New! View global litigation for patent families

US20080125745A1 - Methods and compositions for treating post-cardial infarction damage - Google Patents

Methods and compositions for treating post-cardial infarction damage Download PDF

Info

Publication number
US20080125745A1
US20080125745A1 US11978986 US97898607A US2008125745A1 US 20080125745 A1 US20080125745 A1 US 20080125745A1 US 11978986 US11978986 US 11978986 US 97898607 A US97898607 A US 97898607A US 2008125745 A1 US2008125745 A1 US 2008125745A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
needle
component
delivery
gel
distal
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11978986
Inventor
Shubhayu Basu
Greg W. Chan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Abbott Cardiovascular Systems Inc
Original Assignee
Abbott Cardiovascular Systems Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0021Catheters; Hollow probes characterised by the form of the tubing
    • A61M25/0023Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
    • A61M25/0026Multi-lumen catheters with stationary elements
    • A61M25/003Multi-lumen catheters with stationary elements characterized by features relating to least one lumen located at the distal part of the catheter, e.g. filters, plugs or valves
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0067Catheters; Hollow probes characterised by the distal end, e.g. tips
    • A61M25/0082Catheter tip comprising a tool
    • A61M25/0084Catheter tip comprising a tool being one or more injection needles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0021Catheters; Hollow probes characterised by the form of the tubing
    • A61M25/0023Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
    • A61M25/0026Multi-lumen catheters with stationary elements
    • A61M25/0032Multi-lumen catheters with stationary elements characterized by at least one unconventionally shaped lumen, e.g. polygons, ellipsoids, wedges or shapes comprising concave and convex parts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters

Abstract

Methods and compositions for treating post-myocardial infarction damage are herein disclosed. In some embodiments, a carrier with a treatment agent may be fabricated. The carrier can be formulated from a bioerodable, sustained-release substance. The resultant loaded carrier may then be suspended in at least one component of a two-component matrix system for simultaneous delivery to a post-myocardial infarction treatment area.

