Originator
GastroMARK,Advanced Magnetics, Inc.,USA
Manufacturing Process
A solution of 0.5 M ferrous chloride (FeCl2) and 0.25 M ferric chloride (FeCl3)
(200 ml) was mixed with 5 M sodium hydroxide (200 ml) at 60°C by pouring
both solutions to 100 ml of distilled water. The mixture was stirred for 2 min
during which time a black, magnetic precipitate formed. After settling, the
volume of the settled precipitate was approximately 175 ml. The concentration
of iron oxide in the precipitate was about 60 mg/ml. The precipitate was then
washed with water until a pH of 6-8 was reached
The following washing technique was employed. The particles were suspended
in 1.8 L of water in a beaker and collected by magnetic extraction. The beaker
was placed on top of a ring magnet, 1/2 inch high and 6 inches in diameter,
which caused the magnetic particles to settle. The water was poured off
without the loss of particles by holding the magnet to the bottom of the
beaker while decanting. Typically, three washes were sufficient to achieve
neutral pH. The magnetic oxide was then washed once with 1.0 liter of 0.02 M
sodium chloride.
The water was then replaced with methanol. This was accomplished by
aspirating 800 ml of 0.2 M NaCl and bringing the total volume to 1 L with
methanol. The material was resuspended, and magnetically extracted; 800 ml
of supernatant were removed, and another 800 ml of methanol were added.
After three additions of methanol, the oxide was ready for silanization in a
solution which was approximately 1% (V/V) water. A portion of the precipitate
was dried at 70°C for 24 hours and weighed; 11.2 g of magnetic iron oxide
were formed.
Silanization
Superparamagnetic iron oxide with Fe2+/Fe3+ ratio of 2 was washed with
water. 1 g of particles (about 20 ml of settled particles) was mixed with 2 g of
ortophosphorous acid and then with 100 ml of a 10% solution of 3-
aminopropyltrimethoxysilane in water. The pH was adjusted to 4.5 with glacial
acetic acid. The mixture was mixed for 2 hours at 90-95°C. After cooling, the
particles were washed 3 times with water (100 ml), 3 times with methanol
(100 ml) and 3 times with water (100 ml). Both the heating and cooling steps
were performed under nitrogen with stirring.
Preparation of Carboxylic Acid-Terminated Magnetic Particles
A
A superparamagnetic iron oxide was silanized with 3-
aminopropyltrimethyoxysilane. The amino group of the silane was reacted
with glutaric anhydride to convert the amine groups to carboxylic acid groups.
The conversion of the termination was accomplished as follows: 5 g of
aminopropyl silanized particles in water were washed four times with 1.5 liters
of 0.1 M NaHCO3. The volume was adjusted to 100 ml and 2.85 g glutaric
anhydride was added. The particles were washed 2 times and the reaction
with glutaric anhydride was repeated. The carboxylic acid-terminated
magnetic particles were washed 5 times with water to prepare them for
reaction with protein.
For binding protein and human serum albumin to carboxylic acid-terminated
magnetic particles was used carbodiimide coupling method.
General Description
Ferumoxsil is a turbid,slightly viscous, dark brown to orange-brown aqueous suspensionof silicone-coated, SPIO for oral administration.The suspension distributes to the stomach and small intestinewithin 30 to 45 minutes and passes distally to the largeintestine within 4 to 7 hours after ingestion. It is indicated toenhance the delineation of the bowel and to distinguish itfrom organs and tissues that are adjacent to the upper regionsof the GI tract. Its usefulness in the distal GI regionsis limited by transit time and dilution. Both T1- and T2-weighted images may be enhanced with ferumoxsil.
