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WO1992019260A1 - Solution d'hormone peptidique - Google Patents

Solution d'hormone peptidique Download PDF

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Publication number
WO1992019260A1
WO1992019260A1 PCT/SE1992/000283 SE9200283W WO9219260A1 WO 1992019260 A1 WO1992019260 A1 WO 1992019260A1 SE 9200283 W SE9200283 W SE 9200283W WO 9219260 A1 WO9219260 A1 WO 9219260A1
Authority
WO
WIPO (PCT)
Prior art keywords
hormone
insulin
solution
peptide hormone
peptide
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/SE1992/000283
Other languages
English (en)
Inventor
Tomas Moks
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.)
Individual
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 WO1992019260A1 publication Critical patent/WO1992019260A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • 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
    • A61K38/2221—Relaxins
    • 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
    • A61K38/28—Insulins
    • 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
    • A61K38/30—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2

Definitions

  • the present invention relates to peptide hormone solutions, such as for injection or infusion, containing a hormone in a biologically effective amount dissolved in an aqueous vehicle.
  • the invention also covers the use in a peptide hormone pump for the administration by injection or infusion of the peptide hormone solution of the inven ⁇ tion.
  • the invention involves a method of treating diabetes.
  • Peptide hormones are a class of substances that are involved in different control functions of the body, and examples are insulin, IGF-I, IGF-II, growth hormone, re- laxin, secretin, calcitonin etc. Common to all these sub ⁇ stances is the fact that they exert their action at very low concentrations and, therefore, their artificial use by administration through different routes are subject to problems. Quite frequently peptide hormones are to be sub ⁇ ject to long-term administration and in the past attempts have been made to develop sophisticated hormone delivery systems, such as systems based on implantable pumps. Among such pumps particularly so called micro infusion pumps are of interest in connection with the administration of very small amounts.
  • Insulin solutions for medical treatment were intro ⁇ quizzed as early as 1923.
  • the stability of insulin solutions has since been greatly improved but has not nearly reached any state of perfection.
  • a low pH of the solution was required to protect the insulin from degradation by contaminating pancreatic enzymes. It became later possible to remove such enzymes and the purity of insulin was improved to such an extent as to allow the manufacture of solutions of insulin having a physiological pH, the pH being around 7.
  • Neutral solu ⁇ tions are advantageous in use compared to acidic solu ⁇ tions.
  • Yet another possibility of providing stabilization of hormone solutions is to add amphiphilic surface-active substances to the protein solution. Such substances adsorb to the interface and transform the hydrophobic property of the protein into a hydrophilic one. However, such substan ⁇ ces interact with the insulin and tend to cause denatura ⁇ tion thereof when in solution.
  • the present invention has for its main object to pro ⁇ vide means for effective stabilization of peptide hormone solutions, such as solutions of insulin and insulin-like peptides.
  • Another object of the invention is to provide tech ⁇ niques enabling easy stabilization using a stabilizing additive that is tolerable for the intended purpose and also available at a relatively low cost.
  • Yet another object of the invention is to provide a method of medical treatment, particularly the treatment of diabetes using such stabilized hormone solution.
  • the invention resides in a peptide hormone solution, such as for injection or infu ⁇ sion, containing a hormone in a biologically effective amount dissolved in an aqueous vehicle.
  • the invention is based on the unexpected discovery that such a hormone so ⁇ lution can be effectively stabilized by introducing there ⁇ in a serum albumen in an active amount, such additive ef ⁇ fectively preventing precipitation of the hormone even at an elevated temperature (such as 37°C) and mechanical agi ⁇ tation.
  • the peptide hormone is preferably selected from insulin and insulin-like hor ⁇ mones, such as insulin, IGF-I, IGF-II, relaxin.
  • insulin and insulin-like hor ⁇ mones such as insulin, IGF-I, IGF-II, relaxin.
  • other peptide hormones are operable in the inventive con- cept as well, such as growth hormone, secretin, calci- tonin, etc.
  • HSA human serum albumin
  • the albumin is preferably used in a con ⁇ centration of at least about 0.1 mg/ml solution and expe ⁇ rimental work has indicated that it is preferred that the concentration of albumin does not substantially exceed that of the hormone. It is especially preferred that said concentration is lower than that of the hormone, such as half or even lower.
  • the invention also provides a method of treating dia ⁇ betes, such method comprising the step of administering to a patient in need of such treatment a blood glucose con ⁇ trolling amount of an insulin solution as outlined above.
  • Such method preferably involves the administration in a continuous or discontinuous manner by injection or infu ⁇ sion.
  • Stability was tested at different concentrations of albumin and without added albumin.
  • the different solutions used in the test were kept at 37 C C and the closed flasks containing the different samples were turned upside down at regular intervals i.e. around 30 turns per minute.
  • the degree of precipitation was measured by recording absor ⁇ saye at 600 nm which reflects turbidity and thus the de ⁇ gree of precipitation. The measurements were made in a spectrophotometer.
  • the diagram in the drawing further shows that at a concentration of 3 mg albumin per ml (curve 5) some pre ⁇ cipitation takes place after 40 days, although to a very small degree. However, at a concentration of albumin of 10 mg/ml (curve 6) precipitation starts at about 25 days, and at about 35 days there is a rapid increase in precipita ⁇ tion. The mechanism by which precipitation takes place at this relatively high concentration of albumin is unknown but a different mechanism seems to be involved as compared to that of using no albumin at all (curve 1).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Zoology (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Endocrinology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Diabetes (AREA)
  • Molecular Biology (AREA)
  • Inorganic Chemistry (AREA)

