MXPA99001229A - Process and device for separating magnetic materials from pharmaceutical compositions, their starting or intermediate products and agents produced by means of this device - Google Patents
Process and device for separating magnetic materials from pharmaceutical compositions, their starting or intermediate products and agents produced by means of this deviceInfo
- Publication number
- MXPA99001229A MXPA99001229A MXPA/A/1999/001229A MX9901229A MXPA99001229A MX PA99001229 A MXPA99001229 A MX PA99001229A MX 9901229 A MX9901229 A MX 9901229A MX PA99001229 A MXPA99001229 A MX PA99001229A
- Authority
- MX
- Mexico
- Prior art keywords
- magnetic
- separation chamber
- separation
- particles
- gradient field
- Prior art date
Links
- 239000000696 magnetic material Substances 0.000 title claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 3
- 238000000034 method Methods 0.000 title description 10
- 230000005291 magnetic Effects 0.000 claims abstract description 68
- 238000000926 separation method Methods 0.000 claims abstract description 47
- 238000002347 injection Methods 0.000 claims abstract description 9
- 239000007924 injection Substances 0.000 claims abstract description 9
- 238000001802 infusion Methods 0.000 claims abstract description 7
- 239000002245 particle Substances 0.000 claims description 25
- 239000002872 contrast media Substances 0.000 claims description 15
- 239000000725 suspension Substances 0.000 claims description 12
- 239000000463 material Substances 0.000 claims description 9
- 239000002907 paramagnetic material Substances 0.000 claims description 9
- 230000005294 ferromagnetic Effects 0.000 claims description 7
- 238000003325 tomography Methods 0.000 claims description 7
- 239000004020 conductor Substances 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 230000005293 ferrimagnetic Effects 0.000 claims description 4
- 238000002583 angiography Methods 0.000 claims description 3
- 229910001220 stainless steel Inorganic materials 0.000 claims description 3
- 239000010935 stainless steel Substances 0.000 claims description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 10
- 229910052742 iron Inorganic materials 0.000 description 9
- 239000000825 pharmaceutical preparation Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 229910000831 Steel Inorganic materials 0.000 description 7
- 239000012535 impurity Substances 0.000 description 7
- 239000010959 steel Substances 0.000 description 7
- 239000006249 magnetic particle Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 229940079593 drugs Drugs 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000005298 paramagnetic Effects 0.000 description 5
- SZVJSHCCFOBDDC-UHFFFAOYSA-N Iron(II,III) oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 4
- 230000002706 hydrostatic Effects 0.000 description 4
- 238000007885 magnetic separation Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 3
- 230000005292 diamagnetic Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 239000011241 protective layer Substances 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 210000002268 Wool Anatomy 0.000 description 2
- 238000005260 corrosion Methods 0.000 description 2
- CWYNVVGOOAEACU-UHFFFAOYSA-N fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 2
- 229910000460 iron oxide Inorganic materials 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 238000005374 membrane filtration Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000006011 modification reaction Methods 0.000 description 2
- 238000011045 prefiltration Methods 0.000 description 2
- 230000000717 retained Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000007502 Anemia Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 206010022970 Iron deficiency Diseases 0.000 description 1
- 206010022971 Iron deficiency Diseases 0.000 description 1
- 210000000865 Mononuclear Phagocyte System Anatomy 0.000 description 1
- 239000004698 Polyethylene (PE) Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 229940069575 Rompun Drugs 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N Xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N al2o3 Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000003670 easy-to-clean Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000002309 gasification Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 description 1
- 239000011810 insulating material Substances 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 150000002505 iron Chemical class 0.000 description 1
- MVZXTUSAYBWAAM-UHFFFAOYSA-N iron;sulfuric acid Chemical compound [Fe].OS(O)(=O)=O MVZXTUSAYBWAAM-UHFFFAOYSA-N 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 230000000670 limiting Effects 0.000 description 1
- 230000005415 magnetization Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000002923 metal particle Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000000275 pharmacokinetic Effects 0.000 description 1
- 239000006223 plastic coating Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- -1 polyethylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920000346 polystyrene-polyisoprene block-polystyrene Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002829 reduced Effects 0.000 description 1
- 230000001105 regulatory Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000003068 static Effects 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 230000001954 sterilising Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Abstract
A device for magnetically separating pharmaceutical compositions, as well as their starting or intermediate products, has a separation chamber in which a magnetic gradient field is generated and which is provided with an inlet and an outlet. The device is designed as a filter attached to injection or infusion instruments.