Description

    CROSS REFERENCE TO RELATED APPLICATIONS
  • [0001]
    This is a continuation-in-part of application Ser. No. 11/447,340, filed Jun. 5, 2006, which is a continuation-in-part of application Ser. No. 11/361,920, filed Feb. 23, 2006, which is a continuation-in-part of application Ser. No. 11/110,223, filed Apr. 19, 2005, now pending.
  • FIELD OF INVENTION
  • [0002]
    Post-myocardial infarction treatments and compositions.
  • BACKGROUND OF INVENTION
  • [0003]
    Ischemic heart disease typically results from an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Progressive atherosclerosis with increasing occlusion of coronary arteries leads to a reduction in coronary blood flow. “Atherosclerosis” is a type of arteriosclerosis in which cells including smooth muscle cells and macrophages, fatty substances, cholesterol, cellular waste product, calcium and fibrin build up in the inner lining of a body vessel. “Arteriosclerosis” refers to the thickening and hardening of arteries. Blood flow can be further decreased by additional events such as changes in circulation that lead to hypoperfusion, vasospasm or thrombosis.
  • [0004]
    Myocardial infarction (MI) is one form of heart disease that often results from the sudden lack of supply of oxygen and other nutrients. The lack of blood supply is a result of a closure of the coronary artery (or any other artery feeding the heart) which nourishes a particular part of the heart muscle. The cause of this event is generally attributed to arteriosclerosis in coronary vessels.
  • [0005]
    Formerly, it was believed that an MI was caused from a slow progression of closure from, for example, 95% then to 100%. However, an MI can also be a result of minor blockages where, for example, there is a rupture of the cholesterol plaque resulting in blood clotting within the artery. Thus, the flow of blood is blocked and downstream cellular damage occurs. This damage can cause irregular rhythms that can be fatal, even though the remaining muscle is strong enough to pump a sufficient amount of blood. As a result of this insult to the heart tissue, scar tissue tends to naturally form.
  • [0006]
    Various procedures, including mechanical and therapeutic agent application procedures, are known for reopening blocked arteries. An example of a mechanical procedure includes balloon angioplasty with stenting, while an example of a therapeutic agent application includes the administration of a thrombolytic agent, such as urokinase. Such procedures do not, however, treat actual tissue damage to the heart. Other systemic drugs, such as ACE-inhibitors and Beta-blockers, may be effective in reducing cardiac load post-MI, although a significant portion of the population that experiences a major MI ultimately develop heart failure.
  • [0007]
    An important component in the progression to heart failure is remodeling of the heart due to mismatched mechanical forces between the infracted region and the healthy tissue resulting in uneven stress and strain distribution in the left ventricle. Once an MI occurs, remodeling of the heart begins. The principle components of the remodeling event include myocyte death, edema and inflammation, followed by fibroblast infiltration and collagen deposition, and finally scar formation. The principle component of the scar is collagen. Since mature myocytes of an adult are not regenerated, the infarct region experiences significant thinning. Myocyte loss is the major etiologic factor of wall thinning and chamber dilation that may ultimately lead to progression of cardiac myopathy. In other areas, remote regions experience hypertrophy (thickening) resulting in an overall enlargement of the left ventricle. This is the end result of the remodeling cascade. These changes in the heart result in changes in the patient's lifestyle and their ability to walk and to exercise. These changes also correlate with physiological changes that result in increase in blood pressure and worsening systolic and diastolic performance.
  • SUMMARY OF INVENTION
  • [0008]
    Methods and compositions for treating post-myocardial infarction damage are herein disclosed. In some embodiments, a carrier may be loaded with a treatment agent. The carrier can be formulated from a bioerodable, sustained-release substance. The resultant loaded carrier may then be suspended in one component of a two-component matrix for simultaneous delivery to a post-myocardial infarction treatment area.
  • [0009]
    A device that includes a first and second needle useful for delivering individual components of a gel is herein disclosed. Various needle assembly configurations prevent inadvertent mixture of the gel components but ensure that the components can admix within a patient's tissue to form a gel composition.
  • [0010]
    In alternative embodiment, the distal ends of a first and second needle are moveable relative to each other. The needles can be biased toward a separated configuration, and the separation distance of the needle tips can shorten when the needles engage a patient's tissue.
  • [0011]
    A device is disclosed that includes a first and second needle useful for delivering individual components of a gel in which at least one of the needles can be actuated manually to move relative to the other needle. The device is useful for delivering individual components of a gel.
  • [0012]
    A method is provided for delivering a first and second gel component into a patient anatomy in order to form a gel composition.
  • BRIEF DESCRIPTION OF DRAWINGS
  • [0013]
    FIGS. 1A-1B illustrate the progression of heart damage once the build-up of plaque in an artery induces an infarct to occur;
  • [0014]
    FIG. 2 schematically represents a method for preparing a two-component gel matrix with a sustained carrier loaded with treatment agent interdispersed therein;
  • [0015]
    FIG. 3 schematically represents an alternative method for preparing a two-component gel matrix with a sustained carrier loaded with treatment agent interdispersed therein;
  • [0016]
    FIG. 4 schematically represents a second alternative method for preparing a two-component gel matrix with a sustained carrier loaded with treatment agent interdispersed therein;
  • [0017]
    FIGS. 5A-5B illustrate an embodiment of a dual-needle injection device which can be used to deliver the compositions of the present invention;
  • [0018]
    FIGS. 6A-6C illustrate an alternative embodiment of a dual-needle injection device which can be used to deliver the compositions of the present invention;
  • [0019]
    FIGS. 7A-7B illustrate an alternative embodiment of a needle assembly having needles configured side-by-side that can be used to deliver the compositions of the present invention;
  • [0020]
    FIGS. 8A-8B illustrate an alternative embodiment of a needle assembly having needles configured generally coaxially that can be used to deliver the compositions of the present invention;
  • [0021]
    FIGS. 9A-9B illustrate an alternative embodiment of a needle assembly with divergent lumen ports that can be used to deliver the compositions of the present invention;
  • [0022]
    FIGS. 10A-10B illustrate an alternative embodiment of a needle assembly with divergent lumen ports that can be used to deliver the compositions of the present invention;
  • [0023]
    FIGS. 11A-11C illustrate an alternative embodiment of a needle assembly having offset needles that can be used to deliver the compositions of the present invention;
  • [0024]
    FIGS. 12A-12C illustrate an alternative embodiment of a needle assembly having offset needles that can be used to deliver the compositions of the present invention;
  • [0025]
    FIGS. 13A-13B illustrate an alternative embodiment of a needle assembly having a guide needle and a delivery needle;
  • [0026]
    FIGS. 14A-14C illustrate alternative embodiments of a delivery needle in accordance with the present invention;
  • [0027]
    FIGS. 15A-15B illustrate an alternative embodiment of a needle assembly having biased offset needles that can be used to deliver the compositions of the present invention;
  • [0028]
    FIGS. 16A-16C illustrate an alternative embodiment of needle assemblies configured to provide beneficial delivery characteristics;
  • [0029]
    FIG. 17 illustrates an alternative embodiment of a needle assembly that can be used to deliver the compositions of the present invention; and
  • [0030]
    FIG. 18 illustrates an alternative embodiment of a distal portion of an injection device with a needle assembly that can be used to deliver the compositions of the present invention.
  • DETAILED DESCRIPTION
  • [0031]
    Methods and compositions for treating post-myocardial infarction damage are herein disclosed. In some embodiments, a carrier with a treatment agent may be fabricated. The carrier can be formulated from a bioerodable, sustained-release substance. The resultant loaded carrier may then be suspended in at least one component of a two-component matrix system for simultaneous delivery to a post-myocardial infarction treatment area.
  • [0032]
    FIGS. 1A-1B illustrate the progression of heart damage once the build-up of plaque induces an infarct to occur. FIG. 1A illustrates a site 10 where blockage and restricted blood flow can occur from, for example, a thrombus or embolus. FIG. 1B illustrates resultant damage area 20 to the left ventricle that can result from the lack of oxygen and nutrient flow carried by the blood to the inferior region left of the heart. The damage area 20 will likely undergo remodeling, and eventually scarring, resulting in a non-functional area.
  • Treatment Agents
  • [0033]
    Treatment agents to treat post-myocardial infarction treatment areas may include: (i) agents that promote angiogenesis (angiogenesis promoting factors); (ii) agents that promote cell survival (cell survival promoting factors); and (iii) agents that recruit endogenous progenitor and/or stem cells (endogenous recruiting factors). Various forms of treatment agents are intended to include, but are not intended to be limited to, drugs, biologically active agents, chemically active agents, therapeutic agents, and the like, and pharmaceutical compositions thereof, which can be used in the delivery of a treatment agent to a treatment site as described herein.
  • [0034]
    “Angiogenesis” is the promotion or causation of the formation of new blood vessels. After an MI, the infarct tissue as well as the border zone and the remote zone around the infarct tissue begin to remodel. Scar tissue forms in the infarct region as the granulation is replaced with collagen. Stress from blood pressure cause the scar to thin out and stretch. The perfusion in this region is typically 10% of the healthy zone, decreasing the number of active capillaries. Increasing the number of capillaries may lead to an increase in compliance of the ventricle due to filling up with blood. Other benefits of increasing blood flow to the infarcted region include providing a route for circulating stem cells to seed and proliferate in the infarct region. Angiogenesis may also lead to increased oxygenation for the surviving cellular islets within the infarct region, or to prime the infarct region for subsequent cell transplantation for myocardial regeneration. In the border zone, surviving cells would also benefit from an increase in blood supply through an angiogenesis process. In the remote zone, where cardiac cells tend to hypertrophy and become surrounded with some interstitial fibrosis, the ability of cells to receive oxygen and therefore function to full capacity are also compromised; thus, angiogenesis would be beneficial in these regions as well.
  • [0035]
    In some embodiments, angiogenesis promoting factors include, but are not intended to be limited to, growth factors such as isoforms of vasoendothelial growth factor (VEGF), fibroblast growth factor (FGF, e.g. beta-FGF), Del 1, hypoxia inducing factor (HIF 1-alpha), monocyte chemoattractant protein (MCP-1), nicotine, platelet derived growth factor (PDGF), insulin-like growth factor 1 (IGF-1), transforming growth factor (TGF alpha), hepatocyte growth factor (HGF), estrogens, follistatin, proliferin, prostaglandin E1 and E2, tumor necrosis factor (TNF-alpha), interleukin 8 (Il-8), hematopoietic growth factors, erythropoietin, granulocyte-colony stimulating factors (G-CSF) and platelet-derived endothelial growth factor (PD-ECGF). In some embodiments, angiogenesis promoting factors include, but are not intended to be limited to, peptides, such as PR39, PR11 and angiogenin, small molecules, such as PHD inhibitors, or other agents, such as eNOS enhancers.
  • [0036]
    Endogenous cardiomyocyte (myocytes) apoptosis is the major etiological factor of wall thinning and chamber dilation and may ultimately lead to progression of cardiac myopathy. After an infarction, mature myocytes of an adult are not regenerated which can lead to significant thinning in the infarct region. Thus, factors which promote cell survival applied to the infarct region are believed to be beneficial. In some embodiments, cell survival promoting factors include, but are not intended to be limited to, growth factors such as insulin-like growth factor (IGF-1) and human growth factor (HGF), which are known to mediate cell growth, differentiation and survival of a variety of cell types. In addition, small molecules such as, for example, HMG-CoA reductase inhibitors (statins) and capsase inhibitors can also promote cell survival and inhibit apoptosis.
  • [0037]
    To assist in the generation of new cells at the infarct region, autologous or allogeneic stem cells may be delivered to a patient. “Autologous” means the donor and recipient of the stem cells are the same. “Allogeneic” means the donor and recipient of the stem cells are different. Cell survival promoting factors can also be used to increase the survivability of autologous and allogeneic implanted stem cells at the infarct region.
  • [0038]
    Cardiac progenitor cells are highly specialized stem cells which have shown the ability to differentiate into certain types of fully mature cardiac tissue. Examples of cardiac progenitor cells include, but are not limited to, c-Kit (+), Sca-1 (+) and Isl-1 (+). Thus, factors which recruit endogenous factors when applied to the infarct region are believed to be beneficial. In some embodiments, an endogenous recruiting factor can include, for example, HGF. HGF has been shown to control cell motility and promote cell migration. If applied post-infarction, HGF can assist in mobilizing and recruiting resident cardiac progenitor cells to the infarct region. In some embodiments, an endogenous recruiting factor can include, but is not intended to be limited to, stromal cell-derived factor 1 (SDF-1). SDF-1 is the ligand for the CXCR4 receptor, which is a surface receptor on circulating endothelial progenitor cells. Thus, when applied in or around the infarct region, SDF-1 may facilitate the homing of circulating endothelial progenitor cells to induce neovascularization.
  • [0039]
    It is contemplated that any of the above-described treatment agents can be used singularly or in combination thereof. In addition, other treatment agents, including but not limited to, anti-inflammatory, anti-platelet, anti-coagulant, anti-fibrin, anti-thrombotic, anti-mitotic, anti-biotic, anti-allergic, anti-oxidant, anti-proliferative, or anti-migratory agents, may be optionally used singularly or in combination thereof.
  • Sustained-Release Carriers
  • [0040]
    Bioerodable carriers (hereinafter interchangeably referred to as sustained-release carriers) infused with (or without) a treatment agent can be used for the sustained or controlled release of treatment agent for maximum benefit to the infarct region. It is believed that a large percentage of treatment agent delivered directly to the infarct region, or even diffused within a gel-like matrix, will be substantially washed away by the body's natural mechanisms, thus lessening the benefit of the treatment agent that may otherwise be obtained. Thus, sustained-release carriers infused with treatment agent that release the treatment agent over an extended time period can be beneficial by increasing the amount of time in which the infarct region is exposed to the treatment agent. Sustained-release carriers include, but are not limited to, (i) microparticles or nanoparticles (hereinafter interchangeably referred to as microparticles), (ii) microfibers or nanofibers (hereinafter interchangeably referred to as microfibers) and (iii) liposomes and polymerosomes.
