Encapsulated gas or partial vacuum ct contrast material

Patent metadata

Field	Value
Publication number	US-2022096030-A1
Application number	US-202117473590-A
Country	US
Kind code	A1
Filing date	Sep 13, 2021
Priority date	Apr 20, 2015
Publication date	Mar 31, 2022
Grant date	—

Abstract

The present invention provides an encapsulated gas or partial vacuum particle 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 a encapsulated gas or partial vacuum particle suspended in water. Exemplary encapsulated gas or partial vacuum particle has a specific gravity between 0.2 and 1.5. In various embodiments, the encapsulated gas or partial vacuum particle is suspended in aqueous media by an agent 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 carrier in which the material is suspended homogeneously. In an exemplary embodiment, the encapsulated gas or partial vacuum particle comprises 5% or more of the weight of the contrast material formulation. The invention also provides methods for imaging of the abdomen by dual energy CT or spectral CT contemporaneously with the delivery of the encapsulated gas or partial vacuum particle contrast material into the bowel lumen with or without the deliver of a second complementary contrast material into the blood vessels or other body compartments. The invention also provides methods for the digital separation of CT signal produced by the contrast media of the invention from the CT signal produced by other contrast media or bodily tissues to generate multiple resultant CT images with the contrast medium of the invention subtracted or highlighted.

First claim

1 .- 46 . (canceled)

47 . 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:
an enteric contrast medium comprising a stable suspension of hollow borosilicate microspheres encapsulating gas or partial vacuum, and an aqueous vehicle component, where said aqueous vehicle component is a pharmaceutically acceptable aqueous vehicle comprising xanthan gum as suspension agent maintaining the microspheres in suspension, said encapsulated gas or partial vacuum particle is stable at room or body temperature, wherein said particle comprises a shell defining an interior void, said shell formed of a material contributing at least about 30 Hounsfield Units (HU) to the CT number of said contrast medium formulation or of a body cavity in which said contrast medium is distributed during said medical imaging procedure.

48 . The enteric contrast medium formulation of claim 47 , wherein said formulation is a unit dosage formulation comprising a diagnostically effective amount of said enteric contrast medium;
optionally said unit dosage formulation is of (i) from about 50 to about 100 mL in volume or (ii) from about 100 mL to about 800 mL in volume or (iii) from about 800 mL to about 1500 mL per adult human dose, which may be divided into smaller containers such as 400 mL to 500 mL in volume; and optionally wherein said unit dosage formulation contains more than about 20 g of said encapsulated gas or partial vacuum particle.

49 . The enteric contrast medium formulation claim 47 , wherein said formulation comprises at least about 5% weight/weight percentage of said encapsulated gas or partial vacuum particle, such as from about 5% to about 95% in terms of weight/weight percentage, or at least about 10% weight/weight percentage of said encapsulated gas or partial vacuum particle, such as from about 10% to about 50% in terms of weight/weight percentage.

50 . The enteric contrast medium formulation of claim 47 , wherein said pharmaceutically acceptable aqueous vehicle further comprises an additive to retard dehydration of said formulation in the bowel, a flavoring agent, a thickening agent, a flow agent, a pH buffer, a laxative, an osmolality-adjusting agent, and a combination thereof.

51 . The enteric contrast medium formulation of claim 47 , wherein said enteric contrast medium has an 80:140 kVp CT number ratio of greater than about 2.1 or from about 0.6 to about 0.8 or from about 0.3 to about 0.5 or below 0.3, including negative ratios below zero.

52 . The enteric contrast medium formulation of claim 47 wherein the encapsulated gas or partial vacuum particle has a specific gravity similar to that of water, such as from about 0.7 to about 1.2 g/cc or from about 0.2 to about 0.8; and optionally a mean diameter of from about 5 to about 60 micrometers or from about 60 to about 200 micrometers or from about 0.5 to about 5 micrometers.

53 . The enteric contrast medium formulation of claim 47 wherein said enteric contrast medium is provided in powdered or other concentrated form to be mixed with water or other said acceptable pharmaceutical aqueous vehicle near the time of administration for CT scanning, together with instructions for preparing an administrable enteric contrast medium and, optionally, one or more device for administering said administrable enteric contrast medium to a subject.

54 . The enteric contrast medium formulation of claim 47 , further comprising a radiodense material selected from iodine, barium, tungsten, tantalum, ytterbium, gold, and bismuth present in the contrast formulation as separate suspended particles or as dissolved material in the vehicle.

55 . The enteric contrast medium formulation of claim 47 , comprising 10 to 50% wt/wt borosilicate glass particles of density 0.6 g/cm 3 suspended in water comprising 0.2 to 0.5% xanthan gum.

56 . A method of acquiring contrast enhanced X-ray or computed tomography or dual energy computed tomography or spectral computed tomography or photon counting 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 claim 47 ; and acquiring said projection data of said subject, optionally 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.

57 . The method according to claim 56 , 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, such as an image of a region selected from the abdomen and pelvis of said subject, where preferably said computed tomography images are used to distinguish said enteric contrast medium formulation from other materials in the abdomen.

58 . The method of claim 56 , wherein said enteric contrast agent is imaged using a dual energy or spectral CT scanner with X-ray filters of different material, such as aluminum, copper, gold, or tin, or different thickness, including zero, that modify the energy spectra of the X-ray beams, optionally said enteric contrast agent is 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.

59 . The method according to claim 56 , 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, optionally wherein said computed tomography images are used for 2-material, 3-material, or multi-material decomposition to reconstruct additional CT images.

60 . The method according to claim 56 , 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, optionally 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.

61 . The method according to claim 60 , wherein said enteric contrast medium and said second contrast medium are distinguishable from each other in said image based on x-ray attenuation (CT number) at single energy spectrum CT; or
wherein said enteric contrast medium and said second contrast medium are distinguishable from each other in said image based on their CT number, relative X-ray attenuation at different X-ray spectra, or both.

62 . The method according to claim 60 wherein said enteric contrast medium has CT number of less than about 50 Hounsfield Units in said image or less than about −50 Hounsfield Units in said image or

Assignees

• Univ California

Inventors

• Yeh Benjamin M
• Fu Yanjun

Classifications

• A61B6/03 Primary

  Computed tomography [CT] · CPC title

• A61K9/50

  Microcapsules {having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals (A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167)} · CPC title

• A61K49/0419 Primary

  Microparticles, microbeads, microcapsules, microspheres, i.e. having a size or diameter higher or equal to 1 micrometer · CPC title

• A61K9/10

  Dispersions; Emulsions · CPC title

• A61B6/481 Primary

  involving the use of contrast agents · CPC title