EP0068314A1 - Traitement des troubles arthritiques - Google Patents
Traitement des troubles arthritiques Download PDFInfo
- Publication number
- EP0068314A1 EP0068314A1 EP82105285A EP82105285A EP0068314A1 EP 0068314 A1 EP0068314 A1 EP 0068314A1 EP 82105285 A EP82105285 A EP 82105285A EP 82105285 A EP82105285 A EP 82105285A EP 0068314 A1 EP0068314 A1 EP 0068314A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- desferrioxamine
- treatment
- diseases involving
- joint inflammation
- pharmaceutical preparation
- 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- Withdrawn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
- 230000002917 arthritic effect Effects 0.000 title claims abstract description 14
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 claims abstract description 69
- 229960000958 deferoxamine Drugs 0.000 claims abstract description 68
- 206010003246 arthritis Diseases 0.000 claims abstract description 18
- 201000010099 disease Diseases 0.000 claims abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
- 208000018937 joint inflammation Diseases 0.000 claims abstract description 14
- 230000002035 prolonged effect Effects 0.000 claims abstract description 7
- 239000002502 liposome Substances 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 11
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 11
- 238000009472 formulation Methods 0.000 claims description 7
- 239000002552 dosage form Substances 0.000 claims description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 36
- 229910052742 iron Inorganic materials 0.000 description 18
- 241000700159 Rattus Species 0.000 description 14
- 206010061218 Inflammation Diseases 0.000 description 12
- 230000004054 inflammatory process Effects 0.000 description 12
- 239000003978 infusion fluid Substances 0.000 description 11
- 206010039073 rheumatoid arthritis Diseases 0.000 description 11
- 230000008961 swelling Effects 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 102000008857 Ferritin Human genes 0.000 description 6
- 238000008416 Ferritin Methods 0.000 description 6
- 108050000784 Ferritin Proteins 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000006698 induction Effects 0.000 description 6
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 5
- 230000003307 reticuloendothelial effect Effects 0.000 description 5
- 210000001179 synovial fluid Anatomy 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 4
- 210000001503 joint Anatomy 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 description 3
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 3
- 208000009386 Experimental Arthritis Diseases 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 2
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 2
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 2
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 2
- GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 208000037039 Monarthritis Diseases 0.000 description 2
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 229960000541 cetyl alcohol Drugs 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229960004544 cortisone Drugs 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000010438 iron metabolism Effects 0.000 description 2
- 210000003127 knee Anatomy 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 210000002268 wool Anatomy 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- CITHEXJVPOWHKC-UUWRZZSWSA-N 1,2-di-O-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 210000000593 adipose tissue white Anatomy 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229940099217 desferal Drugs 0.000 description 1
- RNPXCFINMKSQPQ-UHFFFAOYSA-N dicetyl hydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCOP(O)(=O)OCCCCCCCCCCCCCCCC RNPXCFINMKSQPQ-UHFFFAOYSA-N 0.000 description 1
- 229940093541 dicetylphosphate Drugs 0.000 description 1
- 229960003724 dimyristoylphosphatidylcholine Drugs 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 210000003617 erythrocyte membrane Anatomy 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 108010074605 gamma-Globulins Proteins 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940075525 iron chelating agent Drugs 0.000 description 1
- 239000000797 iron chelating agent Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
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
- A61K31/16—Amides, e.g. hydroxamic acids
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- the present invention relates to the treatment of arthritic and like complaints.
- rheumatoid arthritis is a chronic form of arthritis where many joints are affected and the inflammation is often such that gross deformity and immobility of the joint may result.
- Rheumatoid arthritis has, in the past, been treated, for example, with cortisone or with non-steroidal anti-inflammatory drugs.
- Cortisone is effective in combating inflammation but also carries with its use a high risk of dangerous side effects.
- Treatment with non-steroidal anti-inflammatory drugs (NSAID's) has often been found not to be as effective as desired to reduce inflammation.
- the most popular NSAID is aspirin which has to be used in very high doses e.g. 16-18 tablets per day.
- Desferrioxamine is an iron-chelating agent which has long been used in the treatment of iron poisoning and which has also been used extensively in the examination of iron metabolism in many diseases including rheumatoid arthritis. We are not aware, however, that the use of desferrioxamine to reduce the inflammation in the treatment of rheumatoid arthritis has ever been disclosed.
