[go: up one dir, main page]

WO2001036039A2 - Administration transdermique ionophoretique de peptides - Google Patents

Administration transdermique ionophoretique de peptides Download PDF

Info

Publication number
WO2001036039A2
WO2001036039A2 PCT/EP2000/011318 EP0011318W WO0136039A2 WO 2001036039 A2 WO2001036039 A2 WO 2001036039A2 EP 0011318 W EP0011318 W EP 0011318W WO 0136039 A2 WO0136039 A2 WO 0136039A2
Authority
WO
WIPO (PCT)
Prior art keywords
peptide
pth
iontophoretic
skin
drug
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.)
Ceased
Application number
PCT/EP2000/011318
Other languages
English (en)
Other versions
WO2001036039A3 (fr
Inventor
Parminder Bobby Singh
Puchun Liu
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.)
Novartis Pharma GmbH Austria
Novartis AG
Original Assignee
Novartis Erfindungen Verwaltungs GmbH
Novartis AG
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 Novartis Erfindungen Verwaltungs GmbH, Novartis AG filed Critical Novartis Erfindungen Verwaltungs GmbH
Priority to AU12807/01A priority Critical patent/AU1280701A/en
Publication of WO2001036039A2 publication Critical patent/WO2001036039A2/fr
Publication of WO2001036039A3 publication Critical patent/WO2001036039A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
    • A61N1/0432—Anode and cathode
    • A61N1/044—Shape of the electrode
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/29—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/325—Applying electric currents by contact electrodes alternating or intermittent currents for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body
    • 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
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
    • A61N1/0432—Anode and cathode
    • A61N1/0436—Material of the electrode
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
    • A61N1/0448—Drug reservoir

