CA2515426A1 - Uses and formulations for transdermal or transmucosal application of active agents - Google Patents

Uses and formulations for transdermal or transmucosal application of active agents Download PDF

Info

Publication number
CA2515426A1
CA2515426A1 CA002515426A CA2515426A CA2515426A1 CA 2515426 A1 CA2515426 A1 CA 2515426A1 CA 002515426 A CA002515426 A CA 002515426A CA 2515426 A CA2515426 A CA 2515426A CA 2515426 A1 CA2515426 A1 CA 2515426A1
Authority
CA
Canada
Prior art keywords
formulation
active agent
amount
present
estradiol
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.)
Granted
Application number
CA002515426A
Other languages
French (fr)
Other versions
CA2515426C (en
Inventor
Dario Norberto R. Carrara
Arnaud Grenier
Celine Besse
Stephen M. Simes
Leah M. Lehman
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.)
Antares Pharma IPL AG
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of CA2515426A1 publication Critical patent/CA2515426A1/en
Application granted granted Critical
Publication of CA2515426C publication Critical patent/CA2515426C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • 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
    • 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
    • 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
    • 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
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • 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
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • 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
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Uses and formulations for providing transdermal or transmucosal delivery of active agents to subjects in need thereof. The formulations and methods treat symptoms of hormonal disorders including hypogonadism, female sexual desire disorder, female menopausal disorder, and adrenal insufficiency.

Claims (70)

1. A formulation for the transdermal or transmucosal administration of an active agent comprising:
at least one active agent, provided that the active agent is not testosterone alone, and that when the active agent is an estrogen or progestin, a therapeutically effective amount of a progestin or estrogen, respectively, is not present in the formulation; and a delivery vehicle comprising an alkanol, a polyalcohol and a permeation enhances in an amount sufficient to provide permeation enhancement of the active agent through mammalian dermal or mucosal surfaces;
wherein the formulation is substantially free of long-chain fatty alcohols, long-chain fatty acids and long-chain fatty esters to avoid undesirable odor and irritation during use of the formulation.
2. The formulation of claim 1, wherein the alkanol is present in an amount between about 5 to 80% by weight of the delivery vehicle, the polyalcohol is present in an amount between about 1% to 30% by weight of the delivery vehicle, and the permeation enhances is present in an amount between about 0.2 to 30% by weight of the delivery vehicle so that the delivery vehicle facilitates absorption of the at least one active agent by the dermal or mucosal surfaces so that transfer or removal of the formulation from such surfaces is minimized.
3. The formulation of claim 2, wherein the alkanol is in combination with water to form a hydroalcoholic mixture, the hydroalcoholic mixture is present in an amount of between about 40 to about 98% by weight of the delivery vehicle, and the alkanol is present in an amount of between about 5% to 80% by weight of the mixture, and the water is present in an amount of between about 20% to 95% by weight of the mixture.
4. The formulation of claim 2, wherein the active agent is estradiol present in an amount between about 0.01% to 2% of the formulation; the alkanol is present in an amount between about 20 to 65% of the formulation; the polyalcohol is propylene glycol present in an amount between about 1% to 15% of the formulation; the permeation enhances is diethylene glycol monoethyl ether present in an amount between about 1% to 15%
of the formulation, and further wherein the formulation comprises a gelling agent present in an amount of between 0.05% to about 4% of the formulation, a neutralizing agent present in an amount between about 0.05% and 1% of the formulation, and water present in an amount between about 20% to 65% of the formulation.
5. The formulation of claim 4, further comprising a sequestering agent.
6. The formulation of claim 2, wherein the polyalcohol and permeation enhancer are present in a weight ratio of 2:1 to 1:1.
7. The formulation of claim 1, wherein the alkanol is a C2 to C4 alcohol selected from the group consisting of ethanol, isopropanol, and n-propanol, the polyalcohol is polypropylene glycol, and the permeation enhancer is a tetra glycol furol or a monoalkyl ether of diethylene ether.
8. The formulation of claim 1, wherein the active agent is androgen, estrogen, progestin, or a combination thereof.
9. The formulation of claim 8, wherein the androgen is selected from the group consisting of: testosterone, 17-.beta.-hydroxyandrostenone, testosterone esters, methyl testosterone, testolactone, oxymetholone, fluoxymesterone, androsterone, androsterone ace-tate, androsterone propionate, androsterone benzoate, androstenediol, androstenediol-3-ace-tate, androstenediol-17-acetate, androstenediol-3,17-diacetate, androstenediol-17-benzoate, androstenediol-3-acetate-17-benzoate, androstenedione, sodium dehydroepiandrosterone sulfate, 4-dihydrotestosterone, 5 adihydrotestosterone, dromostanolone, dromostanolone propionate, ethylestrenol, nandrolone phenpropionate, nandrolone decanoate, nandrolone furylpropionate, nandrolone cyclohexanepropionate, nandrolone benzoate, nandrolone cyclo-hexanecarboxylate, oxandrolone, and stanozolol or any combination thereof.
10. The formulation of claim 8, wherein the estrogen is selected from the group consisting of: 17 beta-estradiol, estradiol, estradiol benzoate, estradiol 17 beta-cypionate, estriol, estrone, ethynil estradiol, mestranol, moxestrol, mytatrienediol, polyestradiol phosphate, quinestradiol, and quinestrol or any combination thereof.
11. The formulation of claim 1, wherein the formulation further comprises at least one of a gelling agent, neutralizing agent; buffering agent, moisturizing agent, humectant, surfactant, antioxidant, emollient, or buffer.
12. The formulation of claim 1 wherein the formulation is in the form of a gel, lotion, cream, spray, aerosol, ointment, emulsion, suspension, liposomal system, lacquer, patch, bandage, or occlusive dressing.
13. A method for treating hormonal disorders in a subject, the method comprising administering to a subject in need of such treatment a formulation comprising an effective dosage of at least one active agent and a delivery vehicle comprising an alkanol, a polyalcohol and a permeation enhances in an amount sufficient to provide permeation enhancement of the active agent through mammalian dermal or mucosal surfaces;
wherein the hormonal disorder is selected from the group consisting of hypogonadism, female menopausal symptoms, female sexual dysfunction, hypoactive sexual desire disorder, and adrenal insufficiency, and wherein the administration of the formulation decreases the frequency of at least one clinical symptom of the hormonal disorder.
14. The method of claim 13, wherein the formulation is substantially free of long-chain fatty alcohols, long-chain fatty acids, and long-chain fatty esters to avoid undesirable odor and irritation during use of the formulation.
15. The method of claim 13, wherein the active agent is an androgen, estrogen, progestin, or a combination thereof.
16. The method of claim 15, wherein the androgen is selected from the group consisting of: testosterone, 17-.beta.-hydroxyandrosterone, testosterone esters, methyl testosterone, testolactone, oxymetholone, fluoxymesterone, androsterone, androsterone ace-tate, androsterone propionate, androsterone benzoate, androstenediol, androstenediol-3-ace-tate, androstenediol-17-acetate, androstenediol-3,17-diacetate, androstenediol-
17-benzoate, androstenediol-3-acetate-17-benzoate, androstenedione, sodium dehydroepiandrosterone sulfate, 4-dihydrotestosterone, 5 adihydrotestosterone, dromostanolone, dromostanolone propionate, ethylestrenol, nandrolone phenpropionate, nandrolone decanoate, nandrolone furylpropionate, nandrolone cyclohexanepropionate, nandrolone benzoate, nandrolone cyclo-hexanecarboxylate, oxandrolone, and stanozolol or any combination thereof.