Description
METHOD FOR MANUFACTURING AGENTS OF CONTRAST FOR THE TOMOGRAPHY OF MAGNETIC RESONANCE
Description of the Invention The invention relates to the object of the invention, that is to say, a process for manufacturing contrast agents for magnetic resonance tomography, contrast agents that are manufactured with the aid of this method and, the use of these contrast agents. In the pharmaceutical preparations, foreign particles can be introduced in the form of impurities of metal particles by the method steps with metal tools or in metal containers, or by injection instruments. For this reason pharmacopoeias, in the case of parenterally administered preparations, in this case in particular infusions, set maximum limits for the amount of foreign particles weighted according to the size of the particles as protection for patients. In the case of foreign particles, it is often ferro, ferri, superpara or paramagnetic compounds. The ferromagnetic impurities of natural origin of a starting substance can be separated according to a method that is described in the patent document US 4,119,700. In it the ferromagnetic impurities are separated with the help of a magnetic field. Patent methods WO 90/07380 and WO 83/02405 describe methods for separating biological materials. Patent document WO 90/07380 describes an apparatus in which a separation chamber is surrounded by a permanent magnet and having an inlet and an outlet. European patent application EP 670 185 describes a similar apparatus by means of which magnetic-labeled cells are separated. In the case of pharmaceutical preparations to date, the number of foreign particles is reduced as much as possible by filtration processes by adsorption or by
JLO membrane filtration. But above all it is very difficult to achieve a reduction of the foreign particles in the case of impurities that originate due to manipulation where the user, such as the injection of drugs in infusion vessels, by virtue of porosity membrane filters
fine can often only be operated with a pressure
^ Mechanical additional. Therefore, the pore sizes in the filter inserts of the infusion instruments in most cases are in the range of a few micrometers, which only lead to retention rates
unsatisfactory foreign particles. In the case of particular pharmaceutical preparations, * such as eg fat emulsions or parenteral crystalline suspensions as forms of drug depot application, it is generally quite impossible to effect separation of the
foreign particles by membrane filtration or by adsorption. In the patent document US 3,817,389 a filter is described that can be integrated into an injection instrument. This filter is not magnetic and does not contain magnetic particles either. 5 A method for the manufacture of contrast agents for magnetic resonance tomography was developed in which a suspension of particles based on particles for para, superpara, ferro or ferrimagnetic is filtered with the help of a magnetic filter. 0 The magnetic filter allows to separate all the compounds that are ferro, ferri, superpara or paramagnetic. The gradient field used for the separation must be clearly greater than the terrain gradient. The choice of the appropriate gradient field is a function of the magnetic moment of the substance to be separated. To separate the paramagnetic compounds from the diamagnetic pharmaceutical preparations, high gradient fields are required. To separate the undesirable magnetic compounds, the respective pharmaceutical preparation or its starting or intermediate product is passed through the magnetic filter and consequently, through a magnetic gradient field. The higher the gradient of the magnetic gradient field, the greater the force acting on the para, ferri, superpara or ferromagnetic compounds. Medicines and pharmaceutical auxiliary substances (such as water, for example) are usually diamagnetic and consequently experience a very small force compared with ferrous, super-ferrous or ferromagnetic impurities, which otherwise does not cause them to migrate. in the direction of the gradient but rather rejects them. Consequently, in the case of the separation of magnetic impurities from diamagnetic preparations in the magnetic gradient field according to the invention, contrary to filtration through fine-pore filters (for example membrane filters of 0.22 μm), it is not As a rule, it is necessary to apply extraordinary pressure, as a rule, gravitational force or hydrostatic pressure is sufficient. In the magnetic filter according to the invention, the separation of the undesirable magnetic particles is carried out with the aid of a flow-through process. Contrary to the static processes, in the processes of circulation of passage it is necessary to synchronize the circulation rate with the magnetic moments of the ferro, ferri or superparamagnetic substances to be separated and with the applied field gradients. The execution of the magnetic filter according to the invention can be carried out in various ways. The gradient field in the separation chamber can be generated, for example, by a permanent magnet or an electromagnet that is placed outside the separation chamber. In order to increase the locally effective gradient of the magnetic field, it can be extremely useful in this case for the separation chamber to consist of paramagnetic material or soft magnetic material and / or to contain paramagnetic material or preferably soft magnetic material. But the magnetic gradient field can be produced in the separation chamber by a permanently magnetic