WO2008095450A2 - Negative contrast agent for mri comprising a water suspension of clay and iron oxide nanoparticles - Google Patents
Negative contrast agent for mri comprising a water suspension of clay and iron oxide nanoparticles Download PDFInfo
- Publication number
- WO2008095450A2 WO2008095450A2 PCT/CZ2008/000012 CZ2008000012W WO2008095450A2 WO 2008095450 A2 WO2008095450 A2 WO 2008095450A2 CZ 2008000012 W CZ2008000012 W CZ 2008000012W WO 2008095450 A2 WO2008095450 A2 WO 2008095450A2
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- WO
- WIPO (PCT)
- Prior art keywords
- contrast agent
- negative contrast
- mri
- clayey mineral
- fact
- Prior art date
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1806—Suspensions, emulsions, colloids, dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
- A61K49/1887—Agglomerates, clusters, i.e. more than one (super)(para)magnetic microparticle or nanoparticle are aggregated or entrapped in the same maxtrix
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Definitions
- the present invention relates to the field of preparations for medical purposes and concerns the composition of a new oral contrast negative agent, used particularly for examination of the intestinal tract by the method of magnetic resonance imaging (MRI).
- MRI magnetic resonance imaging
- Contrast agents are divided into two groups: positive contrast agents that intensify the sensed signal and negative contrast agents that reduce the sensed signal.
- negative contrast agents it is possible to use either highly concentrated paramagnetic substances or barium or superparamagnetic iron oxides, which are added to the liquid for filling the intestines.
- the negative contrast agent suitable for imaging the intestinal tract, comprising of water suspension containing 25 - 30 weight percent of barium sulphate with 2.5 - 3.5 percent admixture of bentonite is proposed in the patent US 5741477 (Davis Michael A, ... Negative contrast agents for magnetic resonance imaging comprising barium sulfate and a clay).
- the disadvantage of this contrast agent is a big dose of both barium sulphate and bentonite.
- Another similar negative contrast agent comprising of the suspension of small grained particles of clayey mineral in water is described in the patent US 4927624 (Robert G. Bryant, ... Clay magnetic resonance contrast agents for gastrointestinal consumption or introduction). Its disadvantages are the same, high percentage of mineral, c. 50 weight percent in the suspension.
- Highly effective negative contrast agents are superparamagnetic iron oxides. Nanoparticles of ferric oxide, suspended in water, form negative contrast agent described in the document US 2006/0204438 A1 (Sun Hang Cho, ... Water soluble iron oxide nanoparticles and Method of its preparation). In this case, nanoparticles are coated with polyvinylpyrolidone and are suitable for intravenous use. However, this material in proposed composition is unserviceable for MRI of contents of the intestinal tract.
- Another example of used agents are polystyrene spherical particles with the size of c. 3 - 4 ⁇ m with active contrast agent placed inside in the form of nanoparticles of iron oxide with the size of c. 50 nm, which are described for example in the document WO 85/02772 (Schroder UIf, ... Diagnostic and contrast agent) and are usable as negative contrast agent for MRI of the intestinal tract.
- This negative contrast agent has been clinically tested and its disadvantage lies in a high price.
- Another contrast agent with similar structure comprises of agglomerates of iron oxide nanoparticles of c. 10 nm, capsulized into siloxane, where they form spherical paricles of c. 300 nm.
- Last two mentioned negative contrast agents cause practically complete reduction of the MRI signal, however, the high price, connected with the complexity and demandingness of their synthesis, represents the disadvantage of usage of this type contrast agents for MRI.
- the aim of the new invention is to present for application a new negative contrast agent, made by relatively simple synthesis and securing high quality MRI imaging for low purchase costs.
- Fig. 1 X-ray diffraction pattern of the final nanocomposite ,,bentonite-magnetite" (the lines in the bottom show positions of the diffraction lines of Fe 3 O 4 ).
- FIG. 3 Transmission electron microscope picture of the ,,bentonite-magnetite" nanocomposite.