17. The method of claim 16, wherein the active agent is testosterone present in an amount between about 0.05% to 10% of the formulation; the alkanol is present in an amount between about 20 to 65% of the formulation; the polyalcohol is propylene glycol present in an amount between about 1% to 15% of the formulation; the permeation enhancer is diethylene glycol monoethyl ether present in an amount between about 1% to 15%
of the formulation, and further wherein the formulation comprises a gelling agent present in an amount of between 0.01% to about 4% of the formulation, a neutralizing agent present in an amount between about 0.05% and 1% of the formulation, and water present in an amount between about 20% to 65% of the formulation.
18. The method of claim 17, wherein the formulation further includes a sequestering agent.
19. The method of claim 16, wherein the subject is a female subject, the active agent is testosterone and the therapeutically effective dosage of testosterone is from about 2.2 milligrams to about 0.88 grams each 24 hours.
20. The method of claim 16, wherein the subject is a female subject, the active agent is testosterone and further wherein the method increases serum levels of testosterone to about 142 nanograms per deciliter.
21. The method of claim 16, wherein the subject is a female subject, the active agent is testosterone and further wherein the method increases serum levels of testosterone to about 17 picograms per milliliter.
22. The method of claim 15, wherein the estrogen is selected from the group consisting of: 17 beta-estradiol, estradiol, estradiol benzoate, estradiol 17 beta-cypionate, estriol, estrone, ethynil estradiol, mestranol, moxestrol, mytatrienediol, polyestradiol phosphate, quinestradiol, and quinestrol or any combination thereof.
23. The method of claim 22, wherein the subject is a female subject, the active agent is estradiol and the therapeutically effective dosage of estradiol is from about 0.375 to about 1.5 milligrams each 24 hours.
24. The method of claim 22, wherein the subject is a female subject, the active agent is estrdiol and the free serum concentration of estradiol is increased to about 8.8 nanograms.
25. The method of claim 22, wherein the subject is a female subject, the active agent is estradiol and further wherein the method increases serum levels of estrone to about 10.4 nanograms per decliter.
26. The method of claim 22, wherein the subject is a female subject, the active agent is estradiol and further wherein the method increases serum levels of estrone to about 193 nanograms per deciliter.
27. The method of claim 15, wherein the progestin is selected from the group consisting of: allylestrenol, anagestone, chlormadinone acetate, delmadinone acetate, demegestone, desogestrel, dimethisterone, dydrogesterone, ethynilestrenol, ethisterone, ethynodiol, ethynodiol diacetate, flurogestone acetate, gestodene, gestonorone caproate, haloprogesterone, 17-hydroxy-16-methylene-progesterone, 17 alpha -hydroxyprogesterone, 17 alpha-hydroxygesterone caproate, lynestrenol, medrogestone, medroxyprogesterone, megestrol acetate, melengestrol, norethindrone, norethindrone acetate, norethynodrel, norgesterone, norgestimate, norgestrel, norgestrienone, 19-norprogesterone, norvinisterone, pentagestrone, progesterone, natural progesterone, promegestone, quingestrone, and trengestone or any combination thereof.
28. The method of claim 13, wherein the active agent is a combination of two different active agents administered concurrently.
29. The method of claim 15, wherein a female subject is treated for hypogonadism, female menopausal symptoms, or female sexual disorder, and the formulation comprises testosterone in combination with a further active agent selected from the group consisting of estrone, estradiol, 17 .beta. estradiol, ethynil estradiol, estriol, succinate, estriol dihexanate and estriol sulfamate.
30. The method of claim 15, wherein a female subject is treated for hypogonadism or female menopausal symptoms, and the active agent includes estradiol in combination with a progestin.
31. The method of claim 16, wherein a male subject is treated for hypogonadism, and the active agent includes at least one androgen.
32. The method of claim 31, wherein the at least one androgen includes methyl-testosterone in combination with methandrostenolate.
33. The method of claim 13, wherein the method includes treating a subject for adrenal insufficiency, and the active agent includes dehydroepiandrosterone (DHEA).
34. The method of claim 13, wherein the alkanol is a selected from the group consisting of ethanol, isopropanol, and n-propanol, the polyalcohol is propylene glycol, and the permeation enhancer is a monoalkyl ether of diethylene glycol or a tetraglycol furol, the alkanol is in a mixture with water, and the mixture is present in an amount of between about 40 to about 98% of the delivery vehicle.
35. The method of claim 13, wherein the formulation is in the form of a gel, lotion, cream, spray, aerosol, ointment, emulsion, suspension, liposomal system, lacquer, patch, bandage, or occlusive dressing.
36. A method for treating hormonal disorders in a subject, the method comprising administering to a subject in need of such treatment a formulation comprising at least one active agent, provided that the active agent is not testosterone alone, and that when the active agent is an estrogen or progestin, a therapeutically effective amount of a progestin or estrogen, respectively, is not present in the formulation, and a delivery vehicle comprising an aliphatic alcohol, a polyalcohol, and a permeation enhancer in an amount sufficient to provide permeation enhancement of the active agent through dermal or mucosal surfaces;
wherein the formulation is substantially free of long-chain fatty alcohols, long-chain fatty acids, and long-chain fatty esters to avoid undesirable odor and irritation.
37. The method of claim 36, wherein the delivery vehicle is present in an amount sufficient to reduce or prevent transfer of the formulation to clothing or to another being, thereby minimizing contamination of clothing by the formulation.
38. The method of claim 36, wherein the polyalcohol is present in an amount between about 1% and 30% of the vehicle, the aliphatic alcohol is present in an amount of between about 5 to 80% by weight of the vehicle, the permeation enhancer is present in an amount of between about 1% and 30% of the vehicle, and water is optionally present in the vehicle.
39. A formulation for the transdermal or transmucosal administration of an active agent comprising:
at least one active agent; and a delivery vehicle comprising an alkanol, a polyalcohol and a permeation enhancer of a tetraglycol furol in an amount sufficient to provide permeation enhancement of the active agent through mammalian dermal or mucosal surfaces.
40. The formulation of claim 39, wherein the formulation is substantially free of long-chain fatty alcohols, long-chain fatty acids, and long-chain fatty esters to avoid undesirable odor and irritation during use of the formulation.
41. The formulation of claim 39, wherein the alkanol is present in an amount between about 5 to 80% by weight of the delivery vehicle, the polyalcohol is present in an amount between about 1% to 30% by weight of the delivery vehicle, and the permeation enhancer is glcofurol and is present in an amount between about 1 to 30% by weight of the delivery vehicle so that the delivery vehicle facilitates absorption of the at least one active agent by the dermal or mucosal surfaces so that transfer or removal of the formulation from such surfaces is minimized.
42. The formulation of claim 41, wherein the alkanol is in combination with water to form a hydroalcoholic mixture, the hydroalcoholic mixture is present in an amount of between about 40 to about 98% by weight of the delivery vehicle, and the alkanol is present in an amount of between about 5% to 80% by weight of the mixture, and the water is present in an amount of between about 20% to 95% by weight of the mixture.
43. The formulation of claim 41, wherein the polyalcohol and permeation enhancer are present in a weight ratio of 2:1 to 1:1.
44. The formulation of claim 41, wherein the alkanol is a C2 to C4 alcohol selected from the group consisting of ethanol, isopropanol, and n-propanol, and the polyalcohol is polypropylene glycol.
45. The formulation of claim 39, wherein the active agent is androgen, estrogen, progestin, or a combination thereof.
46. The formulation of claim 45, wherein the androgen is selected from the group consisting of : testosterone, 17-.beta.-hydroxyandrostenone, testosterone esters, methyl testosterone, testolactone, oxymetholone, fluoxymesterone, androsterone, androsterone ace-tate, androsterone propionate, androsterone benzoate, androstenediol, androstenediol-3-ace-tate, androstenediol-17-acetate, androstenediol-3,17-diacetate, androstenediol-17-benzoate, androstenediol-3-acetate-17-benzoate, androstenedione, sodium dehydroepiandrosterone sulfate, 4-dihydrotestosterone, 5 adihydrotestosterone, dromostanolone, dromostanolone propionate, ethylestrenol, nandrolone phenpropionate, nandrolone decanoate, nandrolone furylpropionate, nandrolone cyclohexanepropionate, nandrolone benzoate, nandrolone cyclo-hexanecarboxylate, oxandrolone, and stanozolol or any combination thereof.