- the present invention provides a method of treatment of rheumatoid arthritic and like diseases involving joint inflammation, which comprises administering desferrioxamine in a therapeutically effective dosage over a prolonged period.
- the method of the invention may be applied to the treatment of non-specific monoarthritis and any other instances of joint inflammation caused by free iron catalysis.
- the method of the invention may also be applied to any other complaint which is induced by the occurrence of free iron, for example certain instances of myocardial infarction as recently suggested.
- the amount of desferrioxamine administered is suitably a therapeutically effective amount in the range of from 1 to 10 g per day, for example 1 to 5 g per day, suitably 2 to 3 g per day.
- the present invention also provides a pharmaceutical preparation suitable for intra-articular administration which comprises desferrioxamine in admixture or conjunction with a pharmaceutically suitable carrier.
- the present invention further provides a pharmaceutical preparation in the form of a pack which contains a support member together with a plurality of dosage forms comprising desferrioxamine, preferably enough for 3 weeks' supply.
- the amount of desferrioxamine present in each dosage form in a pack of the invention is in the range of from 1 to 10 g, e.g. in the range of from 1 to 5 g, conveniently 2 to 3 g.
- the amount of desferrioxamine may be different in each dosage form, for example a pack may comprise a set of dosage forms one containing 1 g of desferrioxamine, another 2 g of desferrioxamine and so on to 5 g, 7 g or 10 g of desferrioxamine.
- the desferrioxamine is suitably present in lyophilised powder form as desferrioxamine mesylate but may be in a liposome formulation.
- Desferrioxamine may be administered by any one of several routes.
- Administration intravenously, intraperitoneally, subcutaneously, intra-muscularly or intra- articularly by infusion solution are all suitable routes, intra-articular and subcutaneous infusion being preferred.
- Administration by infusion solution may be by continuous pump administration or administration in divided doses, i.e. twice or three times daily, daily, weekly or monthly.
- the active substance may be present in the infusion solution prior to the start of the administration or may be injected in as a "bolus" concentrate.
- Other routes of administration possible are via the skin or by the use of a liposome formulation.
- Administration via the skin may be by the transdermal "delivery system" (Alza Corporation) where medication externally applied by means of a special applicator reaches the affected joint by absorption through the skin.
- Direct topical administration may occur from once to four times daily by means of an ointment or cream containing desferrioxamine.
- Preparations containing desferrioxamine may in addition contain the usual carriers, excipients and auxiliaries.
- pH-regulating substances e.g. sodium phosphate and substances imparting isotonicity to the solutions, e.g. sodium chloride, may be present.
- the period of administration of desferrioxamine will vary depending on the severity of the disease, but is usually at least 5 days. In chronic cases the administration may occur initially over a period of 3 weeks to a month with the treatment being repeated at 3, 6 or 12 month intervals or sooner if chronic inflammation occurs or recurs. In instances of subcutaneous administration by infusion solution, it has been found satisfactory for the initial 3 week treatment to consist of continuous administration over several hours daily for 5 consecutive days, followed by no administration for 2 days and then repeat treatment for the following 5 days and so on.
- the above methods of administration are acceptable methods for introducing desferrioxamine into the body but cannot ensure that all of the active substance reaches the site of the free iron and ferritin stores in the reticuloendothelial stores. Also the most useful preparations, the infusion solutions, have to be made up shortly before use from lyophilised desferrioxamine powder because aqueous desferrioxamine solution is unstable over periods of longer than a week.
- the present invention also provides a method for the treatment of rheumatoid arthritis, wherein a pharmaceutical preparation comprising desferrioxamine as a liposome formulation is administered to the patient orally or parenterally.
- Liposomes are lipoid vesicles of varying sizes which encapsulate an active ingredient.
- the lipoid walls may comprise one or more lipid bi-layers. Suitable lipids are phospholipids; they may be used in pure form or in combination with other suitable substances.
- Desferrioxamine in aqueous solution may be incorporated into liposomes which have an avidity for the reticuloendothelial cells without apparent loss of stability.
- each liposome formulation may contain in the range of 0.1 to 12.5 mg of desferrioxamine.