- Fig. 4. Comparison of the contrast obtained in the MRI imaging: A - siloxane spherical particles with superparamagnetic iron oxides core, B - nanocomposite ,,bentonite- magnetite", C - mixture of bentonite and magnetite, D - pure magnetite, E - pure bentonite.
- the mentioned aim is reached via the invention that represents a negative contrast agent (particularly for the examination of the intestinal tract by the MRI method), created on the basis of superparamagnetic iron oxide nanoparticles.
- the essence of the invention is that the agent is composed of water suspension of clayey mineral and superparamagnetic iron oxide nanoparticles immobilized on the surface of the particles of the clayey mineral, in the process of which the mutual weight ratio of the oxide to the clayey mineral is 1 : 4 to 15.
- iron oxides are selected from the group iron (III) oxide Fe 2 O 3 or iron oxide Fe 3 O 4 and as the clayey mineral, kaolinite or illite is chosen.
- the clayey mineral is chosen from the group of smectites and in the convenient version, bentonite is chosen as the clayey mineral.
- the essence of the invention is that water suspension of the clayey mineral and superparamagnetic iron oxide nanoparticles is made using water or isosmotic solution.
- composition of the contrast agent are following:
- composition of the agent is composition of the agent:
- the characteristics of the final product have been examined with a whole range of analytical methods from the viewpoint of structural, magnetic and size properties.
- the X-ray powder diffraction indicates only the presence of the initial material (bentonite) and iron oxide Fe 3 O 4 (magnetite), as apparent from figure 1. Diffraction lines of Fe 3 O 4 are of very low intensity, which gives the evidence of the existence of Fe 3 O 4 in the form of nanoparticles. Also Mossbauer spectroscopy, results of which are shown in figure 2 and table 1 , shows the presence of Fe 3 O 4 in synthesized nanocomposite in superparamagnetic state, which gives the evidence of nanometre size of the magnetite particles.
- composition of the agent is composition of the agent:
- the ratio of the initial materials is 1 g of bentonite in 200 ml of distilled water, 0.50 g of FeSO 4 . 7H 2 O in 20 ml of distilled water, 0.30 g of KNO 3 in 10 ml of distilled water and 0.42 g of KOH in 10 ml of distilled water.
- composition of the agent is composition of the agent:
- the ratio of the initial materials is 1g of kaolinite in 200 ml of distilled water, 0.75 g of FeSO 4 . 7H 2 O in 20 ml of distilled water, 0.45 g of KNO 3 in 10 ml of distilled water and 0.63 g of KOH in 10 ml of distilled water.
- composition of the agent lsosmotic solution 1 Litre Bentonite 3350 mg
- the contrast agent is not suspended in water, but in isosmotic solution containing NaCI, KCI, NaHCO 3 , Na 2 SO 4 and macrogolum 4000.
- composition of the agent is composition of the agent:
- the contrast agent that comprises of montmorilonite particles on which nanoparticles of gamma-Fe 2 O 3 are immobilized, is not suspended in water, but in isosmotic solution containing NaCI, KCI, NaHCO 3 , Na 2 SO 4 and macrogolum 4000.
- the negative contrast agent according to the invention is utilizable particularly in medicine for examining patients ' intestinal tract by the method of magnetic resonance imaging (MRI).
- MRI magnetic resonance imaging
Abstract
Negative contrast agent, particularly for examination of the intestinal tract by the method of MRI, formed on the basis of superparamagnetic iron oxides nanoparticles. The essence of the invention is that the agent comprises of water suspension of clayey mineral and superparamagnetic iron oxides nanoparticles immobilized on the surface of the clayey mineral particles, in the process of which the mutual weight ratio of the oxide to the clayey mineral is 1 : 4 to 15.
Description
Negative contrast agent
Field of invention
The present invention relates to the field of preparations for medical purposes and concerns the composition of a new oral contrast negative agent, used particularly for examination of the intestinal tract by the method of magnetic resonance imaging (MRI).