47. The formulation of claim 45, wherein the estrogen is selected from the group consisting of: 17 beta-estradiol, estradiol, estradiol benzoate, estradiol 17 beta-cypionate, estriol, estrone, ethynil estradiol, mestranol, moxestrol, mytatrienediol, polyestradiol phosphate, quinestradiol, and quinestrol or any combination thereof.
48. The formulation of claim 39, wherein the formulation further comprises at least one of a gelling agent, neutralizing agents buffering agent, moisturizing agent, humectant, surfactant, antioxidant, emollient, or buffer.
49. The formulation of claim 39, wherein the formulation is in the form of a gel, lotion, cream, spray, aerosol, ointment, emulsion, suspension, liposomal system, lacquer, patch, bandage, or occlusive dressing.
50. A method for treating hormonal disorders in a subject, the method comprising administering to a subject in need of such treatment a formulation comprising at least one active agent and a delivery vehicle comprising an aliphatic alcohol, a polyalcohol, and a permeation enhancer of a tetraglycol furol in an amount sufficient to provide permeation enhancement of the active agent through dermal or mucosal surfaces.
51. The method of claim 50, wherein the formulation is substantially free of long-chain fatty alcohols, long-chain fatty acids, and long-chain fatty esters to avoid undesirable odor and irritation.
52. The method of claim 50, wherein the active agent is an androgen, estrogen, progestin, or a combination thereof.
53. The method of claim 50, the administration of the formulation decreases the frequency of at least one clinical symptom of the hormonal disorder.
54. The method of claim 50, wherein the hormonal disorder includes hypogonadism, female menopausal symptoms, female sexual dysfunction, hypoactive sexual desire disorder, and adrenal insufficiency.
55. The method of claim 54, wherein the administration of the formulation decreases the frequency of at least one clinical symptom including: hot flashes, night sweats, vaginal atrophy, decreased libido, and osteoporosis, impotence, muscle weakness.
56. The method of claim 50, wherein the polyalcohol is present in an amount between about 1% and 30% of the vehicle, the aliphatic alcohol is present in an amount of between about 5 to 80% by weight of the vehicle, the permeation enhancer is glycofurol and is present in an amount of between about 1% and 30% of the vehicle, and water is optionally present in the vehicle.
57. The method of claim 50, wherein the formulation is in the form of a cream, ointment, gel or lotion.
58. The of a formulation according any of the claims 1 to 12 or 39 to 49 for the preparation of a medicament for treating hormonal disorders in a subject.
59. The use according to claim 58, wherein the hormonal disorders are selected from the group consisting of hypogonadism, female menopausal symptoms, female sexual dysfunction, hypoactive sexual desire disorder, and adrenal insufficiency,
60. The use according to claim 58 or 59, wherein the active agent is androgen, estrogen, progestin, or a combination thereof.
61. The use according to claim 60, wherein the androgen is selected from the group consisting of: testosterone, 17-.beta.-hydroxyandrostenone, testosterone esters, methyl testosterone, testolactone, oxymetholone, fluoxymesterone, androsterone, androsterone ace-tate, androsterone propionate, androsterone benzoate, androstenediol, androstenediol-3-ace-tate, androstenediol-17-acetate, androstenediol-3,17-diacetate, androstenediol-17-benzoate, androstenediol-3-acetate-17-benzoate, androstenedione, sodium dehydroepiandrosterone sulfate, 4-dihydrotestosterone, 5 adihydrotestosterone, dromostanolone, dromostanolone propionate, ethylestrenol, nandrolone phenpropionate, nandrolone decanoate, nandrolone furylpropionate, nandrolone cyclohexanepropionate, nandrolone benzoate, nandrolone cyclo-hexanecarboxylate, oxandrolone, and stanozolol or any combination thereof.
62. The use according to claim 60, wherein the estrogen is selected from the group consisting of: 17 beta-estradiol, estradiol, estradiol benzoate, estradiol 17 beta-cypionate, estriol, estrone, ethynil estradiol, mestranol, moxestrol, mytatrienediol, polyestradiol phosphate, quinestradiol, and quinestrol or any combination thereof.
63. The use according to claim 60, wherein the progestin is selected from the group consisting of: allylestrenol, anagestone, chlormadinone acetate, delmadinone acetate, demegestone, desogestrel, dimethisterone, dydrogesterone, ethynilestrenol, ethisterone, ethynodiol, ethynodiol diacetate, flurogestone acetate, gestodene, gestonorone caproate, haloprogesterone, 17-hydroxy-16-methylene-progesterone, 17 alpha -hydroxyprogesterone, 17 alpha-hydroxygesterone caproate, lynestrenol, medrogestone, medroxyprogesterone, megestrol acetate, melengestrol, norethindrone, norethindrone acetate, norethynodrel, norgesterone, norgestimate, norgestrel, norgestrienone, 19-norprogesterone, norvinisterone, pentagestrone, progesterone, natural progesterone, promegestone, quingestrone, and trengestone or any combination thereof.
64. Use of a permeation enhancer to provide permeation enhancement of an effective dosage of at least one active agent through mammalian dermal or mucosal surfaces characterized in that the permeation enhancer is added to a delivery vehicle for the formulation, where the delivery comprises an alkanol and a polyalcohol, and wherein the formulation is intended for treating hormonal disorders in a subject; wherein the hormonal disorder is selected from the group consisting of hypogonadism, female menopausal symptoms, female sexual dysfunction, hypoactive sexual desire disorder, and adrenal insufficiency, and wherein the administration of the formulation decreases the frequency of at least one clinical symptom of the hormonal disorder.
65. Use of a permeation enhancer to provide permeation enhancement of an effectivve dosage of at least one active agent through mammalian dermal or mucosal surfaces characterized in that the permeation enhancer is added to a delivery vehicle comprising an alkanol and a polyalcohol, wherein the formulation is substantially free of long-chain fatty alcohols, long-chain fatty acids, and long-chain fatty esters to avoid undesirable odor and irritation and provided that the active agent is not testosterone alone, and that when the active agent is an estrogen or progestin, a therapeutically effective amount of a progestin or estrogen, respectively, is not present in the formulation.
66. Use of a permeation enhancer to provide permeation enhancement of an effective dosage of at least one active agent through mammalian dermal or mucosal surfaces characterized in that the permeation enhancer is added to a delivery vehicle for the formulation, where the delivery comprises an alkanol and a polyalcohol, and the permeation enhancer is a tetraglycol furol and is present in the formulation in an amount sufficient to provide permeation enhancement of the active agent through dermal or mucosal surfaces.
67. A kit for treating a subject for increasing serum levels of an active agent in a subject comprising: a formulation comprising an effective dosage of at least one active agent and a delivery vehicle comprising an alkanol, a polyalcohol and a permeation enhancer in an amount sufficient to provide permeation enhancement of the active agent through mammalian dermal or mucosal surfaces, wherein the formulation is substantially free of long-chain fatty alcohols, long-chain fatty acids and long-chain fatty esters to avoid undesirable odor and irritation from such compounds during use of the formulation; and a container that retains the formulation and includes a dispenser for releasing or applying a predetermined dosage or volume of the formulation upon demand.
68. The kit of claim 67, wherein the dispenser automatically releases the predetermined dosage or volume upon activation by a user.
69. The kit of claim 67, wherein the dispenser is a pump.
70. A formulation for the transdermal or transmucosal administration of an active agent comprising:
at least one active agent comprising dehydroepiandrosterone (DHEA); and a delivery vehicle comprising an alkanol, a polyalcohol and a permeation enhancer in an amount sufficient to provide permeation enhancement of the active agent through mammalian dermal or mucosal surfaces.
CA2515426A 2003-03-11 2004-03-11 Uses and formulations for transdermal or transmucosal application of active agents Expired - Lifetime CA2515426C (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US45360403P 2003-03-11 2003-03-11
US60/453,604 2003-03-11
US51061303P 2003-10-10 2003-10-10
US60/510,613 2003-10-10
US10/798,111 US20040198706A1 (en) 2003-03-11 2004-03-10 Methods and formulations for transdermal or transmucosal application of active agents
US10/798,111 2004-03-10
PCT/US2004/007291 WO2004080413A2 (en) 2003-03-11 2004-03-11 Uses and formulations for transdermal or transmucosal application of active agents

