Compounds to promote regeneration of bone marrow

a technology of ammonium and compound, which is applied in the field of compounds to promote bone marrow regeneration, can solve the problems of drug candidates not being introduced into clinical practice, further deterioration of physiological conditions, and limiting clinical usefulness

Inactive Publication Date: 2008-09-25
ZOLTAN LAB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are many diseases and treatment regimens that can lead to anemia and some form of cytopenia often leading to further deterioration of physiological condition.
Most established anticancer and many anti-HIV drugs produce severe myelotoxicity that limits their clinical usefulness.
In fact many prospective drug candidates cannot be introduced into the clinical practice because of their bone marrow toxicity that in most cases results in neuotropenia or thrombocytopenia.
There are relatively few safe tools to help recovery of bone marrow function during or after intensive radiation or chemotherapy.
However, such role so far could be proved only for endogenous TPO; unfortunately, TPO administration not only failed to promote hematological recovery after chemotherapy or bone marrow transplantation, but it was also shown to cause immunological complications.
This agent, however, only prevents drug-induced death of differentiated blood cells and does not promote hematopoiesis.

Method used

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  • Compounds to promote regeneration of bone marrow
  • Compounds to promote regeneration of bone marrow
  • Compounds to promote regeneration of bone marrow

Examples

Experimental program
Comparison scheme
Effect test

example 1

Effects of CCcompound1, CCcompound3 and CCcompound26 on Blood Profile in Cyclophosphamide-Treated Mice

[0052]Twelve week old female C57B1 mice were used for the experiments. Each drug was administered intraperitoneally once a day for 5 consecutive days. In the second, third, fourth and fifth groups, mice were administered 120 mg / kg of cyclophosphamide (CP). In a third group, mice were also administered 4.5 mg / kg of CCcompound1. In a fourth group, mice were also administered 4.5 mg / kg of CCcompound3. In a fifth group, mice were also administered 2.0 mg / kg of CCcompound26. In the first group, mice received no treatment. Each group included 5 animals. After 3 hours of the last treatments (on day 5), blood samples were collected from the ocular venous plexus of ether-anesthetized mice by retro-orbital venipuncture in heparanized tubes. Complete cell counts (RBC, red blood cell; WBC, white blood cell; PTL, platelet) were determined with a Sysmex F-800 hematology analyzer (Toa Medical Elec...

example 2

[0054]This experiment was designed to determine whether in a tumor model CC compounds could prevent cyclophosphamide-induced loss of body weight resulting from the depression of blood marrow function. Specified pathogen free (SPF) hygienic category colonies of first generation hybrid BDF1 (C57B1 female×DBA / 2 male) adult female mice, weighing 23-24 g, were used. The animals were kept in macrolon cages at 22-24° C. (45-55% humidity), with a lighting regimen of 12 / 12 h light / dark. The animals had free access to tap water and were fed with a sterilized standard diet (Charles River VRF1, autoclavable, Germany) ad libitum. The animals used in these studies were cared for according to the “Guiding Principles for the Care and Use of Animals” based upon the Helsinki declaration.

[0055]MXT mammary tumor pieces (containing about 106 tumor cells) were implanted subcutaneously to develop the tumors. After six days when the tumor-bearing mice were first treated, the sizes of the tumors were in the...

example 3

CCcompound1 Promotes Recovery of Bone Marrow Function after Sublethal Whole Body Irradiation

[0058]This experiment served to determine if CCcompound1 was able to promote regeneration of partially ablated bone marrow from endogenous stem cells i.e. promote restoration of the capacity of bone marrow to produce blood cells. The CFU-GM assay was performed because the number of CFU-GM per femur is a good indicator of bone marrow regeneration. Ballestrero, A., Ferrando, F., Garuti, A., Basta, P., Gonella, R., Stura, P., Mela, G. S., Sessarego, M, Gobbi, M. and Patrone, F., “Comparative effects of three cytokine regimens after high-dose cyclophosphamide: Granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), and sequential interleukin-3 and GM-CSF,”J. Clin. Oncol., 17, 1296-1303 (1999).

[0059]C57B1 female (10-14 weeks old) mice received sublethal (250 cGy) whole body irradiation from a 137Cesium source (day 0). Starting three days before irradiation...

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Abstract

Embodiments of the present invention include the use of heterocyclic trialkyl ammonium-containing compounds to promote regeneration of bone marrow from endogenous or exogenous stem / progenitor cells and to normalize blood cell and platelet counts.

Description

FIELD OF THE INVENTION[0001]The invention provides heterocyclic trialkyl ammonium-containing compounds, such as [3-(3,4-dimethyl-9-oxo-9H-thioxanthen-2-yloxy)-2-hydroxypropyl]trimethylammonium chloride, or CCcompound1, N,N,-diethyl-N-methyl-2-[9-oxo-9H-thioxanthen-2-yl)methoxy]ethanaminium iodide, or CCcompound3, and N,N-Diethyl-N-allyl-3-(2-methyl-9H-thioxanthen-9-ylidene)-propane-1-aminium bromide, or CCcompound26 to promote bone marrow regeneration from endogenous stem / progenitor cells after administering chemotherapy or radiation treatment, or from external stem / progenitor cells after administering lethal total body irradiation and / or high dose chemotherapy followed by transplantation of bone marrow stem / progenitor cells.BACKGROUND[0002]Differentiated blood cells are formed from hematopoietic (blood-forming) pluripotent stem cells via intermediate stem cell-derived progenitor cells. Differentiated blood cells can be classified as red blood cells (RBC) or erythrocytes and white b...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K31/382A61K31/28
CPCA61K31/20A61K31/33A61K31/38A61K38/1816A61K38/193A61K38/2073A61K38/202A61K38/196A61K2300/00A61P19/08
InventorKISS, ZOLTAN
OwnerZOLTAN LAB