Definitions

  • the subject invention relates to transdermal iontophoretic delivery of pharmaceutical compounds and compositions. More specifically, the subject invention relates to a method for controlling the delivery profile of pharmaceutical compounds and compositions.
  • Iontophoretic transdermal delivery of pharmaceutically active compounds relates to introducing ions or soluble salts of the compounds into tissues of the body under the influence of an applied electric field.
  • iontophoretic transdermal delivery systems As compared with passive transdermal systems, as well as with other means of delivering pharmaceutical compounds into the bloodstream.
  • Such reviews include, for example, O. Wong, "Iontophoresis: Fundamentals, " in Drugs Pharm. Sci. (1994), 62 (Drug Permeation Enhancement), 219-46 (1994); and P.
  • iontophoretic transdermal delivery may provide an advantageous method of delivering that compound.
  • iontophoretic methods appear limited as the drug delivery profile of a particular method depends heavily on the particular drug administered. Generally, once it has been established that a specific drug may be effectively delivered by iontophoresis, researchers have not enjoyed great success in adjusting the delivery profile of that drug. Although researchers have experimented with the iontophoretic delivery of various drugs, specific information allowing one to tailor the delivery profile of a specific drug has not been available.
  • European Patent Application No. 0 643 981 relates to the iontophoretic delivery of physiologically active peptides.
  • the '981 patent briefly mentions the incorporation of dielectricity-conferring electrolytes into the iontophoretic method "as appropriate.”
  • Boericke, et al Iontophoretic Delivery of Human Parathyroid Hormone (1-34) in Swine, Proceed. Intern. Symp. Control. Rel. Mater. (1996) relates to the administration of PTH (1-34), but does not disclose the use of an electrolyte and does not disclose any method used to alter the delivery profile of the hormone.
  • An object of the subject invention is to provide iontophoretic transdermal technology that provides the delivery of peptides through the human skin.
  • an object of the subject invention is to provide a method for the delivery of a peptide, wherein the method includes applying a transdermal patch to the skin of a living body, wherein the transdermal patch has a reservoir comprising the peptide and about 0.005 to about 8 mmoles of a pharmaceutically acceptable electrolyte; and causing current to flow through the skin so as to iontophoreticaUy deliver the peptide.
  • Another object of the invention is to provide an iontophoretic system for the delivery of a peptide through skin, wherein the system includes a transdermal delivery device attachable to the skin with the skin, the device including a first electrode and a second electrode, and a reservoir for containing a pharmaceutically acceptable electrolyte and the peptide in electrical communication with the first and second electrodes; and an electrical power source connected to the first and second electrodes; wherein the reservoir contains the peptide and about 0.005 to about 8 mmoles of the pharmaceutically acceptable electrolyte.
  • Figure 1 plots the drug delivery profile of PTH (1-34) in minipigs as plasma concentration versus time.
  • Figure 2 plots the drug delivery profile of PTH (1-34) in minipigs as plasma concentration versus time.
  • Figure 3 plots the drug delivery profile of PTS 893 in minipigs as plasma concentration versus time.
  • Figure 4 plots the drug delivery profile of PTS 893 in minipigs as plasma concentration versus time.
  • Figure 5 plots the drug delivery profile of a subcutaneous injection of 20 ⁇ g of PTS 893 as plasma concentration versus time.
  • the delivery (dose and profile) by which a particular drug is administered to a patient may be controlled by suitable combination of the initial concentration of the drug and electrolyte and applied current (constant/variable) in the iontophoretic system. More specifically, we found that the combination of current density (constant/variable) and the initial amount of electrolyte allows the drug delivery profile to be adjusted. Even more specifically, we have found that setting the initial amount of the electrolyte in the iontophoretic system allows the drug delivery profile to be adjusted, particularly for peptides such as parathyroid hormones.
  • adjustments to the electrolyte concentration and current profile in an iontophoretic patch result in a drug delivery profile that more closely resembles the drug delivery profile provided by subcutaneous injection of the same drug.
  • the ability to tailor the drug delivery profile in iontophoresis therefore provides increased control of the drug's effects on the user, whether those effects are desired or undesired. Additionally, the ability to tailor drug delivery profile in iontophoresis may cause the iontophoretic delivery of drugs to be a more practically effective mode of administration.
  • drug delivery profile means a plot of plasma concentration of the drug versus time for a given drug delivery period.
  • the electrolyte used in our method may include univalent or divalent ions.
  • Examples of electrolytes used in our method include, but are not limited to, NaCl, CaCl 2 , or MgCl 2 .
  • a preferred electrolyte is NaCl.
  • the electrolyte may be present in amounts ranging from about 0.005 to about 8 mmole, preferably about 0.05 to about 1.0 mmole, more preferably about 0.05 to about 0.2 mmole.
  • the initial amount of electrolyte may be expressed as a concentrations ranging from about 0.005 to about 2 M, preferably about 0.01 to about 0.2 M, more preferably about 0.05 to about 0.2 M.
  • Typical drugs that may be administered by the method described herein include, but are not limited to, peptides such as calcitonin, insulin, and peptides and proteins having molecular weights of 10,000 or lower.
  • Preferred peptides are o ⁇ go-peptides such as parathyroid hormones, or pharmaceutically acceptable salts thereof.
  • parathyroid hormones includes parathyroid hormones such as the gene provided in Mangin et al., (Proc. Natl. Acad. Sci., U.S.A.), 86(7) 2408-12 (1989), the entire contents of which are incorporated herein by reference and analogues thereof.
  • parathyroid hormone and parathyroid hormone analogue refer to peptides and polypeptides and/or proteins having parathyroid activity and having at least 75% identity over the region corresponding to Seq. ED No.: 1 (infra).
  • this invention contemplates using isolated amino acid molecules having an amino acid sequence portion identical to a consecutive 20 amino acid sequence portion of Seq. ID No.: 1.
  • PTH (1-34) is a single peptide chain comprised of 34 amino acids from the
  • PTH(l-34) has a molecular weight of 4118 and a calculated isoelectric point (pi) of 8.9.
  • PTH(l-34) carries a net positive charge in aqueous solution at physiological pH.
  • the hydrochloride salt and acetate salt of PTH (1-34) are freely soluble in water.
  • the hydrochloride salt is preferred.
  • the parathyroid hormones may be administered in a method for the treatment or prophylaxis of osteoporosis and related bone disorders in a host in need thereof.
  • the host may be mammals, particularly humans.
  • our method in one embodiment provides a drug delivery profile that can be varied to resemble or mimic the drug delivery profile attained from the subcutaneous injection of the same hormones.
  • our method provides an acceptable delivery profile without disadvantages associated with injections, such as patient inconvenience and pain, patient compliance, and risk of infection.
  • the iontophoretic drug delivery method described herein generally involves applying a voltage current across two electrodes on the skin so as to cause current to flow between the electrodes, wherein a part of the current is carried by ionic species of the drug. During the delivery period, the current may be caused to flow by applying a constant, pulsed, or alternating voltage/current.