Publications (2)

Publication Number Publication Date
CA2515426A1 true CA2515426A1 (en) 2004-09-23
CA2515426C CA2515426C (en) 2012-01-24

Family

ID=33102163

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2515426A Expired - Lifetime CA2515426C (en) 2003-03-11 2004-03-11 Uses and formulations for transdermal or transmucosal application of active agents

Country Status (13)

Country Link
US (1) US20040198706A1 (en)
EP (1) EP1648406A4 (en)
JP (2) JP4864695B2 (en)
KR (1) KR20050106508A (en)
CN (1) CN105853396A (en)
AU (1) AU2004220498B2 (en)
BR (1) BRPI0408153A (en)
CA (1) CA2515426C (en)
HK (1) HK1225311A1 (en)
IL (1) IL170454A (en)
MX (1) MXPA05008648A (en)
NZ (1) NZ541854A (en)
WO (1) WO2004080413A2 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009021323A1 (en) * 2007-08-10 2009-02-19 Endorecherche, Inc. Dhea compositions for treating menopause
US8835413B2 (en) 2004-10-20 2014-09-16 Endorecherche, Inc. Sex steroid precursors alone or in combination with a selective estrogen receptor modulator and/or with estrogens and/or a type 5 cGMP phosphodiesterase inhibitor for the prevention and treatment of vaginal dryness and sexual dysfunction in postmenopausal women