material, which forms the separation chamber or is inside the separation chamber. In addition, the magnetic gradient field in the separation chamber can also be produced by a current path conductor, which either lies within the separation chamber or surrounds the separation chamber. In both of the abovementioned cases, it may again be very useful for the separation chamber to consist of paramagnetic material or soft magnetic material and / or to contain paramagnetic material or preferably soft magnetic material. The soft magnetic substances are preferably magnetically soft iron or steel, in particular in the form of fine grains (for example spheres with a diameter of a few millimeters) or fried or in the form of a wire (for example steel wool, nets or screens). The walls of the separation chamber, as well as the soft magnetic materials or paramagnetic materials and the electrically-current conductors that are inside the separation chamber can be additionally provided with suitable protective layers as protection against undesirable chemical reactions. , such as corrosion, such protective layers can be the materials known through the theory of knowledge of materials, for example chrome plating, protective layers of stable oxides (such as aluminum oxide), plastic coatings are suitable. (for example PVC, polystyrene, polyethylene) In the case of using current-guided conductors inside the separation chamber for the production of the magnetic gradient fields, an insulation with the known insulating materials is required anyway (as for example synthetic materials in the form of coating lacquer materials) . Examples of possible embodiments of the magnetic filter according to the invention as a prefilter are shown in FIG. 1. The magnetic filter according to the invention can also be integrated into injection and infusion instruments. Examples of magnetic separation filters integrated in infusion instruments are shown in figures 2 and 3. Another embodiment of a magnetic filter integrated in an injection instrument is represented in figure 4. The different embodiments outlined in figure 1, as for example the use of paramagnetic spheres or current-guided conductors can be used in all the filters for the magnetic separation according to the invention integrated in the infusion or injection instruments. Another special embodiment is shown in Figure 5. In this case, the separation chamber contains a soft magnetic plate that must be magnetized during the filtration, which contains holes through which the liquid to be separated or the suspension is guided or the salt. By means of a multitude of holes of small diameter a large magnetic contact surface can be achieved for the liquid to be separated. Such cymbals or cylinders are preferably made of stainless steel, of the type used in pharmaceutical manufacturing processes. They can be integrated into or adapted to pipe systems, which responds favorably to the exceptional purity requirements of a pharmaceutical manufacturing process. Suitable stainless steel saucers are resistant to corrosion with respect to the aggressive components of drugs within a wide range of pH. They are also easy to clean, among other things also by applying the conventional methods of heat sterilization. The magnetization of the soft magnetic plates is carried out by means of an annular magnet or a current-coil which are outside the separation chamber and therefore do not have to be cleaned. By means of the diameter of the steel plates, the quantity and length of the holes, which corresponds to the height of the cymbals or cylinders, the speed of flow of the liquid to be separated and its time of permanence can be regulated, or the ratio of the liquid to be separated with respect to the irrigated magnetized surface of the orifices, so that an optimum degree of separation results. Additionally it is possible to reduce the speed of the flow in the steel plate or in the cylinder, if several steel saucers or successive cylinders are used for the separation, and the orifices of the plates or the cylinders are arranged in a transposed form others. Another special embodiment is obtained if the steel plates in the upper part of the separation chamber are not magnetizable or are constituted by non-magnetized material, and the plates in the lower part of the separation chamber are magnetized by the magnet external annular or by means of a coil traveled by current. By this means, the magnetic particles are retained exclusively in the lower part of the separation chamber. In the case of the magnetic filter according to the invention for the separation of pharmaceutical preparations, it represents a particular advantage that it can be sterilized by simple means, such as heat treatment, exposure to superheated steam in an autoclave, and gasification with oxide. of ethylene. It is also much more robust than conventional membrane or pore filters. The magnetic filter according to the invention can also be particularly useful as a pre-filter for the reduction of the number of particles prior to conventional filtration methods, such as for example sterile filtration. Another aspect of the invention relates to the preparation of pharmaceutical agents, in particular contrast agents which can be obtained with the aid of the magnetic filter according to the invention. The magnetic filter according to the invention serves to select certain particles of pharmaceutical preparations based on para, superpara, ferro or ferrimagnetic particles. This can happen by varying the field