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.

What is claimed is: 
     
         1 . A method of extending pregnancy term in a subject in need thereof, comprising:
 providing a quantity of a composition comprising trimegestone and/or salt thereof; and   administering the quantity of the composition to the subject in need thereof, wherein the composition is administered through oral delivery.   
     
     
         2 . The method of  claim 1 , wherein the composition further comprises one or more solubilizing factors 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. 
     
     
         3 . The method of  claim 1 , wherein the pregnancy term is extended by an additional one day to 22 weeks. 
     
     
         4 . The method of  claim 1 , wherein the effective dosage range of the trimegestone and/or salt thereof is between 0.05 mg and 100 mg. 
     
     
         5 . The method of  claim 1 , wherein the composition is encapsulated, tableted or prepared in an emulsion or syrup for oral delivery. 
     
     
         6 . The method of  claim 1 , wherein the composition further comprises a carrier. 
     
     
         7 . The method of  claim 6 , wherein the carrier is a liquid carrier and the composition is in the form of a syrup, elixir, emulsion or an aqueous or non-aqueous suspension. 
     
     
         8 . The method of  claim 7 , wherein the liquid carrier is peanut oil, olive oil, glycerin, saline, an alcohol or water. 
     
     
         9 . The method of  claim 6 , wherein the carrier is a solid carrier selected from the group consisting of starch, lactose, calcium sulfate dihydrate, terra alba, magnesium stearate, stearic acid, talc, pectin, acacia, agar, and gelatin. 
     
     
         10 . The method of  claim 6 , wherein the carrier is a sustained release material. 
     
     
         11 . The method of  claim 10 , wherein the sustained release material is glyceryl monostearate or glyceryl distearate, alone or with a wax. 
     
     
         12 . 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. 
     
     
         13 . The method of  claim 12 , wherein the one or more compounds is administered after administering the quantity of the composition comprising the trimegestone and/or salt thereof. 
     
     
         14 . The method of  claim 1 , wherein the composition is administered daily. 
     
     
         15 . The method of  claim 1 , wherein the composition is administered at least twice daily. 
     
     
         16 . The method of  claim 1 , wherein the composition is administered to the subject in the range of: 0.1-0.5 mg 0.5-1 mg, 1-5 mg, 5-10 mg, 10-15 mg, 15-20 mg, or 20-100 mg. 
     
     
         17 . The method of  claim 1 , wherein the pregnancy term is at least 22 weeks. 
     
     
         18 . The method of  claim 1 , wherein the pregnancy term is at least 37 weeks. 
     
     
         19 . The method of  claim 1 , wherein the subject is a mammalian subject. 
     
     
         20 . The method of  claim 19 , wherein the mammalian subject is a human.