Families Citing this family (103)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AUPN814496A0 (en) 1996-02-19 1996-03-14 Monash University Dermal penetration enhancer
US20040198706A1 (en) * 2003-03-11 2004-10-07 Carrara Dario Norberto R. Methods and formulations for transdermal or transmucosal application of active agents
US8980290B2 (en) 2000-08-03 2015-03-17 Antares Pharma Ipl Ag Transdermal compositions for anticholinergic agents
US7198801B2 (en) * 2000-08-03 2007-04-03 Antares Pharma Ipl Ag Formulations for transdermal or transmucosal application
ES2283425T3 (en) * 2000-08-03 2007-11-01 Antares Pharma Ipl Ag NEW COMPOSITION FOR THE TRANSDERMAL AND / OR TRANSMUCTIVE ADMINISTRATION OF ACTIVE COMPOUNDS THAT ENSURE ADEQUATE THERAPEUTIC LEVELS.
US6503894B1 (en) 2000-08-30 2003-01-07 Unimed Pharmaceuticals, Inc. Pharmaceutical composition and method for treating hypogonadism
UA78974C2 (en) 2001-10-20 2007-05-10 Boehringer Ingelheim Pharma Use of flibanserin for treating disorders of sexual desire
US10675280B2 (en) 2001-10-20 2020-06-09 Sprout Pharmaceuticals, Inc. Treating sexual desire disorders with flibanserin
MY139721A (en) * 2002-04-19 2009-10-30 Cpex Pharmaceuticals Inc Pharmaceutical composition
IL152486A0 (en) 2002-10-25 2003-05-29 Meir Eini Alcohol-free cosmetic and pharmaceutical foam carrier
US9265725B2 (en) 2002-10-25 2016-02-23 Foamix Pharmaceuticals Ltd. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US10117812B2 (en) 2002-10-25 2018-11-06 Foamix Pharmaceuticals Ltd. Foamable composition combining a polar solvent and a hydrophobic carrier
US9668972B2 (en) 2002-10-25 2017-06-06 Foamix Pharmaceuticals Ltd. Nonsteroidal immunomodulating kit and composition and uses thereof
US20080138296A1 (en) 2002-10-25 2008-06-12 Foamix Ltd. Foam prepared from nanoemulsions and uses
US7704518B2 (en) 2003-08-04 2010-04-27 Foamix, Ltd. Foamable vehicle and pharmaceutical compositions thereof
MXPA05004278A (en) 2002-10-25 2005-10-05 Foamix Ltd Cosmetic and pharmaceutical foam.
US7700076B2 (en) * 2002-10-25 2010-04-20 Foamix, Ltd. Penetrating pharmaceutical foam
CA2519980C (en) * 2003-04-01 2012-04-10 Laboratoires Besins International Prevention and treatment of breast cancer with 4-hydroxy tamoxifen
US8883769B2 (en) * 2003-06-18 2014-11-11 White Mountain Pharma, Inc. Methods for the treatment of fibromyalgia and chronic fatigue syndrome
US20040259852A1 (en) * 2003-06-18 2004-12-23 White Hillary D. Trandsdermal compositions and methods for treatment of fibromyalgia and chronic fatigue syndrome
MXPA06003316A (en) * 2003-10-10 2006-06-08 Antares Pharma Ipl Ag Transdermal pharmaceutical formulation for minimizing skin residues.
EP1579857A1 (en) * 2004-03-22 2005-09-28 Laboratoires Besins International Chemically stable compositions of 4-hydroxy tamoxifen
US7425340B2 (en) * 2004-05-07 2008-09-16 Antares Pharma Ipl Ag Permeation enhancing compositions for anticholinergic agents
WO2005120487A2 (en) * 2004-06-11 2005-12-22 Egon Tech Preparation for the prevention and treatment of stress conditions as well as functional and organic disorders of the nervous system and metabolic disorders
EP1647271A1 (en) * 2004-10-14 2006-04-19 Laboratoires Besins International 4-Hydroxy tamoxifen gel formulations
AP2007003982A0 (en) * 2004-11-01 2007-06-30 Endorech Inc Use of androgens to reduce the likelihood of acquring or to treat skin aging
US8067399B2 (en) 2005-05-27 2011-11-29 Antares Pharma Ipl Ag Method and apparatus for transdermal or transmucosal application of testosterone
AU2006254742C1 (en) * 2005-06-03 2011-11-03 Acrux Dds Pty Ltd Method and composition for transdermal drug delivery
KR20130114229A (en) 2005-06-03 2013-10-16 애크럭스 디디에스 피티와이 리미티드 Method and composition for transdermal drug delivery
WO2006128255A1 (en) * 2005-06-03 2006-12-07 Acrux Dds Pty Ltd Method and composition for transdermal drug delivery
EP1912650B8 (en) 2005-08-03 2017-10-18 Sprout Pharmaceuticals, Inc. Use of flibanserin in the treatment of obesity
MX2008009177A (en) * 2006-01-20 2008-12-05 Pear Tree Pharmaceuticals Inc Method of treating atrophic vaginitis.
ITRM20060154A1 (en) * 2006-03-20 2007-09-21 Alexandra Fede COMPOSITION AND METHOD FOR THE APPLICATION OF SYNTHETIC HUMAN PHENOMENA WITH BIO TECHNOLOGICAL CAPSULES WITH SLOW RELEASE OF SUBSTANCES THROUGH DROPS IN LINEN JEWELERY AND SIMILAR CLOTHES
US20070254036A1 (en) * 2006-04-13 2007-11-01 Besins Healthcare Sa Treatment of menopause associated symptoms
NZ571460A (en) * 2006-04-21 2010-10-29 Antares Pharma Ipl Ag Methods of treating hot flashes with formulations for transdermal or transmucosal application
JP5193196B2 (en) * 2006-06-02 2013-05-08 ペア ツリー ウーマンズ ヘルス ケア Methods of treatment for atrophic vaginitis
DE602007004615D1 (en) 2006-06-30 2010-03-18 Boehringer Ingelheim Pharma FLIBANSERIN FOR THE TREATMENT OF HARNINE INCONTINENCE AND ASSOCIATED DISEASES
US20080260655A1 (en) 2006-11-14 2008-10-23 Dov Tamarkin Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses
EP2129400A2 (en) * 2007-03-28 2009-12-09 Boehringer Ingelheim International GmbH Pharmaceutical compositions comprising flibanserin and a further agent in the treatment of sexual disorders
US8636982B2 (en) 2007-08-07 2014-01-28 Foamix Ltd. Wax foamable vehicle and pharmaceutical compositions thereof
AU2012204083C1 (en) * 2007-08-10 2015-02-05 Myriel Pharmaceuticals, Llc DHEA compositions for treating menopause
UY31335A1 (en) 2007-09-12 2009-04-30 VASOMOTOR SYMPTOMS TREATMENT
WO2009069006A2 (en) 2007-11-30 2009-06-04 Foamix Ltd. Foam containing benzoyl peroxide
WO2009072007A2 (en) 2007-12-07 2009-06-11 Foamix Ltd. Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof
TWI539959B (en) 2008-02-11 2016-07-01 菲瑞茵國際中心股份有限公司 Method of treating metastatic stage prostate cancer
CA2686480A1 (en) 2008-12-15 2010-06-15 Boehringer Ingelheim International Gmbh New salts
WO2010125470A2 (en) 2009-04-28 2010-11-04 Foamix Ltd. Foamable vehicle and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
CA2759888A1 (en) 2009-05-01 2010-11-04 Tine Kold Olesen Composition for the treatment of prostate cancer
TW201113091A (en) * 2009-06-15 2011-04-16 Gojo Ind Inc Methods and compositions for use with gel dispensers
US20100317635A1 (en) * 2009-06-16 2010-12-16 Endorecherche, Inc. Treatment of hot flushes, vasomotor symptoms, and night sweats with sex steroid precursors in combination with selective estrogen receptor modulators
WO2011013009A2 (en) 2009-07-29 2011-02-03 Foamix Ltd. Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses
CA2769677A1 (en) 2009-07-29 2011-02-03 Foamix Ltd. Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses
US9849142B2 (en) 2009-10-02 2017-12-26 Foamix Pharmaceuticals Ltd. Methods for accelerated return of skin integrity and for the treatment of impetigo
CA2776474C (en) 2009-10-02 2021-01-12 Foamix Ltd. Topical tetracycline compositions
WO2011073995A2 (en) 2009-12-14 2011-06-23 Lincoln Pharmaceuticals Limited Liquid vaginal spray of progesterone
EP2447276A1 (en) 2010-10-27 2012-05-02 Ferring B.V. Process for the manufacture of Degarelix and its intermediates
PT2632934T (en) 2010-10-27 2017-01-06 Ferring Bv Process for the manufacture of degarelix and its intermediates
CA2818491A1 (en) 2010-11-18 2012-05-24 White Mountain Pharma, Inc. Methods for treating chronic or unresolvable pain and/or increasing the pain threshold in a subject and pharmaceutical compositions for use therein
JO3755B1 (en) * 2011-01-26 2021-01-31 Ferring Bv Testosterone formulations
US20130040923A1 (en) 2011-05-13 2013-02-14 Trimel Pharmaceuticals Corporation Intranasal lower dosage strength testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder
US9757388B2 (en) 2011-05-13 2017-09-12 Acerus Pharmaceuticals Srl Intranasal methods of treating women for anorgasmia with 0.6% and 0.72% testosterone gels
US20130045958A1 (en) 2011-05-13 2013-02-21 Trimel Pharmaceuticals Corporation Intranasal 0.15% and 0.24% testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder
WO2012156821A1 (en) * 2011-05-13 2012-11-22 Trimel Pharmaceuticals Corp. Intranasal lower dosage strength testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder
KR20210135003A (en) * 2011-05-15 2021-11-11 에이세러스 바이오파마 인크. Intranasal testosterone bio-adhesive gel formulations and use thereof for treating male hypogonadism
SI2723439T1 (en) * 2011-06-27 2019-04-30 Ferring Bv Applicator system for applying a viscous liquid to the human skin
EP3936133A1 (en) 2011-11-23 2022-01-12 TherapeuticsMD, Inc. Natural combination hormone replacement formulations and therapies
US9301920B2 (en) 2012-06-18 2016-04-05 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US20130338122A1 (en) 2012-06-18 2013-12-19 Therapeuticsmd, Inc. Transdermal hormone replacement therapies
US20150196640A1 (en) 2012-06-18 2015-07-16 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
US10806697B2 (en) 2012-12-21 2020-10-20 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
EP2903608B1 (en) 2012-10-03 2019-08-28 Proponent Biotech GmbH Pharmaceutical composition comprising propionic acid for use in the treatment of viral infections
US10471072B2 (en) 2012-12-21 2019-11-12 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11246875B2 (en) 2012-12-21 2022-02-15 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10568891B2 (en) 2012-12-21 2020-02-25 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
US10537581B2 (en) 2012-12-21 2020-01-21 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
US9452173B2 (en) 2013-01-31 2016-09-27 Merz Pharmaceuticals, Llc Topical compositions and methods for making and using same
US9446131B2 (en) 2013-01-31 2016-09-20 Merz Pharmaceuticals, Llc Topical compositions and methods for making and using same
US8778365B1 (en) 2013-01-31 2014-07-15 Merz Pharmaceuticals, Llc Topical compositions and methods for making and using same
US9433680B2 (en) 2013-01-31 2016-09-06 Merz Pharmaceuticals, Llc Topical compositions and methods for making and using same
US11744838B2 (en) 2013-03-15 2023-09-05 Acerus Biopharma Inc. Methods of treating hypogonadism with transnasal testosterone bio-adhesive gel formulations in male with allergic rhinitis, and methods for preventing an allergic rhinitis event
RU2731713C2 (en) 2013-09-05 2020-09-08 Аб2 Био Са Use of il-18-binding protein (il-18bp) in inflammatory diseases
US8785426B1 (en) 2013-12-13 2014-07-22 Upsher-Smith Laboratories, Inc. Testosterone gel compositions and related methods
KR20170005819A (en) 2014-05-22 2017-01-16 쎄러퓨틱스엠디, 인코퍼레이티드 Natural combination hormone replacement formulations and therapies
EP3217967B1 (en) 2014-11-14 2019-09-18 Follea International System and method for preventing alopecia
AU2016227644B2 (en) 2015-03-05 2022-06-16 Ab2 Bio Sa IL-18 Binding Protein (IL-18BP) and antibodies in inflammatory diseases
EP3270914B1 (en) * 2015-03-19 2023-06-07 GTO Pharma, LLC. Compounds and forms of treatment for female sexual disorders
US10064816B2 (en) 2015-06-11 2018-09-04 ReJoy Treatment of sexual dysfunction
US10328087B2 (en) 2015-07-23 2019-06-25 Therapeuticsmd, Inc. Formulations for solubilizing hormones
AU2017239645A1 (en) 2016-04-01 2018-10-18 Therapeuticsmd, Inc. Steroid hormone pharmaceutical composition
US10286077B2 (en) 2016-04-01 2019-05-14 Therapeuticsmd, Inc. Steroid hormone compositions in medium chain oils
WO2017190183A1 (en) * 2016-05-02 2017-11-09 T & A Pharma Pty Limited Compositions for the treatment of chronic vulval and perineal pain and symptoms and conditions associated therewith
MX2020012139A (en) 2016-09-08 2021-01-29 Vyne Pharmaceuticals Inc Compositions and methods for treating rosacea and acne.
US10285998B1 (en) 2018-04-04 2019-05-14 The Menopause Method, Inc. Composition and method to aid in hormone replacement therapy
US11813354B1 (en) * 2019-01-11 2023-11-14 Shear Kershman Laboratories, Inc Trans-mucosal delivery system for testosterone
US11633405B2 (en) 2020-02-07 2023-04-25 Therapeuticsmd, Inc. Steroid hormone pharmaceutical formulations
WO2021224432A1 (en) 2020-05-06 2021-11-11 Ab2 Bio Sa Il-18 binding protein (il-18bp) in respiratory diseases
GB202007404D0 (en) 2020-05-19 2020-07-01 Nasser Syed Muhammad Tahir Treatment for viral respiratory infections
EP3943097A1 (en) 2020-07-24 2022-01-26 AB2 Bio SA Car-t cell therapy
WO2023067348A1 (en) 2021-10-21 2023-04-27 Biosirius Ltd Treatment for virally-induced pneumonia
WO2023166206A1 (en) 2022-03-04 2023-09-07 Ab2 Bio Sa Il-18 binding protein (il-18bp) in the treatment of vexas