Abstract

Solution d'hormone peptidique, pour injection ou perfusion par exemple, contenant une quantité biologiquement efficace d'une hormone dissoute dans un excipient aqueux, cette solution contenant une quantité de sérum-albumine capable de stabiliser l'hormone pour en empêcher la précipitation; utilisation de ces solutions dans des pompes à hormones; méthode de traitement des diabètes.
PCT/SE1992/000283 1991-05-07 1992-04-29 Solution d'hormone peptidique Ceased WO1992019260A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9101381-3 1991-05-07
SE9101381A SE9101381D0 (sv) 1991-05-07 1991-05-07 Peptide hormone solution

Publications (1)

Publication Number Publication Date
WO1992019260A1 true WO1992019260A1 (fr) 1992-11-12

Family

ID=20382669

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE1992/000283 Ceased WO1992019260A1 (fr) 1991-05-07 1992-04-29 Solution d'hormone peptidique

Country Status (2)

Country Link
SE (1) SE9101381D0 (fr)
WO (1) WO1992019260A1 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005049061A3 (fr) * 2003-11-20 2005-10-20 Novo Nordisk As Formulations peptidiques a base de propylene glycol optimales pour la production et l'utilisation dans des dispositifs d'injection
WO2011051486A2 (fr) 2009-11-02 2011-05-05 Novo Nordisk A/S Solution pharmaceutique d'insuline acylée et d'albumine liée de façon non covalente
US8114959B2 (en) 2003-06-03 2012-02-14 Novo Nordisk A/S Stabilized pharmaceutical peptide compositions
US8614181B2 (en) 2003-06-03 2013-12-24 Novo Nordisk A/S Stabilized pharmaceutical peptide compositions
US8710181B2 (en) 2004-08-31 2014-04-29 Novo Nordisk A/S Use of tris(hydroxymethyl) aminomethane for the stabilization of peptides, polypeptides and proteins
US8748376B2 (en) 2004-11-12 2014-06-10 Novo Nordisk A/S Stable formulations of peptides
WO2014096440A2 (fr) 2012-12-21 2014-06-26 Novozymes Biopharma Dk A/S Composition
US8846618B2 (en) 2001-06-28 2014-09-30 Novo Nordisk A/S Stable formulation of modified GLP-1
US9233204B2 (en) 2014-01-31 2016-01-12 Aseko, Inc. Insulin management
US9483619B2 (en) 2012-09-11 2016-11-01 Aseko, Inc. Means and method for improved glycemic control for diabetic patients
US9486580B2 (en) 2014-01-31 2016-11-08 Aseko, Inc. Insulin management
US9886556B2 (en) 2015-08-20 2018-02-06 Aseko, Inc. Diabetes management therapy advisor
US9892234B2 (en) 2014-10-27 2018-02-13 Aseko, Inc. Subcutaneous outpatient management
US9897565B1 (en) 2012-09-11 2018-02-20 Aseko, Inc. System and method for optimizing insulin dosages for diabetic subjects
US11081226B2 (en) 2014-10-27 2021-08-03 Aseko, Inc. Method and controller for administering recommended insulin dosages to a patient
US11318191B2 (en) 2020-02-18 2022-05-03 Novo Nordisk A/S GLP-1 compositions and uses thereof
US11752198B2 (en) 2017-08-24 2023-09-12 Novo Nordisk A/S GLP-1 compositions and uses thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4492684A (en) * 1983-06-08 1985-01-08 Connaught Laboratories Limited Slow release injectable insulin composition
EP0215658A2 (fr) * 1985-09-13 1987-03-25 Cetus Oncology Corporation Formulation pour l'interféron bêta recombinant, procédés pour la récupération et la stabilisation de l'interféron bêta et son application
EP0308725A2 (fr) * 1987-09-25 1989-03-29 SCLAVO S.p.A. Composition pharmaceutique pour administration intrarectale de calcitonine et préparations de formes unitaires
EP0437622A1 (fr) * 1989-07-07 1991-07-24 Kyowa Hakko Kogyo Co., Ltd. Preparation de motiline stable

