds Pty Ltd Transdermal delivery of hormones
US20050175680A1 (en) * 2002-06-25 2005-08-11 Acrux Dds Pty Ltd. Transdermal delivery rate control using amorphous pharmaceutical compositions
US6929801B2 (en) * 1996-02-19 2005-08-16 Acrux Dds Pty Ltd Transdermal delivery of antiparkinson agents
US20050181032A1 (en) * 2002-06-25 2005-08-18 Acrux Dds Pty Ltd. Metastable pharmaceutical compositions
US20050186141A1 (en) * 2002-06-25 2005-08-25 Acrux Dds Pty Ltd. Transdermal aerosol compositions
US6998138B2 (en) * 1996-02-19 2006-02-14 Acrux Dds Pty. Ltd. Topical delivery of anti-alopecia agents
US7094422B2 (en) * 1996-02-19 2006-08-22 Acrux Dds Pty Ltd. Topical delivery of antifungal agents
US20060275218A1 (en) * 2003-08-04 2006-12-07 Foamix Ltd. Foamable vehicle and pharmaceutical compositions thereof
US20060280783A1 (en) * 2005-06-03 2006-12-14 Acrux Dds Pty Ltd. Method and composition for transdermal drug delivery
US20070275943A1 (en) * 2003-11-19 2007-11-29 Acrux Dds Pty Ltd. Method and Composition for Treatment or Prophylaxis of Amyloidosis Disorders
US20100297032A1 (en) * 2007-11-02 2010-11-25 Acrux Dds Pty Ltd. Transdermal delivery system
US20100322844A1 (en) * 2009-06-23 2010-12-23 Hiroshi Sanui Ozone supplying method and ozone supplier

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK534178A (da) 1977-12-16 1979-06-17 Interx Research Corp Anticholinerge midler med sektrtionshaemmende virkning
US5196410A (en) * 1986-10-31 1993-03-23 Pfizer Inc. Transdermal flux enhancing compositions
US4906475A (en) * 1988-02-16 1990-03-06 Paco Pharmaceutical Services Estradiol transdermal delivery system
JPH01308225A (ja) * 1988-06-03 1989-12-12 Nissan Chem Ind Ltd 外用医薬組成物
DE69007886T2 (de) * 1989-07-21 1994-11-17 Izhak Blank Östradiol enthaltende Mittel und Verfahren zur topischen Anwendung.
US5276079A (en) * 1991-11-15 1994-01-04 Minnesota Mining And Manufacturing Company Pressure-sensitive poly(n-vinyl lactam) adhesive composition and method for producing and using same
WO1994006452A1 (en) * 1992-09-21 1994-03-31 The Upjohn Company Sustained-release protein formulations
WO1994007478A1 (en) * 1992-10-06 1994-04-14 The Upjohn Company Topical pharmaceutical compositions
GB9902227D0 (en) * 1999-02-01 1999-03-24 Cipla Limited Pharmaceutical composition for topical administration
RO121628B1 (ro) * 1999-02-05 2008-01-30 Cipla Limited Compoziţie medicinală, topică, pulverizabilă,dozator care o conţine, procedeu de realizare a dozatorului şi utilizarea compoziţiei menţionate
CA2466425A1 (en) * 2001-11-09 2003-05-15 Qlt Inc. Photodynamic therapy for the treatment of hair loss
AUPS317102A0 (en) * 2002-06-25 2002-07-18 Drug Delivery Solutions Pty Ltd Transdermal aerosol compositions
US20060018937A1 (en) * 2002-10-25 2006-01-26 Foamix Ltd. Steroid kit and foamable composition and uses thereof
US20080027033A1 (en) * 2003-11-19 2008-01-31 Acrux Dds Pty Ltd Method and Composition for Treatment of Cutaneous Lesions
UA85871C2 (uk) 2004-03-15 2009-03-10 Такеда Фармасьютікал Компані Лімітед Інгібітори дипептидилпептидази
JP4613622B2 (ja) * 2005-01-20 2011-01-19 住友電気工業株式会社 軟磁性材料および圧粉磁心
US20070088012A1 (en) * 2005-04-08 2007-04-19 Woun Seo Method of treating or preventing type-2 diabetes
WO2006113242A2 (en) * 2005-04-13 2006-10-26 Unimed Pharmaceuticals, Inc. Method of increasing testosterone and related steroid concentrations in women
CN101223421A (zh) * 2005-05-18 2008-07-16 Gi公司 口服给药系统及其使用方法
EP1896038B1 (en) * 2005-06-03 2016-11-09 Acrux DDS Pty Ltd Method and composition for testosterone transdermal delivery
EP1909772A4 (en) * 2005-08-05 2011-07-13 Nuvo Res Inc TRANSDERMAL DRUG FORMULATION
JP5584415B2 (ja) * 2005-10-12 2014-09-03 ユニメッド・ファーマシューティカルズ・エルエルシー 改良したテストステロンゲル製剤及び使用の方法
WO2008073684A1 (en) * 2006-12-08 2008-06-19 Lipo Chemicals Inc. Composition for treating aging skin comprising a hydroxycinnamic acid such as p-coumaric acid