Background of invention
During the examination of the intestinal tract by the method of MRI, it is necessary to fill the intestinal tract with a suitable liquid, so that quality image of the intestinal walls can be reached. The application of MRI for imaging the abdominal cavity, especially intestinal tract, faces many problems, connected with the intestinal peristalsis, breathing and heart pulse movements, which are the causes of a whole range of image artefacts. It is necessary to apply contrast agents to distinguish either liquid filled or empty intestines from other organs located in the abdominal cavity and from possible pathological damages. Contrast agents are divided into two groups: positive contrast agents that intensify the sensed signal and negative contrast agents that reduce the sensed signal.
As for negative contrast agents, it is possible to use either highly concentrated paramagnetic substances or barium or superparamagnetic iron oxides, which are added to the liquid for filling the intestines. The negative contrast agent, suitable for imaging the intestinal tract, comprising of water suspension containing 25 - 30 weight percent of barium sulphate with 2.5 - 3.5 percent admixture of bentonite is proposed in the patent US 5741477 (Davis Michael A, ... Negative contrast agents for magnetic resonance imaging comprising barium sulfate and a clay). The disadvantage of this contrast agent is a big dose of both barium sulphate and bentonite.
Another similar negative contrast agent, comprising of the suspension of small grained particles of clayey mineral in water is described in the patent US 4927624 (Robert G. Bryant, ... Clay magnetic resonance contrast agents for gastrointestinal consumption or introduction). Its disadvantages are the same, high percentage of mineral, c. 50 weight percent in the suspension.
Highly effective negative contrast agents are superparamagnetic iron oxides. Nanoparticles of ferric oxide, suspended in water, form negative contrast agent described in the document US 2006/0204438 A1 (Sun Hang Cho, ... Water soluble iron oxide nanoparticles and Method of its preparation). In this case, nanoparticles are coated with polyvinylpyrolidone and are suitable for intravenous use. However, this material in proposed composition is unserviceable for MRI of contents of the intestinal tract.
Another example of used agents are polystyrene spherical particles with the size of c. 3 - 4 μm with active contrast agent placed inside in the form of nanoparticles of iron oxide with the size of c. 50 nm, which are described for example in the document WO 85/02772 (Schroder UIf, ... Diagnostic and contrast agent) and are usable as negative contrast agent for MRI of the intestinal tract. This negative contrast agent has been clinically tested and its disadvantage lies in a high price. Another contrast agent with similar structure comprises of agglomerates of iron oxide nanoparticles of c. 10 nm, capsulized into siloxane, where they form spherical paricles of c. 300 nm. This substance is described for example in the article: Yi-Xiang J. Wang, Shahid M. Hussain, Gabriel P. Krestin: Superparamagnetic iron oxide contrast agents: physicochemical characteristics and application in MR imaging, Eur. Radiol 11 (2001), 2319-2331). The disadvantage of these substances is again in a high price.
Last two mentioned negative contrast agents cause practically complete reduction of the MRI signal, however, the high price, connected with the complexity and demandingness of their synthesis, represents the disadvantage of usage of this type contrast agents for MRI. The aim of the new invention is to present for application a new negative contrast agent, made by relatively simple synthesis and securing high quality MRI imaging for low purchase costs.
Figure description
Fig. 1. X-ray diffraction pattern of the final nanocomposite ,,bentonite-magnetite" (the lines in the bottom show positions of the diffraction lines of Fe3O4 ).
Fig. 2. Mόssbauer spectrum of the final composite ,,bentonite-magnetite".
Fig. 3. Transmission electron microscope picture of the ,,bentonite-magnetite" nanocomposite.
Fig. 4. Comparison of the contrast obtained in the MRI imaging: A - siloxane spherical particles with superparamagnetic iron oxides core, B - nanocomposite ,,bentonite- magnetite", C - mixture of bentonite and magnetite, D - pure magnetite, E - pure bentonite.
