WO1996026731A1 - Utilisation de vanadate de magnesium dans le traitement du syndrome de resistance insulinique - Google Patents

Utilisation de vanadate de magnesium dans le traitement du syndrome de resistance insulinique Download PDF

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Publication number
WO1996026731A1
WO1996026731A1 PCT/US1995/002349 US9502349W WO9626731A1 WO 1996026731 A1 WO1996026731 A1 WO 1996026731A1 US 9502349 W US9502349 W US 9502349W WO 9626731 A1 WO9626731 A1 WO 9626731A1
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WO
WIPO (PCT)
Prior art keywords
use according
vanadate
magnesium
insulin
glucose
Prior art date
Application number
PCT/US1995/002349
Other languages
English (en)
Inventor
Jay S. Skyler
Phillip Frost
Elliot Hahn
Original Assignee
Baker Norton Pharmaceuticals, Inc.
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 Baker Norton Pharmaceuticals, Inc. filed Critical Baker Norton Pharmaceuticals, Inc.
Priority to PCT/US1995/002349 priority Critical patent/WO1996026731A1/fr
Publication of WO1996026731A1 publication Critical patent/WO1996026731A1/fr

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Classifications

    • 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
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay

Definitions

  • the invention relates to methods and pharmaceutical compositions for
  • Vanadium is a ubiquitous trace element found in very low concentrations in
  • Vanadium was discovered in 1830. It was used by Lyonnet and colleagues
  • insulin levels are either unchanged or
  • diabetic rats genetically diabetic db/db mice, and obese hyperinsulinemic fa/fa fatty
  • vanadyl sulfate trihydrate also used. These have been given to the test animals in
  • Magnesium is a ubiquitous element in nature, forming 2.1 % of the earth's
  • Serum magnesium levels which are those generally measured, reflect
  • hypomagnesemia was only 1 % of the total body magnesium content. Yet, in one study, hypomagnesemia was only 1 % of the total body magnesium content. Yet, in one study, hypomagnesemia was
  • hypertension is associated with an improvement in insulin sensitivity.
  • magnesium chloride and magnesium oxide particularly magnesium chloride and magnesium oxide.
  • compositions for the treatment of diabetes mellitus and other insulin are provided.
  • resistance syndromes e.g., obesity, dyslipidemia and hypertension which may be used.
  • compositions with significant insulinomimetic properties for use in the novel methods
  • the invention resides, briefly stated, in a method of treating a human or animal patient suffering from an insulin resistance syndrome, particularly diabetes
  • composition containing at least one inert ingredient.
  • the composition is preferably an oral dosage
  • FIG. 1 illustrates the protocol for a study of four groups of rats: an untreated
  • control group of normal rats a control group treated with magnesium vanadate
  • FIG. 2 A is a bar graph illustrating the daily intake of magnesium vanadate
  • FIG. 2B is a bar graph illustrating the daily intake of magnesium vanadate
  • FIG. 3A is a graph of fed plasma glucose concentrations versus time (days)
  • FIG. 3B is a graph of fed plasma glucose concentrations versus time (days)
  • FIG. 4 A is a graph of fasting and one hour and two hour post-meal plasma
  • FIG. 4B is a graph of fasting and one hour and two hour post-meal plasma
  • FIG. 5 is a bar graph illustrating rates of glucose metabolism, shown in
  • Magnesium vanadate (MgV 2 0 6 ), also known as magnesium vanadium oxide,
  • magnesium vanadate possesses insulinomimetic properties or would have any
  • insulin resistance syndrome including, but not limited to, diabetes
  • the total daily dosage of magnesium vanadate administered to the patient is the total daily dosage of magnesium vanadate administered to the patient.
  • the daily dosage amount may be any suitable daily dosage amount.
  • the present invention is not
  • magnesium vanadate any specific daily dosage range of magnesium vanadate, but
  • the method of the invention may also be used to provide prophylactic
  • diabetes mellitus or other insulin resistance syndromes who have a predisposition
  • compositions used in the subject method may include
  • active ingredients other than magnesium vanadate for example, other hypoglycemic
  • magnesium vanadate and at least one pharmaceutically acceptable, inert
  • composition may be in any standard pharmaceutical dosage form, but
  • Dosage forms for oral delivery may include conventional tablets, coated
  • liquids, elixirs or any other oral dosage form known in the pharmaceutical arts.
  • fillers such as clays or siliceous earth may be used.
  • excipients and carriers are, for example, release rate, texture and size.
  • excipients and carriers are, for example, release rate, texture and size.
  • waxes such as beeswax, castor wax, glycowax and
  • cellulose compounds such as methylcellulose, ethylcellulose, carboxymethylcellulose, cellulose acetate phthalate, hydroxypropylcellulose and
  • hydrophilic gums are hydrophilic gums.
  • magnesium vanadate active In the compositions of the present invention the magnesium vanadate active
  • ingredient is desirably present in an amount between about 50 and about 1000 mg per
  • treatment also comprehends the administration of magnesium vanadate via the
  • compositions of the invention may include magnesium vanadate in pharmaceutically
  • dosage forms together with suitable inert solvents, excipients and additives.
  • magnesium vanadate active ingredient is preferably from about 2 mg/kg to about 60 mg/kg of patient body weight, although dosage amounts towards the lower
  • magnesium vanadate 0.2 - 0.35
  • rats received a meal tolerance test. At 8:00 a.m. after an
  • rats Six days after the catheter insertion, rats received a euglycemic insulin
  • Insulin was given as a prime-continuous (12 ⁇ U/kg/min) infusion.
  • Plasma samples were obtained at 5 minute
  • Plasma glucose was measured by the glucose oxidase method (Beckman
  • Plasma insulin was
  • the rate of hepatic glucose production was calculated by
  • concentration in drinking water was initiated with 0.2 mg/ml and increased to 0.5-0.6
  • vanadate gained less weight and consumed less water than those rats not treated with
  • vanadate consumed less food and water than diabetic rats receiving no vanadate; weight
  • STZ-diabetic rats remained between 375-425 mg/dl, while STZ-diabetic rats treated with magnesium vanadate (group 4) had significantly lower glucose levels ( ⁇ 150
  • diabetic rats compared to controls (FIG. 4A). Following vanadate treatment diabetic

