Nerve cell differentiation promoter

Details Nerve cell differentiation promoter Nerve cell differentiation promoter

1996-11-13

1998-09-08

Witz, Jean C.

Drug, bio-affecting and body treating compositions

Fermentate of unknown chemical structure

Having a known elemental analysis

435 702, 435 704, 435170, 4352535, 435884, A61K 3574

Patent

active

058041869

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to a novel nerve cell differentiation promoter which comprises a physiologically active substance NK175203 or a pharmacologically acceptable salt thereof as an active ingredient and which is expected to be usable as, for example, a medicine for dementia, a nerve cell protective medicine or a medicine for peripheral neuropathy.


BACKGROUND ART

The physiologically active substance NK175203 is a publicly known compound described in International Patent Publication No. W094/05679.
It is reported that this compound has an activity as a bone marrow cell proliferation promoter.
It has been proved in vitro that a nerve growth factor (hereinafter referred to as NGF) elongates neurites, regulates the production of a neurotransmitter and exerts an effect on the regeneration of the nerve known that when NGF is added to an established cell line PC12 which has been cloned from a rat pheochromocytoma, the PC12 cell ceases the proliferation and differentiates into adrenergic neuron cells having neurites. Because of these effects, NGF has recently attracted attention as one of medicines for dementia. By using these cells, it has been clarified that a fibroblast growth factor and interleukin 6 induce the elongation of neurites similarly to NGF. Recently, it has been reported that staurosporine, which is a low molecular weight substance derived from 26, 200-220 (1987)!.
The staurosporine as described above is highly valuable in medical treatments, since it is a low molecular weight substance, different from NGF. However, it is regrettably considered that there is room for further inventigation in the practical application of the same due to its high toxicity.
Under these circumstances, it is highly important in medical treatments to provide a low molecular weight substance which has a lower toxicity and exhibits the effect of elongating neurites at a low concentration.


DISCLOSURE OF INVENTION

As the results of extensive studies, the present inventors have found out that a physiologically active substance NK175203 or a pharmacologically acceptable salt thereof has an activity for promoting the differentiation of nerve cells.
The present invention has thus been completed on the basis of this finding.
Accordingly, the present invention relates to a nerve cell differentiation promoter which comprises the physiologically active substance NK175203 or a pharmacologically acceptable salt thereof as an active ingredient together with pharmaceutically acceptable excipient(s) or carrier(s). The present invention further relates to a medicine for dementia, a nerve cell protective medicine and a medicine for peripheral neuropathy comprising the physiologically active substance NK175203 or a pharmacologically acceptable salt thereof as an active ingredient together with pharmaceutically acceptable excipient(s) or carrier(s).


BRIEF DESCRIPTION OF DRAWING

FIG. 1 shows the effect of NK175203 on improving the caudal nerve latency increased by the administration of an anticancer agent.
FIG. 2 shows the effect of NK175203 on improving the sensory nerve function (heat sensitivity) depressed by the administration of Adriamycin (ADM). FIG. 2a shows the test result on the 72nd day from the initiation of the experiment, while FIG. 2b shows the test result on the 85th day from the initiation of the experiment.


BEST MODE FOR CARRYING OUT THE INVENTION

The physiologically active substance NK175203 to be used in the present invention can be produced and obtained in accordance with the method described in International Patent Publication No. W094/05679.
More specifically, it can be obtained by culturing a microorganism belonging to a genus Streptomyces and producing the above-mentioned physiologically active substance NK175203 (for example, FERM BP-4372) in a medium, accumulating the physiologically active substance NK175203 in the culture and then collecting the same.
The physiologically active substance NK175203 which is the compound used in the present invention may be in the form of a pharmaco

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