  • [0041]
    In addition, in some embodiments, a bioerodable carrier may be infused with (or without) a treatment agent and delivered to a treatment site to act as a “docking site” for endogenous myocardial stem cells and encourage their differentiation into cardiomyocytes.
  • A.
  • [0042]
    In some embodiments, the sustained-release carrier is a microparticle. Various methods can be employed to formulate and infuse or load the microparticles with treatment agent. In some embodiments, the microparticles are prepared by a water/oil/water (W/O/W) double emulsion method. In the WI phase, an aqueous phase containing treatment agent, is dispersed into the oil phase consisting of polymer dissolved in organic solvent (e.g., dichloromethane) using a high-speed homogenizer. Examples of sustained-release polymers include, but are not limited to, poly(D,L-lactide-co-glycolide) (PLGA), poly(D,L-lactide) (PLA) or PLA-PEEP co-polymers, poly-ester-amide co-polymers (PEA) and polyphophazines. The primary water-in-oil (W/O) emulsion is then dispersed to an aqueous solution containing a polymeric surfactant, e.g., poly(vinyl alcohol) (PVA), and further homogenized to produce a W/O/W emulsion. After stirring for several hours, the microparticles are collected by filtration.
  • B.
  • [0043]
    In some embodiments, the sustained-release carrier is a microfiber or nanofiber. For example, the treatment agent (or no treatment agent) infused microfiber can be formulated by electrospinning. “Electrospinning” is a process by which microfibers are formed by using an electric field to draw a polymer solution from the tip of a capillary to a collector. A voltage is applied to the polymer solution which causes a stream of solution to be drawn toward a grounded collector. Electrospinning generates a web of fibers which can be subsequently processed into smaller lengths.
  • [0044]
    Examples of sustained-release polymers which can be used in electrospinning include, but are not limited to, PLGA, PLA or PLA-PEEP co-polymers, PEA, polyphosphazines and collagen. In one method, the treatment agent is mixed with a bioerodable polymer solution, a solvent and a surfactant. Examples of surfactants can include, but are not limited to, anionic or cationic surfactants. Useful anionic surfactants include, but are not intended to be limited to, bis(2-ethylhexyl) sodium sulfosuccinate (AOT), bis(2-ethylhexyl) phosphate (NaDEHP), tauroglycocholate, and sodium lauryl sulfate. A useful cationic surfactant is tetradecyltrimethyl-ammonium bromide (TTAB). An example of a solvent includes, but is not limited to, hexafluoro isopropanol. The treatment agent-infused polymer solution is then subjected to electrospinning. As the solvent evaporates during electrospinning, the treatment agent incorporates and distributes within the polymer by non-covalent interactions. The resultant microfibers which can be from about 0.5 μm to about 3 μm in diameter form a web which may then be processed into smaller lengths of about 0.5 μm to about 500 μm. Based on the treatment agent, in some applications, microfibers may be a preferred sustained-release carrier due to the non-aqueous process by which they are formed. In some applications, microspheres may be preferable when the treatment agent is hydrophilic. In some applications, a microfiber is a preferred sustained-release carrier due to its release pharmacokinetic profile when compared to the release pharmacokinetic profile of a microsphere. In some cases, microspheres as well as microfibers can be used as a carrier of one or more than one treatment agent as the two types of carriers will provide different pharmacokinetic release profiles which may be advantageous for therapy.
  • [0045]
    In one embodiment, fibers can be electrospun from collagen and elastin dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFP), forming a polymer solution. A treatment agent can be added to the polymer solution. A surfactant and a stabilizer can be used to evenly disperse the treatment agent in the solvent. The polymer solution can then be loaded into a syringe and placed in a syringe pump for metered dispensing at a predetermined rate. A positive output lead of a high voltage supply can be attached to a needle on the syringe. The needle can be directed to a stainless steel grounded target placed approximately 10 cm from the needle tip, which can be rotated at a predetermined speed to ensure an even coating. The distance of the needle from the target can be varied depending upon the diameter of the fibers needed. The resultant microfibers are from about 0.5 μm to about 3 μm in diameter and the resulting non-woven mat of fibers can then be processed into smaller lengths of about 0.5 μm to about 500 μm.
  • C.
  • [0046]
    In some embodiments, the sustained-release carrier is a liposome or a polymerosome. “Liposomes” are artificial vesicles that are approximately spherical in shape and can be produced from natural phospholipids and cholesterol. In one method, phospholipids are mixed with cholesterol in chloroform. Suitable phospholipids include, but are not limited to, dimyristoyl phosphatidyl choline or dipalmitoyl ethanolamine. In some embodiments, hydrophobic treatment agent can be added with an optional co-solvent, such as heptane or toluene. The liposomes may also be hydrophilically modified with an agent such as polyethylene glycol or dextran. After mixing, the solvent (and optional co-solvent) can be evaporated with heat or ambient temperature in a round bottom flask. Resultant lipids will be deposited on the glass surface. In some embodiments, hydrophilic treatment agent and water can be added to the flask and sonicated to form liposomes. The resultant suspension can be pressure filtered through ceramic pore size controlled filters to reduce liposome particle size. In the case of a polymerosome, a similar manufacturing technique can be used as that of a liposome. Polymerosomes can be formed from di-block co-polymers of differing solubility. For example, one block can be hydrophobic, e.g., poly lactic acid, polycaprolactone, n-butyl acrylate, and the other block can be hydrophilic, e.g., poly(ethylene glycol), poly(acrylic acid).
  • Matrix Systems
  • [0047]
    A biocompatible matrix system can be used to suspend the treatment agent or the treatment agent-infused sustained-release carrier for delivery to the infarct region. In some embodiments, the matrix system can be a one-component or a two-component gel. In some embodiments, the matrix system is a two-component gel. Two-component gels can include, for example, fibrin glues (e.g., two components comprising fibrinogen and thrombin), self-assembled peptides or alginate constructs.
  • [0048]
    In some embodiments, the matrix system is a one-component gel. An example of a one-component gel includes an acrylate agent that is biocompatible. The one-component gel serves in one aspect to disperse the sustained-release carrier in order to form a more uniform scaffold over the entire infarct zone and may include border zone as well. For example, the one-component gel may be sodium hyaluronate. The gel disperses the sustained-release carrier acting as a suspending media.
  • A.
  • [0049]
    In some applications, the two-component gelation system includes a fibrin glue. Fibrin glue consists of two main components, fibrinogen and thrombin. Fibrinogen is a plasma glycoprotein of about 340 kiloDaltons (kDa) in its endogenous state. Fibrinogen is a symmetrical dimer comprised of six paired polypeptide chains, alpha, beta and gamma chains. On the alpha and beta chains, there is a small peptide sequence called a fibrinopeptide which prevent fibrinogen from spontaneously forming polymers with itself. In some embodiments, fibrinogen is modified with proteins. Thrombin is a coagulation protein. When combined in equal volumes, thrombin converts the fibrinogen to fibrin by enzymatic action at a rate determined by the concentration of thrombin. The result is a biocompatible gel which gelates when combined at the infarct region. Fibrin glue can undergo gelation at about 10 to about 60 seconds. Examples of other fibrin glue-like systems include, but are not limited to, Tisseel™ (Baxter), CoSeal™ (Baxter), Crosseal™ (Omrix Biopharmaceuticals, Ltd.), Hemaseel® (Haemacure Corp.) and CoStasis® (Angiotech Pharmaceuticals).
  • B.
  • [0050]
    In some embodiments, the two-component gel comprises self-assembled peptides. Self-assembled peptides generally include repeat sequences of alternating hydrophobic and hydrophilic amino acid chains. The hydrophilic amino acids are generally charge-bearing and can be anionic, cationic or both. Examples of cationic amino acids are lysine and arginine. Examples of anionic amino acids are aspartic acid and glutamic acid. Examples of hydrophobic amino acids are alanine, valine, leucine, isoleucine or phenylalanine. Self-assembled peptides can range from 8 to about 40 amino acids in length and can assemble into nanoscale fibers under conditions of physiological pH and osmolarity. In sufficient concentration and over time, the fibers can assemble into an interconnected structure that appears macroscopically as a gel. Self-assembled peptides typically undergo gelation between several minutes to several hours. Examples of self-assembled peptides include, but are not limited to: AcN-RARADADARARADADA-CNH2 (RAD 16-II) wherein R is arginine, A is alanine, D is aspartic acid, and Ac indicates acetylation; VKVKVKVKV-PP-TKVKVKVKV-NH2 (MAX-1) wherein V is valine, K is lysine and P is proline; and AcN-AEAEAKAKAEAEAKAK-CNH2 wherein A is alanine, K is lysine and E is glutamic acid (EAK16-II).
  • EXAMPLE
  • [0051]
    In one example, the self-assembled peptide is RAD 16-II. At low pH and osmolarity, RAD 16-II forms a solution. At physiological pH and osmolarity, RAD 16-II forms a gel although gel formation can be slow. In some embodiments, RAD 16-II is mixed with phosphate buffer saline (PBS) to form a first component solution. In some embodiments, the first component solution can be co-injected with a second component comprising sodium chloride, sucrose or other osmolarity modifying substance using, for example, a dual-injection delivery assembly. In some embodiments, the components can be co-injected with carriers such as angiogenesis promoting factors, cell survival promoting factors and/or endogenous recruiting factors. These factors bind non-specifically to the self-assembled peptides by electrostatic interactions, and this binding can control or retard the release of the factors.
  • C.
  • [0052]
    In some embodiments, the two-component gel is an alginate construct. For example, the alginate construct may be collagen or gelatin grafted alginate. In one example, a first component can be a solution of about 0.5 percent to about 1.0 percent alginate while a second component can be a solution of about 40 mM to about 180 mM calcium chloride. One example of a suitable amount of components is about 200 microliters of alginate solution and about 200 microliters of calcium chloride. In one embodiment, a desired amount of a treatment agent may be introduced with the alginate solution.
  • Methods of Manufacture
  • [0053]
    FIG. 2 schematically represents a method for preparing a two-component gel matrix with a sustained carrier loaded with treatment agent interdispersed therein. A treatment agent, such as an angiogenesis promoting factor, cell survival promoting factor, endogenous recruiting factor or any combination thereof can be added to a bioerodable polymer such as PLGA or PEA and PLA-PEEP co-polymers or polyphosphazenes (100). In some embodiments, a W/O/W process can be used. The mixture can be processed to monodisperse the resultant treatment agent loaded microspheres (110). The microspheres can be in a range from about 5 μm to about 200 μm, preferably from about 10 μm to about 50 μm. Next, the resultant dispersion can be added to one component of a two-component gel such as fibrin glue (120). In one embodiment, the two-component gel includes component A and component B, wherein component A is fibrinogen and component B is thrombin. Component A and component B can then be separately but simultaneously injected into the myocardial infarct region by a dual-injection delivery assembly for treatment thereof (130).
  • [0054]
    FIG. 3 schematically represents an alternative method for preparing a two-component gel matrix with a sustained carrier loaded with treatment agent interdispersed therein. A treatment agent, such as an angiogenesis promoting factor, cell survival promoting factor, endogenous recruiting factor or any combination thereof can be added to a bioerodable polymer such as PLGA or PEA and PLA-PEEP co-polymers or polyphosphazenes or collagen (200) with solvent. For collagen/elastin electrospun fibers, a suitable solvent can be HFP. In some embodiments, an aqueous system may be used. The mixture can then be subjected to electrospinning to create interwoven fibers (210) with a diameter in a range from about 0.2 μm to about 3 μm. The fibers may then be processed into smaller of length from about 0.5 μm to about 500 μm (220). The fibers may be processed by cryogenic grinding, subjected to ultrasound in water, or subjected to ultrasound in a volatile solvent that is a non-solvent for both the polymer and the encapsulated protein or other agent or subjected to any other suitable method to reduce their size. Next, the resultant fibers can be added to one component of a two-component gel such as fibrin glue (230). In one embodiment, the two-component gel includes component A and component B, wherein component A is fibrinogen and component B is thrombin. Component A and component B can then be separately but simultaneously injected into the myocardial infarct region by a dual-injection delivery assembly for treatment thereof (240).
  • [0055]
    FIG. 4 schematically represents another alternative method for preparing a two-component gel matrix with a sustained carrier loaded with treatment agent interdispersed therein. A phospholipid substance can be combined with cholesterol in a solvent such as chloroform (300) in a round bottom flask. In some embodiments, a hydrophobic treatment agent including an optional co-solvent can be added thereto (300A). The solvent(s) can be evaporated depositing lipids on the glass surface (310). Next, water is added and in some embodiments, a hydrophilic treatment agent (320). Then, the mixture is sonicated to form liposomes (330) and optionally pressure-filtered to reduce liposome particle size (340). Next, the resultant liposomes can be added to one component of a two-component gel such as fibrin glue (350). In one embodiment, the two-component gel includes component A and component B, wherein component A is fibrinogen and component B is thrombin. Component A and component B can then be separately but simultaneously injected into the myocardial infarct region by a dual-injection delivery assembly for treatment thereof (360).
  • Example
  • [0056]
    In one embodiment, collagen electrospun fibers can be processed to a range from about 200 nm and about 1300 nm. The range of electrospun fibers is approximately the range of naturally occurring type 1 and type 3 fibers which make up the heart matrix. Thus, the electrospun fibers may mimic endogenous fibers and accelerate growth of repair tissue to the infarct region, in particular, on the heart. The fibers can be dispersed throughout one component of a two-component gel. The two components can then be delivered to myocardial infarct region. The fibers can provide “docking sites” for endogenous myocardial stem cells and encourage their differentiation into cardiomyocytes. The gel can provide temporary containment of the fibers and prevent premature removal by macrophage cells.