- Desferrioxamine has been found to give a significant reduction in joint inflammation in patients suffering from rheumatoid arthritis without any apparent side- effects. It has also been found to give such results when used in conjunction with non-steroidal anti-inflammatory drugs without any apparent undesirable interactions. Desferrioxamine may thus be used as a replacement for or as a supplement to the non-steroidal anti-inflammatory drugs already used.
- the solvent used for the lipoid mixture was chloroform.
- the size of the liposomes was varied in certain cases from multilamellar liposomes to unilamellar liposomes by ultrasonication.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Medicinal Preparation (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)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8119006 | 1981-06-19 | ||
| GB8119006 | 1981-06-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0068314A1 true EP0068314A1 (fr) | 1983-01-05 |
Family
ID=10522661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP82105285A Withdrawn EP0068314A1 (fr) | 1981-06-19 | 1982-06-16 | Traitement des troubles arthritiques |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4397867A (fr) |
| EP (1) | EP0068314A1 (fr) |
| JP (1) | JPS5823619A (fr) |
| BE (1) | BE893559A (fr) |
| IT (1) | IT8248659A0 (fr) |
| NZ (1) | NZ201010A (fr) |
| PH (1) | PH18342A (fr) |
| ZA (1) | ZA824327B (fr) |
Cited By (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0227593A1 (fr) * | 1985-11-25 | 1987-07-01 | The Hospital For Sick Children | Application d'agents chélatants |
| EP0214101A3 (fr) * | 1985-09-03 | 1989-05-31 | Ciba-Geigy Ag | Utilisation des fer(III) chelateurs du type desferrioxamine-B et desferriferrithiocine pour le traitement du paludisme |
| EP0652008A1 (fr) * | 1993-07-23 | 1995-05-10 | The Minister Of National Defence Of Her Majesty's Canadian Government | Ciprofloxacin encapsulé en liposômes |
| EP0706375A4 (fr) * | 1993-06-14 | 1996-11-06 | Emisphere Tech Inc | Excipients proteinoidiques |
| EP0726771A4 (fr) * | 1993-10-26 | 1997-01-29 | Emisphere Tech Inc | Systeme d'administration orale de deferoxamine |
| US5629020A (en) * | 1994-04-22 | 1997-05-13 | Emisphere Technologies, Inc. | Modified amino acids for drug delivery |
| US5643957A (en) | 1993-04-22 | 1997-07-01 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5650386A (en) | 1995-03-31 | 1997-07-22 | Emisphere Technologies, Inc. | Compositions for oral delivery of active agents |
| US5667806A (en) | 1995-06-07 | 1997-09-16 | Emisphere Technologies, Inc. | Spray drying method and apparatus |
| US5709861A (en) | 1993-04-22 | 1998-01-20 | Emisphere Technologies, Inc. | Compositions for the delivery of antigens |
| US5714167A (en) | 1992-06-15 | 1998-02-03 | Emisphere Technologies, Inc. | Active agent transport systems |
| US5766633A (en) | 1993-04-22 | 1998-06-16 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
| US5792451A (en) | 1994-03-02 | 1998-08-11 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
| US5804688A (en) | 1997-02-07 | 1998-09-08 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5811127A (en) | 1992-06-15 | 1998-09-22 | Emisphere Technologies, Inc. | Desferrioxamine oral delivery system |
| US5820881A (en) | 1995-04-28 | 1998-10-13 | Emisphere Technologies, Inc. | Microspheres of diamide-dicarboxylic acids |
| US5824345A (en) | 1995-06-07 | 1998-10-20 | Emisphere Technologies, Inc. | Fragrances and flavorants |
| US5840340A (en) | 1992-06-15 | 1998-11-24 | Emisphere Technologies, Inc. | Proteinoid carriers and methods for preparation and use thereof |
| US5863944A (en) | 1997-04-30 | 1999-01-26 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5866536A (en) | 1995-03-31 | 1999-02-02 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5876710A (en) | 1997-02-07 | 1999-03-02 | Emisphere Technologies Inc. | Compounds and compositions for delivering active agents |
| US5879681A (en) | 1997-02-07 | 1999-03-09 | Emisphere Technolgies Inc. | Compounds and compositions for delivering active agents |
