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Methods of treatment and pharmaceutical compositions using bcn057 or bcn512

a technology of bcn057 and bcn512, applied in the direction of macromolecular non-active ingredients, organic active ingredients, dispersed delivery, etc., can solve the problems of dna deletion, genetic instability, and compound not practical countermeasures for radiation incident, etc., to achieve the effect of increasing hematopoiesis

Inactive Publication Date: 2018-04-19
BCN BIOSCI LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a method of increasing hematopoiesis (the production of blood cells) in subjects with leukemia, AML, ALL, bone marrow ablation, or other related disorders. The method involves administering a therapeutically effective amount of BCN057, BCN512, or an analog thereof. The patent also describes methods of inhibiting cancer cell growth, preventing late effects of clinical radiation, treating fibrosis, improving wound healing, and using pharmaceutical compositions of BCN057 and BCN512. The technical effects of the patent include increasing blood cell production, inhibiting cancer cell growth, and treating fibrotic diseases.

Problems solved by technology

Because of this, these compounds are not practical countermeasures for a radiation incident.
Fundamental to radiation exposure and injury are DNA strand breaks, resulting in genetic instability and DNA deletions which are involved in cell death, cellular dysfunction, as well as longer term consequences such as birth defects and cancer.

Method used

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  • Methods of treatment and pharmaceutical compositions using bcn057 or bcn512
  • Methods of treatment and pharmaceutical compositions using bcn057 or bcn512
  • Methods of treatment and pharmaceutical compositions using bcn057 or bcn512

Examples

Experimental program
Comparison scheme
Effect test

example 1

ll Growth Inhibition

[0189]A cancer cell survival profile on multiple leukemia cell lines was conducted on BCN057 as described in Monks, A.; Scudiero, D. A.; Skehan, P.; Shoemaker, R. H.; Paull, K. D.; Vistica, D. T.; Hose, C.; Langley, J.; Cronice, P.; Vaigro-Wolf, M.; Gray-Goodrich, M.; Campbell, H.; Mayo, M. R. JNCI, J. Natl. Cancer Inst. 1991, 83, 757-766. The assay shows percent growth over 48 h at 10 uM BCN057 vs control (no drug). The drug was inhibitory towards Leukemia and also towards prostate and kidney cancer (data not shown). Examples of cell lines include: SR; large cell immunoblastic lymphoma, RPMI-8226; plasmacytoma and myeloma, MOLT-4; acute T lymphoblastic leukemia, K562; erythromyeloblastoid leukemia or chronic myeloid leukemia cell line, HL-60 (TB); acute myeloid leukemia, CCRF-CEM; T cell lymphoblast-like cell line. Results are shown in FIG. 1 for RPMI-8226, K-562, and CCRF-CEM

[0190]In addition to leukemia and lymphomas, other tumor cell lines were susceptible to...

example 2

Platelet Count

[0194]Normal mice were treated with BCN057 for eight days by oral administration or subcutaneous injection. Dose groups included 75 mg / kg / day, 200 mg / kg / day, 400 mg / kg / day, 500 mg / kg / day, and 800 mg / kg / day

[0195]BCN057 induces platelet production in a dose dependent fashion. FIG. 3 is a graph of the amount of blood platelets from plasma (mouse) demonstrating through multiple doses and multiple routes of entry that the drug stimulates platelet production rapidly.

example 3

on of Cytokines after Irradiation

[0196]Mice were irradiated on Day 0. Animals were dosed with drug for 7 consecutive days (Day 1 to 7) at 200 mg / kg SC, with terminal blood collection on Day 8. Plasma from 3 mice was pooled for each condition Y axis represents relative absorbance units.

[0197]The plasma was tested with the Mouse Cytokine panel ELISA Array panel—by SIGNOSIS™

[0198]Results are shown in FIGS. 4 and 5. There is a general trend of restoring cytokines to levels similar to control with exceptions. PDGF is important for restoration of mesenchyme and endothelial cells along with FGF. IL-6 and IL-10 are anti-inflammatory cytokines while GCSF and GMCSF affect macrophage infiltration and activation. FIG. 5 shows the cytokine analysis of plasma from mice treated with nothing (marked as 0G above), 7 Grey radiation (7G) and 7G+BCN057). A restorative phenotype is observed in the presence of the drug similar to that of the control group receiving no radiation vs the group receiving rad...

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Abstract

The present disclosure is directed to method of treatment for treating or ameliorating various conditions pertaining such as bone marrow recovery (or blood cell production), fibrosis, inflammatory diseases, inhibition of cancer cell growth, propagation or malignancy, thrombocytopenia, wound healing, and conditions related to stem cells by the administration of BCN057, 512, or an analog thereof.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to provisional application U.S. Ser. No. 62 / 408,809, filed Oct. 16, 2016, herein incorporated by reference in its entirety. This application is also related to U.S. Ser. No. 13 / 813,923 and U.S. Ser. No. 14 / 889,719, herein incorporated by reference in their entirety.BACKGROUND OF THE INVENTION[0002]The discovery of compounds that are capable of mitigating the process of normal tissue damage from radiation during radiotherapy, accidents, or acts of war is of great importance. Most currently available treatments for radiation exposure are free radical scavengers that reduce initial radiation-induced DNA damage and work best if added just before or at the time of irradiation. Because of this, these compounds are not practical countermeasures for a radiation incident. In that case, the search for radiomitigators—agents with robust, prolonged efficacy, broad specificity, and minimal toxicity is of great importan...

Claims

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Application Information

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IPC IPC(8): A61K31/4709A61K31/635A61K47/32A61K47/22A61K47/20A61K47/10A61K47/40
CPCA61K31/4709A61K31/635A61K47/32A61K47/22A61K47/20A61K47/10A61K47/40A61K9/0019A61K9/0095Y02A50/30
Inventor NORRIS, ANDREW J.
Owner BCN BIOSCI LLC