  • [0057]
    The fibers can be fabricated such that they include an agent or no agent. Examples of agents can include a chemoattractant, such as SDF-1, or a cell survival promoting factor, such as IGF-1. In one embodiment, SDF-1 may be incorporated within the electrospun fibers and the resultant agent infused electrospun fibers may be dispersed throughout one component of a two-component gel. When delivered, the release of SDF-1 may recruit endogenous stem cells to the infarct region where they will adhere to the electrospun fibers and differentiate into stem cells.
  • [0058]
    In another embodiment, IGF-1 may be incorporated within the electrospun fibers and the resultant agent infused electrospun fibers may be dispersed throughout one component of a two-component gel. Stem cells may be incorporated within the other component of the two-component gel. When delivered, the stem cells may be temporally immobilized in the gel and adhere to the electrospun fibers. IGF-1 may enhance stem cell survival.
  • [0059]
    It should be appreciated that any of the above-described methods may be combined to treat an infarct region.
  • Methods of Treatment
  • [0060]
    Devices which can be used to deliver each component of the gel include, but are not limited to, dual-needle left-ventricle injection devices and dual-needle transvascular wall injection. Methods of access to use the injection devices include access via the femoral artery or the sub-xiphoid. “Xiphoid” or “xiphoid process” is a pointed cartilage attached to the lower end of the breastbone or sternum, the smallest and lowest division of the sternum. Both methods are known by those skilled in the art.
  • [0061]
    FIGS. 5A-5B illustrate an embodiment of a dual-needle injection device which can be used to deliver the compositions of the present invention. Delivery assembly 400 includes lumen 410 which may house delivery lumens, guidewire lumens and/or other lumens. Lumen 410, in this example, extends between distal portion 405 and proximal end 415 of delivery assembly 400.
  • [0062]
    In one embodiment, delivery assembly 400 includes main needle 420 disposed within delivery lumen 430. Main needle 420 is movably disposed within delivery lumen 430. Main needle 420 is, for example, a stainless steel hypotube that extends a length of the delivery assembly. Main needle 420 includes a lumen with an inside diameter of, for example, 0.08 inches (0.20 centimeters). In one example for a retractable needle catheter, main needle 420 has a needle length on the order of 40 inches (1.6 meters) from distal portion 405 to proximal portion 415. Lumen 410 also includes separate, possibly smaller diameter, auxiliary lumen 440 extending, in this example, co-linearly along the length of the catheter (from a distal portion 405 to proximal portion 415). Auxiliary lumen 440 is, for example, a polymer tubing of a suitable material (e.g., polyamides, polyolefins, polyurethanes, etc.). At distal portion 405, auxiliary lumen 440 is terminated to auxiliary needle end 450 co-linearly aligned with a delivery end of needle 420. Auxiliary lumen 440 may be terminated to auxiliary needle end 450 with a radiation-curable adhesive, such as an ultraviolet curable adhesive. Auxiliary needle end 450 is, for example, a stainless steel hypotube that is joined co-linearly to the end of main needle 420 by, for example, solder (illustrated as joint 455). Auxiliary needle end 450 has a length on the order of about 0.08 inches (0.20 centimeters). FIG. 5B shows a cross-sectional front view through line A-A′ of delivery assembly 400. FIG. 5B shows main needle 420 and auxiliary needle 450 in a co-linear alignment.
  • [0063]
    Referring to FIG. 5A, at proximal portion 415, auxiliary lumen 440 is terminated to auxiliary side arm 460. Auxiliary side arm 460 includes a portion extending co-linearly with main needle 420. Auxiliary side arm 460 is, for example, a stainless steel hypotube material that may be soldered to main needle 420 (illustrated as joint 465). Auxiliary side arm 460 has a co-linear length on the order of about, in one example, 1.2 inches (3 centimeters).
  • [0064]
    The proximal end of main needle 420 includes adaptor 470 for accommodating a substance delivery device (e.g., a component of a two-component bioerodable gel material). Adaptor 470 is, for example, a molded female luer housing. Similarly, a proximal end of auxiliary side arm 460 includes adaptor 480 to accommodate a substance delivery device (e.g., a female luer housing).
  • [0065]
    The design configuration described above with respect to FIGS. 5A-5B is suitable for introducing two-component gel compositions of the present invention. For example, a gel may be formed by a combination (mixing, contact, etc.) of a first component and a second component. Representatively, a first component may be introduced by a one cubic centimeters syringe at adaptor 470 through main needle 420. At the same time or shortly before or after, second component including treatment agent loaded sustained-release particles may be introduced with a one cubic centimeter syringe at adaptor 480. When the first and second components combine at the exit of delivery assembly 400 (at an infarct region), the materials combine (mix, contact) to form a bioerodable gel.
  • [0066]
    FIGS. 6A-6C illustrate an alternative embodiment of a dual-needle injection device which can be used to deliver two-component gel compositions of the present invention. In general, the catheter assembly 500 provides a system for delivering substances, such as two-component gel compositions, to or through a desired area of a blood vessel (a physiological lumen) or tissue in order to treat a myocardial infarct region. The catheter assembly 500 is similar to the catheter assembly 500 described in commonly-owned, U.S. Pat. No. 6,554,801, titled “Directional Needle Injection Drug Delivery Device”, and incorporated herein by reference.
  • [0067]
    In one embodiment, catheter assembly 500 is defined by elongated catheter body 550 having proximal portion 520 and distal portion 510. FIG. 6B shows catheter assembly 500 through line A-A′ of FIG. 6A (at distal portion 510). FIG. 6C shows catheter assembly 500 through line B-B′ of FIG. 6A.
  • [0068]
    Guidewire cannula 570 is formed within catheter body (from proximal portion 510 to distal portion 520) for allowing catheter assembly 500 to be fed and maneuvered over guidewire 580. Balloon 530 is incorporated at distal portion 510 of catheter assembly 500 and is in fluid communication with inflation cannula 560 of catheter assembly 500.
  • [0069]
    Balloon 530 can be formed from balloon wall or membrane 335 which is selectively inflatable to dilate from a collapsed configuration to a desired and controlled expanded configuration. Balloon 530 can be selectively dilated (inflated) by supplying a fluid into inflation cannula 560 at a predetermined rate of pressure through inflation port 565. Balloon wall 335 is selectively deflatable, after inflation, to return to the collapsed configuration or a deflated profile. Balloon 530 may be dilated (inflated) by the introduction of a liquid into inflation cannula 560. Liquids containing treatment and/or diagnostic agents may also be used to inflate balloon 530. In one embodiment, balloon 530 may be made of a material that is permeable to such treatment and/or diagnostic liquids. To inflate balloon 530, the fluid can be supplied into inflation cannula 560 at a predetermined pressure, for example, between about one and 20 atmospheres. The specific pressure depends on various factors, such as the thickness of balloon wall 335, the material from which balloon wall 335 is made, the type of substance employed and the flow-rate that is desired.
  • [0070]
    Catheter assembly 500 also includes substance delivery assembly 505 for injecting a substance into a myocardial infarct region. In one embodiment, substance delivery assembly 505 includes needle 515 a movably disposed within hollow delivery lumen 525 a. Delivery assembly 505 includes needle 515 b movably disposed within hollow delivery lumen 525 b. Delivery lumen 525 a and delivery lumen 525 b each extend between distal portion 510 and proximal portion 520. Delivery lumen 525 a and delivery lumen 525 b can be made from any suitable material, such as polymers and copolymers of polyamides, polyolefins, polyurethanes and the like. Access to the proximal end of delivery lumen 525 a or delivery lumen 525 b for insertion of needle 515 a or 515 b, respectively is provided through hub 535. Delivery lumens 525 a and 525 b may be used to deliver first and second components of a two-component gel composition to a myocardial infarct region.
  • [0071]
    Referring now to FIG. 7A, an alternative embodiment of a distal needle portion 405 is shown. In this embodiment, a proximal edge of the distal end of main needle 420 is near the distal edge of the distal end of auxiliary needle 450. As shown, in this configuration it is possible for the planes encompassing the edges of the distal ends of both needles to be nearly co-planar. This is illustrated further in the cross-sectional view of the needle configuration shown in FIG. 7B. As a result of the nearly co-planar configuration of the distal ends, the distal needle portion 405 can puncture tissue and spread the tissue cleanly as it is advanced further. This minimizes tissue damage and allows the tissue to recover more fully after the distal needle portion 405 is removed.
  • [0072]
    FIG. 8A illustrates yet another alternative embodiment of a distal needle portion 405 in accordance with this invention. In this configuration, the distal portion of auxiliary needle 450 is positioned within the distal portion of main needle 420. The distal ends of the needles may be generally coaxial in order to maximize the flow area of the main needle 420. A sectional view of the needle configuration is shown in FIG. 8B. Although the embodiment is shown in a generally coaxial configuration, the auxiliary needle may also be non-concentric with respect to the main needle. In this way, the flow characteristics of the distal needle portion 405 may be modified in accordance with the invention. This will also account for normal manufacturing tolerances. Further, alternative configurations in accordance with this embodiment can be used to affect the piercing capabilities of the distal needle portion 405.
  • [0073]
    It is an object of this invention to prevent the inadvertent mixture of the two gel components of the present invention prior to their delivery into the target tissue. Controlling the flow direction of injectate moved through the distal end of each needle will accomplish this. For example, by providing divergent flow paths for each gel component, when the gel components are injected while the distal needle portion is positioned within the turbulent blood flow of a heart chamber, the gel components will be quickly dispersed by the circulating blood before they are able to interact with each other. In contrast, when the distal needle portion 405 is inserted within the heart tissue and the gel components are injected through the divergent flow paths, the resistance of the heart tissue will moderate the dispersal of the gel components, allowing them to admix and form a two-component gel composition.
  • [0074]
    In accordance with this invention, the distal needle portion 405 may be configured as shown in FIGS. 9A-9B. Distal needle portion 405 includes a main needle 420 aligned collinearly with auxiliary needle 450. Main needle 420 includes a lumen opening defined by a plane that intersects the axis of the needle lumen. Thus, a gel component moved through the main needle will exit the needle lumen along the axis of the needle lumen. In contrast, auxiliary needle 450 includes a lumen opening formed in the wall of the needle lumen such that the lumen opening is generally parallel with the needle lumen axis. Thus, a gel component moved through the auxiliary needle will exit the needle lumen in a direction that is generally perpendicular to the needle lumen axis. Therefore a gel component injected through the auxiliary needle 450 exits the distal needle portion 405 in a direction that diverges from the direction that a gel component injected through the main needle 420 will follow as it exits the distal needle portion 405.
  • [0075]
    As shown in FIG. 9B, the auxiliary needle 450 of this embodiment includes a closed end. The schematic representation of this figure indicates that the end may be closed by forming a needle from one piece with a closed end. Alternatively, an open ended needle tube may be closed by inserting and bonding in place a needle plug. In this case, bonding of the plug may be accomplished by using adhesive or thermal welding, soldering, or any other suitable process that is well known in the art. It may be preferable, though not necessary, to form the plug from the same material as that used to form the auxiliary needle 450, to improve manufacturability.
  • [0076]
    An alternative configuration for a distal needle portion 405 that prevents the inadvertent mixture of injectate is shown in FIGS. 10A-10B. In this embodiment, the lumen openings of main needle 420 and auxiliary needle 450 are not co-planar. Further, in this embodiment, the distal ends of each needle are generally co-planar to each other and the distal edge of a distal end of the auxiliary needle 450 is positioned near the proximal edge of a distal end of the main needle 420. Therefore, a uniform surface is defined by the distal ends of both needles, which improves the piercing characteristics of the needle assembly. In further accordance with the invention, divergent pathways for the gel components are provided to prevent inadvertent mixture outside of the target tissue.
  • [0077]
    It will be appreciated that the main needle 420 and auxiliary needle 450 of the embodiments shown in FIGS. 7 through 10 are interchangeable. That is, while the main needle 420 of FIG. 10A-10B is shown with a closed end, it is possible to instead close the end of auxiliary needle 450 in accordance with this invention. This interchangeability is applied to each of the embodiments and configurations discussed.
  • [0078]
    Another method of ensuring that injectate is not inadvertently mixed is to longitudinally space the distal ends of the needles while they are positioned outside of the target tissue. FIG. 1A-11B shows a distal needle portion 405 with a main needle 420 and an auxiliary needle 450 in a longitudinally spaced configuration. In this embodiment, the needles can be moved relative to one another. It will be appreciated that when the distal needle portion 405 is placed within a chamber of a beating heart, the turbulent blood flow within the beating heart will disperse the injectate from each needle before the two components are able to traverse the offset distance 470 to admix. Therefore, inadvertent mixing is prevented.
  • [0079]
    Referring now to FIG. 11C, when the distal needle portion 405 engages tissue 602, a reactive load is placed on main needle 420 by the tissue 602, causing the main needle 420 to retract relative to auxiliary needle 450 and reducing the offset distance 470. Eventually, both needles engage and puncture the tissue 602. Thus, the subsequent injection of two gel components through the separate needle lumens will result in delivery of the injectate to adjacent locations within the tissue 602, allowing them to effectively mix to form a two-component gel composition in accordance with this invention.
  • [0080]
    FIGS. 12A-12C illustrates an alternative embodiment in accordance with this invention, using an alternative configuration of distal needle portion 405. In this embodiment, the main needle 420 is at least partially enclosed within the auxiliary needle 450 and the distal end of the main needle is offset from the distal end of the auxiliary needle 450 by a distance 470 when in a first position. In this first position, which is shown in FIG. 12A-12B within the chamber of a heart, gel components delivered through each of the needle lumens will be dispersed by the turbulent blood flow before the two components are able to traverse the offset distance 470 to admix.
