WO2001047522A2 - Association of deoxyfructosazine and an antidiabetic of the biguanide family - Google Patents
Association of deoxyfructosazine and an antidiabetic of the biguanide family Download PDFInfo
- Publication number
- WO2001047522A2 WO2001047522A2 PCT/FR2000/003604 FR0003604W WO0147522A2 WO 2001047522 A2 WO2001047522 A2 WO 2001047522A2 FR 0003604 W FR0003604 W FR 0003604W WO 0147522 A2 WO0147522 A2 WO 0147522A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- deoxyfructosazine
- association
- antidiabetic
- metformin
- pharmaceutically acceptable
- Prior art date
Links
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Definitions
- the present invention relates to the combination of deoxyfructosazine and an antidiabetic from the biguanide family, the pharmaceutical compositions containing this combination and their use in the prevention and / or treatment of type 2 diabetes and its complications.
- Antidiabetics of the biguanides family are used in particular in the treatment of insulin-independent diabetes mellitus. They are generally used in addition to a diet.
- metformin Glucophage R , Glucinan R and its pharmaceutically acceptable salts with a mineral or organic acid (US3174901WO9929314, FR2264539, US4080472, US3957853)
- buformin Bigunal R , Bufonamin R , Gliporal R and its pharmaceutically acceptable salts with a mineral or organic acid (US2961377)
- phenformin Glucopostin R , Glyphen R , Insoral R , Normoglucina R , Meltrol R and its pharmaceutically acceptable salts with a mineral or organic acid (US2961377, US3057780).
- the combination of an antidiabetic from the biguanide family and deoxyfructosazine has a synergistic effect in the treatment of type 2 diabetes and its complications. More particularly, the invention relates to combinations of deoxyfructosazine and metformin, buformin or phenformin and their salts with a pharmaceutically acceptable mineral or organic acid.
- the invention relates to the combination of deoxyfructosazine and metformin or its salts with a pharmaceutically acceptable mineral or organic acid.
- the activity of the associations can be determined by the methods commonly used by those skilled in the art in the field of diabetes. Among these methods, the following methods can in particular be used:
- mice Male Wistar rats weighing 180 to 200 g are made diabetic by intravenous injection of 60 mg / kg of streptozotocin. After 72 hours, the blood sugar of the animals is measured on the glucometer. Animals with a blood sugar lower than 2 g / 1 are not selected for the study and those with a blood sugar higher than 2 g / 1 are treated, orally, by gavage using a gastric tube, with a single dose of either deoxyfructosazine alone (5-50-100-150 mg / kg) or metformin alone (100-200 mg / kg) or a combination of deoxyfructosazine and metformin. A group of animals receives only the vehicle. Blood sugar levels are measured at 30 minutes, 1 hour and then every hour for 8 hours after treatment with the products.
- mice Male Wistar rats weighing 180 to 200 g are made diabetic by intravenous injection of 60 mg / kg of streptozotocin. After 72 hours, the blood sugar of the animals is measured on the glucometer. Animals with blood sugar below 2 g / 1 are not considered for the study, those with a blood sugar level higher than 2 g / 1 are treated, orally, by gavage using a gastric tube, by a dose per day for 30 days. either deoxyfructosazine alone (5-50-100-150 mg / kg) or metformin alone (100-200 mg / kg) or a combination of deoxyfructosazine and metformin. A group of animals receives only the vehicle. Blood sugar levels are measured once a day.
- tests A and B demonstrate that, in the animals receiving the association, the blood sugar levels are much lower than those of the control animals and those of the animals treated with a single antidiabetic.
- mice raised in Madagascar are given orally by gavage for 4 days either deoxyfructosazine alone (5-50-100-150 mg / kg) or metformin alone (100-200 mg / kg) or a combination of deoxyfructosazine and metformin.
- deoxyfructosazine alone 50-100-150 mg / kg
- metformin alone 100-200 mg / kg
- a combination of deoxyfructosazine and metformin Three hours after the last treatment, 2 g / kg of an aqueous glucose solution are given orally. Blood glucose levels are determined 20 minutes later using a glucometer.
- Obese Zucker (fa / fa) rats aged 5-6 weeks are treated, orally, in a single gavage, for 7 and 14 days with deoxyfructosazine alone (5-50-100- 150 mg / day / kg) or metformin alone (100-200 mg / kg) or by a combination of deoxyfructosazine and metformin.
- the control groups are force-fed under the same conditions with the excipient alone.
- the food intake and the weight of the animals are measured every day during the experiment.
- the rats are anesthetized with pentobarbital.
- a glucose tolerance test (0.5 g / kg) is carried out intravenously and blood samples are taken 5, 10, 15, 20, 25 and 30 minutes after the injection in order to measure blood sugar and insulinemia .
- these associations are therefore useful in the prevention and / or treatment of type 2 diabetes.
- These associations can also be used in the complications of diabetes such as hyperlipemia, disorders of lipid metabolism, dyslipemia, obesity , diabetic cataracts, diabetic neuropathy in its various forms (peripheral polyneuropathies and its manifestations such as paraesthesia, hyperesthesia and pain, mononeuropathies, radiculopathies, autonomic neuropathies, diabetic muscular atrophies), manifestations of diabetic foot (ulcers of the lower extremities and foot ), diabetic nephropathy in both its diffuse and nodular forms.
- the combination can be used orally, parenterally or rectally either simultaneously or separately or over a period of time.
