Trimegestone (tmg) for treatment of preterm birth

Abstract

As disclosed herein, novel compositions including steroid hormones, such as trimegestone (TMG) and progesterone (P4), provide treatments for term and preterm labor with significant effects on the delay of delivery. Delay and block of delivery occurs when both P4 and TMG are administered late in gestation in pregnant rat and guinea pig animal models. TMG exhibits remarkable drug efficacy, achieving the same inhibition as P4, but at much lower doses. These hereto unknown effects of TMG on the processes of cervical ripening and uterine contraction provide a novel approach for extending pregnancy term, including reducing a likelihood of preterm and/or term labor, along with improved methods of administration. Other diseases and/or conditions may be treated with TMG, such as dysmenorrhea or luteal insufficiency for sustaining pregnancy.

1 . A method of extending pregnancy term in a subject in need thereof, comprising:
 providing a quantity of a composition comprising a 19-norprogesterone, or a pharmaceutical equivalent, derivative, analog, and/or salt thereof; and   administering the quantity of the composition to the subject in need thereof.   
     
     
         2 . The method of  claim 1 , wherein the 19-norprogesterone comprises a compound of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutical equivalent, derivative, analog, and/or salt thereof. 
     
     
         3 . The method of  claim 1 , wherein the composition further comprises one or more solubilizing factors. 
     
     
         4 . The method of  claim 3 , wherein the one or more solubilizing factors is selected from the group consisting of: cyclodextrins, sesame oil, fish oil, corn oil, olive oil, coconut oil, krill oil, omega fatty acids, mineral oil, peppermint oil, flaxseed oil, vitamin E oil, argan oil, saline solution and glucose solution. 
     
     
         5 . The method of  claim 1 , wherein the composition is administered through nasal, oral, subcutaneous, transmucosal, transdermal, parenteral, implantable pump, continuous infusion, topical, intradermal, intravenous, intramuscular, intraperitoneal, inhalation, rectal, non-vaginal and/or vaginal delivery. 
     
     
         6 . The method of  claim 1 , further comprising administering of one or more compounds selected from the group consisting of: nifedipine, indomethacin, magnesium sulfate, oxytocin antagonists, and tocolytics. 
     
     
         7 . The method of  claim 6 , wherein the one or more compounds is administered after administering the quantity of the composition comprising a 19-norprogesterone, or a pharmaceutical equivalent, derivative, analog, and/or salt thereof. 
     
     
         8 . The method of  claim 1 , wherein the composition is administered at least twice daily. 
     
     
         9 . The method of  claim 1 , wherein the composition is administered to the subject in the range of: 0.01-0.1 mg, 0.1-0.5 mg 0.5-1 mg, 1-5 mg, 5-10 mg, 10-15 mg, 15-20 mg, and/or 20-100 mg. 
     
     
         10 . The method of  claim 1 , wherein the pregnancy term is at least 22 weeks. 
     
     
         11 . The method of  claim 1 , wherein the pregnancy term is at least 37 weeks. 
     
     
         12 . A pharmaceutical composition, comprising a therapeutically effective amount of a 19-norprogesterone, or a pharmaceutical equivalent, derivative, analog, and/or salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the 19-norprogesterone comprises a compound of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutical equivalent, derivative, analog, and/or salt thereof. 
     
     
         14 . The pharmaceutical composition of  claim 12 , wherein the composition further comprises one or more solubilizing factors. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the one or more solubilizing factors is selected from the group consisting of: cyclodextrins, sesame oil, fish oil, corn oil, olive oil, coconut oil, krill oil, omega fatty acids, mineral oil, peppermint oil, flaxseed oil, vitamin E oil, argan oil, saline solution and glucose solution. 
     
     
         16 . The pharmaceutical composition of  claim 12 , further comprising one or more compounds selected from the group consisting of: nifedipine, indomethacin, magnesium sulfate, oxytocin antagonists, and tocolytics. 
     
     
         17 . The pharmaceutical composition of  claim 12  provided in a dosage in the range of: 0.01-0.1 mg, 0.1-0.5 mg 0.5-1 mg, 1-5 mg, 5-10 mg, 10-15 mg, 15-20 mg, and/or 20-100 mg. 
     
     
         18 . A method of treating a disease and/or condition in a subject in need thereof, comprising:
 providing a quantity of a composition comprising a 19-norprogesterone, or a pharmaceutical equivalent, derivative, analog, and/or salt thereof; and   administering the quantity of the composition to the subject in need thereof.   
     
     
         19 . The method of  claim 18 , wherein the 19-norprogesterone comprises a compound of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutical equivalent, derivative, analog, and/or salt thereof. 
     
     
         20 . The method of  claim 18 , wherein the composition further comprises one or more solubilizing factors. 
     
     
         21 . The method of  claim 20 , wherein the one or more solubilizing factors is selected from the group consisting of: cyclodextrins, sesame oil, fish oil, corn oil, olive oil, coconut oil, krill oil, omega fatty acids, mineral oil, peppermint oil, flaxseed oil, vitamin E oil, argan oil, saline solution and glucose solution. 
     
     
         22 . The method of  claim 18 , wherein the composition is administered through nasal, oral, subcutaneous, transmucosal, transdermal, parenteral, implantable pump, continuous infusion, topical, intradermal, intravenous, intramuscular, intraperitoneal, inhalation, rectal, non-vaginal and/or vaginal delivery. 
     
     
         23 . The method of  claim 18 , wherein composition further comprises administering one or more compounds selected from the group consisting of: nifedipine, indomethacin, magnesium sulfate, oxytocin antagonists, and tocolytics. 
     
     
         24 . The method of  claim 23 , wherein the one or more compounds is administered after administering the quantity of the composition comprising a 19-norprogesterone, or a pharmaceutical equivalent, derivative, analog, and/or salt thereof. 
     
     
         25 . The method of  claim 18 , wherein the composition is administered twice daily. 
     
     
         26 . The method of  claim 18 , wherein the composition is administered to the subject in the range of: 0.01-0.1 mg, 0.1-0.5 mg 0.5-1 mg, 1-5 mg, 5-10 mg, 10-15 mg, 15-20 mg, and/or 20-100 mg. 
     
     
         27 . The method of  claim 18 , wherein the disease and/or condition is selected from the group consisting of: preterm labor, term labor, luteal insufficiency, dysmenorrhea, dysfunctional uterine bleeding, and combinations thereof. 
     
     
         28 . The method of  claim 27 , wherein the disease and/or condition is dysmenorrhea. 
     
     
         29 . The method of  claim 27 , wherein the disease and/or condition is luteal insufficiency.