AU2006203585B2 - A hemostatic composition - Google Patents
A hemostatic composition Download PDFInfo
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- AU2006203585B2 AU2006203585B2 AU2006203585A AU2006203585A AU2006203585B2 AU 2006203585 B2 AU2006203585 B2 AU 2006203585B2 AU 2006203585 A AU2006203585 A AU 2006203585A AU 2006203585 A AU2006203585 A AU 2006203585A AU 2006203585 B2 AU2006203585 B2 AU 2006203585B2
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- bleeding
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- 239000000203 mixture Substances 0.000 title claims description 38
- 230000002439 hemostatic effect Effects 0.000 title claims description 18
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- 239000012530 fluid Substances 0.000 claims description 25
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 22
- 238000000576 coating method Methods 0.000 claims description 20
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- 230000000740 bleeding effect Effects 0.000 claims description 17
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- IVMYJDGYRUAWML-UHFFFAOYSA-N cobalt(ii) oxide Chemical compound [Co]=O IVMYJDGYRUAWML-UHFFFAOYSA-N 0.000 claims description 2
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- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims 1
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- 229910000480 nickel oxide Inorganic materials 0.000 claims 1
- GNRSAWUEBMWBQH-UHFFFAOYSA-N oxonickel Chemical compound [Ni]=O GNRSAWUEBMWBQH-UHFFFAOYSA-N 0.000 claims 1
- 208000032843 Hemorrhage Diseases 0.000 description 20
- 208000027418 Wounds and injury Diseases 0.000 description 11
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- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
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- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 description 4
- 229910052911 sodium silicate Inorganic materials 0.000 description 4
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- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 description 3
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- VBMVTYDPPZVILR-UHFFFAOYSA-N iron(2+);oxygen(2-) Chemical class [O-2].[Fe+2] VBMVTYDPPZVILR-UHFFFAOYSA-N 0.000 description 2
- 239000011553 magnetic fluid Substances 0.000 description 2
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- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 101150039033 Eci2 gene Proteins 0.000 description 1
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- 229940030225 antihemorrhagics Drugs 0.000 description 1
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- 230000008901 benefit Effects 0.000 description 1
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- 239000003114 blood coagulation factor Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
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- FDWREHZXQUYJFJ-UHFFFAOYSA-M gold monochloride Chemical compound [Cl-].[Au+] FDWREHZXQUYJFJ-UHFFFAOYSA-M 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 239000002874 hemostatic agent Substances 0.000 description 1
- 239000010720 hydraulic oil Substances 0.000 description 1
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- 238000000338 in vitro Methods 0.000 description 1
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
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- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 1
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- Materials For Medical Uses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Description
AUSTRALIA
Patents Act 1990 COMPLETE SPECIFICATION STANDARD PATENT Applicant: MATERIALS MODIFICATION,
INC.
Invention Title: A HEMOSTATIC
COMPOSITION
The following statement is a full description of this invention, including the best method of performing it known to us: 2 Q)A HEMOSTATIC COMPOSITION ;BACKGROUND OF THE INVENTION The present invention is generally directed to hemostatic compositions, and more particularly to a I magnetic hemostatic composition for controlling external 00 i or internal bleeding.
All references, including any patents or patent I 10 application, cited in this specification are hereby
INO
incorporated by reference. No admission is made that any c- reference constitutes prior art. The discussion of the references states what their authors assert, and the applicants reserve the right to challenge the accuracy and pertinency of the cited documents. It will be clearly understood that, although a number of prior art publications are referred to herein, this reference does not constitute an admission that any of these documents form part of the common general knowledge in the art, in Australia or in any other country.
Magnetic fluids are magnetic field responsive fluids containing magnetizable particles dispersed in a liquid carrier. These fluids typically have been used in devices, such as dampers, shock absorbers, seals, valves and the like to provide varying stress levels controlled by an external magnetic field. The variable stress is created by magnetic coupling of the particles in the form of chains or bent wall-like structures upon interaction with an external magnetic field. As to the composition, these fluids are typically made of micron-sized particles dispersed in an engineering medium, such as hydraulic oil, mineral oil, or water, or the like.