Description of the invention
The mentioned aim is reached via the invention that represents a negative contrast agent (particularly for the examination of the intestinal tract by the MRI method), created on the basis of superparamagnetic iron oxide nanoparticles. The essence of the invention is that the agent is composed of water suspension of clayey mineral and superparamagnetic iron oxide nanoparticles immobilized on the surface of the particles of the clayey mineral, in the process of which the mutual weight ratio of the oxide to the clayey mineral is 1 : 4 to 15.
Another essence of the invention is that iron oxides are selected from the group iron (III) oxide Fe2O3 or iron oxide Fe3O4 and as the clayey mineral, kaolinite or illite is chosen.
Also it is the essence of the invention that the clayey mineral is chosen from the group of smectites and in the convenient version, bentonite is chosen as the clayey mineral.
Finally, the essence of the invention is that water suspension of the clayey mineral and superparamagnetic iron oxide nanoparticles is made using water or isosmotic solution.
Usage of the negative contrast agent according to the invention leads to a new effect of acquirement of the same or better parameters of imaging together with much more simple production than complicated synthesis, used so far for production of contrast agents, thus the production price and selling price is much lower, which results in lowering the costs connected with the examination of the patients.
Examples of the implementation of the invention
Concrete examples of composition of the contrast agent are following:
EΞxample 1 :
Composition of the agent:
Water 1 Litre
Bentonite 3350 mg
Magnetite (Fe3O4) 250 mg
Process of preparation:
By adding of 1g of bentonite into 200 ml of distilled water and stirring, homogenous suspension is obtained, into which the solution of 0.25 g FeSO4 7H2O in 20 ml of distilled water is then added. The mixture is then stirred for approximately 2 hours. After this period passes and while still stirring, the solution of 0.15 g KNO3 in 10 ml of distilled water and then the solution of 0.21 g KOH in 10 ml of distilled water is added into the reactive mixture and the reactive mixture is heated up to 90 0C. While stirring continuously, it is then left to cool off to the room temperature, the solid fraction is filtered off, rinsed and air-dried in the room temperature.
The characteristics of the final product (nanocomposite) have been examined with a whole range of analytical methods from the viewpoint of structural, magnetic and size properties. The X-ray powder diffraction indicates only the presence of the initial material (bentonite) and iron oxide Fe3O4 (magnetite), as apparent from figure 1. Diffraction lines of Fe3O4 are of very low intensity, which gives the evidence of the existence of Fe3O4 in the form of nanoparticles. Also Mossbauer spectroscopy, results of which are shown in figure 2 and table 1 , shows the presence of Fe3O4 in synthesized nanocomposite in superparamagnetic state, which gives the evidence of nanometre size of the magnetite particles. Pictures from the transmission electron microscope (figure 3) show that the size of oxidic nanoparticles is under 10 nm, which corresponds with their superparamagnetic behaviour. Testing via nuclear magnetic resonance confirmed that synthetized nanocomposite ,,bentonite - magnetite" in the concentration of 3.6 g of
nanocomposite per 1 L of H2O (which is approximately 3350 mg of bentonite and 250 mg of Fe3O4 per 1L of H2O) leads to complete reduction of MRI signal, which is documented in figure 4.
EΞxample 2:
Composition of the agent:
Water 1 Litre
Bentonite 3350 mg
Magnetite (Fe3O4) 500 mg
Process of preparation:
Is analogical as in example 1 , but the ratio of the initial materials is 1 g of bentonite in 200 ml of distilled water, 0.50 g of FeSO4 . 7H2O in 20 ml of distilled water, 0.30 g of KNO3 in 10 ml of distilled water and 0.42 g of KOH in 10 ml of distilled water.
