CA2487150A1 - New formulation for parental application of sodium channel blocker - Google Patents
New formulation for parental application of sodium channel blocker Download PDFInfo
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- CA2487150A1 CA2487150A1 CA002487150A CA2487150A CA2487150A1 CA 2487150 A1 CA2487150 A1 CA 2487150A1 CA 002487150 A CA002487150 A CA 002487150A CA 2487150 A CA2487150 A CA 2487150A CA 2487150 A1 CA2487150 A1 CA 2487150A1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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Abstract
The invention concerns a novel formulation containing: a BIII 890 cyclodextr in complex or one of its phamacologically acceptable salts; a ternary complex consisting of BIII 890 or one of its phamacologically acceptable salts, a cyclodextrin and a hydroxylic acid; and BIII 890 or one of its phamacologically acceptable salts combined with a substituted or an unsubstituted cyclodextrin.
Description
Boehringer Ingelheim Pharma GmbH & Co. KG Case 01/1349 55216 Ingelheim CA 02487150 2004-11-24 foreign filing text 80943fft.207 New formulation for the parenteral application of a sodium channel blocker The invention relates to a new formulation of (-)-(1 R,2"S)-2-(2"-benzyloxy)-propyl-4'-hydroxy-5,9,9-trimethyl-6,7-benzomorphan (BIII 890) or one of the pharmacologically acceptable salts thereof, particularly the hydrochloride thereof, containing a complex of the active substance and a cyclodextrin, particularly hydroxypropyl-y-cyclodextrin, optionally in the presence of a hydroxy acid, for parenteral, particularly intravenous administration, the preparation and use thereof.
The terms "BIII 890" and "active substance" always refer to the compound (-)-(1 R,2"S)-2-(2"-benzyloxy)propyl-4'-hydroxy-5,9,9-trimethyl-6,7-benzomorphan of formula OH O ~ /
N~ , Me- H
\ Me - Me Me known from WO 99/14199, in the form of the free base or the corresponding acid addition salts with pharmacologically acceptable acids, particularly in the form of the hydrochloride. Other names for BIII 890 are crobenetine and [2R-[2,3(S*),6]]-1,2,3,4,5,6-hexahydro-6,11,11-trimethyl-3-[2-(phenylmethoxy)propyl]-2,6-methano-3-benzazocin-10-ol. BIII 890 is a sodium channel blocker with neuroprotective properties; the main indications for its use are thromboembolic stroke, brain injury and pain.
The aim of the invention is to prepare a new formulation for the active substance BIII 890, particularly for the hydrochloride thereof.
The terms "BIII 890" and "active substance" always refer to the compound (-)-(1 R,2"S)-2-(2"-benzyloxy)propyl-4'-hydroxy-5,9,9-trimethyl-6,7-benzomorphan of formula OH O ~ /
N~ , Me- H
\ Me - Me Me known from WO 99/14199, in the form of the free base or the corresponding acid addition salts with pharmacologically acceptable acids, particularly in the form of the hydrochloride. Other names for BIII 890 are crobenetine and [2R-[2,3(S*),6]]-1,2,3,4,5,6-hexahydro-6,11,11-trimethyl-3-[2-(phenylmethoxy)propyl]-2,6-methano-3-benzazocin-10-ol. BIII 890 is a sodium channel blocker with neuroprotective properties; the main indications for its use are thromboembolic stroke, brain injury and pain.
The aim of the invention is to prepare a new formulation for the active substance BIII 890, particularly for the hydrochloride thereof.
The invention relates to pharmaceutical compositions containing the active substance BIII 890 or one of the pharmaceutically acceptable salts thereof, particularly the hydrochloride thereof, and a cyclodextrin derivative, particularly gamma-cyclodextrin (y-CD), hydroxypropyl-gamma-cyclodextrin (HP-y-CD), hydroxypropyl-beta-cyclodextrin (HP-~3-CD) or sulphobutylether-beta-cyclodextrin (SBE-~3-CD). The preferred cyclodextrin derivative is hydroxypropyl-y-cyclodextrin. Hydroxypropyl-y-cyclodextrin with a molar substitution rate of 0.5 to 0.7 is sold for example by Messrs Wacker-Chemie GmbH, D-Burghausen, under the name "CAVASOL ~ W8 HP Pharma".
"CAVASOL ~ W8 HP Pharma" is particularly preferred for the pharmaceutical composition according to the invention.