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

Abstract

L'invention porte sur l'utilisation du composé vanadate de magnésium dans la fabrication d'une composition pharmaceutique destinée à traiter des patients, homme ou animal, souffrant de syndromes de résistance insulinique, notamment du diabète sucré. Les gammes posologiques quotidiennes ont de préférence environ 2 à environ 60 mg de vanadate de magnésium par kilogramme de poids corporel du patient. La composition pharmaceutique, qui comprend au moins un ingrédient inerte, acceptable du point de vue pharmacologique, peut avoir des formes galéniques orale, parentérale, transdermique ou transmuqueuse, et elle contient une dose de vanadate de magnésium comprise entre environ 50 et environ 1000 mg par unité.
PCT/US1995/002349 1995-02-27 1995-02-27 Utilisation de vanadate de magnesium dans le traitement du syndrome de resistance insulinique WO1996026731A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/US1995/002349 WO1996026731A1 (fr) 1995-02-27 1995-02-27 Utilisation de vanadate de magnesium dans le traitement du syndrome de resistance insulinique

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US1995/002349 WO1996026731A1 (fr) 1995-02-27 1995-02-27 Utilisation de vanadate de magnesium dans le traitement du syndrome de resistance insulinique

Publications (1)

Publication Number Publication Date
WO1996026731A1 true WO1996026731A1 (fr) 1996-09-06

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PCT/US1995/002349 WO1996026731A1 (fr) 1995-02-27 1995-02-27 Utilisation de vanadate de magnesium dans le traitement du syndrome de resistance insulinique

Country Status (1)

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WO (1) WO1996026731A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4343794A (en) * 1980-05-06 1982-08-10 Mt. Sinai Method of reducing intraocular pressure with salts of vanadic acid
US5422125A (en) * 1993-07-12 1995-06-06 Baker Norton Pharmaceuticals, Inc. Method and composition for treatment of insulin resistance syndromes

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4343794A (en) * 1980-05-06 1982-08-10 Mt. Sinai Method of reducing intraocular pressure with salts of vanadic acid
US5422125A (en) * 1993-07-12 1995-06-06 Baker Norton Pharmaceuticals, Inc. Method and composition for treatment of insulin resistance syndromes

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
D.J. BECKER: "Comparison of the effects of various vanadium salts on glucose homeostasis in streptozotocin-diabetic rats.", EUR. J. PHARMACOL., vol. 260, no. 2-3, 1994, pages 169 - 175, XP023750568, DOI: doi:10.1016/0014-2999(94)90334-4 *
L. ROSSETTI: "Insulinomimetic properties of trace elements and characterization of their in vivo mode of action", DIABETES, vol. 39, no. 10, 1990, pages 1243 - 1250 *

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