Family Cites Families (95)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3797494A (en) * 1969-04-01 1974-03-19 Alza Corp Bandage for the administration of drug by controlled metering through microporous materials
DE2350315C2 (en) * 1973-10-06 1984-01-12 Johnson & Johnson GmbH, 4000 Düsseldorf Pharmaceutical and cosmetic preparations for external use
US3891696A (en) * 1973-11-02 1975-06-24 Interx Research Corp Novel, transient pro-drug forms of l-dopa
US4082881A (en) * 1976-12-23 1978-04-04 E. R. Squibb & Sons, Inc. Topical and other type pharmaceutical formulations containing isosorbide carrier
US4338993A (en) * 1980-02-22 1982-07-13 R. W. Fernstrum & Co. Underwater outboard marine heat exchanger
US4315925A (en) * 1980-05-30 1982-02-16 University Of Kentucky Research Foundation Method of administering natural female sex hormones
US4537776A (en) * 1983-06-21 1985-08-27 The Procter & Gamble Company Penetrating topical pharmaceutical compositions containing N-(2-hydroxyethyl) pyrrolidone
CA1249968A (en) * 1984-04-05 1989-02-14 Kazuo Kigasawa Ointment base
US4597961A (en) * 1985-01-23 1986-07-01 Etscorn Frank T Transcutaneous application of nicotine
US5731303A (en) * 1985-12-04 1998-03-24 Conrex Pharmaceutical Corporation Transdermal and trans-membrane delivery compositions
US4764381A (en) * 1985-12-06 1988-08-16 Key Pharmaceuticals, Inc. Percutaneous penetration enhancer of oleic acid and 2-ethyl-1, 3-hexanediol
US5041439A (en) * 1986-06-13 1991-08-20 The Procter & Gamble Company Penetrating topical pharmaceutical compositions
US4863970A (en) * 1986-11-14 1989-09-05 Theratech, Inc. Penetration enhancement with binary system of oleic acid, oleins, and oleyl alcohol with lower alcohols
US4808411A (en) * 1987-06-05 1989-02-28 Abbott Laboratories Antibiotic-polymer compositions
US4832953A (en) * 1987-08-13 1989-05-23 Alza Corporation Method for preventing the formation of a crystalline hydrate in a dispersion of a liquid in a monaqueous matrix
US5925372A (en) * 1987-12-16 1999-07-20 Novartis Corporation Mixed solvent mutually enhanced transdermal therapeutic system
US5225189A (en) * 1988-02-18 1993-07-06 The Upjohn Company Minoxidil gel
US5059426A (en) * 1989-03-22 1991-10-22 Cygnus Therapeutic Systems Skin permeation enhancer compositions, and methods and transdermal systems associated therewith
US5053227A (en) * 1989-03-22 1991-10-01 Cygnus Therapeutic Systems Skin permeation enhancer compositions, and methods and transdermal systems associated therewith
US4973468A (en) * 1989-03-22 1990-11-27 Cygnus Research Corporation Skin permeation enhancer compositions
EP0409383B1 (en) * 1989-07-21 1994-04-06 Izhak Blank Estradiol compositions and methods for topical applications
US5232703A (en) * 1989-07-21 1993-08-03 Izhak Blank Estradiol compositions and methods for topical application
US5230896A (en) * 1989-10-12 1993-07-27 Warner-Lambert Company Transdermal nicotine delivery system
DE3937271A1 (en) * 1989-11-09 1991-05-16 Boehringer Ingelheim Kg TRANSDERMAL APPLICATION OF 2-AMINO-6-N-PROPYLAMINO-4,5,6,7-TETRAHYDROBENZOTHIAZOLE
US5188825A (en) * 1989-12-28 1993-02-23 Iles Martin C Freeze-dried dosage forms and methods for preparing the same
KR0166088B1 (en) * 1990-01-23 1999-01-15 . Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof
US5602017A (en) * 1990-04-10 1997-02-11 Kyowa Hakko Kogyo Co., Ltd. Cholesterol oxidase
US5397771A (en) * 1990-05-10 1995-03-14 Bechgaard International Research And Development A/S Pharmaceutical preparation
GB9021674D0 (en) * 1990-10-05 1990-11-21 Ethical Pharma Ltd Transdermal device
US5238933A (en) * 1991-10-28 1993-08-24 Sri International Skin permeation enhancer compositions
US5786357A (en) * 1991-12-02 1998-07-28 Sepracor Inc. Methods and compositions for treating sleep disorders, convulsive seizures and other disorders using optically pure (+) zopiclone
US5178879A (en) * 1992-04-17 1993-01-12 Michael Adekunle Capsaicin gel
US5278176A (en) * 1992-08-21 1994-01-11 Abbott Laboratories Nicotine derivatives that enhance cognitive function
JP2937667B2 (en) * 1992-11-19 1999-08-23 高砂香料工業株式会社 Skin external preparation for acne vulgaris
US5776923A (en) * 1993-01-19 1998-07-07 Endorecherche, Inc. Method of treating or preventing osteoporosis by adminstering dehydropiandrosterone
WO1995001766A1 (en) * 1993-07-09 1995-01-19 Cygnus Therapeutic Systems Method and device for providing nicotine replacement therapy transdermally/transbuccally
US5549888A (en) * 1994-01-31 1996-08-27 Procter & Gamble Aqueous topical anti-acne compositions of low pH
CN1106259A (en) * 1994-02-05 1995-08-09 日东制药株式会社 Antiphlogistic and analgesic gel agent for external use containing propanoic acid non steroid pharmaceutical as effective composition
DE4405898A1 (en) * 1994-02-18 1995-08-24 Schering Ag Transdermal therapeutic systems containing sex steroids
US5552153A (en) * 1994-04-28 1996-09-03 Hoffman-La Roche Inc. Pharmaceutical composition for transdermal delivery
FR2722102B1 (en) * 1994-07-11 1996-08-23 Cird Galderma USE OF DEFORMABLE HOLLOW PARTICLES IN A COSMETIC AND / OR DERMATOLOGICAL COMPOSITION CONTAINING FAT MATERIALS
US6309843B1 (en) * 1994-10-25 2001-10-30 The Curators Of The University Of Missouri Glycoprotein for use in determining endometrial receptivity
US5629021A (en) * 1995-01-31 1997-05-13 Novavax, Inc. Micellar nanoparticles
US5897539A (en) * 1995-09-28 1999-04-27 Schering Aktiengesellschaft Hormone replacement therapy method and hormone dispenser
FR2739558B1 (en) * 1995-10-05 1997-11-28 Innothera Lab Sa UNITAL GALENIC FORM FOR LOCAL HORMONOTHERAPY OF VAGINAL DROUGHT
EP0785212A1 (en) * 1996-01-22 1997-07-23 Laboratoire Theramex New 19-nor-pregnene derivatives
AUPN814496A0 (en) * 1996-02-19 1996-03-14 Monash University Dermal penetration enhancer
US6923983B2 (en) * 1996-02-19 2005-08-02 Acrux Dds Pty Ltd Transdermal delivery of hormones
US6929801B2 (en) * 1996-02-19 2005-08-16 Acrux Dds Pty Ltd Transdermal delivery of antiparkinson agents
GB9610862D0 (en) * 1996-05-23 1996-07-31 Evans Brian K Pharmaceutical products
IT1283102B1 (en) * 1996-06-06 1998-04-07 Permatec Nv THERAPEUTIC COMPOSITION FOR THE TRANSDERMAL ADMINISTRATION OF AN ESTROGENIC OR PROGESTINIC ACTIVE SUBSTANCE OR OF THEIR MIXTURES
GB9614902D0 (en) * 1996-07-16 1996-09-04 Rhodes John Sustained release composition
US5855920A (en) * 1996-12-13 1999-01-05 Chein; Edmund Y. M. Total hormone replacement therapy
US5945405A (en) * 1997-01-17 1999-08-31 Abbott Laboratories Crystal form O of clarithromycin
US20010023261A1 (en) * 1997-01-27 2001-09-20 Lg Chemical Limited. Novel composition for the transdermal administration of drugs
US6426078B1 (en) * 1997-03-17 2002-07-30 Roche Vitamins Inc. Oil in water microemulsion
ATE253941T1 (en) * 1997-06-13 2003-11-15 Cydex Inc COMPOSITION WITH INCREASED STORAGE STABILITY CONTAINING CYCLODEXTRIN AND ACTIVE INGREDIENTS OR ACTIVE INGREDIENTS WHICH ARE DECOMPOSED INTO WATER-INSOLUBLE COMPONENTS
GB9720470D0 (en) * 1997-09-25 1997-11-26 Ethical Pharmaceuticals South Inhibition of crystallization in transdermal devices
US5968919A (en) * 1997-10-16 1999-10-19 Macrochem Corporation Hormone replacement therapy drug formulations for topical application to the skin
IL136042A (en) * 1997-11-10 2005-12-18 Cellegy Pharma Inc Alcohol-containing composition for topical application
DE19827732A1 (en) * 1998-06-22 1999-12-23 Rottapharm Bv Transdermal patch useful for hormone replacement therapy used for treatment of menopausal symptoms
CA2336682C (en) * 1998-07-07 2006-10-10 Transdermal Technologies, Inc. Compositions for rapid and non-irritating transdermal delivery of pharmaceutically active agents and methods for formulating such compositions and delivery thereof
US6284234B1 (en) * 1998-08-04 2001-09-04 Johnson & Johnson Consumer Companies, Inc. Topical delivery systems for active agents
US6096733A (en) * 1998-12-10 2000-08-01 Virginia Lubkin Drugs for topical application of sex steroids in the treatment of dry eye syndrome, and methods of preparation and application
US6267985B1 (en) * 1999-06-30 2001-07-31 Lipocine Inc. Clear oil-containing pharmaceutical compositions
US6383471B1 (en) * 1999-04-06 2002-05-07 Lipocine, Inc. Compositions and methods for improved delivery of ionizable hydrophobic therapeutic agents
US6451300B1 (en) * 1999-05-03 2002-09-17 The Procter & Gamble Company Anti-dandruff and conditioning shampoos containing polyalkylene glycols and cationic polymers
US6962691B1 (en) * 1999-05-20 2005-11-08 U & I Pharmaceuticals Ltd. Topical spray compositions
FR2798065B1 (en) * 1999-09-02 2003-09-05 Assist Publ Hopitaux De Paris USE OF NICOTINE OR DERIVATIVES THEREOF IN A MEDICAMENT FOR THE TREATMENT OF NEUROLOGICAL DISEASES, ESPECIALLY PARKINSON'S DISEASE
US6562368B2 (en) * 1999-12-16 2003-05-13 Dermatrends, Inc. Transdermal administration of oxybutynin using hydroxide-releasing agents as permeation enhancers
US6586000B2 (en) * 1999-12-16 2003-07-01 Dermatrends, Inc. Hydroxide-releasing agents as skin permeation enhancers
US6562370B2 (en) * 1999-12-16 2003-05-13 Dermatrends, Inc. Transdermal administration of steroid drugs using hydroxide-releasing agents as permeation enhancers
US7029694B2 (en) * 2000-04-26 2006-04-18 Watson Laboratories, Inc. Compositions and methods for transdermal oxybutynin therapy
ATE488233T1 (en) * 2000-04-26 2010-12-15 Watson Pharmaceuticals Inc REDUCING SIDE EFFECTS OF OXYBUTYNIN THERAPY
US20040198706A1 (en) * 2003-03-11 2004-10-07 Carrara Dario Norberto R. Methods and formulations for transdermal or transmucosal application of active agents
US8980290B2 (en) * 2000-08-03 2015-03-17 Antares Pharma Ipl Ag Transdermal compositions for anticholinergic agents
US7198801B2 (en) * 2000-08-03 2007-04-03 Antares Pharma Ipl Ag Formulations for transdermal or transmucosal application
US20070225379A1 (en) * 2001-08-03 2007-09-27 Carrara Dario Norberto R Transdermal delivery of systemically active central nervous system drugs
ES2283425T3 (en) * 2000-08-03 2007-11-01 Antares Pharma Ipl Ag NEW COMPOSITION FOR THE TRANSDERMAL AND / OR TRANSMUCTIVE ADMINISTRATION OF ACTIVE COMPOUNDS THAT ENSURE ADEQUATE THERAPEUTIC LEVELS.
US6503894B1 (en) * 2000-08-30 2003-01-07 Unimed Pharmaceuticals, Inc. Pharmaceutical composition and method for treating hypogonadism
US20040092494A9 (en) * 2000-08-30 2004-05-13 Dudley Robert E. Method of increasing testosterone and related steroid concentrations in women
US20030139384A1 (en) * 2000-08-30 2003-07-24 Dudley Robert E. Method for treating erectile dysfunction and increasing libido in men
US20040002482A1 (en) * 2000-08-30 2004-01-01 Dudley Robert E. Androgen pharmaceutical composition and method for treating depression
FR2814074B1 (en) * 2000-09-15 2003-03-07 Theramex NOVEL TOPICAL ESTRO-PROGESTIVE COMPOSITIONS WITH SYSTEMIC EFFECT
US6596740B2 (en) * 2000-10-24 2003-07-22 Richard L. Jones Nicotine mucosal spray
WO2002055020A2 (en) * 2000-12-11 2002-07-18 Testocreme Llc Topical testosterone formulations and associated methods
JP4707297B2 (en) * 2001-03-23 2011-06-22 ロート製薬株式会社 Skin composition
US6951846B2 (en) * 2002-03-07 2005-10-04 The United States Of America As Represented By The Secretary Of The Army Artemisinins with improved stability and bioavailability for therapeutic drug development and application
DE10253216A1 (en) * 2002-11-15 2004-05-27 Cognis Deutschland Gmbh & Co. Kg Use of low molecular weight protein hydrolyzates in washing and cleaning agents
US6995265B2 (en) * 2003-08-26 2006-02-07 North Carolina State University Synthesis of nicotine derivatives from nicotine
MXPA06003316A (en) * 2003-10-10 2006-06-08 Antares Pharma Ipl Ag Transdermal pharmaceutical formulation for minimizing skin residues.
US8668925B2 (en) * 2003-12-12 2014-03-11 Bayer Intellectual Property Gmbh Transdermal delivery of hormones without the need of penetration enhancers
US7425340B2 (en) * 2004-05-07 2008-09-16 Antares Pharma Ipl Ag Permeation enhancing compositions for anticholinergic agents
US8067399B2 (en) * 2005-05-27 2011-11-29 Antares Pharma Ipl Ag Method and apparatus for transdermal or transmucosal application of testosterone
US20070048360A1 (en) * 2005-08-23 2007-03-01 R Carrara Dario N Pharmaceutical compositions with melting point depressant agents and method of making same