  • the pulsed or alternating voltage may have a frequency from about 0.01 Hz to about 100 kHz using substantially any type of waveform shape, including sine, square, triangular, sawtooth, rectangular, etc.
  • the pulsed or alternating voltage may be applied on a duty cycle less than 100%.
  • the iontophoretic systems used to practice the subject invention may include devices and/or components selected from a wide variety of commercially available devices or components and/or from a wide range of methods and materials such as taught, for example, by patents and publications relating to such iontophoretic systems.
  • the iontophoretic transdermal system may comprise an iontophoretic device such as is available from Iomed of Salt Lake City, Utah (e.g. IOMEDTM model PM700 phoresor II), or a device such as manufactured by Empi of St. Paul, Minnesota (e.g. Empi DUPELTM), or a device known as the LECTROTM Patch, manufactured by General Medical Device Corp. of Los Angeles, California.
  • the electrodes may be comprised of reactive or non-reactive electrodes.
  • reactive electrodes are those made from metal salts, such as silver chloride or materials described in U.S. Pat. 4,752,285, the entire contents of which are incorporated herein by reference.
  • the silver chloride electrodes are available from Iomed.
  • Alternative reactive electrodes can be made from a combination of ion-exchange resins, exemplified by electrodes available from Empi.
  • non-reactive electrodes are those made from metals such as gold or platinum, or from carbon particles dispersed in polymeric matrices such as one used in the LECTROTM Patch.
  • Adhesives used to fix the iontophoretic patch to the skin may be comprised of pressure sensitive adhesives used in passive transdermal delivery systems, such those derived from silicone or acrylic polymers, or those derived from rubbers such as polyisobutylene.
  • pressure sensitive adhesives used in passive transdermal delivery systems, such those derived from silicone or acrylic polymers, or those derived from rubbers such as polyisobutylene.
  • a combination of pressure sensitive and conductive adhesives can also be used, such as those described EPA 0 542 294, the entire contents of which are incorporated herein by reference.
  • the drug reservoir contains the drug and electrolyte in either an aqueous solution or a gel.
  • the reservoir gel may be comprised of water soluble polymers or hydrogels, such as polyvinyl alcohol, or crosslinked hydrogels described in U.S. Pat. 5,069,908, the entire contents of which are incorporated herein by reference.
  • the concentration of the drug may typically range from 0.1 to about 30 mg/ml, preferably about 1 to about 10 mg/ml, and more preferably about 1 to about 3 mg/ml.
  • Th pH of the solution in the drug reservoir will typically range from 3.0 to
  • the drug reservoir of the iontophoretic system may include additives that are well known and conventional in the iontophoresis art.
  • additives include, for example, permeation enhancers, antioxidants, and buffers.
  • the representative unit dosage that may typically be delivered during a single delivery period may vary in amount from about 0.01 ⁇ g to about 200 mg.
  • a preferred unit dosage for parathyroid hormones is about 0.005 to about 0.2 mg, more preferably about 0.005 to about 0.1 mg.
  • the unit dosage that is delivered may be determined on the basis of a wide range of factors, including the compound, condition, age, body weight, clearance, etc.
  • the iontophoretic delivery method of pharmaceutical compounds comprises a drug delivery treatment protocol that includes periodically applying an iontophoretic transdermal patch at intervals that may be as frequent as twice daily or as infrequent as once a week or once a month.
  • a single treatment step the patch is applied, the drug is iontophoreticaUy delivered and the patch is then removed, with another patch being applied again, when the next treatment step is due to be carried out.
  • a unit dosage is herein defined to be that quantity of drug, however large or small, that is delivered during a single treatment step by a single patch application at an individual site.
  • the iontophoretic system may be comprised of still other methods and materials, such as described in WO 92 17239, EPA 0 547 482, and U.S. Patent No. 4,764,164, the entire contents of which are incorporated herein by reference.
  • the iontophoretic drug delivery comprises a direct/pulsed/alternating current flow of about 0.001 to about 4 mA/cm during the delivery phase of the drug.
  • a preferred range for the current flow may be from about 0.01 to about 2 mA cm .
  • a more preferred range for the current flow may be from about 0.1 to about 0.5 mA cm 2 .
  • the transport area of the patch ranges from about 1.0 to about 100 cm 2 , preferably about 1 to about 50 cm 2 , and more preferably about 1 to about 30 cm 2 .
  • Time period for drug delivery may typically range from about 10 seconds to about 48 hours, wherein the drug delivery period may preferably be from about 1 minute to about 24 hours.
  • reduction in the drug delivery period may rninimize the formation of PTH (1-33) in the system.
  • Example 1 A TransQTM iontophoretic system supplied by Dermion was modified by depositing additional silver chloride on silver foil by to increase the negative electrode's charge capacity to 810 mA.min. Polyethylene oxide was used as donor reservoir matrix for conditions #1 and 2 and Sontara nonwoven was used for conditions #3-6. The fill volume was 1.5 ml for conditions 1-5 and 1 ml for condition #6, transport area was 7 cm 2 . Current was generated by constant current source (supplied by Dermion) and was manually adjusted to obtain variable current in cond #4 with PTS 893.
  • PTH (1-34) was iontophoreticaUy administered to male miniature pigs of the Gottinger strain and 12.4 - 18.0 kg body weight.
  • the iontophoretic device had a sUver foU anode (charge capacity of 1000 mA.min) and a silver chloride plated silver plate cathode (charge capacity of 810 rr_A.rnin).
  • the electrodes were applied on the dorsum of the animals 5 cm apart and the constant current generated by a Phoresor.
  • a comparison of Condition 4 shown in Rgure 1 and Condition 5 shown in Rgure 2 reveals that when the NaCl concentration in the reservoir solution was lowered from 0.2 to 0.1 M, the plasma peak was delayed and total deUvery increased.
  • the conditions used for the iontophoretic administration of PTS-893 to minipigs are shown below in Table 2.
  • the iontophoretic patch used contained 3.0 mg ml of PTS- 893 in a Sontara matrix. Blood samples were taken during the apphcation of current, and also up to 2 hours after the current was shut off. For comparative purposes, 20 ⁇ g of PTS 893 was also administered by subcutaneous injection to minipigs. TABLE 2
  • Figures 3 and 4 show the data observed using the above iontophoretic conditions
  • Figure 5 shows the data observed after subcutaneous injection.
  • a comparison of Figure 4 and Figure 5 shows that iontophoretic delivery provided a drug deUvery profile substantiaUy simUar to subcutaneous injection.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Radiology & Medical Imaging (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Chemical & Material Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une méthode permettant d'administrer un médicament à un mammifère de manière ionophorétique. Pour régler le profil d'administration du médicament, on peut procéder à un ajustement de la concentration d'électrolytes dans la solution se trouvant dans le réservoir du système ionophorétique.
PCT/EP2000/011318 1999-11-17 2000-11-15 Administration transdermique ionophoretique de peptides Ceased WO2001036039A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU12807/01A AU1280701A (en) 1999-11-17 2000-11-15 Iontophoretic transdermal delivery of peptides