  • [0081]
    Referring now to FIG. 12C, when the distal needle portion 405 engages tissue 602, a reactive load is placed on main needle 420 by the tissue 602, causing the main needle 420 to retract relative to auxiliary needle 450 and reducing offset distance 470. Eventually, both needles engage and puncture the tissue 602. Thus, the subsequent injection of two gel components through the separate needles will result in delivery of the injectate to adjacent locations within the tissue 602, allowing them to effectively mix to form a two-component gel composition in accordance with this invention.
  • [0082]
    In the embodiments that include an offset distance between needle tips such as those described in FIGS. 11 through 12, it is desirable to ensure that both needle tips pierce the tissue nearly simultaneously. This can be accomplished by constructing the leading needle from a softer material than the other needle. For example, referring to FIG. 12A-12C, if the main needle 420 is fabricated from a polymeric compound such as PEEK, nylon, PEBAX, polyurethane, or another suitable polymer, it will be less likely to pierce the tissue as the catheter is advanced. Instead, it will retract until the auxiliary needle 450 contacts and pierces the tissue, forming a pathway by which the distal needle portion 405 can enter the tissue 602 to deliver the two gel components.
  • [0083]
    Alternatively, the leading needle may have a blunted distal tip to prevent it from puncturing the tissue before the lagging needle has contacted the tissue also.
  • [0084]
    Referring now to FIG. 13A, an alternative embodiment of a needle assembly 600 in accordance with this invention utilizes a guide needle 610 and a delivery needle 620 (hidden). The guide needle 610 is designed to facilitate the puncture of the target tissue, while the delivery needle 620 is intended to deliver the two gel components to the target site. The delivery needle 620 is at least partially positioned within the guide needle 610 and may be moveable within the guide needle. Therefore, the delivery needle may be configured in an initial leading or lagging position relative to the guide needle 610. In accordance with their purpose, the guide needle 610 and the delivery needle 620 may be fabricated from different materials. The guide needle 610 is preferably fabricated from a harder material than the delivery needle 620. Therefore, the guide needle 610 may be formed from a metal such as stainless steel or cobalt chromium, while suitable shape memory metals such as Nitinol may also be used. This provides a guide needle configuration that can puncture tissue easily. The delivery needle 620 may be formed from suitable polymeric compounds such as polyurethane, polyimide, polyamide, PEEK, nylon, Pebax and other suitable plastics that are well known in the art.
  • [0085]
    Referring now to FIG. 13B, a cross-sectional view of the needle assembly 600 shown in FIG. 13A is illustrated. This illustrates that the delivery needle 620 includes at least two lumens defined by first lumen 622 and second lumen 624. Further, these lumens may be separated by a partition 626. The main function of the guide needle 610 in this embodiment is to puncture the target tissue thereby forming a channel for the insertion of delivery needle 620. The structure of delivery needle 620 allows different components of a therapeutic composition to be delivered through first lumen 622 and second lumen 624. The components are separated by partition 626 until they exit the distal end of needle assembly 600 and enter the target tissue, where the components admix to form a composition in accordance with this invention.
  • [0086]
    FIGS. 14A-14C are cross-sectional views of alternative embodiments of delivery needle 620 in accordance with this invention. Each of the variations includes the basic structural components of the delivery needle 620: a first lumen 622, a second lumen 624, and a partition 626. FIG. 14A includes two elliptical lumens 622 and 624 and also exhibits a relatively high amount of material in the sidewall portion that contributes to improved torque transmission. In FIG. 14B, the crescent-shaped second lumen 624 meshes with the circular first lumen 622. The cross-sectional areas of the first lumen 622 and second lumen 624 in this embodiment may be varied to achieve the desired flow rate through each lumen. In FIG. 14C, the delivery needle is generally oval shaped and the first lumen 622 and second lumen 624 are D-shaped. This configuration resists torsion and provides a higher level of flexibility about a first axis 628 compared to the flexibility about a second axis 630. It will be appreciated that many other needle configurations may be contemplated by one skilled in the art that will ensure the separation of injectate during delivery in accordance with this invention.
  • [0087]
    As discussed in several of the embodiments above, the needle assembly may advantageously comprise a leading needle that is offset from another needle in a first configuration. This prevents mixing of gel components when they are released from the needle assembly outside of the presence of tissue, and therefore mitigates the risk of a thromboembolic event. A suitable offset distance for preventing inadvertent mixture of gel components outside of the target tissue is contemplated to be about 1-5 mm. In a second configuration, the leading needle is moved relative to the lagging needle by a reactive load applied by the target tissue until both needles contact and puncture the tissue. Following tissue puncture, gel components may be delivered through each needle lumen to admix within the target tissue and form a two-component gel composition in accordance with this invention. The two needles may be configured to slide over one another. This can be enabled, for example, by housing the needles within a sheath over at least a portion of their length. Alternatively, the needle components may be constrained within bands placed at predetermined positions along the length of the catheter device.
  • [0088]
    Referring now to FIG. 15A, a needle assembly 600 is shown in a first configuration prior to making contact with tissue 700. The needle assembly includes a first needle 640 with a distal end that leads the distal end of a second needle 642 in the first configuration. First needle 640 is further associated with first stop 644, while the second needle 642 is associated with a second stop 646. Biasing element 650 is associated with first stop 644 and second stop 646 and applies a separation force to the stops, which biases the distal ends of the first needle 640 and second needle 642 away from each other, as shown.
  • [0089]
    Referring now to FIG. 15B, as the needle assembly 600 is advanced, the distal end of the leading needle 640 contacts tissue 700 and a reactive load is applied to the first needle 640. This reactive load opposes the biasing force of the biasing element 650 and the first needle 640 moves relative to second needle 642, reducing the offset distance of the distal ends of each needle. When the second needle 642 contacts the tissue 700, the needles puncture the tissue 700. Gel components can then be delivered through first needle 640 and second needle 642 into the tissue in order to form a gel composition therein.
  • [0090]
    Upon retraction of the needle assembly 600 from the tissue, the biasing element 650 will again force the separation of the distal ends of needle 640 and 642, thereby preventing gelation of the two gel components within the heart chamber and mitigating the risk of a thromboembolic event.
  • [0091]
    In this embodiment, the stops 644 and 646 may be formed from collars that are bonded to the surface of the needles as described. Bonding may be facilitated through the use of adhesive or thermal welding. Alternatively, the collars may be press fit with the corresponding needle components. The collars are sized and configured to provide adequate seating for the biasing element 650 without excessively impeding the flow of fluid within the needle components.
  • [0092]
    It may be desirable to vary the distance of the offset between the first and second needle. In this case, an adjustable stop may be provided to on one or both needles to affect this offset distance. The stop may be threaded, for example, and be engaged with a screw thread on the corresponding needle surface. Rotation of the needle via an association with a proximal handle component of the delivery device (not shown) would cause movement of the stop, which would in turn adjust the offset distance between the distal ends of the needle components.
  • [0093]
    Biasing element 650 is preferably formed from a compression spring that applies a separation load to first needle 640 and second needle 642. However, alternative embodiments are possible, such as the use of a volute, Belleville, tension, v-spring and leaf-type spring, or other configurations that may be contemplated by one skilled in the art.
  • [0094]
    Ideally, a needle assembly for delivering injectate into tissue will have a minimized cutting profile to reduce tissue damage caused by needle puncture. The ideal needle assembly will also prevent excessive back pressure in order to ease delivery of the injectate. These are competing goals since needle profile can be decreased to minimize puncture size while lumen profile can be increased to reduce back pressure.
  • [0095]
    Referring now to FIG. 16A-16C, several embodiments of a needle assembly that minimize puncture area and reduce back pressure are shown. The embodiments generally include a tapered or stepped transition near the distal end of the needle.
  • [0096]
    FIG. 16A shows a needle assembly 702 comprised of a first needle 710 and a second needle 712. Each needle includes a proximal portion 720 and a distal portion 722, these two portions being separated by a stepped transition zone 714 in the first needle and a stepped transition zone 716 in the second needle. It will be appreciated that the distal portion 722 has a reduced needle profile, which will minimize the cutting profile as it pierces into tissue. In contrast, the proximal portion 720 has a larger lumen profile, which reduces back pressure and eases delivery of an injectate through the needle assembly 702.
  • [0097]
    Referring now to FIG. 16B, a needle assembly 702 in accordance with this invention is shown in which a distal portion 722 and a proximal portion 720 are separated by a tapered transition zone 714 in a first needle 710 and a tapered transition zone 716 in a second needle 712. This configuration provides the benefit of a needle assembly that minimizes the cutting profile as it pierces tissue and reduces back pressure to ease delivery of injectate through the needle assembly 702.
  • [0098]
    Referring now to FIG. 16C, an alternative embodiment of a needle assembly 702 in accordance with this invention is shown in which a distal portion 722 and a proximal portion 720 are separated by a stepped transition in first needle 710 and second needle 712. This configuration provides a needle assembly 702 that advantageously minimizes the cutting profile as it pierces tissue and reduces back pressure to ease delivery of injectate through the needle assembly 702. First needle 710 and second needle 712 are arranged in a side-by-side configuration, which optimizes the internal volume in each needle and further contributes to a reduction in back pressure in accordance with this invention.
  • [0099]
    An alternative embodiment of a needle assembly 800 in accordance with this invention is shown in FIG. 17. In this embodiment, a first needle 802 and a second needle 804 are configured in a side-by-side fashion over a portion of their length and they are configured in a generally coaxial fashion over another portion of their length. The needles transition from one configuration to another configuration at a transition point 806 located at a discontinuity in the wall of the second needle 804. The first needle 802 may optionally be sealed to the second needle 804 at the transition point 806. It will be appreciated that this configuration creates a minimized needle profile in the distal portion of the needle assembly 800, while lumen profile may be optimized in the proximal portion of the needle assembly 800, in accordance with this invention.
  • [0100]
    Referring now to FIG. 18, yet another embodiment in accordance with this invention is shown. An injection catheter 900 includes a needle assembly that comprises a first needle 902 disposed within a second needle 904, the second needle 904 of this embodiment is shorter than the first needle 902. The second needle 904 is associated with an intermediate catheter shaft 908 by a dynamic seal 906. This seal opposes fluid flow from within the catheter shaft so that fluid exits the injection catheter through second needle 904. Likewise, injectate may be delivered through the lumen of the first needle 902. An actuation element 910 is associated with the second needle 904 near a proximal end of the second needle 904. The actuation element 910 transmits loads to the second needle 904 that cause the needle to either extend or retract. Therefore, the distance between the distal ends of both needles can be controlled by the manipulation of the actuation element 910. In this way, the puncturing of tissue and the creation of a composition therein can be controlled. Further, this configuration provides beneficial reduction in back pressure since the lumen of the catheter shaft is larger than the lumen of second needle 904.
  • [0101]
    Notwithstanding the description above, the needle components of this invention may be formed from any material that is suitable for the intended purpose. Needle components may therefore be formed from an appropriate metal, such as stainless steel, Nitinol, or cobalt-chromium alloys such as L605 or MP35N, any equivalents thereof, alloys thereof, and combinations thereof. Further, the one or both needle components may be formed from a suitable polymeric compound such as nylon, urethane, polyurethane, polyvinylchloride, polyester, PEEK, PTFE, PVDF, Kyner, polyimide, or polyethylene of various suitable densities. Further, one or both needle components may be a combination of metal and polymer materials, such as a polymer tube reinforced by a metal braid or coil, as are well known in the art.
  • [0102]
    The needle components described above are sized and configured to puncture the target tissue and effectively deliver the intended gel components therein. Accordingly, a wide range of needle sizes exist for achieving the goal of the invention. Nonetheless, it is contemplated that needle components in accordance with this invention may have an outer dimension at the distal end of between 23 and 33 Gauge.
  • [0103]
    In accordance with this invention, the bevel angle of the needles may be varied to facilitate tissue puncture. Therefore, the bevel angle could be in the range of 5 to 80 degrees. More preferably, the bevel angle could be in the range of 10 to 65 degrees, and even more preferably, the bevel angle could be in the range of 15 to 45 degrees. Further, it may only be necessary for one of the needle components to include a beveled tip. The beveled tip needle would facilitate tissue puncture, while the second needle may have a blunted or flat tip that is inserted within the punctured tissue.
  • [0104]
    From the foregoing detailed description, it will be evident that there are a number of changes, adaptations and modifications of the present invention which come within the province of those skilled in the part. The scope of the invention includes any combination of the elements from the different species and embodiments disclosed herein, as well as subassemblies, assemblies and methods thereof. However, it is intended that all such variations not departing from the spirit of the invention be considered as within the scope thereof.