For the indications mentioned above it is essential that the dosage is easily controlled so as to ensure that steady-state plasma levels are safely maintained. BIII 890 is therefore conveniently administered by parenteral route.
Apart from the active substance and the cyclodextrin derivative the pharmaceutical compositions according to the invention intended for parenteral administration may contain hydroxy acids such as for example malic acid, lactic acid, tartaric acid or citric acid. They may optionally also contain conventional excipients and carriers such as for example the isotonic agents glucose, mannitol or sodium chloride or sodium acetate or sodium acetate trihydrate as a buffer combined with acetic acid or a citric acid/phosphate buffer consisting e.g. of citric acid and disodium hydrogen phosphate or disodium hydrogen phosphate-dihydrate. The solvent used is normally water for injections.
The individual embodiments of the invention will be explained in more detail hereinafter.
Complexingi the active substance with cyclodextrins Suitable cyclodextrins include for example substituted ~3-cyclodextrin (consisting of 7 glucopyranose units), hydroxypropyl-~3-cyclodextrin (HP~CD), sulphobutylether-~-cyclodextrin (SBE~3CD), y-cyclodextrin (consisting of 8 glucopyranose units) and hydroxypropyl-y-cyclodextrin (HPyCD).
Solubility experiments and'H-NMR spectra have surprisingly shown that y-cyclodextrin as well as hydroxypropyl-y-cyclodextrin (HPyCD), hydroxy-propyl-~3-cyclodextrin (HPf3CD) and sulphobutylether-f3-cyclodextrin (SBEf3CD) complex the hydrochloride of BIII 890.
Complexina the active substance with cyclodextrins and hydroxy acids Another embodiment of the invention relates to the complexing of the active substance or one of the salts thereof with cyclodextrins and hydroxy acids.
The amount of cyclodextrin required can be reduced by the formation of a ternary complex consisting of BIII 890, the cyclodextrin in question and a hydroxy acid. The suitable cyclodextrins include, for example, hydroxypropyl-~-cyclodextrin (HPaCD), sulphobutylether-~-cyclodextrin (SBE~3CD), y-cyclodextrin and hydroxypropyl-y-cyclodextrin (HPyCD). Suitable hydroxy acids include for example malic acid, lactic acid, tartaric acid and citric acid.
One embodiment according to the invention of a parenteral preparation of BIII
890 or one of the physiologically acceptable salts thereof, such as e.g. the hydrochloride, contains the active substance in doses of 1 mg/kg of body weight to 30 mg/kg of body weight per day, preferably in the range from 3-15 mg/kg of body weight. The amounts, concentrations and dosages specified relate in each case to the active substance base regardless of whether BIII
890 is used in the form of the "base" (= compound of the formula given on page 1 ) or in the form of one of the pharmacologically acceptable salts thereof.
The preparation is preferably administered by continuous infusion over 24 hours or optionally several days in order to maintain a steady-state plasma level. The volumes administered are in the range from 50 to 500 ml, preferably 100 to 250 ml, i.e. the concentrations for administration of the active substance are in the range from 150 mg/500 ml = 0.3 mg/ml (0.03 %) to 1500 mg/100 ml = 15 mg/ml (1.5 %). An active substance concentration of 0.5 mg/ml = 0.05 % (g/v) to 3.5 mg/ml = 0.35 % (g/v) is preferred.
The molar ratio of active substance to cyclodextrin is between 1:1 and 1:5 according to the invention. A molar ratio of 1 : 2.5 to 1 : 3.5 is preferred.
In the presence of hydroxy acid the molar ratio of active substance to cyclodextrin is between 1 : 0.5 and 1 : 3 according to the invention; a molar ratio of 1 : 0.5 to 1 : 1.5 is preferred.