More recently, the use of magnetic particles has been extended to both in vitro and in vivo applications, including drug targeting, bimolecular separation and detection, and magnetic resonance imaging (MRI). The compositions of such particles are, however, limited only H:\cintae\Keep\peci\P61866 doc 15/08/06 O 3 00 0 to certain types of iron oxides, for example, magnetite, due to its biodegradibility and biocompatibility.
O
O However, many properties of such particles, for example, I\O toxicity and immunological response, are still unknown.
Various prior art methods and compositions disclose the use of hemostatic agents to attenuate bleeding.
00 Examples include U.S. Patents 3,047,507; 3,937,839; 4,107,288; 4,268,413; 4,443,430; 4,501,726; 4,554,088; S 4,637,394; 4,721,618; 4,992,190; 4,999,188; 5,180,583; \D 10 5,202,352; 5,207,675; 5,236,410; 5,354,488; 5,358,659; 5,374,246; 5,427,767; 5,507,744; 5,595,735; 5,624,685; 5,635,162; 5,635,215; 5,645,849; 5,670,078; 5,695,480; 5,702,630; 5,782,954; 5,800,372; 6,036,955; 6,051,607; 6,096,021; 6,189,538; 6,299,619; 6,315,709; 6,335,384 and 6,355,275.
There is a need in the industry, however, for a hemostatic composition or fluid which controls both external and internal hemorrhage.
OBJECTS AND SUMMARY OF THE INVENTION One embodiment of the present invention provides a magnetic, biocompatible, non-toxic hemostatic fluid composition, which exhibits rheological changes upon interaction with an external magnetic field is easily disposable, noninteracting with other biological structures or biomolecules present in the bloodstream, and which can be effectively used to control both internal and external hemorrhage anywhere in the circulatory system of a subject.
The inventors disclose a hemostatic composition and/or fluid, which controls or stops bleeding in a very short time, for example, in less than about five minutes.
The inventors also disclose a hemostatic composition and/or fluid, which undergoes a reversible liquid-solid transition under the action of an external magnetic field that causes localized hemostasis at the site of an injury N: \Melboune\Caises\Patent\51000-51999NP519 .AU. Specis\P51969.AU. 1 nAended pagesdoc 13/10/08 4 00 or lesion.
The inventors also disclose a hemostatic composition 0 O and/or fluid, wherein the particle dispersed therein can IND be easily produced with tailored dimensions, such as size, shape and distribution, to optimize magnetic response, to make the particles biocompatible and non-toxic, and to 00 easily dispose off the particles after treatment.
n An additional embodiment of the present invention provides a method of controlling or arresting hemorrhage ID 10 or bleeding (external or internal) by the use of magnetic particles dispersed in various fluids.
In summary, the present invention generally provides magnetically responsive and biocompatible particles that, when dispersed in various fluids, exhibit rheological changes upon interaction with an external magnetic field.
These fluids, when injected at the site of a lesion or injury, for example, a capillary hemorrhage, form a seal once a magnetic field is positioned adjacent the site of the injury or lesion. The seal formation is due to the formation of particle chains or clusters upon induction of a magnetic moment. The particles range in size from about nm to 10 pm, with shapes, such as spherical, needlelike, oval, etc., and include compositions, such as iron, iron oxides, Ni, Co, etc. To achieve inertness, the particles are coated. The use of a polymer coating is considered preferable to disperse the particles in carrier liquids, such as saline, ringer's solution, water, blood plasma, and the like. The particle parameters, such as size, shape and magnetism, can be optimized so as to make the particles non-toxic, biocompatible, chemically inert, easily disposable, substantially non-immunogenic, substantially insoluble in blood, and non-interacting with other biological structures or biomolecules present in the blood stream. The application of the present invention include both external and internal hemorrhage as applied to civilian as well as military injuries.
