Methods and compositions for treating trauma-hemorrhage using estrogen and derivatives thereof

Abstract

Disclosed are methods and materials for treating or preventing complications due to traumatic injuries using estrogen or derivatives thereof.

1 . A method of ameliorating one or more effects of a traumatic injury in a subject comprising administering estrogen to the subject in a low volume of solution.  
   
   
       2 . The method of  claim 1 , wherein the estrogen is administered to the subject in less than 40 mL of solution.  
   
   
       3 . The method of  claim 1 , wherein 0.5 ml/kg or less of estrogen in solution is administered to the subject.  
   
   
       4 . The method of  claim 1 , wherein the estrogen is in a cyclodextrin complex.  
   
   
       5 . The method of  claim 1 , wherein the administration is intravenous or intraosseous.  
   
   
       6 . The method of  claim 1 , wherein the estrogen is in the form of β-estradiol or equiline sulfate.  
   
   
       7 . The method of  claim 1 , wherein the traumatic injury involves an inflammatory response.  
   
   
       8 . The method of  claim 1 , wherein the traumatic injury involves low blood pressure compared to a control blood pressure.  
   
   
       9 . The method of  claim 1 , wherein the traumatic injury involves severe blood loss.  
   
   
       10 . The method of  claim 9 , wherein the severe blood loss comprises 40% or more blood loss from the subject.  
   
   
       11 . The method of  claim 1 , wherein administration of estrogen maintains a state of permissive hypotension.  
   
   
       12 . The method of  claim 4 , wherein the cyclodextrin complex comprises 2-hydroxypropyl-β-cyclodextrin or sulfobutyl ether cyclodextran.  
   
   
       13 . The method of  claim 1 , wherein the estrogen is administered prior to the traumatic injury.  
   
   
       14 . The method of  claim 1 , wherein the estrogen is administered after the traumatic injury but prior to treatment.  
   
   
       15 . The method of  claim 1 , wherein the estrogen is administered after treatment.  
   
   
       16 . A method of ameliorating one or more effects of severe blood loss in a subject comprising administering estrogen to the subject.  
   
   
       17 . The method of  claim 1 , wherein the estrogen is administered to the subject in a low volume of solution.  
   
   
       18 . The method of  claim 17 , wherein the estrogen is administered to the subject in less than 40 mL of solution.  
   
   
       19 . The method of  claim 17 , wherein 0.5 ml/kg or less of estrogen in solution is administered to the subject.  
   
   
       20 . The method of  claim 16 , wherein the estrogen is in a cyclodextrin complex.  
   
   
       21 . The method of  claim 20 , wherein the cyclodextrin complex comprises 2-hydroxypropyl-β-cyclodextrin or sulfobutyl ether cyclodextran.  
   
   
       22 . The method of  claim 16 , wherein the administration is intravenous or intraosseous.  
   
   
       23 . The method of  claim 16 , wherein the estrogen is in the form of β-estradiol or equiline sulfate.  
   
   
       24 . The method of  claim 16 , wherein the severe blood loss comprises 40% or more blood loss from the subject.  
   
   
       25 . The method of  claim 16 , wherein the severe blood loss comprises 50% or more blood loss from the subject.  
   
   
       26 . The method of  claim 16 , wherein the severe blood loss comprises 60% or more blood loss from the subject.  
   
   
       27 . The method of  claim 16 , wherein the estrogen is administered prior to the severe blood loss.  
   
   
       28 . The method of  claim 16 , wherein the estrogen is administered after the severe blood loss but prior to treatment.  
   
   
       29 . The method of  claim 16 , wherein the estrogen is administered after treatment of the subject.  
   
   
       30 . A method of prolonging viability of tissue, organ, cell, or an entire body for donation comprising contacting the tissue, organ, cell, or entire body with estrogen.  
   
   
       31 . The method of  claim 30 , wherein the contacting step is performed in vivo by administering estrogen to the donor.  
   
   
       32 . The method of  claim 30 , wherein the contacting step is performed in vitro.  
   
   
       33 . The method of  claim 30 , wherein the contacting step is performed ex vivo.  
   
   
       34 . A method of improving viability of a tissue, organ or cell to be transplanted by contacting the tissue, organ, or cell with estrogen.  
   
   
       35 . The method of  claim 34 , wherein the contacting step is performed in vivo by administering estrogen to the recipient of the donated tissue, organ, or cell.  
   
   
       36 . The method of  claim 34 , wherein the contacting step is performed in vitro.  
   
   
       37 . A method of ameliorating one or more effects of an aortic cross clamp used during surgery in a subject in need thereof, comprising administering estrogen in a cyclodextrin complex to the subject.  
   
   
       38 . The method of  claim 37 , wherein administration of estrogen after use of the aortic cross clamp maintains a state of permissive hypotension.  
   
   
       39 . A kit comprising microencapsulated estrogen, wherein the estrogen is in less than 40 mL of vehicle.  
   
   
       40 . The kit of  claim 39 , wherein the estrogen is in a syringe.  
   
   
       41 . The kit of  claim 39 , wherein the estrogen is in a cyclodextrin complex.  
   
   
       42 . The kit of  claim 39 , wherein the syringe is in a bulletproof container.  
   
   
       43 . The kit of  claim 39 , comprising two separate compartments, one of which comprises sterile dried estrogen, and one comprises diluent.