Patent Citations (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6964777B2 (en) * 1996-02-19 2005-11-15 Acrux Dds Pty Ltd Transdermal delivery of antianxiety agents
US20080152597A1 (en) * 1996-02-19 2008-06-26 Acrux Dds Pty Ltd. Dermal penetration enhancers and drug delivery systems involving the same
US6818226B2 (en) * 1996-02-19 2004-11-16 Acrux Dds Pty. Ltd. Dermal penetration enhancers and drug delivery systems involving same
US7438203B2 (en) * 1996-02-19 2008-10-21 Acrux Dds Pty Ltd Dermal penetration enhancers and drug delivery systems involving same
US6998138B2 (en) * 1996-02-19 2006-02-14 Acrux Dds Pty. Ltd. Topical delivery of anti-alopecia agents
US6916486B2 (en) * 1996-02-19 2005-07-12 Acrux Dds Pty Ltd Transdermal delivery of analgesics
US6916487B2 (en) * 1996-02-19 2005-07-12 Acrux Dds Pty Ltd Transdermal delivery of antiemetics
US6923983B2 (en) * 1996-02-19 2005-08-02 Acrux Dds Pty Ltd Transdermal delivery of hormones
US7387789B2 (en) * 1996-02-19 2008-06-17 Acrux Dds Pty. Ltd. Transdermal delivery of non-steroidal anti-inflammatory drugs
US6929801B2 (en) * 1996-02-19 2005-08-16 Acrux Dds Pty Ltd Transdermal delivery of antiparkinson agents
US20080131494A1 (en) * 1996-02-19 2008-06-05 Acrux Dds Pty Ltd. Dermal Penetration enhancers and drug delivery systems involving same
US20070071803A1 (en) * 1996-02-19 2007-03-29 Acrux Dds Pty Ltd Dermal penetration enhancers and drug delivery systems involving same
US6299900B1 (en) * 1996-02-19 2001-10-09 Monash University Dermal penetration enhancers and drug delivery systems involving same
US7094422B2 (en) * 1996-02-19 2006-08-22 Acrux Dds Pty Ltd. Topical delivery of antifungal agents
US20020103372A1 (en) * 1999-11-24 2002-08-01 Sumika Fine Chemicals Co., Ltd. Anhydrous mirtazapine crystals and process for preparing the same
US20050090488A1 (en) * 2000-01-19 2005-04-28 Akzo Nobel N.V. Drug combination for the treatment of depression and related disorders comprising mirtazapine
US20050186141A1 (en) * 2002-06-25 2005-08-25 Acrux Dds Pty Ltd. Transdermal aerosol compositions
US20050181032A1 (en) * 2002-06-25 2005-08-18 Acrux Dds Pty Ltd. Metastable pharmaceutical compositions
US20050175680A1 (en) * 2002-06-25 2005-08-11 Acrux Dds Pty Ltd. Transdermal delivery rate control using amorphous pharmaceutical compositions
US20050002868A1 (en) * 2003-06-23 2005-01-06 Acrux Dds Pty Ltd. Method of treatment of a female suffering from androgen insufficiency
US20060275218A1 (en) * 2003-08-04 2006-12-07 Foamix Ltd. Foamable vehicle and pharmaceutical compositions thereof
US20070275943A1 (en) * 2003-11-19 2007-11-29 Acrux Dds Pty Ltd. Method and Composition for Treatment or Prophylaxis of Amyloidosis Disorders
US20060280783A1 (en) * 2005-06-03 2006-12-14 Acrux Dds Pty Ltd. Method and composition for transdermal drug delivery
US20100297032A1 (en) * 2007-11-02 2010-11-25 Acrux Dds Pty Ltd. Transdermal delivery system
US20100322844A1 (en) * 2009-06-23 2010-12-23 Hiroshi Sanui Ozone supplying method and ozone supplier