strength. Thus, for example, of a pharmaceutical formulation containing a mixture of different magnetic particles (such as for example suspensions containing magnetite, which are used in magnetic resonance tomography) can separate particles that have an exceptionally high magnetic moment. Agents containing magnetic particles are used, for example, as contrast agents in nuclear resonance tomography. Among other things, suspensions based on superparamagnetic magnetites are used in it. Surprisingly, it is possible in this case to separate a mixture of particles according to their magnetic moments, among other things as a function of the field strength of the gradient, ie in this case the method according to the invention can be manipulated in such a way that a complete separation of the magnetic particles is not carried out but rather a selective separation, in particular particles with high magnetic moments being retained. The agents which are surprisingly obtained thereby have considerably improved properties for their field of application in diagnosis than the suspensions of original particles. This results in agents for new special fields of application, such as the use as a contrast agent in magnetic resonance angiography or magnetic resonance lymphography. Thus, for example, with the aid of the magnetic filter according to the invention, an influence can be exerted on the relaxation behavior of the resulting agents and thus on the increase of contrast in TRM processes. For certain diagnostic medical devices or for certain diagnostic questions, a T1 modification of the relaxation is preferred, in other cases the T2 modification of the relaxation (or a suitable combination thereof) of the hydrogen atoms to the molecules physiological factors adjacent to the superparamagnetic particles applied to make a diagnosis or a diagnostic picture. Through the magnetic separation an influence can be exerted on these parameters - as also shown in the following examples. Therefore, with the help of the magnetic filter
it is possible to elaborate a medicine with magnetic properties modified from an existing medicine. By virtue of which the assimilation in the reticuloendothelial system
(SRE) of the particles that are introduced parenterally in
^^ Humans or animals depend among other things on the size,
The magnetic separation also makes it possible to exert an influence on the in vivo pharmacokinetic properties of the pharmaceutical preparations. The hitherto known methods for controlling the size distribution are unsatisfactory. These are based on little expensive precipitation methods
controllable during the preparation of the substance of
^^ medicine or in filtration processes. The latter, as already explained, suffer from intrinsic disadvantages. Also the separation of comparatively larger superparamagnetic particles from medicinal preparations
Colloidal by means of centrifugation or sedimentation processes is very expensive in terms of the process technique, or is eliminated for other reasons, such as insufficient stability of the drug or its formulation. The magnetic filter according to the invention is
, further applies for the separation of ferrous or ferrimagnetic impurities particles from paramagnetic pharmaceutical preparations, such as iron dextran or iron salt solutions (for example, dextran iron injection, USP XXV), which are applied for the therapy of anemia of iron deficiency. The following examples serve to explain the object of the invention in more detail, without limiting it to them.
Example 1 In 10 ml of an aqueous solution of 4.69 g of gadopentent of dimeglumine about 100 mg of iron filings are suspended. A magnetic filter is assembled, as shown in the diagram in Figure 1, from an annular magnet (RL 19, IBS Magnet, Berlin) of 19 mm external diameter, 6.5 mm internal diameter and 10 mm high, and of a separating chamber, arranged in the internal space of the magnet. This separating chamber is constituted by a plastic wall and is filled with steel wool. The suspension is passed through the magnetic filter by the action of the hydrostatic pressure, without applying any additional pressure-after the magnetic filtration, a microscopic examination shows that the filter has eliminated the iron filings from the solution of the contrast medium . Example 2 A magnetic filter as shown schematically in FIG. 1 is assembled from an annular magnet (NE
1556, IBS Magnet, Berlin), 15 mm external diameter, 5 mm internal diameter and 6 mm high, and a separating chamber disposed in the internal space of the magnet. The separating chamber
is constituted by a wall of plastic material and filled with iron pellets about 0.3 mm in diameter. By this magnetic filter is passed, by action of hydrostatic pressure, 0.8 ml of a superparamagnetic colloidal solution
^ of iron oxide nanoparticles (obtained according to the patent
North American No 4 101 435, example 7) containing 500 millimoles of iron per liter and have a relaxivity T2 (r2) of about 160 1 / (mmol s). The relaxivity T2 (r2) of the filtrate is around 60 1 / (mmol s). It was determined that the ratio r2 / t1 between the relaxivities for the untreated solution was 7.4, while ^^ that for the filtering was 3.2. All MR angiograms (Figures 6 to 8) were recorded on an experimental TRM (SISCO SIS 85, 2.0 tesla) using the A 3 D FLASH technique (10/2, 6/40 °). 20 Han Wistar rats weighing 200 g, anaesthetized with a mixture of Rompun® / Ke avet®, 1: 1 were used as test animals. With the initial substance "unfiltered" and with the "filtered" preparation of the invention, firstly,