.Example 3:
Composition of the agent:
Water 1 Litre
Kaolinite 3350 mg
Magnetite (Fe3O4) 750 mg
Process of preparation:
Is analogical as in example 1 , but the ratio of the initial materials is 1g of kaolinite in 200 ml of distilled water, 0.75 g of FeSO4 . 7H2O in 20 ml of distilled water, 0.45 g of KNO3 in 10 ml of distilled water and 0.63 g of KOH in 10 ml of distilled water.
EΞxample 4:
Composition of the agent: lsosmotic solution 1 Litre
Bentonite 3350 mg
Magnetite (Fe3O4) 250 mg
Process of preparation:
Is the same as in example 1 , but the contrast agent is not suspended in water, but in isosmotic solution containing NaCI, KCI, NaHCO3, Na2SO4 and macrogolum 4000.
EΞxample 5:
Composition of the agent:
Isosmotic solution 1 Litre
Montmorilonite 3350 mg
Gama-Fe2O3 250 mg
Process of preparation:
By adding of 1g of montmorilonite into 200 ml of distilled water and stirring, homogenous suspension is obtained, into which the solution of 0.25g of FeSO4 . 7H2O and 0.5g of FeCi3 in 20 ml of distilled water is then added. The mixture is then stirred for approximately 2 hours. After this period passes and while still stirring, the solution of 0.4g of KOH in 10 ml of distilled water is added into the reactive mixture. The solid fraction is filtered off, rinsed and air-dried in the room temperature. The contrast agent that comprises of montmorilonite particles on which nanoparticles of gamma-Fe2O3 are immobilized, is not suspended in water, but in isosmotic solution containing NaCI, KCI, NaHCO3, Na2SO4 and macrogolum 4000.
Industrial utility
The negative contrast agent according to the invention is utilizable particularly in medicine for examining patients' intestinal tract by the method of magnetic resonance imaging (MRI).
Claims
1. Negative contrast agent, particularly for examining the intestinal tract by the MRI method, created on the basis of superparamagnetic nanoparticles of iron oxides, characterized by the fact, that it comprises of water suspension of clayey mineral and superparamagnetic nanoparticles of iron oxides immobilized on the surface of clayey mineral particles, in the process of which the mutual weight ratio of the oxide to the clayey mineral is 1 : 4 to 15.
2. Negative contrast agent according to claim 1 , characterized by the fact that iron oxides are selected from the group iron (III) oxide Fe2O3 or iron oxide Fe3O4
3. Negative contrast agent according to claim 1 , characterized by the fact that as the clayey mineral kaolinite or illite is selected.
4. Negative contrast agent according to claim 1 , characterized by the fact that the clayey mineral is selected from the group of smectites.
5. Negative contrast agent according to claim 4, characterized by the fact that as the clayey mineral bentonite is selected.
6. Negative contrast agent according to claim 1 , characterized by the fact that water suspension of the clayey mineral and superparamagnetic iron oxides nanoparticles is formed using water or isosmotic solution.