The following Examples are intended to illustrate the invention in more detail:
EXAMPLES
Example 1:
Solution for infusions/injection containing a hydroxypropyl-y-cyclodextrin complex BIII 890 hydrochloride 767 mg*
HpyCD**) 10000 mg mannitol 11000 mg acetic acid 99% 125.25 mg sodium acetate trihydrate 56.5 mg water for injections ad 250 ml *) corresponds to 700 mg BIII 890 in the form of the base **) for example "CAVASOL ~ W8 HP Pharma" sold by Wacker Example 2:
Solution for infusion/injection containing a y-cyclodextrin complex BIII 890 CL 383.5 mg***
YCD 5000 mg NaCI 2250 mg water for injections ad 250 ml ***) corresponds to 350 mg BIII 890 in the form of the base Example 3:
Solution for infusion/injection containing a hydroxypropyl-~-cyclodextrin complex BIII 890 CL 767 mg*
HP~CD 7500mg mannitol 12500 mg acetic acid 99% 125.25 mg sodium acetate trihydrate 56.5 mg water for injections ad 250 ml *) corresponds to 700 mg BIII 890 in the form of the base Example 4:
Solution for infusion/injection containing a sulphobutylether-~-cyclodextrin complex BIII 890 CL 767 mg*
SBE~iCD 5000 mg mannitol 12500 mg acetic acid 99% 125.25 mg sodium acetate trihydrate56.5 mg water for injections ad 250 ml *) corresponds to 700 mg BIII 890 in the form of the base Example 5:
Solution for infusion/injection containing a hydroxypropyl-y-cyclodextrin complex in the presence of hydroxy acids BIII 890 CL 767 mg*
HPyCD 2500 mg citric acid 708 mg mannitol 12500 mg acetic acid 99% 125.25 mg sodium acetate trihydrate56.5 mg water for injections ad 250 ml *) corresponds to 700 mg BIII 890 in the form of the base Example 6:
Solution for infusion/injection containing a Y-cyclodextrin complex in the presence of a hydroxy acid BIII 890 CL 767 mg*
yCD 2500 mg tartaric acid 138.25 mg NaCI 2250 mg water for injections 250 ml ad *) corresponds to 700 mg BIII 890 in the form of the base The quantity of active substance administered can be controlled by the administration of a specific volume of one of the solutions described above.
For example the daily administration of 100 ml of a solution according to Example 1 corresponds to the administration of 280 mg of BIII 890 per day.
"CAVASOL ~ W8 HP Pharma" is particularly preferred for the pharmaceutical composition according to the invention.
For the indications mentioned above it is essential that the dosage is easily controlled so as to ensure that steady-state plasma levels are safely maintained. BIII 890 is therefore conveniently administered by parenteral route.
Apart from the active substance and the cyclodextrin derivative the pharmaceutical compositions according to the invention intended for parenteral administration may contain hydroxy acids such as for example malic acid, lactic acid, tartaric acid or citric acid. They may optionally also contain conventional excipients and carriers such as for example the isotonic agents glucose, mannitol or sodium chloride or sodium acetate or sodium acetate trihydrate as a buffer combined with acetic acid or a citric acid/phosphate buffer consisting e.g. of citric acid and disodium hydrogen phosphate or disodium hydrogen phosphate-dihydrate. The solvent used is normally water for injections.
The individual embodiments of the invention will be explained in more detail hereinafter.
Complexingi the active substance with cyclodextrins Suitable cyclodextrins include for example substituted ~3-cyclodextrin (consisting of 7 glucopyranose units), hydroxypropyl-~3-cyclodextrin (HP~CD), sulphobutylether-~-cyclodextrin (SBE~3CD), y-cyclodextrin (consisting of 8 glucopyranose units) and hydroxypropyl-y-cyclodextrin (HPyCD).
Solubility experiments and'H-NMR spectra have surprisingly shown that y-cyclodextrin as well as hydroxypropyl-y-cyclodextrin (HPyCD), hydroxy-propyl-~3-cyclodextrin (HPf3CD) and sulphobutylether-f3-cyclodextrin (SBEf3CD) complex the hydrochloride of BIII 890.
Complexina the active substance with cyclodextrins and hydroxy acids Another embodiment of the invention relates to the complexing of the active substance or one of the salts thereof with cyclodextrins and hydroxy acids.
The amount of cyclodextrin required can be reduced by the formation of a ternary complex consisting of BIII 890, the cyclodextrin in question and a hydroxy acid. The suitable cyclodextrins include, for example, hydroxypropyl-~-cyclodextrin (HPaCD), sulphobutylether-~-cyclodextrin (SBE~3CD), y-cyclodextrin and hydroxypropyl-y-cyclodextrin (HPyCD). Suitable hydroxy acids include for example malic acid, lactic acid, tartaric acid and citric acid.