| US5939381A (en) | 1997-02-07 | 1999-08-17 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5958457A (en) | 1993-04-22 | 1999-09-28 | Emisphere Technologies, Inc. | Compositions for the delivery of antigens |
| US5962710A (en) | 1997-05-09 | 1999-10-05 | Emisphere Technologies, Inc. | Method of preparing salicyloylamino acids |
| US5965121A (en) | 1995-03-31 | 1999-10-12 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5972387A (en) | 1992-12-21 | 1999-10-26 | Emisphere Technologies, Inc. | Modified hydrolyzed vegetable protein microspheres and methods for preparation and use thereof |
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|---|---|---|---|---|
| USRE34313E (en) * | 1983-09-23 | 1993-07-13 | National Research Development Corporation | Pharmaceutical compositions |
| US4912118A (en) * | 1983-09-23 | 1990-03-27 | National Research Development Corporation | Pharmaceutical compositions |
| US5177068A (en) * | 1984-04-19 | 1993-01-05 | National Research Development Corporation | Pharmaceutical compositions |
| US4863964A (en) * | 1985-07-02 | 1989-09-05 | Biomedical Frontiers, Inc. | Method for the stabilization of deferoxamine to chelate free ions in physiological fluid |
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| US4743587A (en) * | 1985-09-10 | 1988-05-10 | G. D. Searle & Co. | Hydroxamic acid based collagenase inhibitors |
| US4599361A (en) * | 1985-09-10 | 1986-07-08 | G. D. Searle & Co. | Hydroxamic acid based collagenase inhibitors |
| US4698431A (en) * | 1985-11-12 | 1987-10-06 | The United States Of America As Represented By The United States Department Of Energy | Hydroxypyridonate chelating agents |
| US4797285A (en) * | 1985-12-06 | 1989-01-10 | Yissum Research And Development Company Of The Hebrew University Of Jerusalem | Lipsome/anthraquinone drug composition and method |
| US5672334A (en) * | 1991-01-16 | 1997-09-30 | Access Pharmaceuticals, Inc. | Invivo agents comprising cationic metal chelators with acidic saccharides and glycosaminoglycans |
| US5707604A (en) * | 1986-11-18 | 1998-01-13 | Access Pharmaceuticals, Inc. | Vivo agents comprising metal-ion chelates with acidic saccharides and glycosaminoglycans, giving improved site-selective localization, uptake mechanism, sensitivity and kinetic-spatial profiles |
| US5043166A (en) * | 1987-01-09 | 1991-08-27 | Hadasit Medical Research, Inc. | Liposome/anthraquinone drug composition and method |
| US6106866A (en) * | 1995-07-31 | 2000-08-22 | Access Pharmaceuticals, Inc. | In vivo agents comprising cationic drugs, peptides and metal chelators with acidic saccharides and glycosaminoglycans, giving improved site-selective localization, uptake mechanism, sensitivity and kinetic-spatial profiles, including tumor sites |
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| BR112015000174A2 (pt) * | 2012-07-05 | 2017-06-27 | Taiwan Liposome Co Ltd | método para o tratamento da artrite |
| KR102310786B1 (ko) | 2013-02-01 | 2021-10-12 | 존원 파마, 인코포레이티드 | 리포좀 내로 난수용성 약물의 원격 부하 |
| CN106999419A (zh) | 2014-08-04 | 2017-08-01 | 佐尼奥尼制药股份有限公司 | 远程装载略微水溶性药物至脂质膜泡 |
| US11331288B2 (en) | 2017-09-14 | 2022-05-17 | The Board Of Trustees Of The Leland Stanford Junior University | Conditioning irradiated tissue for increasing vascularity |
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| GB999583A (en) * | 1959-09-25 | 1965-07-28 | Ciba Ltd | Pharmaceutical preparations containing trihydroxamic acids |
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1982
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- 1982-06-15 US US06/388,573 patent/US4397867A/en not_active Expired - Fee Related
- 1982-06-16 EP EP82105285A patent/EP0068314A1/fr not_active Withdrawn
- 1982-06-16 PH PH27434A patent/PH18342A/en unknown
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- 1982-06-18 ZA ZA824327A patent/ZA824327B/xx unknown
- 1982-06-18 BE BE0/208382A patent/BE893559A/fr not_active IP Right Cessation