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8835413B2 (en) 2004-10-20 2014-09-16 Endorecherche, Inc. Sex steroid precursors alone or in combination with a selective estrogen receptor modulator and/or with estrogens and/or a type 5 cGMP phosphodiesterase inhibitor for the prevention and treatment of vaginal dryness and sexual dysfunction in postmenopausal women
US10076525B2 (en) 2004-10-20 2018-09-18 Endorecherche, Inc. Sex steroid precursors alone or in combination with selective estrogen receptor modulators for the prevention and treatment of dyspareunia in postmenopausal women
US10478443B2 (en) 2004-10-20 2019-11-19 Endorecherche, Inc. Sex steroid precursors alone or in combination with selective estrogen receptor modulators for the prevention and treatment of sexual dysfunction in postmenopausal women
WO2009021323A1 (en) * 2007-08-10 2009-02-19 Endorecherche, Inc. Dhea compositions for treating menopause
US8268806B2 (en) 2007-08-10 2012-09-18 Endorecherche, Inc. Pharmaceutical compositions
US8629129B2 (en) 2007-08-10 2014-01-14 Endorecherche, Inc. Pharmaceutical compositions
EA020683B1 (en) * 2007-08-10 2015-01-30 Эндорешерш, Инк. Method for treating or reducing acquiring symptoms or diseases in postmenopausal women, intravaginal composition and suppository used therein
US8957054B2 (en) 2007-08-10 2015-02-17 Endorecherche, Inc. Pharmaceutical compositions
CN109893526A (en) * 2007-08-10 2019-06-18 恩多研究公司 The DEHA composition for treating menopause
US10881650B2 (en) 2007-08-10 2021-01-05 Endorecherche, Inc. Pharmaceutical compositions