One embodiment according to the invention of a parenteral preparation of BIII
890 or one of the physiologically acceptable salts thereof, such as e.g. the hydrochloride, contains the active substance in doses of 1 mg/kg of body weight to 30 mg/kg of body weight per day, preferably in the range from 3-15 mg/kg of body weight. The amounts, concentrations and dosages specified relate in each case to the active substance base regardless of whether BIII
890 is used in the form of the "base" (= compound of the formula given on page 1 ) or in the form of one of the pharmacologically acceptable salts thereof.
The preparation is preferably administered by continuous infusion over 24 hours or optionally several days in order to maintain a steady-state plasma level. The volumes administered are in the range from 50 to 500 ml, preferably 100 to 250 ml, i.e. the concentrations for administration of the active substance are in the range from 150 mg/500 ml = 0.3 mg/ml (0.03 %) to 1500 mg/100 ml = 15 mg/ml (1.5 %). An active substance concentration of 0.5 mg/ml = 0.05 % (g/v) to 3.5 mg/ml = 0.35 % (g/v) is preferred.
The molar ratio of active substance to cyclodextrin is between 1:1 and 1:5 according to the invention. A molar ratio of 1 : 2.5 to 1 : 3.5 is preferred.
In the presence of hydroxy acid the molar ratio of active substance to cyclodextrin is between 1 : 0.5 and 1 : 3 according to the invention; a molar ratio of 1 : 0.5 to 1 : 1.5 is preferred.
The following Examples are intended to illustrate the invention in more detail:
EXAMPLES
Example 1:
Solution for infusions/injection containing a hydroxypropyl-y-cyclodextrin complex BIII 890 hydrochloride 767 mg*
HpyCD**) 10000 mg mannitol 11000 mg acetic acid 99% 125.25 mg sodium acetate trihydrate 56.5 mg water for injections ad 250 ml *) corresponds to 700 mg BIII 890 in the form of the base **) for example "CAVASOL ~ W8 HP Pharma" sold by Wacker Example 2:
Solution for infusion/injection containing a y-cyclodextrin complex BIII 890 CL 383.5 mg***
YCD 5000 mg NaCI 2250 mg water for injections ad 250 ml ***) corresponds to 350 mg BIII 890 in the form of the base Example 3:
Solution for infusion/injection containing a hydroxypropyl-~-cyclodextrin complex BIII 890 CL 767 mg*
HP~CD 7500mg mannitol 12500 mg acetic acid 99% 125.25 mg sodium acetate trihydrate 56.5 mg water for injections ad 250 ml *) corresponds to 700 mg BIII 890 in the form of the base Example 4:
Solution for infusion/injection containing a sulphobutylether-~-cyclodextrin complex BIII 890 CL 767 mg*
SBE~iCD 5000 mg mannitol 12500 mg acetic acid 99% 125.25 mg sodium acetate trihydrate56.5 mg water for injections ad 250 ml *) corresponds to 700 mg BIII 890 in the form of the base Example 5:
Solution for infusion/injection containing a hydroxypropyl-y-cyclodextrin complex in the presence of hydroxy acids BIII 890 CL 767 mg*
HPyCD 2500 mg citric acid 708 mg mannitol 12500 mg acetic acid 99% 125.25 mg sodium acetate trihydrate56.5 mg water for injections ad 250 ml *) corresponds to 700 mg BIII 890 in the form of the base Example 6:
Solution for infusion/injection containing a Y-cyclodextrin complex in the presence of a hydroxy acid BIII 890 CL 767 mg*
yCD 2500 mg tartaric acid 138.25 mg NaCI 2250 mg water for injections 250 ml ad *) corresponds to 700 mg BIII 890 in the form of the base The quantity of active substance administered can be controlled by the administration of a specific volume of one of the solutions described above.
For example the daily administration of 100 ml of a solution according to Example 1 corresponds to the administration of 280 mg of BIII 890 per day.
Claims (31)
1. Pharmaceutical composition containing a cyclodextrin complex of BIII 890 or one of the pharmacologically acceptable salts thereof.
2. Pharmaceutical composition containing a ternary complex consisting of BIII
890 or one of the pharmacologically acceptable salts thereof, a cyclodextrin and a hydroxy acid.
890 or one of the pharmacologically acceptable salts thereof, a cyclodextrin and a hydroxy acid.
3. Pharmaceutical composition containing BIII 890 or one of the pharmacologically acceptable salts thereof in combination with a substituted or unsubstituted cyclodextrin.