Cited By (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090098069A1 (en) * 2007-09-14 2009-04-16 Drugtech Corporation Transdermal, alcohol-free, pharmaceutical compositions
US20090075963A1 (en) * 2007-09-14 2009-03-19 Drugtech Corporation Transdermal hormone spray
US9078810B2 (en) 2007-11-02 2015-07-14 Acrux Dds Pty Ltd Transdermal delivery system
US20100297032A1 (en) * 2007-11-02 2010-11-25 Acrux Dds Pty Ltd. Transdermal delivery system
US11793819B2 (en) 2011-11-23 2023-10-24 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US9114146B2 (en) 2011-11-23 2015-08-25 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US10675288B2 (en) 2011-11-23 2020-06-09 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US8993548B2 (en) 2011-11-23 2015-03-31 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US8993549B2 (en) 2011-11-23 2015-03-31 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US11103516B2 (en) 2011-11-23 2021-08-31 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US8987237B2 (en) 2011-11-23 2015-03-24 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US9248136B2 (en) 2011-11-23 2016-02-02 Therapeuticsmd, Inc. Transdermal hormone replacement therapies
US9114145B2 (en) 2011-11-23 2015-08-25 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US9012434B2 (en) 2012-06-18 2015-04-21 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US10052386B2 (en) 2012-06-18 2018-08-21 Therapeuticsmd, Inc. Progesterone formulations
US11865179B2 (en) 2012-06-18 2024-01-09 Therapeuticsmd, Inc. Progesterone formulations having a desirable PK profile
US9289382B2 (en) 2012-06-18 2016-03-22 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US9301920B2 (en) 2012-06-18 2016-04-05 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US11529360B2 (en) 2012-06-18 2022-12-20 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US11166963B2 (en) 2012-06-18 2021-11-09 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US10471148B2 (en) 2012-06-18 2019-11-12 Therapeuticsmd, Inc. Progesterone formulations having a desirable PK profile
US11110099B2 (en) 2012-06-18 2021-09-07 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US9006222B2 (en) 2012-06-18 2015-04-14 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US11033626B2 (en) 2012-06-18 2021-06-15 Therapeuticsmd, Inc. Progesterone formulations having a desirable pk profile
US10806740B2 (en) 2012-06-18 2020-10-20 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US8987238B2 (en) 2012-06-18 2015-03-24 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US10639375B2 (en) 2012-06-18 2020-05-05 Therapeuticsmd, Inc. Progesterone formulations
US8933059B2 (en) 2012-06-18 2015-01-13 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US10568891B2 (en) 2012-12-21 2020-02-25 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11116717B2 (en) 2012-12-21 2021-09-14 Therapeuticsmd, Inc. Soluble estradiol capsule for vaginal insertion
US10537581B2 (en) 2012-12-21 2020-01-21 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10471072B2 (en) 2012-12-21 2019-11-12 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US9180091B2 (en) 2012-12-21 2015-11-10 Therapeuticsmd, Inc. Soluble estradiol capsule for vaginal insertion
US11622933B2 (en) 2012-12-21 2023-04-11 Therapeuticsmd, Inc. Soluble estradiol capsule for vaginal insertion
US11497709B2 (en) 2012-12-21 2022-11-15 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11351182B2 (en) 2012-12-21 2022-06-07 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10806697B2 (en) 2012-12-21 2020-10-20 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10835487B2 (en) 2012-12-21 2020-11-17 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10888516B2 (en) 2012-12-21 2021-01-12 Therapeuticsmd, Inc. Soluble estradiol capsule for vaginal insertion
US11304959B2 (en) 2012-12-21 2022-04-19 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11266661B2 (en) 2012-12-21 2022-03-08 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11065197B2 (en) 2012-12-21 2021-07-20 Therapeuticsmd, Inc. Soluble estradiol capsule for vaginal insertion
US11246875B2 (en) 2012-12-21 2022-02-15 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11241445B2 (en) 2012-12-21 2022-02-08 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11123283B2 (en) 2012-12-21 2021-09-21 Therapeuticsmd, Inc. Soluble estradiol capsule for vaginal insertion
WO2015031412A1 (en) * 2013-08-27 2015-03-05 Professional Compounding Centers Of America Testosterone booster transdermal compositions
US11103513B2 (en) 2014-05-22 2021-08-31 TherapeuticsMD Natural combination hormone replacement formulations and therapies
US10206932B2 (en) 2014-05-22 2019-02-19 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US10668082B2 (en) 2014-10-22 2020-06-02 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10258630B2 (en) 2014-10-22 2019-04-16 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10398708B2 (en) 2014-10-22 2019-09-03 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10912783B2 (en) 2015-07-23 2021-02-09 Therapeuticsmd, Inc. Formulations for solubilizing hormones
US10328087B2 (en) 2015-07-23 2019-06-25 Therapeuticsmd, Inc. Formulations for solubilizing hormones
US9931349B2 (en) 2016-04-01 2018-04-03 Therapeuticsmd, Inc. Steroid hormone pharmaceutical composition
US10286077B2 (en) 2016-04-01 2019-05-14 Therapeuticsmd, Inc. Steroid hormone compositions in medium chain oils
US10532059B2 (en) 2016-04-01 2020-01-14 Therapeuticsmd, Inc. Steroid hormone pharmaceutical composition
WO2018031576A1 (en) * 2016-08-08 2018-02-15 Baucom Karan Y Hormone delivery system and method
WO2019140087A1 (en) * 2018-01-10 2019-07-18 Celista Pharmaceuticals Llc Testosterone transdermal spray with film
US11523994B2 (en) 2018-01-10 2022-12-13 Celista Pharmaceuticals Llc Testosterone transdermal spray with film
EP3737374A4 (en) * 2018-01-10 2021-09-29 Celista Pharmaceuticals Llc TRANSDERMAL TESTOSTERONE SPRAY WITH FILM
US12208169B2 (en) 2018-01-10 2025-01-28 Celista Pharmaceuticals Llc Testosterone transdermal spray with film