Priority Applications (1)
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SK50046-2009U SK5402Y1 (en) | 2007-02-08 | 2008-01-28 | Negative contrast agent for MRI |
Applications Claiming Priority (2)
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CZ20070102A CZ300445B6 (en) | 2007-02-08 | 2007-02-08 | Negative contrast agent |
CZPV2007-102 | 2007-02-08 |
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WO2008095450A2 true WO2008095450A2 (en) | 2008-08-14 |
WO2008095450A3 WO2008095450A3 (en) | 2008-12-31 |
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PCT/CZ2008/000012 WO2008095450A2 (en) | 2007-02-08 | 2008-01-28 | Negative contrast agent for mri comprising a water suspension of clay and iron oxide nanoparticles |
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SK (1) | SK5402Y1 (en) |
WO (1) | WO2008095450A2 (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102649954A (en) * | 2012-05-17 | 2012-08-29 | 兰州大学 | Immobilized enzyme for magnetic nanometer clay carrier and regenerating method thereof |
JP2020044365A (en) * | 2012-05-15 | 2020-03-26 | パルス セラピューティクス インコーポレイテッド | Magnetic-based system and method for manipulation of magnetic particles |
US11612655B2 (en) | 2009-11-02 | 2023-03-28 | Pulse Therapeutics, Inc. | Magnetic particle control and visualization |
US11918315B2 (en) | 2018-05-03 | 2024-03-05 | Pulse Therapeutics, Inc. | Determination of structure and traversal of occlusions using magnetic particles |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4927624A (en) * | 1987-11-19 | 1990-05-22 | The University Of Rochester | Clay magnetic resonance contrast agents for gastrointestinal comsumption or introduction |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
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DE59508069D1 (en) * | 1994-07-27 | 2000-04-27 | Herbert Pilgrimm | SUPERPARAMAGNETIC PARTICLES, METHOD FOR THE PRODUCTION AND USE THEREOF |
US20050260137A1 (en) * | 2004-05-18 | 2005-11-24 | General Electric Company | Contrast agents for magnetic resonance imaging |
KR100637275B1 (en) * | 2005-01-28 | 2006-10-23 | 한국지질자원연구원 | Preparation of nano size Iron oxide for MRI contrast agent by ultrasonic and manufaturing method thereof and manufaturing method of MRI contrast agent using Iron oxide nano particle and MRI contrast agent thereof |
-
2007
- 2007-02-08 CZ CZ20070102A patent/CZ300445B6/en not_active IP Right Cessation
-
2008
- 2008-01-28 WO PCT/CZ2008/000012 patent/WO2008095450A2/en active Application Filing
- 2008-01-28 SK SK50046-2009U patent/SK5402Y1/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4927624A (en) * | 1987-11-19 | 1990-05-22 | The University Of Rochester | Clay magnetic resonance contrast agents for gastrointestinal comsumption or introduction |
Non-Patent Citations (3)
Title |
---|
BARTONKOVA H ET AL: "Magnetically Modified Bentonite as a Possible Contrast Agent in MRI of Gastrointestinal Tract" XVIIITH SLOVAK SPECTROSCOPIC CONFERENCE SPISSKÁ NOVÁ VES, 15 October 2006 (2006-10-15), XP008098242 * |
BARTONKOVA H ET AL: "Mössbauer study of iron oxide modified montmorillonite" HYPERFINE INTERACTIONS, KLUWER ACADEMIC PUBLISHERS, DO, vol. 165, no. 1-4, 7 November 2006 (2006-11-07), pages 221-225, XP019480204 ISSN: 1572-9540 * |
DAVIS M A ET AL: "Optimization of a negative oral contrast agent for magnetic resonance imaging." INVESTIGATIVE RADIOLOGY JUN 1994, vol. 29 Suppl 2, June 1994 (1994-06), pages S120-S122, XP008098241 ISSN: 0020-9996 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11612655B2 (en) | 2009-11-02 | 2023-03-28 | Pulse Therapeutics, Inc. | Magnetic particle control and visualization |
JP2020044365A (en) * | 2012-05-15 | 2020-03-26 | パルス セラピューティクス インコーポレイテッド | Magnetic-based system and method for manipulation of magnetic particles |
JP7037536B2 (en) | 2012-05-15 | 2022-03-16 | パルス セラピューティクス インコーポレイテッド | Magnetic-based systems and methods for manipulating magnetic particles |
CN102649954A (en) * | 2012-05-17 | 2012-08-29 | 兰州大学 | Immobilized enzyme for magnetic nanometer clay carrier and regenerating method thereof |
US11918315B2 (en) | 2018-05-03 | 2024-03-05 | Pulse Therapeutics, Inc. | Determination of structure and traversal of occlusions using magnetic particles |
Also Published As
Publication number | Publication date |
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CZ2007102A3 (en) | 2008-11-26 |
SK500462009U1 (en) | 2009-09-07 |
SK5402Y1 (en) | 2010-03-08 |
WO2008095450A3 (en) | 2008-12-31 |
CZ300445B6 (en) | 2009-05-20 |
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