EP1223943A2 - Therapeutische verwendung von einem abc-protein-hemmer oder -antagonisten in knochen - Google Patents
Therapeutische verwendung von einem abc-protein-hemmer oder -antagonisten in knochenInfo
- Publication number
- EP1223943A2 EP1223943A2 EP00927525A EP00927525A EP1223943A2 EP 1223943 A2 EP1223943 A2 EP 1223943A2 EP 00927525 A EP00927525 A EP 00927525A EP 00927525 A EP00927525 A EP 00927525A EP 1223943 A2 EP1223943 A2 EP 1223943A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- compound
- bone
- disease
- inhibitor
- antagonist
- 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- Withdrawn
Links
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Classifications
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- 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
-
- 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
- A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
-
- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to the use of a compound and composition
- osteoclast associated ABC protein for use in bone, more particularly an osteoclast associated ABC protein, for use in osteoclast associated ABC protein
- osteoclast associated ABC protein for use in the manufacture of
- Such diseases include,
- osteopenia such as osteoporosis, Paget's disease, bone
- the invention also relates to a method of screening for a compound which
- osteoclast associated ABC protein comprising
- ABC proteins ATP binding cassette proteins
- traffic ATP ases also called traffic ATP ases
- ABC proteins are abundant in prokaryotes where they represent almost 5% of the total genome and show specificity for a diverse range of
- cystic fibrosis cystic fibrosis, multi-drug resistance of tumour cells, non-insulin dependent diabetes
- osteoclast associated ABC protein may be useful in treating conditions arising out of osteoclastic function.
- ABC cassette proteins have been implicated in many cellular
- Osteoclasts are terminally differentiated cells and are hence programmed to
- osteoclast associated ABC transporters associated with ion channels will enhance
- adhesion may be promoted by annexin-mediated binding between phospholipids and
- inhibitors or antagonists of ABC proteins will be useful therapeutic agents in the
- osteopenia which includes osteoporosis, Paget's disease, bone metastases, myeloma
- PTH a known stimulant of bone resorption
- urea, Glibenclamide include:
- the compounds may be administered orally, intravenously, subcutaneously
- inventions can be administered in such oral dosage forms as tablets, capsules (each of
- the dosage regimen utilising the compounds of the present invention is
- the adult dosage may, for oral application, range from 0.001 to 5g daily,
- the preferred daily dose is from 0.000014g to 0.0715g per kg of body weight
- dose can range from 0.00 lg to 5.0g, more preferably from 0.01 to 0.5g. This daily
- dose may be administered in divided doses from 1 to 4 times a day giving unit doses
- the compounds of the present invention can form the active ingredient, and
- active drug component can be combined with an oral, non-toxic, pharmaceutically
- inert carrier such as lactose, starch, sucrose, glucose, methyl cellulose,
- magnesium stearate dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the
- the oral drug components can be any suitable oral drug components.
- binders can also be incorporated in to the mixture.
- Suitable binders include starch, gelatin, natural sugars such as
- glucose or beta-lactose corn sweeteners, natural and synthetic gums such as acacia,
- Lubricants used in these dosage forms include sodium oleate, sodium oleate, sodium
- Disintegrators include, without limitation, starch, methyl cellulose, agar,
- the compounds may be administered by any means that treat and/or prevent
- osteopenia which includes osteoporosis, Paget ' s disease, bone
- the compounds of the present invention may be useful in any combination.
- composition which will act as an inhibitor or antagonist of an ABC protein for use
- PTH parathyroid hormone
- the compounds may be administered concomitantly with PTH.
- the dosage of PTH may vary according to the criterion set out for the
- the adult dosage may, for oral application, range from 1 to 200 International
- Units daily more preferably 50 to 100 International Units.
- the preferred daily dose of PTH is from 0.014 to 2.9 International Units per
- This daily dose may be administered in
- inventions include all animals which may benefit therefrom. Included in such animals
- bone reso ⁇ tion which comprises determining whether the compound acts as an
- osteoclast precursors are obtained from human blood.
- Monoclonal antibodies were raised against cells from human bone.
- osteoclasts and Methods in Molecular Medicine, Human cell culture protocols, ed
- the active factors included parathyroid hormone (PTH), which is known to stimulate bone reso ⁇ tion in this
- Fig 1 shows inhibition of reso ⁇ tion by
- Glibenclamide enhanced inhibition of reso ⁇ tion by Glibenclamide and PTH
- Fig.2 shows inhibition of reso ⁇ tion by Glibenclamide using human
- osteoclasts derived from a giant cell tumor according to the above test
- Fig. 3 shows the dose response as inhibition of reso ⁇ tion by Glibenclamide
- the vehicle is tissue culture medium containing 0.1% dimethyl sulphoxide.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Physical Education & Sports Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9910693.2A GB9910693D0 (en) | 1999-05-07 | 1999-05-07 | A compound for use in medicine |
| GB9910693 | 1999-05-07 | ||
| PCT/GB2000/001736 WO2000067736A2 (en) | 1999-05-07 | 2000-05-05 | Therapeutic use of an inhibitor or an antagonist of an abc protein in bone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1223943A2 true EP1223943A2 (de) | 2002-07-24 |
Family
ID=10853073
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP00927525A Withdrawn EP1223943A2 (de) | 1999-05-07 | 2000-05-05 | Therapeutische verwendung von einem abc-protein-hemmer oder -antagonisten in knochen |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1223943A2 (de) |
| JP (1) | JP2003501350A (de) |
| AU (1) | AU4592000A (de) |
| GB (1) | GB9910693D0 (de) |
| WO (1) | WO2000067736A2 (de) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI238064B (en) * | 1995-06-20 | 2005-08-21 | Takeda Chemical Industries Ltd | A pharmaceutical composition for prophylaxis and treatment of diabetes |
| WO1998037764A1 (en) * | 1997-02-27 | 1998-09-03 | Baylor College Of Medicine | Nucleic acid sequences for atp-binding cassette transporter |
-
1999
- 1999-05-07 GB GBGB9910693.2A patent/GB9910693D0/en not_active Ceased
-
2000
- 2000-05-05 AU AU45920/00A patent/AU4592000A/en not_active Abandoned
- 2000-05-05 EP EP00927525A patent/EP1223943A2/de not_active Withdrawn
- 2000-05-05 JP JP2000616763A patent/JP2003501350A/ja active Pending
- 2000-05-05 WO PCT/GB2000/001736 patent/WO2000067736A2/en not_active Ceased
Non-Patent Citations (1)
| Title |
|---|
| See references of WO0067736A2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| GB9910693D0 (en) | 1999-07-07 |
| WO2000067736A3 (en) | 2002-05-10 |
| WO2000067736A2 (en) | 2000-11-16 |
| AU4592000A (en) | 2000-11-21 |
| JP2003501350A (ja) | 2003-01-14 |
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