Procollagen (III) Propeptides and Related Substances for Treating Fibrotic Diseases
OwnerElmar Reinhold Burchardtinventor
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Abstract
A medicament for treating or preventing fibrotic diseases contains an antifibrotic substance that is a (poly) peptide having antifibrotic activity and comprising at least one of an N-terminal procollagen (III) propeptide and a C-terminal procollagen (III) propeptide, or a fragment of the (poly) peptide defined having antifibrotic activity or a derivative of the (poly) peptide having antifibrotic activity. The antifibrotic substance is combined with a pharmaceutically tolerable carrier or dilutant.
Claims7
A medicament comprising:
- A) an antifibrotic substance selected from the group consisting of:
- a) a (poly) peptide having antifibrotic activity and being selected from the group consisting of at least one of an N-terminal procollagen (III) propeptide and a C-terminal procollagen (III) propeptide;
- b) a fragment of the (poly) peptide defined under a) having the antifibrotic activity;
- and
- c) a derivative of the (poly) peptide defined under a) having the antifibrotic activity;
- B) a pharmaceutically tolerable carrier or dilutant.
A method of producing at least one of a renatured N-terminal procollagen (III) propeptide and a renatured C-terminal procollagen (III) propeptide, comprising the steps of:
- a) producing inclusion bodies in E. coli, wherein the inclusion bodies are dissolved in a 0.5 to 8 M denaturing buffer;
- b) pipetting the buffer of step a) dropwise into a limited dilution buffer, buffered around neutral pH and containing L-arginine in a final concentration between 200 to 1,000 nM and a disulifide bridge-reducing coupled redox system, until a volume ratio of maximally 1:3 is reached of the denaturing buffer and the limited dilution buffer, respectively;
- c) dialyzing the buffer mixture of step b) for at least 2 hours against a physiological buffer that contains L-arginine at a final concentration of 50 to 200 nM and a disulifide bridge-reducing coupled redox system;
- d) dialyzing the buffer mixture of step c) for at least 2 hours against a physiological buffer that contains a disulfide bridge-reducing coupled redox system;
- e) dialyzing the buffer mixture according to step d) against a physiological buffer for at least 2 hours.
Dependencies are inferred from the claim text.