Claims (20)

  1. 1. A device comprising:
    a) a first delivery needle, and
    b) a second delivery needle,
    c) whereby a first gel component can be delivered through the first delivery needle without contacting a second gel component that may be disposed in the second delivery needle.
  2. 2. The device of claim 1, wherein the first delivery needle and the second delivery needle are arranged in a side-by-side configuration.
  3. 3. The device of claim 1, wherein the first delivery needle and the second delivery needle are arranged in a coaxial configuration.
  4. 4. The device of claim 1, further comprising a port disposed in the wall of the first delivery needle adapted such that a first gel component delivered through the port and a second gel component delivered through the second delivery needle will diverge.
  5. 5. The device of claim 2 adapted to have at least two configurations and wherein the distal end of the first delivery needle and the distal end of the second delivery needle are longitudinally separated by an offset distance.
  6. 6. The device of claim 5, wherein the offset distance is less in a second configuration than in the first configuration.
  7. 7. The device of claim 6, further including a biasing element associated with the first delivery needle and the second delivery needle, whereby the biasing element urges the device toward the first configuration.
  8. 8. The device of claim 7 wherein the biasing element is a spring.
  9. 9. The device of claim 8 wherein the spring is selected from the group consisting of compression, volute, Belleville, tension, v-spring and leaf-type springs.
  10. 10. The device of claim 3, wherein the distal end of the first delivery needle and the distal end of the second delivery needle are longitudinally separated by an offset distance in a first configuration.
  11. 11. The device of claim 10 adapted to have at least two configurations and wherein the distal end of the first delivery needle and the distal end of the second delivery needle are longitudinally separated by an offset distance that is less in a second configuration than in the first configuration.
  12. 12. The device of claim 11, further including a biasing element associated with the first delivery needle and the second delivery needle, whereby the biasing element urges the device toward the first configuration.
  13. 13. The device of claim 12 wherein the biasing element is a spring.
  14. 14. The device of claim 13 wherein the spring is selected from the group consisting of compression, volute, Belleville, tension, v-spring and leaf-type springs.
  15. 15. The device of claim 3, wherein the second delivery needle includes at least two lumens separated from each other, and separated from the first needle lumen.
  16. 16. The device of claim 1, wherein the proximal portion of the first delivery needle and second delivery needle have a larger lumen profile than the distal portion and the proximal portion connects to the distal portion through a transition portion.
  17. 17. The device of claim 16, wherein the transition portion has a step, a taper, or a combination of a step and taper.
  18. 18. A device comprising:
    a) a first delivery needle, and
    b) a second delivery needle wherein a lumen at the second needle is separated from the lumen of the first needle,
    c) an actuation element associated with a proximal edge of the second delivery needle,
    d) a catheter shaft, and
    e) a dynamic seal formed between the catheter shaft inner lumen and the second delivery needle,
    f) whereby a first component can be delivered through the first delivery needle without contacting a second component disposed in the second delivery needle.
  19. 19. A method of performing a medical procedure, comprising:
    a) advancing within a patient's body lumen a device comprising a first delivery needle, and a second delivery needle,
    b) delivering a first gel component through the first delivery needle,
    c) delivering a second gel component through the second delivery needle, and
    d) allowing the first and second gel components to admix within the patient's body tissue to form a gel composition.
  20. 20. The method of claim 19 wherein the device is further adapted to have at least two configurations and wherein the distal end of the first needle and the distal end of the second needle are longitudinally separated by an offset distance.
US11978986 2005-04-19 2007-10-29 Methods and compositions for treating post-cardial infarction damage Abandoned US20080125745A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US11110223 US8828433B2 (en) 2005-04-19 2005-04-19 Hydrogel bioscaffoldings and biomedical device coatings
US11361920 US8303972B2 (en) 2005-04-19 2006-02-23 Hydrogel bioscaffoldings and biomedical device coatings
US11447340 US8187621B2 (en) 2005-04-19 2006-06-05 Methods and compositions for treating post-myocardial infarction damage
US11978986 US20080125745A1 (en) 2005-04-19 2007-10-29 Methods and compositions for treating post-cardial infarction damage