- 1982-06-18 JP JP57104083A patent/JPS5823619A/ja active Pending
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| GB999583A (en) * | 1959-09-25 | 1965-07-28 | Ciba Ltd | Pharmaceutical preparations containing trihydroxamic acids |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0214101A3 (fr) * | 1985-09-03 | 1989-05-31 | Ciba-Geigy Ag | Utilisation des fer(III) chelateurs du type desferrioxamine-B et desferriferrithiocine pour le traitement du paludisme |
| EP0227593A1 (fr) * | 1985-11-25 | 1987-07-01 | The Hospital For Sick Children | Application d'agents chélatants |
| US6221367B1 (en) | 1992-06-15 | 2001-04-24 | Emisphere Technologies, Inc. | Active agent transport systems |
| US6071538A (en) | 1992-06-15 | 2000-06-06 | Emisphere Technologies, Inc. | Oral delivery composition comprising supramolecular complex |
| US5840340A (en) | 1992-06-15 | 1998-11-24 | Emisphere Technologies, Inc. | Proteinoid carriers and methods for preparation and use thereof |
| US6099856A (en) | 1992-06-15 | 2000-08-08 | Emisphere Technologies, Inc. | Active agent transport systems |
| US6413550B1 (en) | 1992-06-15 | 2002-07-02 | Emisphere Technologies, Inc. | Proteinoid carriers and methods for preparation and use thereof |
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| US5811127A (en) | 1992-06-15 | 1998-09-22 | Emisphere Technologies, Inc. | Desferrioxamine oral delivery system |
| US5714167A (en) | 1992-06-15 | 1998-02-03 | Emisphere Technologies, Inc. | Active agent transport systems |
| US5972387A (en) | 1992-12-21 | 1999-10-26 | Emisphere Technologies, Inc. | Modified hydrolyzed vegetable protein microspheres and methods for preparation and use thereof |
| US6100298A (en) | 1993-04-22 | 2000-08-08 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
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| US5958457A (en) | 1993-04-22 | 1999-09-28 | Emisphere Technologies, Inc. | Compositions for the delivery of antigens |
| EP0706375A4 (fr) * | 1993-06-14 | 1996-11-06 | Emisphere Tech Inc | Excipients proteinoidiques |
| EP0652008A1 (fr) * | 1993-07-23 | 1995-05-10 | The Minister Of National Defence Of Her Majesty's Canadian Government | Ciprofloxacin encapsulé en liposômes |
| EP0726771A4 (fr) * | 1993-10-26 | 1997-01-29 | Emisphere Tech Inc | Systeme d'administration orale de deferoxamine |
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| US6461545B1 (en) | 1995-06-07 | 2002-10-08 | Emisphere Technologies, Inc. | Method of solubilizing and encapsulating itraconazole |
| US6100285A (en) | 1995-06-07 | 2000-08-08 | Emisphere Technologies, Inc. | Method of solubilizing itraconazole |
| US6051258A (en) | 1995-06-07 | 2000-04-18 | Emisphere Technologies, Inc. | Proteinoid emulsions and methods for preparation and use thereof |
| US6084112A (en) | 1995-09-11 | 2000-07-04 | Emisphere Technologies, Inc. | Method for preparing ω-aminoalkanoic acid derivatives from cycloalkanones |
| US7417022B2 (en) | 1996-03-29 | 2008-08-26 | Mhr Institutional Partners Iia Lp | Compounds and compositions for delivering active agents |
| US6375983B1 (en) | 1996-06-14 | 2002-04-23 | Emisphere Technologies, Inc. | Microencapsulated fragrances and method for preparation |
| US5990166A (en) | 1997-02-07 | 1999-11-23 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
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| US5962710A (en) | 1997-05-09 | 1999-10-05 | Emisphere Technologies, Inc. | Method of preparing salicyloylamino acids |
| US6960560B2 (en) | 1999-12-30 | 2005-11-01 | Gwathmey, Inc. | Iron chelator delivery system |
| WO2001049266A3 (fr) * | 1999-12-30 | 2002-03-21 | Judith K Gwathemy | Systeme de distribution de chelateur de fer |
Also Published As
| Publication number | Publication date |
|---|---|
| BE893559A (fr) | 1982-12-20 |
| JPS5823619A (ja) | 1983-02-12 |
| US4397867A (en) | 1983-08-09 |
| NZ201010A (en) | 1986-02-21 |
| PH18342A (en) | 1985-06-05 |
| ZA824327B (en) | 1984-01-25 |
| IT8248659A0 (it) | 1982-06-17 |
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