4. Pharmaceutical composition according to one of claims 1 to 3, wherein the cyclodextrin is selected from the group consisting of .gamma.-CD, HP-.gamma.-CD, HP-.beta.-CD
and SBE-.beta.-CD.
and SBE-.beta.-CD.
5. Pharmaceutical composition according to one of claims 1 to 4, wherein HP-.gamma.-CD is used as the cyclodextrin.
6. Pharmaceutical composition according to one of claims 2, 4 or 5, wherein the hydroxy acid is selected from the group consisting of malic acid, lactic acid, tartaric acid and citric acid.
7. Pharmaceutical composition according to one of claims 2 to 6, wherein citric acid is used as the hydroxy acid.
8. Pharmaceutical composition according to one of claims 1 to 7, wherein the hydrochloride of BIII 890 is used as the active substance.
9. Pharmaceutical composition according to claim 3 containing the hydrochloride of BIII 890 and HP-.gamma.-CD.
10. Pharmaceutical composition according to claim 2 containing the hydrochloride of BIII 890, HP-.gamma.-CD and citric acid.
11. Pharmaceutical composition according to one of claims 1 to 10 for paren-teral administration.
12. Pharmaceutical composition according to one of the preceding claims, characterised in that it is intended for intravenous administration.
13. Pharmaceutical composition according to one of the preceding claims, characterised in that the concentration of active substance is between 0.3 mg/ml and 15 mg/ml.
14. Pharmaceutical composition according to one of the preceding claims, characterised in that the concentration of active substance is between 0.5 mg/ml and 3.5 mg/ml.
15. Pharmaceutical composition according to one of the preceding claims, characterised in that the molar ratio of active substance to cyclodextrin is between 1:1 and 1:5.
16. A complex of BIII 890 or one of the pharmacologically acceptable salts thereof with a cyclodextrin as complexing agent.
17. A complex according to claim 16, wherein the cyclodextrin is selected from the group consisting of .gamma.-CD, HP-.gamma.-CD, HP-.beta.-CD and SBE-.beta.-CD.
18. A complex of BIII 890 or one of the pharmacologically acceptable salts thereof with hydroxypropyl-.gamma.-cylcodextrin.
19. Use of a) a cyclodextrin complex or b) a cyclodextrin complex in the presence of a hydroxy acid for preparing a pharmaceutical composition containing BIII 890 or one of the pharmacologically acceptable salts thereof for the treatment of stroke.
20. Use of a substituted .gamma.-cyclodextrin for preparing a pharmaceutical composition containing BIII 890 or one of the pharmacologically acceptable acid addition salts thereof, particularly the hydrochloride thereof, for the treatment of stroke.
21. Use of HP-.gamma.-CD for preparing a pharmaceutical composition containing BIII 890 or one of the pharmacologically acceptable acid addition salts thereof, particularly the hydrochloride thereof, for the treatment of stroke.
22. Use of HP-.gamma.-CD and a hydroxy acid for preparing a pharmaceutical composition containing BIII 890 or one of the pharmacologically acceptable acid addition salts thereof, particularly the hydrochloride thereof, for the treatment of stroke.
23. Use according to claim 22, wherein the hydroxy acid is malic acid, lactic acid, tartaric acid or citric acid.
24. Use according to claim 22, wherein the hydroxy acid is tartaric acid or malic acid.
25. Use according to one of claims 19 to 24, characterised in that the pharmaceutical composition is intended for intravenous administration.
26. Use according to one of claims 19 to 25, characterised in that the concentration of active substance is between 0.3 mg/ml and 15 mg/ml.
27. Use according to one of claims 19 to 25, characterised in that the concentration of active substance is between 0.5 mg/ml and 3.5 mg/ml.
28. Use according to one of claims 19 to 25, characterised in that the molar ratio of active substance to cyclodextrin is between 1:1 and 1:5.
29. Use of the pharmaceutical composition according to one of claims 1 to 15 for the treatment of acute stroke.
30. Process for the treatment of acute stroke, characterised in that a pharmaceutical composition according to one of claims 1 to 15 is used.
