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Particles for NMR imaging and method of manufacture

A technology of nuclear magnetic resonance imaging and particles, applied in preparations, applications, and pharmaceutical formulations for in vivo experiments

Inactive Publication Date: 2001-12-19
BRACCO INT BV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the prior art has not succeeded in providing long-lasting magnetic particles and thus blood pool contrast agents that would enable these analytical techniques to make such measurements and produce satisfactory data

Method used

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  • Particles for NMR imaging and method of manufacture
  • Particles for NMR imaging and method of manufacture
  • Particles for NMR imaging and method of manufacture

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Dissolve 81.1mg (0.3mmol) FeCl in 40ml water 3·6H 2 O and 25.8mg (0.13mmol) FeCl 2 ·4H 2 O (total Fe=0.43 mmol or 24.01 mg). Add FeCl to it 3 0.1mCi of the form 59 Fe (number of tracers). The mixture was stirred, and a 7.5% aqueous ammonia solution was added dropwise until the pH reached a stable value of 8.6. The formed black particle suspension was heated at 75°C for 5 minutes, and then left at room temperature to precipitate the particles. The precipitate was washed three times by decantation with 100 ml of water. After washing, the particles were resuspended in 45ml of water under stirring, and the iron concentration in the suspension was 0.533mg / ml.

[0040] To 10ml of this suspension (5.33mg Fe) was added component (a) 100mg dipalmitoyl phosphoric acid-sodium salt (DPPA Na), sonicated for 20 minutes (BRANSON250 Sonifier, 1 / 8" microprobe, output 20(15-20W)). The temperature raised to 68℃ during sonic treatment is lowered to room temperature, and component (b) 100mg Syn...

Embodiment 2

[0053] The experiments performed under the conditions described in Example 1 and the description given in Figure 2 and Table 3 further support the observation of the phenomenon reported in the discussion of the results of Example 1. The representative samples of groups b), c), d) and f) were prepared according to the methods of EP-A-0 272 091 and EP-A-0 274285, while other samples were prepared as described in Example 1. Prepared by the method of the present invention. The results clearly prove that the magnetic iron oxide particles (group a) prepared with only non-ionic surfactants can only stay in the circulation for a short time. The use of DSPC / cholesterol liposome capsules with or without nonionic surfactants did not improve the characteristics of the blood pool reagents (group b). Various phospholipids are known as useful materials for preparing stable iron oxide particles. However, in fact, if a negatively charged phospholipid such as dipalmitoylphosphatidylcholine (DPPC) o...

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Abstract

Magnetite particles suitable for injection into the blood stream of patients having enhanced resistance against agglomeration and uptake by the RES of the liver and spleen. The particles essentially consist of an iron oxide core and a phosphoric acid mono alkyl or alkenyl ester or glycerophospholipid / surfactant three dimensional shell surrounding the core. The core and the monoester or a micellar glycerophospholipid form an urchin-like structure which is further interlaced or intertwined with a non-ionic surfactant to produce a protective three dimensional shell which renders particles almost undetectable by the macrophages. Particles prepared according to the invention are kept in the blood circulation for long periods and represent excellent long lasting blood pool agents. Key components in the shell are (a) a polybasic mineral-organic species such as glycero phosphatidic acid in micellar form and (b) a block copolymer having successive hydrophilic and hydrophobic segments.

Description

Invention field [0001] The present invention relates to iron oxide particles that can be injected into the bloodstream of a patient when in suspension. The anti-agglutination stability of the particles is enhanced, they are relatively imperceptible to the reticuloendothelial system (RES), and their resistance to the clearance of macrophages is increased. This kind of particles is useful for preparing blood pool contrast agent. technical background [0002] Titanium oxide particles are used for diagnostic purposes in the form of an injectable aqueous suspension, which has attracted much interest in the past. Ferromagnetic materials or superparamagnetic iron ore microcrystals have been used as contrast agents for MRI of the liver and spleen. Their use as contrast agents in these organs is based on the idea that these particles are recognized by RES and captured quickly after injection. These particles are then cleared from the bloodstream, stored in the liver and sple...

Claims

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Application Information

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IPC IPC(8): A61K49/18A61K9/127A61B5/055A61KA61K49/00
CPCA61K49/1806A61K49/1839Y10S977/904Y10S977/838Y10S977/927Y10S977/905Y10S977/96Y10T428/2998Y10T436/24Y10T428/2991
Inventor H·图尼耶R·亚森特M·施奈德
Owner BRACCO INT BV
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