In accordance with the present invention, a N:\Melbourne\Cases\Patent\5100-51999\P51969.AU.1\Spccis\P5196.AU.1 Amended paqes.doc )3/10/08 00 hemostatic composition includes a carrier medium including a predetermined amount of a magnetic particulate material.
0 O The particulate material is comprised of core particles ND with a coating. The core particles have an average particle size of about 5 nm to 10 pm, and the coating is one of gold, silica, silver, platinum, steel, cobalt, In 00 carbon, a biocompatible polymer, procoagulant molecules, sorbitol or a combination of any two or more thereof.
SIn accordance with the present invention, a method ND 10 of controlling bleeding in a subject in need thereof includes administering to a subject having internal or external bleeding a predetermined amount of a hemostatic fluid including a particulate material in a carrier medium, and applying a magnetic field adjacent the site of a lesion or injury causing the bleeding, so as to form a cluster, coagulation, or agglomeration of the particulate material to thereby prevent the flow of blood through the lesion or injury.
In the claims of this application and in the description of the invention, except where the context requires otherwise due to express language or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" is used in an inclusive sense, i.e. to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS The above and other novel features and advantages of the present invention will become apparent from the following detailed description of the invention, as illustrated in the drawings, in which: Figure 1 is a schematic illustration showing the formation of a cluster or agglomeration of the magnetic particles at the site of an injury upon application of a magnetic field; N: \Me1bourne\Cases\Patent\51000-51999\P51969.AU.1\Specis\P51969AU I Amended pages.doc 13/10/08 6 00 0 Figure 2 is an illustration comparing the size of a Stypical red blood cell to a 250 nm magnetic particle; and O Figure 3 illustrates various shapes of the particles \NO for use in the present invention.
DETAILED DESCRIPTION OF THE INVENTION n00 oo SThe present invention provides novel approaches to 0 control internal or external hemorrhage using magnetic \0 10 fluids. The technique can be applied to control bleeding Sfrom sites located on the extremities and/or from lacerations involving the femoral or axillary vessels, and also from major vascular or visceral injuries in the body cavities. The novel approach is termed as an Innate Magnetic Tourniquet (IMT). IMT is defined as a tourniquet, which can be applied to all types of hemorrhages (both external and internal), can selectively arrest bleeding only at the site of an injury or lesion without affecting other healthy areas, and is small so that it is portable.
An IMT is one of the objectives of the present invention, which serves to magnetically accelerate the coagulation cascade using coated paramagnetic or superparamagnetic particles, or a combination thereof (see Figure 1).
The particles for use in the present invention may be synthesized by various methods, such as chemical synthesis, sol-gel, chemical co-precipitation and microwave plasma technique. The microwave plasma technique, described in pending U.S. Application S.N.
09/262,848, filed March 5, 1999, now U.S. Patent No.
6,409,851, (incorporated herein in its entirety by reference) is the preferred technique as it is unique in that it gives better control over particle size, shape and purity, and can be readily extended to produce different compositions of powders. The composition includes a carrier medium and a particulate material of coated paramagnetic or super-paramagnetic core particles, such as iron, iron oxide, cobalt, cobalt oxide, nickel, nickel N:\elibourne\Cases\Patent\51000 -51999\P51969AU.1\Specis\P51969.AU.1 Amended pagesdoc 13/10/08 -7- 00 oxide, or an alloy or a combination thereof. Preferably, the particulate material includes core particle of iron
O
O and its oxides.
IND The average size of the particles can be from about 5 nm to 10 pm. The preferred size is about 10 nm to 1 pm, while the most preferred size is about 10 nm to 300 nm.
