EP1615631A2 - Verwendung von l-dopa, seiner derivate und diese verbindungen enthaltender arzneimittel zur prophylaxe psychotischer erkrankungen - Google Patents
Verwendung von l-dopa, seiner derivate und diese verbindungen enthaltender arzneimittel zur prophylaxe psychotischer erkrankungenInfo
- Publication number
- EP1615631A2 EP1615631A2 EP03785594A EP03785594A EP1615631A2 EP 1615631 A2 EP1615631 A2 EP 1615631A2 EP 03785594 A EP03785594 A EP 03785594A EP 03785594 A EP03785594 A EP 03785594A EP 1615631 A2 EP1615631 A2 EP 1615631A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- dopa
- derivatives
- physiologically tolerable
- tolerable salts
- prophylaxis
- 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- Withdrawn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
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 title claims abstract description 35
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 208000028017 Psychotic disease Diseases 0.000 title claims abstract description 16
- 238000011321 prophylaxis Methods 0.000 title claims abstract description 15
- 239000003814 drug Substances 0.000 title claims description 8
- 150000001875 compounds Chemical class 0.000 title description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 37
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- 108010035075 Tyrosine decarboxylase Proteins 0.000 claims abstract description 10
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- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229960004940 sulpiride Drugs 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000002700 tablet coating Substances 0.000 description 1
- 238000009492 tablet coating Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical group COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
- A61K31/175—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine having the group, >N—C(O)—N=N— or, e.g. carbonohydrazides, carbazones, semicarbazides, semicarbazones; Thioanalogues thereof
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- L-DOPA L-DOPA
- its derivatives and medicaments containing these compounds for the prophylaxis of psychotic diseases
- the invention relates to the use of 3, 4-dihydroxy-L-phenylalanine (L-DOPA) and its derivatives for the manufacture of medicaments and their use for the prophylaxis of psychotic diseases and for the treatment of diseases caused by disturbed tyrosine transport or tyrosine decarboxylase become.
- L-DOPA 3, 4-dihydroxy-L-phenylalanine
- the treatment of symptoms of schizophrenic diseases is currently usually carried out using neuroleptics such as chlorpromazine, haloperidol, sulpiride and their chemical relatives.
- neuroleptics such as chlorpromazine, haloperidol, sulpiride and their chemical relatives.
- the suspension of the treatment usually leads to a relapse of the patient.
- L-DOPA acts on the level of dopamine in the nerve cells of the brain. Unlike dopamine itself, it can cross the blood-brain barrier and is converted to dopamine in the brain.
- L-DOPA is usually administered in drugs with active additives.
- combinations of L-DOPA with peripheral decarboxylase inhibitors with inhibitors of catechol-O-methyltransferase (COMT), with inhibitors of monoamine oxidase (MAO) and inhibitors for dopamine- ⁇ -hydroxylase are used.
- CCT catechol-O-methyltransferase
- MAO monoamine oxidase
- Decarboxylase inhibitors used in this connection are, for example, D, L-serine-2- (2, 3, 4-trihydroxybenzyl) hydrazide (benserazide), (-) - La-hydrazino-3, 4-dihydroxy-a-methylhydrocinnamic acid (carbide-opa ), L-serine-2- (2, 3, 4-trihydroxybenzyl) hydrazide, glycine-2- (2, 3, 4-trihydroxybenzyl) hydrazide and L-tyrosine-2- (2, 3, 4-trihydroxybenzyl) hydrazide ,
- Examples of combination preparations made from L-DOPA and decarboxylase inhibitors include Madopar® (L-DOPA and benserazide
- COMT inhibitors examples include entacapone (Comtan®) and cabergoline and frequently used MAO inhibitors are selegiline hydrochloride, moclobemide and tranylcypromine.
- Calcium 5-butylpicolinate and calcium 5-pentylpicolinate are described as inhibitors for dopamine- ⁇ -hydroxylase (DE-A 2 049 115).
- use for relapse prophylaxis in psychotic diseases, in particular in schizophrenic diseases is preferred.
