Silicone-based enteric ct contrast material

Abstract

The present invention provides a silicon-based polymer contrast media for use in CT imaging. In an exemplary embodiment, the invention provides an enteric contrast medium formulation. An exemplary formulation comprises, (a) an enteric contrast medium comprising silicon-based polymer oil emulsified in water. Exemplary silicon-based polymer oil has a viscosity between about 50 eSt and 100,000 eSt. In various embodiments, the silicon-based polymer oil is emulsified with a vehicle or dispersing medium compatible with enteric administration of the formulation to a subject in need of such administration. In an exemplary embodiment, the contrast material is incorporated into a pharmaceutically acceptable vehicle in which the material is emulsified in the presence of a surfactant. In an exemplary embodiment, the silicon-based polymer comprises 30% or more of the weight of the contrast material formulation.

What is claimed is: 
     
         1 . An enteric contrast medium formulation which is formulated for oral delivery to a subject contemporaneously with a medical imaging procedure performed on the abdomen of said subject, said formulation comprising:
 an enteric contrast medium comprising an emulsion or suspension of at least one silicon-based polymer or copolymer material (e.g., polysiloxane), an aqueous vehicle component, and an emulsifying or dispersing agent maintaining said at least one silicon-based polymer in an oil-in-water emulsion or suspension with said aqueous component which is a pharmaceutically acceptable aqueous vehicle, wherein said silicon-based polymer or copolymer material is a member selected from a linear, branched, or cross-linked structure comprising silicon-based polymer components and a polymer blend comprising silicon-based polymers or copolymers, and a combination thereof   
     
     
         2 . An enteric contrast medium formulation which is formulated for oral delivery to a subject contemporaneous with a medical imaging procedure performed on the abdomen of said subject, said formulation comprising a silicon-based polymer. 
     
     
         3 . An enteric contrast medium formulation which is formulated for use in X-ray imaging or computed tomography, said formulation comprising a silicon-based polymer. 
     
     
         4 . The enteric contrast medium formulation of any preceding claim, wherein said formulation is a unit dosage formulation comprising a diagnostically effective amount of said enteric contrast medium. 
     
     
         5 . The enteric contrast medium formulation of any preceding claim, wherein said formulation is a unit dosage formulation of from about 800 mL to about 1200 mL per adult human dose, which may be divided into smaller containers such as 400 mL to 500 mL in volume. 
     
     
         6 . The enteric contrast medium formulation of any preceding claim wherein said formulation is a unit dosage formulation of from about 50 to about 100 mL in volume. 
     
     
         7 . The enteric contrast medium formulation of any preceding claim wherein formulation is a unit dosage formulation of from about 100 mL to about 800 mL in volume. 
     
     
         8 . The enteric contrast medium formulation of any preceding claim, wherein said silicon-based polymer is liquid at room or body temperature (e.g., silicone oil, fluorosilicone polymer, branched silicone polymer, crosslinked silicon-based polymers including silicon-based polymer gels, and silicon-based polymer solids). 
     
     
         9 . The enteric contrast medium formulation of any preceding claim, wherein said formulation comprises at least about 30% weight/weight of said silicon-based polymer (30-100% weight/weight percentage). 
     
     
         10 . The enteric contrast medium formulation of any preceding claim, wherein said formulation comprises at least about 60% weight/weight of said silicon-based polymer. 
     
     
         11 . The enteric contrast medium formulation of any preceding claim, wherein said emulsifying agent and dispersing agent has a hydrophilicity-lipophilicity balance (HLB) value of between 0 to 20, preferentially an HLB value of between 9 to 18. 
     
     
         12 . The enteric contrast medium formulation of any preceding claim, wherein said emulsifier is a Tween surfactant, for example Tween-20 
     
     
         13 . The enteric contrast medium formulation of any preceding claim, wherein said formulation is not of use as an oral care formulation. 
     
     
         14 . The enteric contrast medium formulation of any preceding claim, wherein said formulation is not of use to prevent flatulence. 
     
     
         15 . The enteric contrast medium formulation of any preceding claim, wherein said formulation is a unit dosage formulation and it contains more than about 25 g of said silicon-based polymer, for example, 200 g to 2000 g. 
     
     
         16 . The enteric contrast medium formulation of any preceding claim, wherein said silicon-based polymer is the main component of the emulsion particles/droplets, but not adsorbed onto a solid particle. 
     
     
         17 . The enteric contrast medium formulation of any preceding claim, wherein from about 30% (w/w) to 100% (w/w) of the weight of said formulation is said silicon-based polymer. 
     
     
         18 . The enteric contrast medium formulation of any preceding claim, wherein emulsifier comprises a water-soluble polymer. 
     
     
         19 . The enteric contrast medium formulation of any preceding claim, wherein said emulsifier comprises one or more poly(ethylene glycol) chains. 
     
     
         20 . The enteric contrast medium formulation of any preceding claim, wherein said pharmaceutically acceptable vehicle further comprises an additive (to retard dehydration of said formulation in the bowel), a flavoring agent, a sweetener, a thickening agent, a suspending agent, a flow agent, a pH buffer, a laxative, an osmolality-adjusting agent, and a combination thereof 
     
     
         21 . The enteric contrast medium formulation of any preceding claim, wherein said enteric contrast medium has an 80:140 kVp CT number ratio of greater than about 2.1. 
     
     
         22 . The enteric contrast medium formulation of any preceding claim, wherein said enteric contrast medium has an 80:140 kVp CT number ratio from about 1.5 to 2.1. 
     