In 00 The size of the particles is directly related to toxicity, n as the particles should be large enough so that they do Snot get absorbed inside the body, and yet small enough to ID 10 escape the immunological response of the macrophages. In addition, the particle size also directly translates into the magnetic mass of the mixture, thereby affecting the magnetic properties. Figure 2 shows a comparison of a 250 nm particle to a typical red blood cell in size. A typical body cell is about twenty-eight times larger than the particle. Figure 2 also illustrates the importance of proper size selection for the particles.
The shape of the particles is important for two reasons. First, the magnetic effect is dependent upon the particle volume fraction, which in turn is a function of the particle shape. For instance, needle-shaped particles exhibit similar magnetic effect at concentrations ten times smaller than spherical particles because of larger surface area per volume. Second, the flow characteristics of the particles in a liquid medium are dependent upon their shape. The shapes utilized in this invention include, but are not limited to, spherical, needle-like, cubic, irregular, cylindrical, diamond, oval, or a combination thereof. Figure 3 shows preferred particle shapes.
In the present invention, the surface coating on the particles serve several purposes, such as preventing particle agglomeration, rendering the particles biocompatible, preventing dissolution of the magnetic materials, and facilitating either selective interactions with particular biomolecules, such as antibodies and clotting factors, or interactions with specific cell N:\Melbourne\Cases\Pient\51000- 51999\P51969.AU.1\Specis\P51969AU.1 Amended pagesdoc 13/10/O0 8 00 Stypes.
The types of coatings that may be utilized in the 0 O present invention, include silica, gold, silver, platinum, Ssteel, cobalt, carbon, a polymer, procoagulant molecules, sorbitol, mannitol or a combination thereof. The polymer can be one of polyethylene glycol, dextran, Tween, 00 sorbitol, mannitol, or a combination thereof. The Sprocoagulant molecules can be thrombin or Factor VII a.
0 The most preferred coating is silica or gold. Silica and sD gold are both effectively inert with respect to Sdissolution in biological fluids and both are amenable to many types of surface chemical reactions, allowing the surface of the particles to be engineered for various applications.
Many techniques have been developed for depositing controlled silica layers on various substrates, including iron and iron oxide based particles. Some approaches make use of controlled hydrolysis of tetraethylorthosilicate (TEOS) in solutions containing core particles, ethyl alcohol, and ammonium hydroxide. See Azuma, Y. et al.
"Coating of ferric oxide particles with silica by hydrolysis of TEOS", Journal of the Ceramic Society of Japan, 100(5), 646-51 (May 1992). The thickness of silica coating can be controlled by varying the reaction conditions.
Other techniques for depositing silica on particles, include acidification of sodium silicate solutions (Atarashi, T. et al. "Synthesis of ethylene-glycol-based magnetic fluid using silica-coated iron particle", Journal of Magnetism and Magnetic Materials, 201, 7-10 (1999)) or controlled heterocoagulation of silica nanoparticles (5-7 nm) with large core particles (Homola, A. M. et al., "Novel Magnetic Dispersions Using Silica Stabilized Particles", IEEE Transactions on Magnetics, 22 716- 719 (September 1986).
In the present invention, a precipitation technique is preferred because of the thin layers that can be N:\Melbourne\Cases\Patent\5100O-51999\P51969.AU.1\Specis\P51969.AU.1 Amended pagesdoc 13/10/08 9 00 0 achieved. An example of the procedure utilized is provided below in the Example. Sodium silicate is precipitated on
O
O the nanoparticle surface to obtain coatings. The amount of sodium silicate can vary from (1 to 80 depending upon the thickness of the coating desired. The thickness of the coating can be from about 1 nm to 1 pm, but the preferred 00 range is about 5 nm to 50 nm.
V) In order to obtain gold coatings, an approach 0 developed by Giri et al. "AC Magnetic Properties of \0 Compacted FeCo Nanocomposites", Mater. Phys. and SMechanics, 1, 1-10 (2000) for coating iron particles with other transition metals may be utilized. Magnetic particles are placed in a solution of gold chloride (10 ethylene glycol (5-40 and water (15-85 The solution is heated, and at high temperatures (between 80 0 C) ethylene glycol acts as a mild reducing agent, resulting in the formation of a thin coating of metallic gold on the nanoparticles. The thickness of the coating can be from about 1 nm to 1 pm, but the preferred range is about 5 nm to 50 nm.