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4492684A (en) * 1983-06-08 1985-01-08 Connaught Laboratories Limited Slow release injectable insulin composition
EP0215658A2 (fr) * 1985-09-13 1987-03-25 Cetus Oncology Corporation Formulation pour l'interféron bêta recombinant, procédés pour la récupération et la stabilisation de l'interféron bêta et son application
EP0308725A2 (fr) * 1987-09-25 1989-03-29 SCLAVO S.p.A. Composition pharmaceutique pour administration intrarectale de calcitonine et préparations de formes unitaires
EP0437622A1 (fr) * 1989-07-07 1991-07-24 Kyowa Hakko Kogyo Co., Ltd. Preparation de motiline stable

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DIALOG INFORMATION SERVICES, File 155; Medline 66-90 May, Dialog accession no. 06509387, Medline accession no. 88154387, SMITH, R.M.: "Preparation and Characterization of a Colloidal Gold-Insulin Complex with Binding and Biological Activities Identical to Native Insulin"; & J. HISTOCHEM CYTOCHEM APR. *

Cited By (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8846618B2 (en) 2001-06-28 2014-09-30 Novo Nordisk A/S Stable formulation of modified GLP-1
US8114959B2 (en) 2003-06-03 2012-02-14 Novo Nordisk A/S Stabilized pharmaceutical peptide compositions
US8614181B2 (en) 2003-06-03 2013-12-24 Novo Nordisk A/S Stabilized pharmaceutical peptide compositions
WO2005049061A3 (fr) * 2003-11-20 2005-10-20 Novo Nordisk As Formulations peptidiques a base de propylene glycol optimales pour la production et l'utilisation dans des dispositifs d'injection
EP2394656A3 (fr) * 2003-11-20 2012-01-18 Novo Nordisk A/S Formulations de peptide contenant du propylèneglycol qui sont optimales pour la production et l'utilisation dans des dispositifs d'injection
US8114833B2 (en) 2003-11-20 2012-02-14 Novo Nordisk A/S Propylene glycol-containing peptide formulations which are optimal for production and for use in injection devices
US8710181B2 (en) 2004-08-31 2014-04-29 Novo Nordisk A/S Use of tris(hydroxymethyl) aminomethane for the stabilization of peptides, polypeptides and proteins
US8748376B2 (en) 2004-11-12 2014-06-10 Novo Nordisk A/S Stable formulations of peptides
US8865647B2 (en) 2009-11-02 2014-10-21 Novo Nordisk A/S Pharmaceutical solution of non covalently bound albumin and acylated insulin
WO2011051486A2 (fr) 2009-11-02 2011-05-05 Novo Nordisk A/S Solution pharmaceutique d'insuline acylée et d'albumine liée de façon non covalente
WO2011051486A3 (fr) * 2009-11-02 2011-12-22 Novo Nordisk A/S Solution pharmaceutique d'insuline acylée et d'albumine liée de façon non covalente
US9897565B1 (en) 2012-09-11 2018-02-20 Aseko, Inc. System and method for optimizing insulin dosages for diabetic subjects
US11733196B2 (en) 2012-09-11 2023-08-22 Aseko, Inc. System and method for optimizing insulin dosages for diabetic subjects
US9483619B2 (en) 2012-09-11 2016-11-01 Aseko, Inc. Means and method for improved glycemic control for diabetic patients
US11131643B2 (en) 2012-09-11 2021-09-28 Aseko, Inc. Method and system for optimizing insulin dosages for diabetic subjects
US10629294B2 (en) 2012-09-11 2020-04-21 Aseko, Inc. Means and method for improved glycemic control for diabetic patients
US10410740B2 (en) 2012-09-11 2019-09-10 Aseko, Inc. Means and method for improved glycemic control for diabetic patients
US9773096B2 (en) 2012-09-11 2017-09-26 Aseko, Inc. Means and method for improved glycemic control for diabetic patients
US9811638B2 (en) 2012-09-11 2017-11-07 Aseko, Inc. Means and method for improved glycemic control for diabetic patients
US10102922B2 (en) 2012-09-11 2018-10-16 Aseko, Inc. Means and method for improved glycemic control for diabetic patients