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US16615099P 1999-11-17 1999-11-17
US60/166,150 1999-11-17

Publications (2)

Publication Number Publication Date
WO2001036039A2 true WO2001036039A2 (fr) 2001-05-25
WO2001036039A3 WO2001036039A3 (fr) 2002-03-07

Family

ID=22602026

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/011318 Ceased WO2001036039A2 (fr) 1999-11-17 2000-11-15 Administration transdermique ionophoretique de peptides

Country Status (2)

Country Link
AU (1) AU1280701A (fr)
WO (1) WO2001036039A2 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1595542A1 (fr) * 2004-03-26 2005-11-16 Solvay Pharmaceuticals B.V. Administration iontophoretique de composés piperazinyl-2(3h)-benzoxazoloniques
US7596407B2 (en) 2004-03-26 2009-09-29 Solvay Pharmaceuticals, B.V. Transdermal iontophoretic delivery of piperazinyl-2(3H)-benzoxazolone compounds
US8088734B2 (en) 2003-01-21 2012-01-03 Unigene Laboratories Inc. Oral delivery of peptides
US9555014B2 (en) 2010-05-12 2017-01-31 Radius Health, Inc. Therapeutic regimens
US9920044B2 (en) 2010-09-28 2018-03-20 Radius Pharmaceuticals, Inc. Selective androgen receptor modulators
US10385008B2 (en) 2017-01-05 2019-08-20 Radius Pharmaceuticals, Inc. Polymorphic forms of RAD1901-2HCL
WO2022119391A1 (fr) * 2020-12-03 2022-06-09 바이오센서연구소 주식회사 Composition de formulation pour administration transdermique de peptides pour améliorer l'administration transdermique de peptides
US11413258B2 (en) 2015-04-29 2022-08-16 Radius Pharmaceuticals, Inc. Methods for treating cancer
US11643385B2 (en) 2018-07-04 2023-05-09 Radius Pharmaceuticals, Inc. Polymorphic forms of RAD1901-2HCl
US11771682B2 (en) 2016-06-22 2023-10-03 Ellipses Pharma Ltd. AR+ breast cancer treatment methods
US12263142B2 (en) 2014-03-28 2025-04-01 Duke University Method of treating cancer using selective estrogen receptor modulators
US12441745B2 (en) 2019-02-12 2025-10-14 Radius Pharmaceuticals, Inc. Processes and compounds

