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EP0825872A1 - Forme d'administration pharmaceutique d'hormone parathyroidienne ayant une periode de liberation de l'ingredient actif de deux a six heures - Google Patents

Forme d'administration pharmaceutique d'hormone parathyroidienne ayant une periode de liberation de l'ingredient actif de deux a six heures

Info

Publication number
EP0825872A1
EP0825872A1 EP96919738A EP96919738A EP0825872A1 EP 0825872 A1 EP0825872 A1 EP 0825872A1 EP 96919738 A EP96919738 A EP 96919738A EP 96919738 A EP96919738 A EP 96919738A EP 0825872 A1 EP0825872 A1 EP 0825872A1
Authority
EP
European Patent Office
Prior art keywords
hours
parathyroid hormone
administration form
active ingredient
quart
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.)
Withdrawn
Application number
EP96919738A
Other languages
German (de)
English (en)
Inventor
Peter-Paul Ochlich
Bernd MÜLLER-BECKMANN
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.)
Roche Diagnostics GmbH
Original Assignee
Roche Diagnostics GmbH
Boehringer Mannheim GmbH
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 Roche Diagnostics GmbH, Boehringer Mannheim GmbH filed Critical Roche Diagnostics GmbH
Publication of EP0825872A1 publication Critical patent/EP0825872A1/fr
Withdrawn legal-status Critical Current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
    • A61K9/0002—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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
    • A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention is directed to a pharmaceutical administration form of parathyroid hormone or parathyroid hormone derivatives having an active ingredient release period of from two to six hours, the use of parathyroid hormone in the treatment of osteoporosis by applying said pharmaceutical administration form, and a method for the treatment of osteoporosis in the human body.
  • Parathyroid hormone and N-terminal parathyroid hormone fragments are known to have osteogenous activity which has been observed in animal experimental studies on rats as well as in clinical studies on osteoporotic patients and has been described in technical literature (Selye, Endocrinology 16 (1932), 547-558; Hefti et al., Clin. Sci. 62 (1982), 389-396; Gunnes-Hey et al., Metab. Bone Dis. Relat. Res. 5 (1984), 177-181; Reeve et al., Br. Med. J. 280 (1980), 1340-1344; Slovik et al., J. Bone Miner. Res. 1 (1986), 377- 381, EP 0,197,514).
  • the invention is directed to a pharmaceutical administration form of PTH or derivatives thereof having an active ingredient release period of from two to six hours, and preferably of four hours.
  • the pharmaceutical administration form may be an infusion solution or a transdermic or enteric pharmaceutical system having an active ingredient release period of up to six hours.
  • the transdermic or enteric application of PTH offers the decisive advantage of retarded active ingredient release. Abrupt PTH pulses and the associated substantial disturbance of the patient's well-being due to the necessary injection can be dismissed.
  • the pharmaceutical administration form contains biologically active parathyroid hormone or parathyroid hormone derivatives, particularly human PTH(l-84) or an N-terminal human PTH fragment having the sequences 1-29 to
  • PT ⁇ - analogous peptides, variants or modifications of parathyroid hormone (PTH agonists) resulting from the replacement of single or multiple amino acids in the amino acid se ⁇ quence of unmodified parathyroid hormone may also be employed.
  • PTH fragments appropriately abridged at the N terminus and/or the C terminus are also possible within the meaning of the invention. Such fragments have been described in WO 90/10067, EP 0,301,484 or EP 0,301,485, for example.
  • PTH peptides are effected in such a manner that release of the pharmacologically active substance in the body within a period of from 2 to 6 hours is ensured. Such release may be obtained in different ways.
  • One method is to administer the required amount of PTH intravenously over the appropriate period of time.
  • Another method involves transdermic application, releasing the active ingredient within the desired period of time. This may be effected using a patch which is applied to the skin for the desired period of time. By adding permeation accelerators, release of the active ingredient through the skin as regularly as possible can be ensured so that during appli ⁇ cation of the patch to the skin, continuous release of the active ingredient and permeation through the skin take place.
  • Another way of transdermic application involves ion ⁇ tophoresis. To this end. an appropriate dosage unit (iontophoretic patch) is applied to the skin, and release of the active ingredient through the skin within the desired period of time is controlled by applying an electrical potential.
  • loaded liposomes Preferably, loaded liposomes.
  • PTH or a PTH fragment may be administered in the form of a continuous infusion preferably over two to six hours, particularly about four hours.