For in vivo use, magnetic hemostatic (MH) fluids must incorporate water (or a biological medium, such as blood plasma) as the continuous phase. Therefore, there is a need to stabilize the particles keep the particles unaggregated and dispersed) in an aqueous carrier fluid, such as water, Ringer's solution, normal saline, sugar solution, blood plasma, or a combination thereof.
N:\Me1bourne\Cases\Patelt\5100-51999\P51969AU.\Specis\P51969.AU. Amended pages.doc 13/10/08 10 Colloidal particles have an inherent tendency to aggregate and form clusters or agglomerate due to ;attractive van der Waals (vdW) forces. To stabilize the particles against these attractive forces, it is necessary to introduce a repulsive interparticle force, either by an electrostatic or a steric means. Electrostatic n stabilization utilizes the surface charge typically 00 Spresent on the particles, which is effective in a medium having a high dielectric constant, such as water, while in 0 steric stabilization, a sufficiently thick layer of a Spolymeric or surfactant molecules is introduced around the Cl particles. The surface layer functions as a steric barrier to particle aggregation, and thereby ensures the stability of the fluid. This technique is preferred for the present invention. The steric stabilizer for the particles were chosen from, but are not limited to, polyethylene oxide (PEO), dextran, and Pluronic® surfactants (available from BASF).
Magnetic particles are preferably coated with a surfactant by physical or chemical adsorption in a solution phase. Magnetic particles and surfactants in a ratio of 10:1 are mixed under a high-speed shear and ultrasonic irradiation. However, this range can vary from about 1 to 100%, depending upon various material systems.
A typical procedure preferred in the present invention for polyethylene glycol coating is described in the Example provided below.
The particle concentration in the final fluid can be about 0.1% to 70% depending upon the type of hemorrhage. For example, for an external hemorrhage higher concentrations would be preferable than internal bleeding.
Coated particles are dispersed in carrier liquids, and mixing is accomplished under high-speed shear and ultrasonification to form a homogeneous fluid.
H:\cintae\Keep\speci\P61866.doc 15/08/06
QEXAMPLE
nm spherical iron particles are synthesized by utilizing the microwave plasma technique described in pending U.S. Application S.N. 09/262,848, filed March 1999, now U.S. Patent No. 6,409,851, (incorporated herein in its entirety by reference). The particles are mixed OO 00 with a 10% aqueous sodium silicate solution to obtain a final iron concentration of 20%. The pH of the solution is I 10 maintained at about 10 and the suspension is thoroughly Smixed. This is followed by slow heating at a temperature c- of up to 80 0 C at which silica precipitates out and forms a coating of approximately 10 nm thickness on the surface of iron nanoparticles. The solution is dried in an oven at a temperature of 110 0 C for approximately 12 hours to remove the water. The resulting silica coated iron nanoparticles are dispersed in normal saline at a concentration of using poly(ethylene) glycol as the surfactant (or dispersing agent). The mixing is accomplished using a high-speed shear mixer for about 3 hours, followed by ultrasonification for about 2 hours. The result is a uniformly dispersed hemostatic fluid which gels upon interaction with an external magnetic field. The magnetic field is generated by using a permanent millimeter sized magnet.