- L-DOPA can be used for the prophylaxis of psychotic diseases. This is all the more astonishing since psychotic disorders are known as side effects with high doses of L-DOPA.
- L-DOPA L-DOPA
- its derivatives and their physiologically tolerable salts in combination with an enzyme inhibitor or several enzyme inhibitors for the prophylaxis of psychotic diseases and for the treatment of diseases caused by disturbed tyro- sintransport or disturbed tyrosine decarboxylase.
- the enzyme inhibitor or the enzyme inhibitors are decarboxylase inhibitors and / or catechol-O-methyltransferase inhibitors and / or monoa inoxidase inhibitors and / or ⁇ -hydroxylase inhibitors.
- the decarboxylase inhibitor is selected from the group consisting of D, L-serine-2- (2, 3,4-trihydroxybenzyl) hydrazide (benserazide), (-) -La-hydrazino-3 , 4-dihydroxy-a-methylhydrocinnamic acid (carbidopa), L-serine-2- (2,3, 4-trihydroxybenzyl) ydrazide, glycine-2- (2, 3, 4-trihydroxybenzyl) hydrazide and L-tyrosine-2- (2, 3, 4-trihydroxybenzyl) hydrazide and their physiologically tolerable salts.
- catechol-O-methyltransferase inhibitor is selected from entacon and cabergoline and their physiologically tolerable salts.
- the monoamine oxidase inhibitor is selected from the group consisting of selegiline, moclobemide and tranylcypromine and their physiologically tolerable salts.
- the ⁇ -hydroxylase inhibitor is selected from calcium 5-butylpicolinate and calcium 5-pentylpicolinate and their physiologically tolerable salts.
- Another object of the invention is the use of L-DOPA, its derivatives and their physiologically questionable salts for the production of medicaments for the prophylaxis of psychotic diseases and for the treatment of treatment of diseases caused by impaired tyrosine transport or tyrosine decarboxylase.
- Another object of the present invention is a pharmaceutical composition which L-DOPA, its derivatives and their physiologically tolerable salts for the prophylaxis of psychotic diseases and for the treatment of diseases which are caused by disturbed tyrosine transport or disturbed tyrosine decarboxylase, in addition to pharmaceutically acceptable auxiliaries and additives , contains.
- a pharmaceutical composition which contains L-DOPA, its derivatives and their physiologically compatible salts for the prophylaxis of psychotic diseases and for the treatment of diseases which are caused by disturbed tyrosine transport or tyrosine decarboxylase and one or more enzyme inhibitors, in addition to pharmaceutically acceptable auxiliary substances, is particularly advantageous. and additives.
- composition in which the enzyme inhibitor or the enzyme inhibitors are decarboxylase inhibitors and / or catechol-O-
- Methyltransferase inhibitors and / or monoamine oxidase inhibitors and / or b-hydroxylase inhibitors are included in Methyltransferase inhibitors and / or monoamine oxidase inhibitors and / or b-hydroxylase inhibitors.
- the decarboxylase inhibitor is selected from the group consisting of D, L-serine-2- (2,3,4-trihydroxybenzyl) hydrazide (benserazide), (-) - La-hydrazino- 3, -dihydroxy-a-methylhydrocinnamic acid (carbide-opa), L-serine-2- (2, 3, 4-trihydroxybenzyl) hydrazide, glycine-2- (2, 3, -trihydroxybenzyl) hydrazide and L-tyrosine-2 - (2, 3, 4-trihydroxybenzyl) hydrazide and their physiologically tolerable salts.
- the decarboxylase inhibitor is selected from the group consisting of D, L-serine-2- (2,3,4-trihydroxybenzyl) hydrazide (benserazide), (-) - La-hydrazino- 3, -dihydroxy-a-methylhydrocinnamic acid (carbide-opa), L-
- Inhibitors are selected from entacapone and cabergoline and their physiologically tolerable salts.
- composition in which the monoamine oxidase inhibitor is selected from the group consisting of selegiline, moclobe id and tranylcypromine and their physiologically tolerable salts.
- ⁇ -hydroxylase inhibitor is selected from calcium 5-butyl picolinate and calcium 5-pentyl picolinate and their physiologically tolerable salts.
- physiologically compatible inorganic and organic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, oxalic acid, maleic acid, fumaric acid, lactic acid, tartaric acid, malic acid, citric acid, salicylic acid, adipic acid and Benzoic acid.
- Other acids that can be used are described, for example, in Progress in Pharmaceutical Research, vol. 10, pages 224-225, Birkhäuser Verlag, Basel and Stuttgart (1966) and Journal of Pharmaceutical Sciences, vol. 66, pages 1-5 (1977).
- the acid addition salts of L-DOPA and its derivatives are generally in a manner known per se by mixing the free base or its solutions with the corresponding acid or their solutions in an organic solvent, for example a lower alcohol such as methanol, ethanol, etc. -Propanol or isopropanol or a lower ketone such as acetone, methyl ethyl ketone or methyl isobutyl ketone or an ether such as diethyl ether, tetrahydrofuran or dioxane. Mixtures of the solvents mentioned can also be used for better crystal deposition.
- physiologically compatible aqueous solutions of acid addition salts of the compounds used according to the invention can be prepared in an aqueous acid solution.
- the acid addition salts of L-DOPA and its derivatives can be used in a manner known per se, e.g. B. with alkalis or ion exchangers, are converted into the free base. Additional salts can be obtained from the free base by reaction with inorganic or organic acids, in particular those which are suitable for forming therapeutically usable salts. These or other salts of the new compound, such as. B. the picrate, can also be used to purify the free base by converting the free base into a salt, separating it and releasing the base from the salt.
- the present invention also relates to medicaments for oral, buccal, sublingual, nasal, rectal, subeutan, intravenous or intramuscular application and for inhalation, which, in addition to conventional carriers and diluents, contain L-DOPA, a derivative or the acid addition salt thereof as an active ingredient.
- the medicaments of the invention are produced in a known manner with the customary solid or liquid carriers or diluents and the commonly used pharmaceutical technical adjuvants in accordance with the desired type of application with a suitable dosage.
- the preferred preparations are in a dosage form which is suitable for oral administration. Dosage forms of this type are, for example, tablets, lozenges, film-coated tablets, coated tablets, capsules, pills, powders, solutions, aerosols or suspensions or depot forms.
- parenteral preparations such as injection solutions are also suitable. Suppositories may also be mentioned as preparations.
- Corresponding tablets can be mixed, for example, by mixing the active ingredient with known auxiliaries, for example inert diluents such as dextrose, sugar, sorbitol, mannitol, polyvinylpyrrolidone, disintegrants such as corn starch or alginic acid, binders such as starch or gelatin, lubricants such as magnesium stearate or talc and / or agents Achieving a depot effect such as carboxyl polymethylene, carboxylmethyl cellulose, cellulose acetate phthalate or polyvinyl acetate can be obtained.
- auxiliaries for example inert diluents such as dextrose, sugar, sorbitol, mannitol, polyvinylpyrrolidone, disintegrants such as corn starch or alginic acid, binders such as starch or gelatin, lubricants such as magnesium stearate or talc and / or agents Achieving a depot effect such
- Coated tablets also for controlled or delayed release preparation forms, can accordingly be produced by coating cores produced analogously to the tablets with agents commonly used in tablet coatings, for example polyvinylpyrrolidone or shellac, gum arabic, talc, titanium dioxide or sugar.
- the coated tablet can also consist of several layers exist, wherein the excipients mentioned above for the tablets can be used.
- Solutions or suspensions with the active ingredient used according to the invention can additionally taste-improving agents such as saccharin, cyclamate or sugar and z.
- B. contain flavorings such as vanillin or orange extract. They can also contain suspending agents such as sodium carboxymethyl cellulose or preservatives such as p-hydroxybenzoates.
- Capsules containing active ingredients can be produced, for example, by mixing the active ingredient with an inert carrier such as milk sugar or sorbitol and encapsulating it in gelatin capsules.
- Suitable suppositories can be produced, for example, by mixing them with carriers such as neutral fats or polyethylene glycol or their derivatives.
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Emergency Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10261808A DE10261808A1 (de) | 2002-12-19 | 2002-12-19 | Verwendung von L-DOPA, seiner Derivate und diese Verbindungen enthaltender Arzneimittel zur Prophylaxe psychotischer Erkrankungen |
PCT/DE2003/004204 WO2004056306A2 (de) | 2002-12-19 | 2003-12-18 | Verwendung von l-dopa, seiner derivate und diese verbindungen enthaltender arzneimittel zur prophylaxe psychotischer erkrankungen |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1615631A2 true EP1615631A2 (de) | 2006-01-18 |
Family
ID=32478131
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP03785594A Withdrawn EP1615631A2 (de) | 2002-12-19 | 2003-12-18 | Verwendung von l-dopa, seiner derivate und diese verbindungen enthaltender arzneimittel zur prophylaxe psychotischer erkrankungen |
Country Status (10)
Country | Link |
---|---|
EP (1) | EP1615631A2 (de) |
JP (1) | JP2006511558A (de) |
CN (1) | CN1756542A (de) |
AU (1) | AU2003294664A1 (de) |
CA (1) | CA2513077A1 (de) |
DE (1) | DE10261808A1 (de) |
EA (1) | EA200500957A1 (de) |
MX (1) | MXPA05006409A (de) |
PL (1) | PL377524A1 (de) |
WO (1) | WO2004056306A2 (de) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE0401842D0 (sv) * | 2004-07-12 | 2004-07-12 | Dizlin Medical Design Ab | Infusion and injection solution of levodopa |
EA017983B1 (ru) * | 2006-02-17 | 2013-04-30 | Бедс Фарма Гмбх Беролина Инновейтив Ресёч Энд Девелопмент Сёвисиз | Дейтерированные производные катехоламина и лекарственные средства, содержащие указанные соединения |
CN105078952A (zh) * | 2015-08-10 | 2015-11-25 | 中国康复研究中心 | 一种左旋多巴制剂及其应用 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS52102431A (en) * | 1976-02-25 | 1977-08-27 | Kyowa Hakko Kogyo Co Ltd | Remedies for mental disorder |
CA1161451A (en) * | 1977-07-01 | 1984-01-31 | Brian W. Metcalf | .alpha.-ACETYLENIC AMINO ACIDS |
US5149786A (en) * | 1989-10-12 | 1992-09-22 | Chiron Corporation | Dopamine releasing protein and antibody |
-
2002
- 2002-12-19 DE DE10261808A patent/DE10261808A1/de not_active Ceased
-
2003
- 2003-12-18 EP EP03785594A patent/EP1615631A2/de not_active Withdrawn
- 2003-12-18 EA EA200500957A patent/EA200500957A1/ru unknown
- 2003-12-18 AU AU2003294664A patent/AU2003294664A1/en not_active Abandoned
- 2003-12-18 JP JP2004561055A patent/JP2006511558A/ja active Pending
- 2003-12-18 WO PCT/DE2003/004204 patent/WO2004056306A2/de not_active Application Discontinuation
- 2003-12-18 CN CNA2003801066148A patent/CN1756542A/zh active Pending
- 2003-12-18 PL PL377524A patent/PL377524A1/pl not_active Application Discontinuation
- 2003-12-18 CA CA002513077A patent/CA2513077A1/en not_active Abandoned
- 2003-12-18 MX MXPA05006409A patent/MXPA05006409A/es unknown
Non-Patent Citations (1)
Title |
---|
See references of WO2004056306A3 * |
Also Published As
Publication number | Publication date |
---|---|
EA200500957A1 (ru) | 2006-02-24 |
WO2004056306A2 (de) | 2004-07-08 |
WO2004056306A3 (de) | 2004-11-11 |
DE10261808A1 (de) | 2004-07-08 |
CN1756542A (zh) | 2006-04-05 |
AU2003294664A1 (en) | 2004-07-14 |
PL377524A1 (pl) | 2006-02-06 |
CA2513077A1 (en) | 2004-07-08 |
MXPA05006409A (es) | 2006-05-31 |
JP2006511558A (ja) | 2006-04-06 |
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