Also Published As

Publication number Publication date
EP1648406A2 (en) 2006-04-26
NZ541854A (en) 2008-05-30
WO2004080413A3 (en) 2006-07-20
IL170454A (en) 2014-02-27
EP1648406A4 (en) 2012-03-21
HK1225311A1 (en) 2017-09-08
JP5441966B2 (en) 2014-03-12
JP2007524589A (en) 2007-08-30
JP4864695B2 (en) 2012-02-01
JP2011236250A (en) 2011-11-24
AU2004220498B2 (en) 2009-04-23
CA2515426C (en) 2012-01-24
MXPA05008648A (en) 2006-02-10
AU2004220498A1 (en) 2004-09-23
WO2004080413A2 (en) 2004-09-23
BRPI0408153A (en) 2006-04-04
CN105853396A (en) 2016-08-17
US20040198706A1 (en) 2004-10-07
KR20050106508A (en) 2005-11-09

Similar Documents

Publication Publication Date Title
CA2515426A1 (en) Uses and formulations for transdermal or transmucosal application of active agents
US7470433B2 (en) Formulations for transdermal or transmucosal application
CA2646667C (en) Methods of treating hot flashes with formulations for transdermal or transmucosal application
EP0811381B1 (en) A novel composition for transdermal administration of an estrogen, a progestin or a mixture thereof
AU2008318283B2 (en) Transdermal delivery system for hormones and steroids
CA2612456C (en) Gel compositions for topical administration
US20110195114A1 (en) Transdermal delivery systems for active agents
CA2419573C (en) Method of increasing testosterone and related steroid concentrations in women
CA2470200C (en) Pharmaceutical composition
KR20030031568A (en) Novel composition for transdermal and/or transmucosal administration of active compounds that ensures adequate therapeutic levels
ZA200301705B (en) Pharmaceutical composition and method for treating hypogonadism.
CA2919648C (en) Natural solubilizer agent comprising a synergistic blend of heptyl glucoside and olive oil glycereth-8 esters for transdermal compositions
CN103189064B (en) There is the low-dose transdermal of high drug release
CN1997357A (en) Uses and formulations for transdermal or transmucosal application of active agents

Legal Events

Date Code Title Description
EEER Examination request