Methods of treatment and pharmaceutical compositions using bcn057 or bcn512

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.

1 . A method of increasing hematopoiesis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of BCN057, BCN512, or an analog thereof. 
     
     
         2 . The method of  claim 1 , wherein the subject has leukemia, AML, ALL, bone marrow ablation, bone marrow transplant, bone marrow suppression due to radiation or chemotherapy, a platelet disorder, or clinical radiation related exposure. 
     
     
         3 . The method of  claim 2 , wherein the platelet disorder is caused by bone marrow failure, bone marrow suppression, chronic alcohol abuse, congenital macrothrombocytopenias, infection, cytomegalovirus, Epstein-Barr virus, hepatitis C virus, HIV, mumps, parvovirus B19, rickettsia, rubella, varicella-zoster virus, myelodysplastic syndrome, neoplastic marrow infiltration, a nutritional deficiency, a vitamin B12 deficiency, or a folate deficiency. 
     
     
         4 . The method of  claim 1 , wherein the analog is selected from the group consisting of Formula IB-H, Formula IA, Formula IIB-H, and Formula IIA. 
     
     
         5 . The method of  claim 1 , wherein the subject received radiation therapy. 
     
     
         6 . A method of inhibiting cancer cell growth in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of BCN057, BCN512 or an analog thereof, wherein the cancer is selected from the group consisting of renal cancer, prostate cancer, non-small cell lung cancer, head and neck cancers, breast cancer, colon cancer, ovarian, leukemia, skin cancer such as melanoma, central nervous system cancers including pediatric brain cancers and adult brain cancers. 
     
     
         7 . The method of  claim 6 , wherein the analog is selected from the group consisting of Formula IB-H, Formula IA, Formula IIB-H, and Formula IIA. 
     
     
         8 . A method of preventing late effects of clinical radiation, the method comprising administering to the subject a therapeutically effective amount of BCN057, BCN512 or an analog thereof, wherein the effects are reduction of tissue fibrosis, reduction in hormonal deficits, reduction in neurological impairment from radiation, reduction in growth retardation from radiation treatment, reduction of pulmonary, prostate, colon or kidney damage from radiation, reduction in leukemia arising from radiation treatment. 
     
     
         9 . The method of  claim 8 , wherein the analog is selected from the group consisting of Formula IB-H, Formula IA, Formula IIB-H, and Formula IIA. 
     
     
         10 . A method of treating fibrosis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of BCN057, BCN512, or an analog thereof. 
     
     
         11 . The method of  claim 10 , wherein the fibrosis is a fibrotic disease selected from the group consisting of idiopathic pulmonary fibrosis, liver fibrosis, gastrointestinal fibrosis and renal fibrosis from kidney dialysis. 
     
     
         12 . The method of  claim 11 , wherein the fibrotic disease is pulmonary fibrosis, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, cystic fibrosis, non-cystic fibrosis bronchiectasis, cirrhosis, liver fibrosis, endomyocardial fibrosis, old myocardial infarction, atrial fibrosis, mediastinal fibrosis (soft tissue of the mediastinum), myelofibrosis, retroperitoneal fibrosis, progressive massive fibrosis, nephrogenic systemic fibrosis, Crohn's disease, gastrointestinal fibrosis, keloid conditions, scleroderma/systemic sclerosis, arthofibrosis, peyronie's disease, dupuytren's contracture, oral submucous fibrosis, or adhesive capsulitis. 
     
     
         13 . The method of  claim 10 , wherein the analog is selected from the group consisting of Formula IB-H, Formula IA, Formula IIB-H, and Formula IIA. 
     
     
         14 . The method of  claim 10 , wherein the subject received radiation therapy. 
     
     
         15 . A method of improving wound and tissue healing in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of BCN057, BCN512 or an analog thereof. 
     
     
         16 . The method of  claim 15 , wherein the wound is a dermal wound. 
     
     
         17 . The method of  claim 15 , wherein the wound is caused by sun, radiation or heat exposure. 
     
     
         18 . The method of  claim 15 , wherein the analog is selected from the group consisting of Formula IB-H, Formula IA, Formula IIB-H, and Formula IIA. 
     
     
         19 . A pharmaceutical composition of BCN057 comprising 100 mM methanesulfonic acid/10% povidone (PVP); and 100 mM MSA/2% benzyl alcohol/2% N-methylpyrrolidone (NMP). 
     
     
         20 . The pharmaceutical composition of  claim 19 , further comprising 30 wt % Captisol (SBE-beta-CD) and 100 mM MSA. 
     
     
         21 . The pharmaceutical composition of  claim 20 , further comprising 30 wt % Captisol (SBE-beta-CD) and 100 mM MSA at pH 4.1 or higher (adjusted with 1.0 N NaOH). 
     
     
         22 . A nanoparticle pharmaceutical composition of BCN512.