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US11978986 US20080125745A1 (en) 2005-04-19 2007-10-29 Methods and compositions for treating post-cardial infarction damage
PCT/US2008/079111 WO2009058525A1 (en) 2007-10-29 2008-10-07 Compositions for treating post-cardial infarction damage
US12963397 US20110077618A1 (en) 2005-04-19 2010-12-08 Methods and Compositions for Treating Post-Cardial Infarction Damage
US13898412 US9687630B2 (en) 2005-04-19 2013-05-20 Methods and compositions for treating post-cardial infarction damage
US13898413 US9539410B2 (en) 2005-04-19 2013-05-20 Methods and compositions for treating post-cardial infarction damage

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US11447340 Continuation-In-Part US8187621B2 (en) 2005-04-19 2006-06-05 Methods and compositions for treating post-myocardial infarction damage

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12963397 Division US20110077618A1 (en) 2005-04-19 2010-12-08 Methods and Compositions for Treating Post-Cardial Infarction Damage

Publications (1)

Publication Number Publication Date
US20080125745A1 true true US20080125745A1 (en) 2008-05-29

Family

ID=40084261

Family Applications (3)

Application Number Title Priority Date Filing Date
US11978986 Abandoned US20080125745A1 (en) 2005-04-19 2007-10-29 Methods and compositions for treating post-cardial infarction damage
US12963397 Abandoned US20110077618A1 (en) 2005-04-19 2010-12-08 Methods and Compositions for Treating Post-Cardial Infarction Damage
US13898412 Active 2027-12-16 US9687630B2 (en) 2005-04-19 2013-05-20 Methods and compositions for treating post-cardial infarction damage

Family Applications After (2)

Application Number Title Priority Date Filing Date
US12963397 Abandoned US20110077618A1 (en) 2005-04-19 2010-12-08 Methods and Compositions for Treating Post-Cardial Infarction Damage
US13898412 Active 2027-12-16 US9687630B2 (en) 2005-04-19 2013-05-20 Methods and compositions for treating post-cardial infarction damage

Country Status (2)

Country Link
US (3) US20080125745A1 (en)
WO (1) WO2009058525A1 (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090012536A1 (en) * 2006-08-03 2009-01-08 Rassman William R Hair harvesting device and method with localized subsurface dermal fluid insertion
US20090240208A1 (en) * 2008-03-19 2009-09-24 Warsaw Orthopedic, Inc. Microparticle delivery syringe and needle for placing particle suspensions and removing vehicle fluid
US20140128810A1 (en) * 2011-03-23 2014-05-08 Nanbu Plastics Co., Ltd. Percutaneous medication device and needle formation used for the device
US20140257190A1 (en) * 2011-10-18 2014-09-11 Tsinghua University Disposable Array-Type Micro Injection Needle Head And Pre-Filling Injector Thereof
US20150374915A1 (en) * 2014-06-30 2015-12-31 Elwha Llc Active Lubrication of Penetrating Devices
US20160073937A1 (en) * 2014-09-11 2016-03-17 Becton, Dickinson And Company Blood sampling system for improving draw success and reducing hemolysis
US9919112B2 (en) 2014-06-30 2018-03-20 Elwha Llc Active lubrication of penetrating devices
US9919111B2 (en) 2014-06-30 2018-03-20 Elwha Llc Active lubrication of penetrating devices