31. Process for preparing a pharmaceutical composition for parenteral administration for the treatment of stroke containing BIII 890 or one of the pharmacologically acceptable salts thereof, characterised in that the active substance is present in the form of a) a cyclodextrin complex or b) a cyclodextrin complex in the presence of a hydroxy acid.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10223783A DE10223783A1 (en) | 2002-05-29 | 2002-05-29 | New formulation for parenteral administration of a Na-channel blocker |
| DE10223783.2 | 2002-05-29 | ||
| PCT/EP2003/005399 WO2003099336A1 (en) | 2002-05-29 | 2003-05-23 | Formulation for parenteral administration of sodium channel blockers |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2487150A1 true CA2487150A1 (en) | 2003-12-04 |
Family
ID=29432393
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002487150A Abandoned CA2487150A1 (en) | 2002-05-29 | 2003-05-23 | New formulation for parental application of sodium channel blocker |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP1511517B1 (en) |
| JP (1) | JP2005527615A (en) |
| AR (1) | AR040134A1 (en) |
| AT (1) | ATE373492T1 (en) |
| AU (1) | AU2003237664A1 (en) |
| CA (1) | CA2487150A1 (en) |
| DE (2) | DE10223783A1 (en) |
| ES (1) | ES2294295T3 (en) |
| PE (1) | PE20040066A1 (en) |
| TW (1) | TW200400029A (en) |
| UY (1) | UY27823A1 (en) |
| WO (1) | WO2003099336A1 (en) |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4239877C1 (en) * | 1992-11-27 | 1994-03-17 | Boehringer Ingelheim Int | Stabilized superoxide dismutase (SOD) composition |
| DE4313408A1 (en) * | 1993-04-23 | 1994-10-27 | Boehringer Mannheim Gmbh | Cyclodextrin-biocid complex |
| FR2713934B1 (en) * | 1993-12-22 | 1996-01-12 | Commissariat Energie Atomique | Use of amino cyclodextrins for the aqueous solubilization of hydrophobic compounds, in particular of pharmaceutically active molecules. |
| DE19740110A1 (en) * | 1997-09-12 | 1999-03-18 | Boehringer Ingelheim Pharma | New hydroxy substituted benzomorphan derivatives |
| WO2002007772A2 (en) * | 2000-07-24 | 2002-01-31 | Boehringer Ingelheim Pharmaceuticals, Inc. | Improved oral dosage formulations |
| DE10223784A1 (en) * | 2002-05-29 | 2003-12-11 | Boehringer Ingelheim Pharma | New formulation for parenteral administration of crobenetine |
-
2002
- 2002-05-29 DE DE10223783A patent/DE10223783A1/en not_active Withdrawn
-
2003
- 2003-05-23 CA CA002487150A patent/CA2487150A1/en not_active Abandoned
- 2003-05-23 JP JP2004506859A patent/JP2005527615A/en active Pending
- 2003-05-23 DE DE50308227T patent/DE50308227D1/en not_active Expired - Fee Related
- 2003-05-23 AU AU2003237664A patent/AU2003237664A1/en not_active Abandoned
- 2003-05-23 WO PCT/EP2003/005399 patent/WO2003099336A1/en active IP Right Grant
- 2003-05-23 AT AT03735445T patent/ATE373492T1/en not_active IP Right Cessation
- 2003-05-23 EP EP03735445A patent/EP1511517B1/en not_active Expired - Lifetime
- 2003-05-23 ES ES03735445T patent/ES2294295T3/en not_active Expired - Lifetime
- 2003-05-27 PE PE2003000511A patent/PE20040066A1/en not_active Application Discontinuation
- 2003-05-27 UY UY27823A patent/UY27823A1/en not_active Application Discontinuation
- 2003-05-28 TW TW092114414A patent/TW200400029A/en unknown
- 2003-05-28 AR ARP030101863A patent/AR040134A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| DE50308227D1 (en) | 2007-10-31 |
| ATE373492T1 (en) | 2007-10-15 |
| JP2005527615A (en) | 2005-09-15 |
| TW200400029A (en) | 2004-01-01 |
| AU2003237664A1 (en) | 2003-12-12 |
| EP1511517A1 (en) | 2005-03-09 |
| DE10223783A1 (en) | 2003-12-11 |
| ES2294295T3 (en) | 2008-04-01 |
| PE20040066A1 (en) | 2004-03-22 |
| WO2003099336A1 (en) | 2003-12-04 |
| EP1511517B1 (en) | 2007-09-19 |
| UY27823A1 (en) | 2003-12-31 |
| AR040134A1 (en) | 2005-03-16 |
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| FZDE | Discontinued |