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5961482A (en) * 1986-07-25 1999-10-05 Rutgers, The State University Of New Jersey Iontotherapeutic device and process and iontotherapeutic unit dose
EP0643981B1 (fr) * 1993-09-22 2002-01-09 Hisamitsu Pharmaceutical Co., Inc. Electrode concrétée pour iontophorèse

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8088734B2 (en) 2003-01-21 2012-01-03 Unigene Laboratories Inc. Oral delivery of peptides
EP1595542A1 (fr) * 2004-03-26 2005-11-16 Solvay Pharmaceuticals B.V. Administration iontophoretique de composés piperazinyl-2(3h)-benzoxazoloniques
US7596407B2 (en) 2004-03-26 2009-09-29 Solvay Pharmaceuticals, B.V. Transdermal iontophoretic delivery of piperazinyl-2(3H)-benzoxazolone compounds
US9555014B2 (en) 2010-05-12 2017-01-31 Radius Health, Inc. Therapeutic regimens
US9920044B2 (en) 2010-09-28 2018-03-20 Radius Pharmaceuticals, Inc. Selective androgen receptor modulators
US12263142B2 (en) 2014-03-28 2025-04-01 Duke University Method of treating cancer using selective estrogen receptor modulators
US12263141B2 (en) 2015-04-29 2025-04-01 Radius Pharmaceuticals, Inc. Methods for treating cancer
US11413258B2 (en) 2015-04-29 2022-08-16 Radius Pharmaceuticals, Inc. Methods for treating cancer
US11819480B2 (en) 2015-04-29 2023-11-21 Radius Pharmaceuticals, Inc. Methods for treating cancer
US11771682B2 (en) 2016-06-22 2023-10-03 Ellipses Pharma Ltd. AR+ breast cancer treatment methods
US12329746B2 (en) 2016-06-22 2025-06-17 Ellipses Pharma Ltd AR+breast cancer treatment methods
US11708318B2 (en) 2017-01-05 2023-07-25 Radius Pharmaceuticals, Inc. Polymorphic forms of RAD1901-2HCL
US10385008B2 (en) 2017-01-05 2019-08-20 Radius Pharmaceuticals, Inc. Polymorphic forms of RAD1901-2HCL
US12398094B2 (en) 2017-01-05 2025-08-26 Radius Pharmaceuticals, Inc. Polymorphic forms of RAD1901-2HCL
US11643385B2 (en) 2018-07-04 2023-05-09 Radius Pharmaceuticals, Inc. Polymorphic forms of RAD1901-2HCl
US12441745B2 (en) 2019-02-12 2025-10-14 Radius Pharmaceuticals, Inc. Processes and compounds
WO2022119391A1 (fr) * 2020-12-03 2022-06-09 바이오센서연구소 주식회사 Composition de formulation pour administration transdermique de peptides pour améliorer l'administration transdermique de peptides

Also Published As

Publication number Publication date
AU1280701A (en) 2001-05-30
WO2001036039A3 (fr) 2002-03-07

Similar Documents

Publication Publication Date Title
US8463373B2 (en) Transdermal systems for the delivery of therapeutic agents including granisetron using iontophoresis
US8155738B2 (en) Composition and device structure for iontophoresis
KR100482229B1 (ko) 전기운반작용제전달방법및장치
US5540669A (en) Iontophoretic drug delivery system and method for using same
JPH06506616A (ja) イオン電気導入薬剤投与中の刺激を軽減させるためのデバイス
US6718201B1 (en) Electrotransport agent delivery method and apparatus
US6526316B2 (en) Iontophoresis method
WO2001036039A2 (fr) Administration transdermique ionophoretique de peptides
US5954684A (en) Iontophoretic drug delivery system and method for using same
US6697668B2 (en) Ocular iontophoretic device and method for using the same
US5843015A (en) Molecules for iontophoretic delivery
WO1997024157A1 (fr) Molecules a administrer par iontophorese
WO1997024157A9 (fr) Molecules a administrer par iontophorese
CN1480150A (zh) 乳腺膜
MXPA97009641A (en) Method and apparatus for the release of an agentepor electrotranspo

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
AK Designated states

Kind code of ref document: A3

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
DPE2 Request for preliminary examination filed before expiration of 19th month from priority date (pct application filed from 20040101)