USE AND OPERATION In order to control internal or external bleeding, an effective amount of the hemostatic composition, preferably in the form of a liquid, is administered to a subject in need thereof. The composition is preferably injected intravenously (or via a catheter) adjacent the site of an injury or lesion 10 so that the particles 12 reach the site of injury 10 in, for example, a blood vessel 14 (Figure A magnetic field, in the range of about 0.01-3 Tesla, is then applied by using a H:\cintae\Keep\speci\P61866.doc 15/08/06 12 O conventional permanent magnet 16. Due to magnetic induction, the particles 12 would cluster or agglomerate ;preventing the flow of blood through the lesion The composition of the invention may also include a conventional marking agent to allow, for example, a surgeon to track the flow of the particles on a scope, Setc., in the event a catheter is used to deliver the 00 Scomposition to control internal bleeding.
10 While this invention has been described as having INO preferred sequences, ranges, steps, materials, or designs, Cl it is understood that it includes further modifications, variations, uses and/or adaptations thereof following in general the principle of the invention, and including such departures from the present disclosure as those come within the known or customary practice in the art to which the invention pertains, and as may be applied to the central features hereinbeforesetforth, and fall within the scope of the invention and of the limits of the appended claims.
The following references, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated herein by reference.
The entire disclosure in the complete specification of our Australian Patent Application No. 2003237809 is by this cross-reference incorporated into the present specification.
H:\cintae\Keep\speci\P61866.doc 15/08/06 13
REFERENCES
3 1. Azuma, Y. et al. "Coating of ferric oxide particles with silica by hydrolysis of TEOS", Journal of the Ceramic Society of Japan, 100(5), 646-51 (May 1992).
2. Atarashi, T. et al. "Synthesis of ethylene- Sglycol-based magnetic fluid using silica-coated iron 00 V) particle", Journal of Magnetism and Magnetic Materials, S201, 7-10 (1999).
4 10 3. Homola, A. M. et al., "Novel Magnetic SDispersions Using Silica Stabilized Particles", IEEE C Transactions on Magnetics, 22 716-719 (September 1986).
4. Giri, A. et al. "AC Magnetic Properties of Compacted FeCo Nanocomposites", Mater. Phys. and Mechanics, 1, 1-10 (2000).
H:\cintae\Keep\speci\P61866.doc 15/08/06
Claims (14)
1. A magnetic, fluid composition internal bleeding comprising: biocompatible, non-toxic hemostatic when used for controlling external or in a subject, the composition 00 On Va 0 CI a) b) a carrier fluid; a predetermined amount of a magnetic particulate material in said fluid; wherein said particulate material comprises paramagnetic or super-paramagnetic core particles with a coating, said coating 'has a thickness of about 1 nm to 1 m and comprising a member selected from the group consisting of gold, silica, silver, platinum, steel, cobalt, carbon, a biocompatible polymer, procoagulant molecules, sorbitol, mannitol, and a combination of any two or more thereof, in which the concentration of said particulate material is about 0.1% to 70% of the composition, said core particles having an average particle size of about 5 nm to 10 pm and comprising a member selected from the group consisting of iron, iron oxide, cobalt, cobalt oxide, nickel, nickel oxide, and an alloy or a combination thereof.
2. A composition according to claim 1, wherein said core particles have an average particle size of about nm to 1 Pm.
3. A composition according to claim 1 or claim 2, wherein said core particles have an average particle size of about 10 nm to 300 nm.
N: \KelbourneaseskPaten t\51000-599 \P519s69. AU. I \Slpcis sP5I965.AT. I Amended pagss.doc 2210/08 COMS ID No: ARCS-211227 Received by IP Australia: Time 16:34 Date 2008-10-27 27/10 2008 17:35 FAX U0005/0010 00 15 0 S4. A composition according to any one of claims 1 to 4, o wherein said core particles comprise a general shape 00 selected from the group consisting of a sphere, a needle, CI a cube, an oval, irregular, a cylinder, a diamond, and a combination thereof. 00 l
5. A composition according to any preceding claim Swherein said core particles comprise clusters. I
6. A composition according to any preceding claim, wherein said core particles comprise the general shape of blood platelets.
7. A composition according to any preceding claim wherein said biocompatible polymer is selected from the group consisting of polyethylene glycol, dextran, Tween and a combination thereof.