  • a tendency to higher anabolic activity can be observed following an infusion of about four hours compared to a one hour infusion or subcutaneous bolus administration.
  • An exceedingly good osteogenous activity was observed following a four hour intravenous infusion of hPTH(l-34) on five working days within two successive weeks.
  • water is used as injection medium, containing additives common with injection solutions, such as stabilizers, solubilizers and buffers.
  • additives are. e.g., tartrate and citrate buffers, ethanol, complexing agents such as ethylenediaminetetra- acetic acid and non-toxic salts thereof, high molecular weight polymers such as liquid poly(ethylene oxide) for viscosity control.
  • Liquid carrier substances must be sterile and are preferably filled into ampoules.
  • the dosage may depend on various factors such as mode of application, species, age or individual condition. Usually, from 30 to 50 ⁇ g/kg/day are administered.
  • the invention relates to the use of parathyroid hormone or a parathyroid hormone derivative in the treatment of osteoporosis by application in the form of a continuous infusion for two to six hours or a transdermic or enteric administration form having an active ingredient release period of from two to six hours.
  • Such examinations relating to the use of PTH or PTH fragments, according to the invention will be subject to protection, particularly within the scope of clinical tests for the purpose of authorization according to the drug law.
  • the corresponding petitioned authorization according to the drug law relates to the treatment of calcium-metabolic dis ⁇ eases in general and to the treatment of osteoporosis, in particular.
  • the invention is directed to a method for osteoporosis treatment of the human body wherein, in order to increase the bone matter, a therapeutically effective amount of parathyroid hormone or parathyroid hormone derivative is applied in the form of a continuous infusion for two to six hours or a transdermic or enteric administration form having an active ingredient release period of from two to six hours.
  • a therapeutically effective amount of parathyroid hormone or parathyroid hormone derivative is applied in the form of a continuous infusion for two to six hours or a transdermic or enteric administration form having an active ingredient release period of from two to six hours.
  • the method according to the invention is conducted within the scope of clinical tests for the purpose of authorization according to the drug law.
  • a venous permanent catheter was implanted in male Wistar rats weighing about 230-250 g.
  • the animals were assigned to 5 different groups of treatment of 6 animals each, which were treated as follows:
  • the compa- rison comprises intravenous infusion of 40 ⁇ g/kg and 80 ⁇ g/kg over four and eight hours, respectively, as well as subcutaneous injection of 40 ⁇ g/kg and intravenous bolus injection of 80 ⁇ g/kg.
  • Group 1 4 hours iv; 40 ⁇ g/kg/day
  • Group 2 8 hours iv; 80 ⁇ g/kg/day
  • a pilot experiment on transdermic application by iontophoresis was conducted on two rabbits. The animals were trimmed in the flanks, and the skin was cleaned with ethanol. A filter paper soaked with hPTH(l-34) solution was placed on the skin and fixated with a chlorinated silver electrode. Iontophoresis was carried out over a time period of 90 and 105 minutes, respectively, under the following conditions: current intensity: 5-7 mA, current density: 0.44-0.62 mA/cm , current pulses: 8 ms at 2 ms intervals. During the experiment, blood was taken from the ear artery at various times (see table below), and the serum obtained was deep frozen. Using the Nichols RIA INS-PTH, the PTH concentration in the serum samples was measured. Result: In both animals, a significant level of hPTH(l-34) could be detected after a period of 1 to 1.5 hours.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Endocrinology (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Nutrition Science (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Forme d'administration pharmaceutique d'hormone parathyroïdienne ou de dérivés d'hormone parathyroïdienne ayant une période de libération de l'ingrédient actif de deux à six heures, utilisation de ladite hormone pour la préparation de ladite forme d'administration et méthode de traitement de l'ostéoporose dans le corps humain.
EP96919738A 1995-05-12 1996-05-09 Forme d'administration pharmaceutique d'hormone parathyroidienne ayant une periode de liberation de l'ingredient actif de deux a six heures Withdrawn EP0825872A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19517430A DE19517430A1 (de) 1995-05-12 1995-05-12 Pharmazeutische Darreichungsform von Parathormon mit einer zwei- bis sechsstündigen Wirkstoff-Freisetzungsperiode
DE19517430 1995-05-12
PCT/EP1996/001962 WO1996035447A1 (fr) 1995-05-12 1996-05-09 Forme d'administration pharmaceutique d'hormone parathyroidienne ayant une periode de liberation de l'ingredient actif de deux a six heures

