Low x-ray attenuation change hard shelled oral contrast material

Patent metadata

Field	Value
Publication number	US-2022401587-A1
Application number	US-202217736957-A
Country	US
Kind code	A1
Filing date	May 4, 2022
Priority date	May 5, 2021
Publication date	Dec 22, 2022
Grant date	—

Abstract

The present invention provides a hollow borosilicate microparticle contrast media for use in CT imaging with shell material containing less than 8% oxides of non-silicon elements with atomic number greater than 10. In an exemplary embodiment, the invention provides an enteric contrast medium formulation which provides CT numbers distinct from those of water, soft tissue, and fat. In an exemplary embodiment, the invention provides an enteric contrast medium formulation that shows iodine concentrations less than 1.0 mg iodine/mL at dual energy CT or multi-energy CT image reformations. An exemplary formulation comprises, (a) an enteric contrast medium comprising a hollow borosilicate microparticle suspended in water. Exemplary hollow borosilicate microparticle has a true gravity between 0.1 and 0.4 g/cm3. In various embodiments, the hollow borosilicate microparticle 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. In an exemplary embodiment, the hollow borosilicate microparticle comprises 1% to 15% of the weight of an aqueous contrast material formulation. The invention also provides methods for imaging of the abdomen and pelvis by CT imaging contemporaneously with the delivery of the hollow borosilicate microparticle contrast material into the bowel lumen.

First claim

1 . An enteric contrast medium formulation which is formulated for oral delivery to a subject contemporaneous with a medical CT imaging procedure performed on the abdomen or pelvis of said subject, said formulation comprising:
an enteric contrast medium comprising a suspension of a hollow borosilicate microparticle with shell containing more than 90% SiO 2 and less than 8% non-silicon oxides of z>10 and an aqueous vehicle component, with said aqueous component which is a pharmaceutically acceptable aqueous vehicle, where at CT imaging the contrast medium formulation gives CT number between −70 to −20 HU or between −160 and −300 HU when imaged at 120 kVp.

2 . An enteric contrast medium formulation which is formulated for oral delivery to a subject contemporaneous with a CT imaging procedure performed on the abdomen or pelvis of said subject, said formulation comprising a hollow borosilicate microparticle with shell material and CT imaging characteristics described in claim 1 .

3 . The enteric contrast medium formulation of claim 1 , wherein said formulation is a unit dosage formulation comprising a diagnostically effective amount of said enteric contrast medium.

4 . The enteric contrast medium formulation of claim 1 , wherein said formulation is a unit dosage formulation of from about 800 mL to about 2000 mL per adult human dose, which may be divided into smaller containers such as 400 mL to 600 mL in volume.

5 . The enteric contrast medium formulation of claim 1 wherein said formulation is a unit dosage formulation of from about 50 to about 100 mL in volume.

6 . The enteric contrast medium formulation of claim 1 , wherein formulation is a unit dosage formulation of from about 100 mL to about 800 mL in volume.

7 . The enteric contrast medium formulation of claim 1 , wherein the apparent iodine concentration of the formulation at dual energy CT, multienergy CT, or photon counting CT is <1.0 mg iodine/mL at iodine image reconstructions.

8 . The enteric contrast medium formulation of claim 1 , wherein said hollow borosilicate microparticle does not contain sulfur.

9 . The enteric contrast medium formulation of claim 1 , wherein said formulation comprises at least about 0.5% weight/weight percentage of said hollow borosilicate microparticle (from about 1.0% to about 15% in terms of weight/weight percentage in aqueous formulation).

10 . The enteric contrast medium formulation of claim 1 , wherein said suspension agent is selected from xanthan gum, guar gum, gellan gum, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, alginates, polyethylene glycol chains, and sodium carboxylmethylcellulose.

11 . The enteric contrast medium formulation of claim 1 , wherein said formulation is a unit dosage formulation and it contains more than about 3 g of said hollow borosilicate microparticle per 400 mL of aqueous suspension.

12 . The enteric contrast medium formulation of claim 1 , wherein said suspension agent comprises xanthan gum or gellan gum.

13 . The enteric contrast medium formulation of claim 1 , wherein said pharmaceutically acceptable 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, a preservative, and a combination thereof.

14 . The enteric contrast medium formulation of claim 1 , wherein the hollow borosilicate microparticle has a true gravity from about 0.15 to about 0.40.

15 . The enteric contrast medium formulation of claim 1 , wherein the hollow borosilicate microparticle has a mean diameter of from about 10 to about 60 micrometers.

16 . The enteric contrast medium formulation of claim 1 , wherein the hollow borosilicate microparticle has a mean diameter of from about 60 to about 200 micrometers.

17 . The enteric contrast medium formulation of claim 1 , wherein said enteric contrast medium is provided in powdered or other concentrated form to be mixed with water or other said acceptable medical aqueous vehicle near the time of administration for CT imaging, together with instructions for preparing an administrable enteric contrast medium and, optionally, one or more device for administering said administratable enteric contrast medium to a subject.

18 . The enteric contrast medium formulation of claim 1 , wherein the hollow borosilicate microparticle makes up 1.0% or more of the weight of the formulation.

19 . A method of acquiring contrast enhanced CT imaging of a subject, said method comprising: administering to said subject a diagnostically effective amount of said enteric contrast medium formulation of claim 1 .

20 . The method according to claim 19 , wherein said CT projection data are reconstructed into a CT image.

21 . The method according to claim 19 , wherein said CT images are used to distinguish said enteric contrast medium formulation from other materials or tissues in the abdomen or pelvis.

22 . The method according to claim 19 , wherein machine learning or artificial intelligence is used to segment the anatomy within said CT images.

23 . The method according to claim 19 wherein computer aided diagnosis, machine learning, or artificial intelligence is used to identify CT findings within said CT images

24 . The method according to claim 19 wherein computer aided diagnosis, machine learning, or artificial intelligence is used to identify diagnoses within said CT images

25 . The method according to claim 19 , wherein said image is an image of a region selected from the abdomen and pelvis of said subject.

26 . The method of claim 19 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, Hartmans 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.

27 . A kit comprising:
(a) a first vial or set of vials containing the enteric contrast medium of claim 1 ; (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.

28 . The method of claim 19 , comprising diagnosing said subject.

29 . The method of claim 28 , wherein said subject is diagnosed as having injury selected from a malignancy, inflammation, infection, and ischemia, and a combination thereof.

30 . The method of claim 29 , wherein said subject is evaluated for anatomical detail that involves the bowel or tissues adjacent to bowel.

Assignees

• Univ California

Inventors

• Yeh Benjamin M
• Sun Yuxin

Classifications

• A61B6/481

  involving the use of contrast agents · CPC title

• A61K49/0419 Primary

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

• A61K49/04 Primary

  X-ray contrast preparations · CPC title

• A61B6/032

  Transmission computed tomography [CT] · CPC title

• A61B6/5217

  extracting a diagnostic or physiological parameter from medical diagnostic data · CPC title