precontrast shots (before applying the contrast medium), and then after 1, 15 and 30 minutes of applying the respective contrast medium intravenously. In each case a dose of about 100 μmol of iron per kg of body weight was applied. Figure 6 shows MR angiograms of the magnetic suspension, "unfiltered", before contrast (a), and contrast after 1 minute (b) and 15 minutes (c), respectively. The contrast effect after 1 minute and 15 minutes has little value for a diagnosis. 10 Figure 7 shows the MR angiograms of the magnetite suspension, 'filtered' [(a) precontrast; (b) 1 minute from the intravenous application; (c) 30 minutes after intravenous application]. In this case, a large number of vessels can be unequivocally detected after 1 minute, and 15 the effect is increased impressively after 30 minutes of application of the contrast medium. In comparison with the untreated substance, the preparation of the contrast medium, obtained according to the invention, is excellently suited for magnetic resonance angiography. Example 3 A magnetic filter as shown schematically in FIG. 1 is assembled from an annular magnet (NE
2016, IBS Magnet, Berlin) of 20 mm external diameter, 10 mm internal diameter and 6 mm high, and a separating chamber
arranged in the interior space of the annular magnet. The separating chamber is made of plastic material and filled with iron shot of approximately 0.3 mm in diameter. Through this magnetic filter, 0.8 ml of a superparamagnetic colloidal solution of iron oxide particles (obtained according to the North American patent No, 4 101 435, example 7), containing 500 millimoles of water, is filtered by hydrostatic pressure. iron per liter and has a relaxivity T2 (r2) of around 160 1 / (mmol s). In the filtering, the relation between the relaxivities r2 and t1 is: r2 / r1 = 2.1. The angiograms obtained with this preparation are reproduced in figure 8. Even after one minute (b) it is possible to recognize a differentiation of the vessels, similar to that which is achieved only after a much longer period with the preparation obtained according to the Example 2. Figure 8a corresponds to the precontrast and 8c to the contrast after 30 minutes of the intravenous application of the preparation.
Claims (16)
1. Method for the development of contrast agents for magnetic resonance tomography, characterized by the 5 fact that with the help of a magnetic filter a suspension of particles based on particles for super, ferro or ferrimagnetic is filtered.
2. Method according to claim 1, characterized by the fact that the particle suspension is 10 a suspension based on superparamagnetic magnetites. Method according to claim 1, characterized in that the magnetic filter contains a separation chamber having an inlet and an outlet and in which a magnetic gradient field reigns. 4. Method according to claim 1 or 3, ^^ characterized by the fact that the magnetic filter is integrated in injection or infusion instruments. Method according to claim 3, characterized in that the magnetic gradient field 20 in the separation chamber is formed by a permanent magnet or an electromagnet that is disposed outside the separation chamber. Method according to claim 3 or 5, characterized in that the separation chamber 25 consists of paramagnetic material or soft magnetic material and / or contains paramagnetic material or soft magnetic material. Method according to claim 3, characterized in that the magnetic gradient field in the separation chamber is generated by paramagnetic material, which forms the separation chamber or is inside the separation chamber. 8. Method according to claim 3, characterized in that the magnetic gradient field in the separation chamber is generated by a traveled conductor TJO by current, which either is inside the separation chamber or surrounds the separation chamber. Method according to claim 7 or 8, characterized in that the separation chamber additionally contains paramagnetic material or material 15 magnetic soft. ^ k 10. Method according to claim 1, characterized in that the magnetic filter is sterile. Method according to claim 3, characterized in that the separation chamber 20 contains one or several soft magnetic cymbals which must be magnetized during the separation, which are provided with holes through which the liquid to be separated is conducted. Method according to claim 11, characterized in that several successive plates are located in the separation chamber, the orifices of which are arranged transposed from one another. 1
3. Method according to claim 11 or 12, characterized in that the plates in the upper part of the separation chamber are not magnetizable or consist of non-magnetizable material, and the cymbals in the lower part of the separation chamber are magnetized by an external annular magnet or a current-coil. Method according to one of claims 11 to 13, characterized in that the soft magnetic plates are made of stainless steel. 15. Contrast agent for magnetic resonance tomography, characterized in that it is prepared according to the method according to one of claims 1 - 1
4. 16. Use of contrast agents that were made with the aid of a method according to one of claims 1-14 on magnetic resonance angiography or magnetic resonance lymphography.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19632416.5 | 1996-08-05 |
Publications (1)
Publication Number | Publication Date |
---|---|
MXPA99001229A true MXPA99001229A (en) | 2000-02-02 |
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