- the present invention also relates to pharmaceutical compositions comprising the combination of deoxyfructosazine and an antidiabetic agent of the biguanide family and, in particular, metformin, buformin or phenformin and their salts pharmaceutically acceptable with a mineral or organic acid and, more particularly metformin and its pharmaceutically acceptable salts with a mineral or organic acid, in the pure state or in the form of a combination with one or more diluents and / or adjuvants compatible and pharmaceutically acceptable and / or optionally in combination with another pharmaceutically compatible and physiologically active product.
- the products which constitute the association can be administered simultaneously, separately or in a spread over time so as to obtain the maximum effectiveness of the association.
- compositions for oral administration tablets, pills, powders (gelatin capsules, cachets) or granules can be used.
- the active ingredients are mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica, under a stream of argon.
- these compositions can also comprise substances other than diluents, for example one or more lubricants such as magnesium stearate or talc, a colorant, a coating (dragees) or a varnish.
- compositions for oral administration use may be made of pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerol, vegetable oils or oil paraffin.
- inert diluents such as water, ethanol, glycerol, vegetable oils or oil paraffin.
- These compositions can include substances other than diluents, for example wetting, sweetening, thickening, flavoring or stabilizing products.
- the sterile compositions for parenteral administration can preferably be aqueous or non-aqueous solutions, suspensions or emulsions.
- solvent or vehicle water, propylene glycol, a polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, can be used. example ethyl oleate or other suitable organic solvents.
- These compositions can also contain adjuvants, in particular wetting agents, isotonizers, emulsifiers, dispersants and stabilizers. Sterilization can be done in several ways, for example by aseptic filtration, by incorporating sterilizing agents into the composition, by irradiation or by heating. They can also be prepared in the form of sterile solid compositions which can be dissolved at the time of use in sterile water or any other sterile injectable medium.
- compositions for rectal administration are suppositories or rectal capsules which contain, in addition to the active product, excipients such as cocoa butter, semisynthetic glycerides or polyethylene glycols.
- the present invention also relates to the method of prevention and / or treatment of type 2 diabetes and its complications in a patient which consists in administering to the patient a combination of deoxyfructosazine and an antidiabetic from the biguanide family preferably chosen from metformin, buformin or phenformin and their pharmaceutically acceptable salts with a mineral or organic acid and, more particularly, metformin and its pharmaceutically acceptable salts with a mineral or organic acid, either simultaneously or separately or spread over time.
- the doses depend on the desired effect, the duration of the treatment and the route of administration used and the initial blood sugar level.
- the dose of the anti-diabetic of the biguanides family being adjusted to obtain a normal blood sugar level.
- the doses of the biguanide antidiabetic will be determined on a case-by-case basis. They will generally be identical to or lower than the doses recommended for single use. Thus, the dose will be 300 to 2500 mg / day of metformin.
- the doctor will determine the appropriate dosage based on age, weight and all other factors specific to the subject to be treated such as the initial blood sugar level.
- the present invention also relates to the use of a combination of deoxyfructosazine and an antidiabetic from the biguanide family preferably chosen from metformin, buformin or phenfo ⁇ riin and their pharmaceutically acceptable salts with a mineral or organic acid and, more in particular, metformin and its pharmaceutically acceptable salts with a mineral or organic acid for the preparation of a medicament useful for the prevention and / or the treatment of type 2 diabetes and its complications.
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- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU26877/01A AU2687701A (en) | 1999-12-23 | 2000-12-20 | Association of deoxyfructosazine and an antidiabetic of the biguanide family |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9916357A FR2802813A1 (en) | 1999-12-23 | 1999-12-23 | Associations of deoxyfructosazine and a biguanide antidiabetic agent have a synergistic activity in the treatment of type 2 diabetes |
FR99/16357 | 1999-12-23 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2001047522A2 true WO2001047522A2 (en) | 2001-07-05 |
WO2001047522A3 WO2001047522A3 (en) | 2002-04-04 |
Family
ID=9553729
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FR2000/003604 WO2001047522A2 (en) | 1999-12-23 | 2000-12-20 | Association of deoxyfructosazine and an antidiabetic of the biguanide family |
Country Status (3)
Country | Link |
---|---|
AU (1) | AU2687701A (en) |
FR (1) | FR2802813A1 (en) |
WO (1) | WO2001047522A2 (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2766183A1 (en) * | 1997-07-17 | 1999-01-22 | Rhone Poulenc Rorer Sa | MEDICAMENTS CONTAINING POLYHYDROXYBUTYLPYRAZINES, NEW POLYHYDROXYBUTYLPYRAZINES AND THEIR PREPARATION |
WO1999029314A1 (en) * | 1997-12-08 | 1999-06-17 | Bristol-Myers Squibb Company | Novel salts of metformin and method |
-
1999
- 1999-12-23 FR FR9916357A patent/FR2802813A1/en not_active Withdrawn
-
2000
- 2000-12-20 AU AU26877/01A patent/AU2687701A/en not_active Abandoned
- 2000-12-20 WO PCT/FR2000/003604 patent/WO2001047522A2/en active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2766183A1 (en) * | 1997-07-17 | 1999-01-22 | Rhone Poulenc Rorer Sa | MEDICAMENTS CONTAINING POLYHYDROXYBUTYLPYRAZINES, NEW POLYHYDROXYBUTYLPYRAZINES AND THEIR PREPARATION |
WO1999029314A1 (en) * | 1997-12-08 | 1999-06-17 | Bristol-Myers Squibb Company | Novel salts of metformin and method |
Also Published As
Publication number | Publication date |
---|---|
AU2687701A (en) | 2001-07-09 |
FR2802813A1 (en) | 2001-06-29 |
WO2001047522A3 (en) | 2002-04-04 |
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