Also Published As

Publication number Publication date
EP2214643A1 (en) 2010-08-11
KR101662186B1 (ko) 2016-10-04
PL2219603T3 (pl) 2014-10-31
CN101888830A (zh) 2010-11-17
AU2008318283A1 (en) 2009-05-07
WO2009055860A1 (en) 2009-05-07
HK1143091A1 (en) 2011-03-18
CN101883556B (zh) 2013-05-29
US20130317122A1 (en) 2013-11-28
JP5737942B2 (ja) 2015-06-17
NZ585033A (en) 2011-12-22
US20160022820A1 (en) 2016-01-28
PT2219603E (pt) 2014-09-02
CA2704117A1 (en) 2009-05-07
CA2704117C (en) 2015-11-17
EP2219603A4 (en) 2010-11-17
EA019760B1 (ru) 2014-06-30
CN101888830B (zh) 2013-01-23
EA201000747A1 (ru) 2010-10-29
DK2219603T3 (da) 2014-09-01
ZA201003553B (en) 2011-02-23
CN101883556A (zh) 2010-11-10
ES2466676T3 (es) 2014-06-10
ES2494853T3 (es) 2014-09-16
US20130317462A1 (en) 2013-11-28
AU2008318284A1 (en) 2009-05-07
DK2214643T3 (da) 2014-05-26
EP2219603A1 (en) 2010-08-25
AU2008318283B2 (en) 2012-03-29
MX2010004789A (es) 2010-07-05
KR20100094495A (ko) 2010-08-26
CA2704116A1 (en) 2009-05-07
HK1144375A1 (en) 2011-02-18
KR20100094983A (ko) 2010-08-27
US9078810B2 (en) 2015-07-14
EP2219603B1 (en) 2014-07-16
PT2214643E (pt) 2014-05-26
JP2011502173A (ja) 2011-01-20
AU2008318284B2 (en) 2012-03-22
EP2214643B1 (en) 2014-04-02
US20100297032A1 (en) 2010-11-25
BRPI0819245A2 (pt) 2016-07-19
EP2214643A4 (en) 2010-12-01
PL2214643T3 (pl) 2014-09-30
JP2011502172A (ja) 2011-01-20
EA201000746A1 (ru) 2010-10-29
BRPI0819235A2 (pt) 2017-08-22
MX2010004788A (es) 2010-09-14
NZ585034A (en) 2011-08-26
WO2009055859A1 (en) 2009-05-07

Similar Documents

Publication Publication Date Title
AU2008318283B2 (en) Transdermal delivery system for hormones and steroids
EP0971705B1 (en) Hormone replacement therapy drug formulations for topical application to the skin
CN100391462C (zh) 增强的透皮给药系统
DK2473161T3 (en) TOPICAL FORMULATIONS INCLUDING A STEROID
HK1143091B (en) Transdermal delivery system for hormones and steroids
US9649384B2 (en) Natural solubilizer agent comprising a synergistic blend of heptyl glucoside and olive oil glycereth-8 esters for transdermal compositions
HK1144375B (en) Transdermal delivery system

Legal Events

Date Code Title Description
AS Assignment

Owner name: ACRUX DDS PTY LTD., AUSTRALIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SETIAWAN, KERRIE;WATKINSON, ADAM;SIGNING DATES FROM 20100614 TO 20100618;REEL/FRAME:024679/0288

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION