EP1499636A2 - Peptides neurotrophes et neuroprotecteurs - Google Patents

Peptides neurotrophes et neuroprotecteurs

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Publication number
EP1499636A2
EP1499636A2 EP03707885A EP03707885A EP1499636A2 EP 1499636 A2 EP1499636 A2 EP 1499636A2 EP 03707885 A EP03707885 A EP 03707885A EP 03707885 A EP03707885 A EP 03707885A EP 1499636 A2 EP1499636 A2 EP 1499636A2
Authority
EP
European Patent Office
Prior art keywords
peptides
prepared
administration
medicament
disease
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Withdrawn
Application number
EP03707885A
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German (de)
English (en)
Inventor
Manfred Windisch
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
JSW-Research Forschungslabor GmbH
JSW Research Forschungslabor GmbH
Original Assignee
JSW-Research Forschungslabor GmbH
JSW Research Forschungslabor GmbH
Priority date (The priority date 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 date listed.)
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Application filed by JSW-Research Forschungslabor GmbH, JSW Research Forschungslabor GmbH filed Critical JSW-Research Forschungslabor GmbH
Publication of EP1499636A2 publication Critical patent/EP1499636A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0819—Tripeptides with the first amino acid being acidic
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06043—Leu-amino acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/101—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/1013—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1019—Tetrapeptides with the first amino acid being basic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1021—Tetrapeptides with the first amino acid being acidic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present invention relates to peptides of 4 to 14 amino acids in length.
  • the peptides according to the invention can be used as active ingredients in medicaments for the treatment of degenerative diseases of the central nervous system, such as Alzheimer's disease, Lewy body dementia, Parkinson's disease, Huntington's disease (chorea), multisystem atrophy and other similar diseases.
  • degenerative diseases of the central nervous system such as Alzheimer's disease, Lewy body dementia, Parkinson's disease, Huntington's disease (chorea), multisystem atrophy and other similar diseases.
  • Alzheimer's disease In neurodegenerative diseases, aggregates of proteins in the brain generally appear as a common feature. In the case of Alzheimer's disease, it is the so-called senile plaques, extracellular protein deposits, which consist primarily of amyloid beta peptides, and the so-called neurofibrillary tangles, intracellular protein knuckles made of hyperphosphorylated tau protein. In Parkinson's disease there are intracellular emptying bodies consisting of aggregated alpha-synuclein. According to the latest scientific findings, such bodies, namely Lewy Bodies, were also found in more than 70% of familial and sporadic Alzheimer's sufferers, and they can also be found in patients suffering from Down syndrome.
  • Some of the sufferers have mutated proteins that have a particularly pronounced aggregation behavior. In the majority of patients, however, the aggregates consist of normal wild-type proteins. Various causes are assumed which suddenly change the solubility behavior of the proteins, whereby, for example, increased oxidative stress could play an important role during the aging process. Changes in the capacity of various protein-degrading enzymes can also be considered as a cause, since malfunctions can result in incorrectly modified proteins, which are then deposited and can no longer be processed by different disposal enzymes.
  • Another triggering pathophysiological mechanism consists in a disturbed balance between aggregatic and anti-aggregate proteins.
  • other representatives of this protein family include gamma-synuclem and beta-synuclem, as well as the recently discovered synoretin (Surgurchov et al., Mol. Cell. Neurosci. 13 (2): 95-103 [1999]).
  • beta-synuclein a very close relative of alpha-synuclein, is able to inhibit the aggregation of alpha-synuclein in a dose-dependent manner (Hashimoto et al., Neuron 32 (2): 213- 23 [2001]).
  • Experiments in cell cultures in which a disturbance in normal cell proliferation and differentiation was triggered by overexpression of alpha-synuclem also showed a therapeutic effect of beta-synuclein, which normalized the attachment, survival and outgrowth of neurites in these cultures.
  • mice that are transgenic for alpha-synuclem show an increased production of this protein and therefore have a disturbed ratio in the amounts between alpha and beta-synuclein. Over the course of their age, they form intraneuronal embryos similar to the Lewy Bodies and also show progressive motor disorders that are comparable to the functional disorder in Parkinson's disease. If these animals are crossed with beta-synuclein transgenic animals which show an increased expression of this protein, homeostasis can be restored at a much higher level in the total expression of the synucleins. As a result, the number of emptying bodies is reduced significantly and the characteristic loss of neuronal function is completely prevented.
  • Alpha-Synuclem was also allowed to play a particularly important role in the pathology of Alzheimer's disease. This is supported by the fact that a part of this protein, the NACP (non-amyloid component protein) domain, could be detected as part of the senile plaques (Yoshimoto et al., Proc. Natl. Acad. Sei 92, 9141-5 [1995 ] and WO-9506407), and also the fact that - as mentioned above - about 70% of Alzheimer's sufferers have Lewy Bodies in various areas of the brain, which also contain alpha-synuclein (Eizo et al., Neurosci. Lett. 290 (1), 41-4 [2000]).
  • beta-amyloid increases the accumulation and neurotoxicity of alpha-synuclein (Masliah et al., Proc. Natl. Acad. Sci 98 (21): 12245-50 [2001]).
  • alpha-synuclein as a synaptic protein could play an important role in the initial synaptic degeneration and thus play a key role in the pathogenesis.
  • beta-synuclein and in particular peptides derived therefrom in connection with alpha-synuclein is known, see, for example, octapeptides according to WO-A-02/04482 and three others
  • WO-A-002/0020 and WO-A-01/60794 describe the use of beta-synuclein as a whole molecule or of methods which increase its expression in vivo for the therapy of neurological diseases associated with alpha-synuclein
  • WO-A-01/60794 does not provide any Evidence of an actual protective effect of this peptide on living, neuronal cells and contains no evidence of other effective peptides in this sequence region.
  • shorter peptides were very advantageous for use as pharmaceuticals, since the problems of chemical and biological stability and bioavailability generally decrease significantly with decreasing chain length.
  • the object of the present invention is to avoid the disadvantages known from the prior art.
  • peptides are proposed which are from the group
  • peptides according to the invention are derived from the N-terminal sequence of the beta synuclein and antagonize the influence of toxic or vitality-damaging noxae, such as are present in neurodegenerative diseases.
  • peptides whose individual components are L-amino acids, but also peptides whose individual components are D-amino acids are within the scope of the invention. Also considered in the context of the invention are N- or C-terminally modified peptides.
  • the invention further relates to medicaments which contain the peptides according to the invention as active pharmaceutical ingredients.
  • the peptides of the invention can be synthesized in a variety of ways.
  • Chemical synthesis of a peptide is a conventional process and can be achieved, for example, by the Memfield solid phase synthesis technique (Memfield, J., Am. Ch ⁇ m. Soc, 85: 2149-2154 [1963]; Kent et al., Syntheti c Pepti des n Bi ology and Medi ane, 29 ff eds.Alitalo et al., Elsevier Science Publishers 1985; Haug, JD Peptide Synthesis and the protecting group strategy, Ameri can Bi otechnology Laboratory, 5 (1): 40-47 [1987 ]).
  • Chemical peptide synthesis methods also include the use of automated peptide synthesizers using commercially available protected amino acids such as Biosearch (Model 9500 and 9600), Applied Biosystems Inc. (Model 430; Miligen (Model 9050) and others.
  • these can Peptides are produced in cells of bacteria, fungi or mammals using recombinant technology and purified using conventional methods.
  • Cysteinyl residues can also be obtained by reaction with bromot ⁇ fluoroacetone, alpha-bromo-beta (5-imidozoyl) propionic acid, chloroacetyl-phosphate, N-alkylmalemides, 3-nitro2-pyridyldisulfide, methyl-2-pyridyldi-sulfide, p-chloromerkuribenzo Chloromeric 4-nitrophenol or chloro-7-nitrobenzo-2-oxa-1,3-diazole are de-vatized.
  • amino acid histidm can also be easily derivatized by reaction with diethylprocarbonate at a pH of 5.5 - 7, as this substance is relatively specific for the histidyl side chain.
  • Parabromophenacyl bromide is also an option, the reaction preferably being carried out in 0.1 molar sodium cacodylate at pH 6.0.
  • Lys and amino terminal residues can also be derivatized with succinate or other carboxylic acid anhydrides.
  • the reaction with these agents has the effect of reversing the charge on the lysinyl residue.
  • suitable reagents for the derivatization of residues containing alphaammo include imido esters such as methyl bicolinimidate, py ⁇ doxal phosphate, py ⁇ doxal, chloroborohyd ⁇ d, trinitrobenzenesulfonic acid, O-methyl isourea, 2, 4 pentanedione and transaminase-catalyzed reactions with glyoxylate.
  • the arginyl residues can be modified by the reaction with one or more conventional reagents such as phenylglyoxal, 2,3-butanedione, 1,2-cyclohexanedione and ninhydrin.
  • the derivatization of the arginyl residues requires that the reaction be carried out under alkaline conditions because of the high PK value of the guanidine group.
  • these reagents can also react with groups of the Lysm, as well as with the Arginine-Epsilon Ammo group.
  • Tyrosyl residues are known targets for the introduction of spectral labels by the reaction with aromatic diazonium substances or tetranitromethane.
  • aromatic diazonium substances or tetranitromethane Most commonly, N-acetylimidizole and tetranitromethane are used to make O-acetyltyrosil and 3- To produce nitroderivatives.
  • Such derivatizations can serve to improve solubility, absorption, biological half-life and the like. Alternatively, the derivatizations could also serve to minimize any undesired side effects of the proteins.
  • one day old, fertilized chicken eggs are incubated at +12 +/- 0.1 ° C and 80 +/- 5% humidity for eight days.
  • the eggs are transferred to an incubation incubator and incubated until embryonic day 8 at 38 +/- 0, 5 ° C and 55 +/- 5%.
  • the cortices are isolated, homogenized and neurons taken into primary culture (culture conditions: Dulbecco's Modified Eagle's Medium, 20% v / v fetal calf serum, 0.01% gentamycin, 1 g / 1 glucose, 2 mM L-glutamate, + 37 ° C, 5% C0 2 and 95% humidity).
  • the peptide to be tested is added (final concentrations from 1.56 to 200 ⁇ M) and the specified noxa is carried out. A damaged control and a vehicle control are carried out with each attempt. After the specified stress period has elapsed, the proportion of neurons still alive is determined using a metabolic colorimetric assay (the yellow chromophore MTT is only converted to a blue formazan product by living cells).
  • Example 2 Chronic calcium metabolism disorder caused by ionomycin It is believed that various neurodegenerative diseases result in chronic calcium overload due to metabolic malfunctions, which ultimately causes cell death through the activation of various enzyme systems. In the present model, this damage is induced by adding ionomycin in a methanolic solution (final concentration: 10 ⁇ M) over a period of 24 hours. Methanol, diluted in medium, serves as a vehicle control.
  • Beta-amyloid - peptides in aggregate form represent a potent neurotoxin, the addition of which to nerve cell cultures leads to rapid and progressive cell death. Since beta-amyloid peptides play an essential role in the pathogenesis of Alzheimer's disease, this model is to be regarded as particularly relevant.
  • the present biological test is a method for testing anti-aggregatory substance potential specially developed for this project.
  • the newly synthesized peptides are added directly to a fresh solution of amyloid beta peptides to prevent the formation of neurotoxic aggregates.
  • the effect of aggregates that still arise on the growth and survival of nerve cell cultures is the measurement parameter.
  • ß-A beta-amyloid peptide
  • phosphate-buffered cooking acid 1 mM
  • this solution is pipetted into the cultures at a final concentration of 20 ⁇ M and, after 24 hours of exposure, the proportion of living cells is determined as usual.
  • the compounds of the invention m therapeutically effective amounts administered in pharmaceutically acceptable carriers or solvents.
  • Such carriers include (but are not limited to) physiological saline, buffered saline, dextrose, water, glycine, ethanol, and combinations thereof.
  • the respective formulation should be adapted to the type of administration.
  • the composition can also contain different amounts of moisturizers or emulsifiers or pH-buffering substances.
  • the pharmaceutical composition can be a liquid solution, a suspension, an emulsion, a tablet, a pill, a capsule, a sustained-release formulation or a powder.
  • the preparation can also be produced as a supplement with traditional binders and carriers such as triglycerides.
  • Oral formulations can contain standard carriers such as mannitol, lactose, starch, magnesium sterate, sodium sacarin, cellulose, magnesium carbonate and others of pharmaceutical grade.
  • Various administration systems are known and can be used to ensure the therapeutic use of the substances according to the invention, e.g. encapsulation in liposomes, microparticles, microcapsules etc.
  • the dosage form is prepared in accordance with routine procedures as a pharmaceutical dosage form adapted for intravenous administration to humans or other mammals.
  • the compositions for intravenous administration are solutions in sterile isotonic aqueous buffer solution. If necessary, the preparation can also contain solubilizers and locally effective anesthetics to relieve the pain at the injection site.
  • the ingredients are either provided separately or mixed in a unit dose.
  • a dry lyophilized powder or anhydrous concentrate in a hermetically sealed container such as an ampoule, on which the amount of the active pharmaceutical is noted.
  • the dosage form has to be administered as an infusion, it can be dissolved in an infusion bottle containing sterile water or saline solution of pharmaceutical grade. Whenever the preparation is given by injection, one can Ampoules with sterile water for injections or saline are made available in such a way that the individual components can be mixed correctly before administration.
  • the therapeutic substances described in the invention can be formulated both as a neutral form and as a salt.
  • Pharmaceutically acceptable salts include those formed with the free amino groups, e.g. those derived from hydrochloric acid or oxalic acid and those formed with free carboxyl groups such as those derived from sodium, potassium, ammonium, calcium, iron oxides, isopropylamine, triethylamm, 2-ethyloaminoethanol, histidine, procaine and others.
  • the amount of therapeutic agent described in the invention must be effective for the treatment of the particular disease or condition, will depend on the nature of the disease or condition, and will be determined by standardized clinical procedures.
  • the exact dose to be used in the invention also depends on the mode of administration and the severity of the disease or disorder, and this amount should be adjusted according to the experienced physician, taking into account the specific patient circumstances.
  • Suitable dosage ranges for intravenous administration are generally between 20-4,000 ⁇ g of the active ingredient per kg of body weight.
  • Suitable dosages for intranasal applications range from 0.01 pg per kg body weight to 1 mg per kg body weight.
  • Effective dosages for oral applications are in the range of 1 mg to 1,000 mg per kg body weight and day.
  • the effective doses are extrapolated from dose-response curves derived from in vitro models or animal model test systems.

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  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne de nouveaux peptides dont les composants individuels sont des L-aminoacides ou des D-aminoacides. Ces peptides sont utilisés en tant que principes actifs dans des médicaments pour le traitement de maladies dans lesquelles l'augmentation de l'apparition de radicaux libres joue un rôle pathophysiologique, ou bien pour le traitement de maladies impliquant une hypoxie aiguë ou une ischémie dans un système organique du corps, en particulier dans le système nerveux central, ou pour le traitement de maladies liées au stockage du fer telles que la maladie de Hallervorden-Spatz, ou bien pour le traitement de maladies neurodégénératives, en particulier de la maladie d'Alzheimer, de la variante à corps de Lewy de la maladie d'Alzheimer, de la maladie de Parkinson, de l'atrophie multisystémique, de la démence à corps de Lewy, de la chorée de Huntington, et de tous les syndromes similaires auxdites maladies dégénératives.
EP03707885A 2002-03-28 2003-03-10 Peptides neurotrophes et neuroprotecteurs Withdrawn EP1499636A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
AT2002495 2002-03-28
AT0049502A AT500282A3 (de) 2002-03-28 2002-03-28 Neurotrophe und neuroprotektive peptide
PCT/AT2003/000065 WO2003082906A2 (fr) 2002-03-28 2003-03-10 Peptides neurotrophes et neuroprotecteurs

Publications (1)

Publication Number Publication Date
EP1499636A2 true EP1499636A2 (fr) 2005-01-26

Family

ID=28458152

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03707885A Withdrawn EP1499636A2 (fr) 2002-03-28 2003-03-10 Peptides neurotrophes et neuroprotecteurs

Country Status (8)

Country Link
US (1) US20060036073A1 (fr)
EP (1) EP1499636A2 (fr)
JP (1) JP2006508022A (fr)
AT (1) AT500282A3 (fr)
AU (1) AU2003212074A1 (fr)
CA (1) CA2480633A1 (fr)
NZ (1) NZ535623A (fr)
WO (1) WO2003082906A2 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK1778637T3 (da) * 2004-06-29 2012-06-18 Aventis Pharma Inc FKBP-bindingssammensætninger og farmaceutisk anvendelse deraf
WO2007126111A1 (fr) * 2006-04-28 2007-11-08 Kagoshima University PEPTIDE POUVANT INHIBER LA FIBROSE AMYLOIDE-β
AT504553B1 (de) * 2006-12-06 2008-09-15 Jsw Res Forschungslabor Gmbh Peptidomimetika aus rechtsdrehenden aminosäuren sowie diese enthaltende arzneimittel zur behandlung von neurodegenerativen erkrankungen
PL2406279T3 (pl) 2009-03-09 2016-07-29 Univ Ramot Kompozycje do zapobiegania i leczenia chorób neurodegeneratywnych.
JP5664992B2 (ja) * 2009-08-26 2015-02-04 国立大学法人名古屋大学 細胞特異的ペプチド及びその用途

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US20060036073A1 (en) 2006-02-16
AT500282A3 (de) 2006-06-15
AU2003212074A1 (en) 2003-10-13
CA2480633A1 (fr) 2003-10-09
WO2003082906A2 (fr) 2003-10-09
AT500282A2 (de) 2005-11-15
JP2006508022A (ja) 2006-03-09
NZ535623A (en) 2007-03-30

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