     
         23 . The enteric contrast medium formulation of any preceding claim, wherein said enteric contrast medium has an 80:140 kVp CT number ratio of less than about 1.5. 
     
     
         24 . The enteric contrast medium formulation of any preceding claim wherein the silicon-based polymer has a specific gravity similar to that of water (e.g., from about 0.9 to about 1.1). 
     
     
         25 . The enteric contrast medium formulation of any preceding claim wherein the silicon-based polymer has a viscosity of from about 0.5 cSt to about 200 cSt at room temperature. 
     
     
         26 . The enteric contrast medium formulation of any preceding claim wherein the silicon-based polymer has a viscosity of from about 200 cSt to about 600 cSt at room temperature. 
     
     
         27 . The enteric contrast medium formulation of any preceding claim wherein the silicon-based polymer has a viscosity of 600 cSt to 1200 cSt at room temperature. 
     
     
         28 . The enteric contrast medium formulation of any preceding claim wherein the silicon-based polymer has a viscosity of between 1200 cSt and 100,000 cSt at room temperature. 
     
     
         29 . The enteric contrast medium formulation of any preceding claim wherein the silicon-based polymer has a molecular weight of from about 0.4 kDa to about 5 kDa. 
     
     
         30 . The enteric contrast medium formulation of any preceding claim wherein the silicon-based polymer has a molecular weight of from about 5 kDa to about 50 kDa. 
     
     
         31 . The enteric contrast medium formulation of any preceding claim wherein the silicon-based polymer has a molecular weight of from about 50 kDa to about 1000 kDa 
     
     
         32 . A method of acquiring contrast enhanced X-ray or computed tomography or dual energy computed tomography or spectral computed tomography projection data of a subject, said method comprising: administering to said subject a diagnostically effective amount of said enteric contrast medium formulation of any preceding claim; and acquiring said projection data of said subject. 
     
     
         33 . The method according to  claim 32 , wherein said X-ray or computed tomography or dual energy computed tomography or spectral computed tomography projection data is reconstructed into a computed tomography image. 
     
     
         34 . The method of any of  claims 32 - 33 , wherein said contrast agent is imaged using a dual energy or spectral CT scanner with X-ray filters of different material or thickness (including zero) that modify the energy spectra of the X-ray beams. Example materials to filter the energy spectra of the X-ray beams include but are not limited to aluminum, copper, or tin. 
     
     
         35 . The method according to  claims 32 - 34 , wherein said X-ray or computed tomography or dual energy computed tomography or spectral computed tomography projection data are used for 2-material, 3-material, or multi-material decomposition and reconstructed into CT images. 
     
     
         36 . The method according to  claims 32 - 35 , wherein said computed tomography images are used for 2-material, 3-material, or multi-material decomposition to reconstruct additional CT images. 
     
     
         37 . The method according to  claims 32 - 36 , wherein said computed tomography images are used to distinguish said enteric contrast medium formulation from other materials in the abdomen. 
     
     
         38 . The method according to any of  claims 32 - 37 , wherein said image is an image of a region selected from the abdomen and pelvis of said subject. 
     
     
         39 . The method according to any of  claims 32 - 38 , wherein said method further comprises administering to said subject a second contrast medium different from said enteric contrast medium, and said second contrast medium is administered through a route selected from oral administration, intrathecal administration, intravesicular administration, enteric administration, anal administration, intracatheter administration, intra-device administration, intravascular administration, administration into a fistula, and administration into a surgically created pouch. 
     
     
         40 . The method according to  claim 39 , wherein said second contrast medium is a member selected from an iodinated contrast medium, a Ba-, Gd- W-, Bi-, Mg-, Yb- and a Ta-based contrast medium and a silicon based contrast medium. 
     
     
         41 . The method according to any of  claims 34 - 40 , wherein said enteric contrast medium and said second contrast medium are distinguishable from each other in said image based on their relative X-ray attenuation at different X-ray spectra. 
     
     
         42 . The method according to any of  claims 32 - 41 -, wherein said enteric contrast medium has an 80:140 kVp CT number ratio of greater than about 2.1 in said image. 
     
     
         43 . The method of DECT or spectral CT, wherein the formulations of the invention are imaged on dual energy or spectral CT scanners which use different filters for the low and high kVp imaging, such as aluminum or copper filters for the low kVp images and tin filters for the high kVp imaging. 
     
     
         44 . The method of any of  claims 32 - 42 , wherein said enteric contrast agent is administered to said subject by delivery through:
 (a) a natural cavity selected from the mouth, vagina, bladder, rectum and urethra;   (b) a surgically created space selected from an ileal pouch, and a neobladder;   (c) a space created by injury selected from a fistula, sinus tract, and abscess; or   (d) a medical device selected from a catheter, a tube, a reservoir, a pouch and a pump.   
     
     
         45 . A kit comprising:
 (a) a first vial or set of vials containing the enteric contrast medium of any of  claims 1 - 30 ;   (b) a second vial containing a second contrast medium; and   (c) directions for formulating said enteric contrast medium with or without said second contrast medium.   
     
     
         46 . The method of  claim 32 , comprising diagnosing said subject. 
     
     
         47 . The method of  claim 46 , wherein said subject is diagnosed as having injury selected from a malignancy, inflammation, infection, and ischemia, and a combination thereof 
     
     
         48 . The method of  claim 46 , wherein said subject is evaluated for anatomical detail that involves the bowel or tissues adjacent to bowel.