8. A composition according to any preceding claim, wherein said coating has a thickness of about 5nm to
9. A composition according to any preceding claim, wherein said procoagulant molecules are selected from the group consisting of thrombin and Factor VII a.
A composition according to any preceding claim, further comprising a surfactant or dispersant.
11. A composition according to any preceding claim, wherein said particulate material is non-toxic to bio- cells or biomolecules.
12. A composition according to any preceding claim, wherein said carrier fluid is selected from the group consisting of water, saline solution, sugar solution, Lactose Ringer's, and blood plasma. N elbourne\Cases\Patent\51000-51999\P5969.AU. l\Specis\P51969.Au. l Amendd pagesdoc 22/10/08 COMS ID No: ARCS-211227 Received by IP Australia: Time 16:34 Date 2008-10-27 27/10 2008 17:36 FAX 0006/0010 16
13. A method of controlling bleeding in a subject in need thereof, comprising the steps of: a) administering to a subject having internal or external bleeding a predetermined amount of a hemostatic fluid composition according to any of claims 1 to 12. b) applying a magnetic field adjacent the site of a lesion causing the bleeding so as to form a cluster of the particulate material, thereby to prevent the flow of blood through the lesion. Vn 00 Ci VO c
14. any for Use of a hemostatic fluid composition according to of claims 1 to 12 in the manufacture of a medicament controlling bleeding. A composition according to claim 1, a method according to claim 13 or a use according to claim 14, substantially as herein described with reference to any one of the examples or drawings. :\Melblre\cases\ pt 5 d 51999n pgede 22110/o COMS ID No: ARCS-211227 Received by IP Australia: Time 16:34 Date 2008-10-27
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| AU2006203585A AU2006203585B2 (en) | 2002-05-31 | 2006-08-15 | A hemostatic composition |
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| AU2003237809A AU2003237809A1 (en) | 2002-05-31 | 2003-05-28 | A hemostatic composition |
| AU2006203585A AU2006203585B2 (en) | 2002-05-31 | 2006-08-15 | A hemostatic composition |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4951675A (en) * | 1986-07-03 | 1990-08-28 | Advanced Magnetics, Incorporated | Biodegradable superparamagnetic metal oxides as contrast agents for MR imaging |
| US5069216A (en) * | 1986-07-03 | 1991-12-03 | Advanced Magnetics Inc. | Silanized biodegradable super paramagnetic metal oxides as contrast agents for imaging the gastrointestinal tract |
| US5178947A (en) * | 1989-12-27 | 1993-01-12 | Rhone-Poulenc Chimie | Magnetizable composite microspheres based on a crosslinked organosilicon polymer |
| US5427767A (en) * | 1991-05-28 | 1995-06-27 | Institut Fur Diagnostikforschung Gmbh An Der Freien Universitat Berlin | Nanocrystalline magnetic iron oxide particles-method for preparation and use in medical diagnostics and therapy |
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2006
- 2006-08-15 AU AU2006203585A patent/AU2006203585B2/en not_active Ceased
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4951675A (en) * | 1986-07-03 | 1990-08-28 | Advanced Magnetics, Incorporated | Biodegradable superparamagnetic metal oxides as contrast agents for MR imaging |
| US5069216A (en) * | 1986-07-03 | 1991-12-03 | Advanced Magnetics Inc. | Silanized biodegradable super paramagnetic metal oxides as contrast agents for imaging the gastrointestinal tract |
| US5178947A (en) * | 1989-12-27 | 1993-01-12 | Rhone-Poulenc Chimie | Magnetizable composite microspheres based on a crosslinked organosilicon polymer |
| US5427767A (en) * | 1991-05-28 | 1995-06-27 | Institut Fur Diagnostikforschung Gmbh An Der Freien Universitat Berlin | Nanocrystalline magnetic iron oxide particles-method for preparation and use in medical diagnostics and therapy |
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