Publications (1)

Publication Number Publication Date
EP0825872A1 true EP0825872A1 (fr) 1998-03-04

Family

ID=7761731

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96919738A Withdrawn EP0825872A1 (fr) 1995-05-12 1996-05-09 Forme d'administration pharmaceutique d'hormone parathyroidienne ayant une periode de liberation de l'ingredient actif de deux a six heures

Country Status (7)

Country Link
EP (1) EP0825872A1 (fr)
JP (1) JPH11505222A (fr)
AU (1) AU5816596A (fr)
DE (1) DE19517430A1 (fr)
IL (1) IL118202A0 (fr)
WO (1) WO1996035447A1 (fr)
ZA (1) ZA963714B (fr)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0922467A3 (fr) 1997-12-12 2000-05-24 Takeda Chemical Industries, Ltd. Administration de médicaments par ionophorèse
US8088734B2 (en) 2003-01-21 2012-01-03 Unigene Laboratories Inc. Oral delivery of peptides
CN101355959B (zh) 2005-11-10 2013-02-27 密歇根理工大学管理委员会 黑熊甲状旁腺素和使用黑熊甲状旁腺素的方法
EP2509996A1 (fr) 2009-12-07 2012-10-17 Michigan Technological University Hormone parathyroïde de l'ours noir et ses procédés d'utilisation
PT2568806T (pt) 2010-05-12 2016-08-05 Radius Health Inc Regimes terapêuticos
WO2012047617A1 (fr) 2010-09-28 2012-04-12 Radius Health, Inc. Modulateurs sélectifs du récepteur des androgènes
PL3122426T3 (pl) 2014-03-28 2023-05-15 Duke University Leczenie raka sutka z zastosowaniem selektywnych modulatorów receptora estrogenowego
WO2016176665A1 (fr) 2015-04-29 2016-11-03 Radius Health, Inc. Procédés de traitement du cancer
SMT202200199T1 (it) 2016-06-22 2022-07-21 Ellipses Pharma Ltd Metodi di trattamento del cancro del seno ar+.
EP4374925A3 (fr) 2017-01-05 2025-01-15 Radius Pharmaceuticals, Inc. Formes polymorphes de rad90-2 hcl
CN112423844B (zh) 2018-07-04 2024-08-13 雷迪厄斯制药公司 Rad1901-2hcl的多晶型形式
CN119390714A (zh) 2019-02-12 2025-02-07 雷迪厄斯制药公司 方法和化合物

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4692433A (en) * 1983-10-12 1987-09-08 The Regents Of The University Of California Method and composition for regulating serum calcium levels of mammals
DE3935738A1 (de) * 1989-10-27 1991-05-08 Forssmann Wolf Georg Arzneimittel, enthaltend das humane parathormon-fragment (1-37) als aktiven wirkstoff
DE69429603T2 (de) * 1993-09-22 2002-08-14 Hisamitsu Pharmaceutical Co., Inc. Iontophoresematrix

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9635447A1 *

Also Published As

Publication number Publication date
DE19517430A1 (de) 1996-11-14
JPH11505222A (ja) 1999-05-18
AU5816596A (en) 1996-11-29
WO1996035447A1 (fr) 1996-11-14
ZA963714B (en) 1997-11-10
IL118202A0 (en) 1996-09-12

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