US9965596B2 (en) 2012-09-11 2018-05-08 Aseko, Inc. Means and method for improved glycemic control for diabetic patients
WO2014096440A3 (fr) * 2012-12-21 2014-08-14 Novozymes Biopharma Dk A/S Composition
WO2014096440A2 (fr) 2012-12-21 2014-06-26 Novozymes Biopharma Dk A/S Composition
US11490837B2 (en) 2014-01-31 2022-11-08 Aseko, Inc. Insulin management
US11311213B2 (en) 2014-01-31 2022-04-26 Aseko, Inc. Insulin management
US9898585B2 (en) 2014-01-31 2018-02-20 Aseko, Inc. Method and system for insulin management
US9892235B2 (en) 2014-01-31 2018-02-13 Aseko, Inc. Insulin management
US9965595B2 (en) 2014-01-31 2018-05-08 Aseko, Inc. Insulin management
US12288620B2 (en) 2014-01-31 2025-04-29 Glytec, Llc Method and system for insulin management
US12127831B2 (en) 2014-01-31 2024-10-29 Aseko, Inc. Insulin management
US10255992B2 (en) 2014-01-31 2019-04-09 Aseko, Inc. Insulin management
US12027266B2 (en) 2014-01-31 2024-07-02 Aseko, Inc. Insulin management
US11857314B2 (en) 2014-01-31 2024-01-02 Aseko, Inc. Insulin management
US9710611B2 (en) 2014-01-31 2017-07-18 Aseko, Inc. Insulin management
US10453568B2 (en) 2014-01-31 2019-10-22 Aseko, Inc. Method for managing administration of insulin
US10535426B2 (en) 2014-01-31 2020-01-14 Aseko, Inc. Insulin management
US9604002B2 (en) 2014-01-31 2017-03-28 Aseko, Inc. Insulin management
US10811133B2 (en) 2014-01-31 2020-10-20 Aseko, Inc. System for administering insulin boluses to a patient
US11804300B2 (en) 2014-01-31 2023-10-31 Aseko, Inc. Insulin management
US11081233B2 (en) 2014-01-31 2021-08-03 Aseko, Inc. Insulin management
US9504789B2 (en) 2014-01-31 2016-11-29 Aseko, Inc. Insulin management
US11158424B2 (en) 2014-01-31 2021-10-26 Aseko, Inc. Insulin management
US11783945B2 (en) 2014-01-31 2023-10-10 Aseko, Inc. Method and system for insulin infusion rate management
US11783946B2 (en) 2014-01-31 2023-10-10 Aseko, Inc. Method and system for insulin bolus management
US11468987B2 (en) 2014-01-31 2022-10-11 Aseko, Inc. Insulin management
US9486580B2 (en) 2014-01-31 2016-11-08 Aseko, Inc. Insulin management
US9233204B2 (en) 2014-01-31 2016-01-12 Aseko, Inc. Insulin management
US11621074B2 (en) 2014-01-31 2023-04-04 Aseko, Inc. Insulin management
US12023127B2 (en) 2014-10-27 2024-07-02 Aseko, Inc. Subcutaneous outpatient management
US10128002B2 (en) 2014-10-27 2018-11-13 Aseko, Inc. Subcutaneous outpatient management
US10403397B2 (en) 2014-10-27 2019-09-03 Aseko, Inc. Subcutaneous outpatient management
US9892234B2 (en) 2014-10-27 2018-02-13 Aseko, Inc. Subcutaneous outpatient management
US11081226B2 (en) 2014-10-27 2021-08-03 Aseko, Inc. Method and controller for administering recommended insulin dosages to a patient
US11694785B2 (en) 2014-10-27 2023-07-04 Aseko, Inc. Method and dosing controller for subcutaneous outpatient management
US11678800B2 (en) 2014-10-27 2023-06-20 Aseko, Inc. Subcutaneous outpatient management
US11574742B2 (en) 2015-08-20 2023-02-07 Aseko, Inc. Diabetes management therapy advisor
US9886556B2 (en) 2015-08-20 2018-02-06 Aseko, Inc. Diabetes management therapy advisor
US10380328B2 (en) 2015-08-20 2019-08-13 Aseko, Inc. Diabetes management therapy advisor
US12040096B2 (en) 2015-08-20 2024-07-16 Aseko, Inc. Diabetes management therapy advisor
US12214017B2 (en) 2017-08-24 2025-02-04 Novo Nordisk A/S GLP-1 compositions and uses thereof
US11752198B2 (en) 2017-08-24 2023-09-12 Novo Nordisk A/S GLP-1 compositions and uses thereof
US11318191B2 (en) 2020-02-18 2022-05-03 Novo Nordisk A/S GLP-1 compositions and uses thereof

Also Published As

Publication number Publication date
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