Citations (96)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6183432B2 (en) *
US3804097A (en) * 1972-12-14 1974-04-16 P Rudie Method of irrigating and treating an abcess
US4794931A (en) * 1986-02-28 1989-01-03 Cardiovascular Imaging Systems, Inc. Catheter apparatus, system and method for intravascular two-dimensional ultrasonography
US5000185A (en) * 1986-02-28 1991-03-19 Cardiovascular Imaging Systems, Inc. Method for intravascular two-dimensional ultrasonography and recanalization
US5024234A (en) * 1989-10-17 1991-06-18 Cardiovascular Imaging Systems, Inc. Ultrasonic imaging catheter with guidewire channel
US5092130A (en) * 1988-11-09 1992-03-03 Mitsubishi Denki Kabushiki Kaisha Multi-stage cold accumulation type refrigerator and cooling device including the same
US5092848A (en) * 1988-10-13 1992-03-03 Deciutiis Vincent L Intravenous catheter with built-in cutting tip and method for making the same
US5100185A (en) * 1989-03-14 1992-03-31 Kiekert Gmbh & Co. Motor-vehicle door latch
US5128326A (en) * 1984-12-06 1992-07-07 Biomatrix, Inc. Drug delivery systems based on hyaluronans derivatives thereof and their salts and methods of producing same
US5202745A (en) * 1990-11-07 1993-04-13 Hewlett-Packard Company Polarization independent optical coherence-domain reflectometry
US5203338A (en) * 1990-12-17 1993-04-20 Cardiovascular Imaging Systems, Inc. Vascular catheter having low-profile distal end
US5291267A (en) * 1992-01-22 1994-03-01 Hewlett-Packard Company Optical low-coherence reflectometry using optical amplification
US5306250A (en) * 1992-04-02 1994-04-26 Indiana University Foundation Method and apparatus for intravascular drug delivery
US5321501A (en) * 1991-04-29 1994-06-14 Massachusetts Institute Of Technology Method and apparatus for optical imaging with means for controlling the longitudinal range of the sample
US5328955A (en) * 1988-11-21 1994-07-12 Collagen Corporation Collagen-polymer conjugates
US5380292A (en) * 1993-12-22 1995-01-10 Wilson-Cook Medical, Inc. Gastrointestinal needle mechanism
US5419777A (en) * 1994-03-10 1995-05-30 Bavaria Medizin Technologie Gmbh Catheter for injecting a fluid or medicine
US5485486A (en) * 1989-11-07 1996-01-16 Qualcomm Incorporated Method and apparatus for controlling transmission power in a CDMA cellular mobile telephone system
US5499630A (en) * 1993-11-22 1996-03-19 Kabushiki Kaisha Toshiba Catheter type ultrasound probe
US5540912A (en) * 1992-03-30 1996-07-30 Alza Corporation Viscous suspensions of controlled-release drug particles
US5621610A (en) * 1994-06-30 1997-04-15 Compaq Computer Corporation Collapsible computer keyboard structure with associated collapsible pointing stick
US5642234A (en) * 1995-10-30 1997-06-24 Lumatec Industries, Inc. Illuminated magnifying lens assembly
US5722403A (en) * 1996-10-28 1998-03-03 Ep Technologies, Inc. Systems and methods using a porous electrode for ablating and visualizing interior tissue regions
US5740808A (en) * 1996-10-28 1998-04-21 Ep Technologies, Inc Systems and methods for guilding diagnostic or therapeutic devices in interior tissue regions
US5785689A (en) * 1996-07-18 1998-07-28 Act Medical, Inc. Endoscopic catheter sheath position control
US5879713A (en) * 1994-10-12 1999-03-09 Focal, Inc. Targeted delivery via biodegradable polymers
US5900433A (en) * 1995-06-23 1999-05-04 Cormedics Corp. Vascular treatment method and apparatus
US5919449A (en) * 1995-05-30 1999-07-06 Diacrin, Inc. Porcine cardiomyocytes and their use in treatment of insufficient cardiac function
US6022540A (en) * 1997-09-04 2000-02-08 Osiris Therapeutics, Inc. Ligands that modulate differentiation of mesenchymal stem cells
US6045565A (en) * 1997-11-04 2000-04-04 Scimed Life Systems, Inc. Percutaneous myocardial revascularization growth factor mediums and method
US6051648A (en) * 1995-12-18 2000-04-18 Cohesion Technologies, Inc. Crosslinked polymer compositions and methods for their use
US6051071A (en) * 1994-12-05 2000-04-18 Societe Nationale D'etude Et De Construction De Moteurs D'aviation Device for extracting gas from an oven for chemical vapor deposition or infiltration in an installation for fabricating composite material parts
US6058329A (en) * 1998-10-13 2000-05-02 Cardiac Pacemakers, Inc. Optimization of pacing parameters based on measurement of acoustic noise
US6056744A (en) * 1994-06-24 2000-05-02 Conway Stuart Medical, Inc. Sphincter treatment apparatus
US6060053A (en) * 1993-04-30 2000-05-09 Children's Medical Center Corp. Injectable chondrocyte-carrier suspension for treatment of vesicoureteral reflux and incontinence
US6071305A (en) * 1996-11-25 2000-06-06 Alza Corporation Directional drug delivery stent and method of use
US6086582A (en) * 1997-03-13 2000-07-11 Altman; Peter A. Cardiac drug delivery system
US6093177A (en) * 1997-03-07 2000-07-25 Cardiogenesis Corporation Catheter with flexible intermediate section
US6175669B1 (en) * 1998-03-30 2001-01-16 The Regents Of The Universtiy Of California Optical coherence domain reflectometry guidewire
US6177407B1 (en) * 1998-08-13 2001-01-23 University Of Southern California Methods to increase blood flow to ischemic tissue
US6179809B1 (en) * 1997-09-24 2001-01-30 Eclipse Surgical Technologies, Inc. Drug delivery catheter with tip alignment
US6183330B1 (en) * 1997-05-01 2001-02-06 Phillips Plastics Corporation Display device and method therefor
US6183432B1 (en) * 1997-11-13 2001-02-06 Lumend, Inc. Guidewire and catheter with rotating and reciprocating symmetrical or asymmetrical distal tip
US6190353B1 (en) * 1995-10-13 2001-02-20 Transvascular, Inc. Methods and apparatus for bypassing arterial obstructions and/or performing other transvascular procedures
US6191144B1 (en) * 1998-08-17 2001-02-20 Warner-Lambert Company Method of using angiotensin converting enzyme inhibitor to stimulate angiogenesis
US6193763B1 (en) * 1998-12-17 2001-02-27 Robert A. Mackin Apparatus and method for contemporaneous treatment and fluoroscopic mapping of body tissue
US6197324B1 (en) * 1997-12-18 2001-03-06 C. R. Bard, Inc. System and methods for local delivery of an agent
US6201608B1 (en) * 1998-03-13 2001-03-13 Optical Biopsy Technologies, Inc. Method and apparatus for measuring optical reflectivity and imaging through a scattering medium
US6206893B1 (en) * 1993-11-08 2001-03-27 Perclose, Inc. Device and method for suturing of internal puncture sites
US6206914B1 (en) * 1998-04-30 2001-03-27 Medtronic, Inc. Implantable system with drug-eluting cells for on-demand local drug delivery
US6207180B1 (en) * 1997-04-03 2001-03-27 Thomas B. Ottoboni Intravesical drug delivery
US6210392B1 (en) * 1999-01-15 2001-04-03 Interventional Technologies, Inc. Method for treating a wall of a blood vessel
US6217527B1 (en) * 1998-09-30 2001-04-17 Lumend, Inc. Methods and apparatus for crossing vascular occlusions
US6217554B1 (en) * 1999-02-12 2001-04-17 Pharmaspec Corporation Methods and apparatus for delivering substances into extravascular tissue
US6231546B1 (en) * 1998-01-13 2001-05-15 Lumend, Inc. Methods and apparatus for crossing total occlusions in blood vessels
US6241710B1 (en) * 1999-12-20 2001-06-05 Tricardia Llc Hypodermic needle with weeping tip and method of use
US6251104B1 (en) * 1995-05-10 2001-06-26 Eclipse Surgical Technologies, Inc. Guiding catheter system for ablating heart tissue
US6334872B1 (en) * 1994-02-18 2002-01-01 Organogenesis Inc. Method for treating diseased or damaged organs
US6346098B1 (en) * 2000-03-07 2002-02-12 The Board Of Trustees Of The Leland Stanford Junior University Methods and kits for locally administering an active agent to an interstitial space of a host
US6346515B1 (en) * 1994-07-19 2002-02-12 Colbar R & D Ltd. Collegan-based matrix
US6346099B1 (en) * 1998-08-11 2002-02-12 Biocardia, Inc. Catheter drug delivery system and method for use
US6358258B1 (en) * 1999-09-14 2002-03-19 Abbott Laboratories Device and method for performing end-to-side anastomosis
US6368285B1 (en) * 1999-09-21 2002-04-09 Biosense, Inc. Method and apparatus for mapping a chamber of a heart
US20020042473A1 (en) * 1995-12-18 2002-04-11 Trollsas Olof Mikael Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use
US6371935B1 (en) * 1999-01-22 2002-04-16 Cardeon Corporation Aortic catheter with flow divider and methods for preventing cerebral embolization
US6371992B1 (en) * 1997-12-19 2002-04-16 The Regents Of The University Of California Acellular matrix grafts: preparation and use
US6379379B1 (en) * 1998-05-05 2002-04-30 Scimed Life Systems, Inc. Stent with smooth ends
US6385476B1 (en) * 1999-09-21 2002-05-07 Biosense, Inc. Method and apparatus for intracardially surveying a condition of a chamber of a heart
US6391052B2 (en) * 1994-04-29 2002-05-21 Scimed Life Systems, Inc. Stent with collagen
US6395023B1 (en) * 1997-02-07 2002-05-28 Endovasc Ltd., Inc. Prosthesis with biodegradable surface coating and method for making same
US20020072706A1 (en) * 2000-12-11 2002-06-13 Thomas Hiblar Transluminal drug delivery catheter
US20020076441A1 (en) * 2000-04-27 2002-06-20 Macromed, Inc. Bioactive agent delivering system comprised of microparticles within a biodegradable to improve release profiles
US6409716B1 (en) * 1989-12-15 2002-06-25 Scimed Life Systems, Inc. Drug delivery
US6415510B2 (en) * 2000-02-08 2002-07-09 Airbus Deutschland Gmbh Method of fabricating leading edge nose structures of aerodynamic surfaces
US20020090725A1 (en) * 2000-11-17 2002-07-11 Simpson David G. Electroprocessed collagen
US20030023202A1 (en) * 2001-07-26 2003-01-30 Nielson David H. Apparatus for delivering aerosolized fibrin endoscopically to a wound
US20030040712A1 (en) * 1999-07-13 2003-02-27 Pinaki Ray Substance delivery apparatus and a method of delivering a therapeutic substance to an anatomical passageway
US20030050597A1 (en) * 2001-09-12 2003-03-13 3M Innovative Properties Company Apparatus and methods for dispensing an adhesive tissue sealant
US6548081B2 (en) * 2000-07-28 2003-04-15 Anika Therapeutics, Inc. Bioabsorbable composites of derivatized hyaluronic acid and other biodegradable, biocompatible polymers
US20030078671A1 (en) * 2001-04-27 2003-04-24 Lesniak Jeanne M. Prevention of myocardial infarction induced ventricular expansion and remodeling
US6554801B1 (en) * 2000-10-26 2003-04-29 Advanced Cardiovascular Systems, Inc. Directional needle injection drug delivery device and method of use
US6599267B1 (en) * 2000-12-22 2003-07-29 Advanced Cardiovascular Systems, Inc. Transluminal injection device for intravascular drug delivery
US6682730B2 (en) * 1997-05-28 2004-01-27 Genzyme Corporation Transplants for myocardial scars
US6689608B1 (en) * 1993-02-01 2004-02-10 Massachusetts Institute Of Technology Porous biodegradable polymeric materials for cell transplantation
US6692466B1 (en) * 2000-12-21 2004-02-17 Advanced Cardiovascular Systems, Inc. Drug delivery catheter with retractable needle
US6702744B2 (en) * 2001-06-20 2004-03-09 Advanced Cardiovascular Systems, Inc. Agents that stimulate therapeutic angiogenesis and techniques and devices that enable their delivery
US6706034B1 (en) * 1999-12-30 2004-03-16 Advanced Cardiovascular Systems, Inc. Process for agent retention in biological tissues
US6737072B1 (en) * 1998-12-03 2004-05-18 Michael Nerlich Matrix for tissue engineering formed of a hyaluronic acid ester and hydrolyzed collagen
US6748258B1 (en) * 1999-11-05 2004-06-08 Scimed Life Systems, Inc. Method and devices for heart treatment
US6749617B1 (en) * 1997-11-04 2004-06-15 Scimed Life Systems, Inc. Catheter and implants for the delivery of therapeutic agents to tissues
US6759431B2 (en) * 1996-05-24 2004-07-06 Angiotech Pharmaceuticals, Inc. Compositions and methods for treating or preventing diseases of body passageways
US6858229B1 (en) * 1999-04-26 2005-02-22 California Institute Of Technology In situ forming hydrogels
US20050042254A1 (en) * 2003-07-16 2005-02-24 Toby Freyman Aligned scaffolds for improved myocardial regeneration
US6916648B2 (en) * 1997-10-17 2005-07-12 Genentech, Inc. Secreted and transmembrane polypeptides and nucleic acids encoding the same
US6992172B1 (en) * 1999-11-12 2006-01-31 Fibrogen, Inc. Recombinant gelatins
US7393339B2 (en) * 2003-02-21 2008-07-01 C. R. Bard, Inc. Multi-lumen catheter with separate distal tips

Family Cites Families (221)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2512569A (en) 1947-09-26 1950-06-20 Jacob A Saffir Hypodermic needle
US3144868A (en) * 1960-10-21 1964-08-18 Mario E Jascalevich Drainage and feeding cannulae
US3584624A (en) 1969-02-24 1971-06-15 Vincent L De Ciutiis Flexible intravenous catheter provided with cutting tip means
US3890976A (en) 1972-10-26 1975-06-24 Medical Products Corp Catheter tip assembly
US3780733A (en) 1972-07-24 1973-12-25 Manzor M Martinez Catheter
US6436135B1 (en) 1974-10-24 2002-08-20 David Goldfarb Prosthetic vascular graft
US4141973B1 (en) * 1975-10-17 1989-08-08
JPH0324223B2 (en) 1983-12-14 1991-04-02 Terumo Corp
US4617186A (en) 1984-12-28 1986-10-14 Alcon Laboratories, Inc. Sustained release drug delivery system utilizing bioadhesive polymers
JPH0449384B2 (en) 1985-03-08 1992-08-11 Nippon Carbide Kogyo Kk
GB2194144B (en) 1986-08-22 1990-04-25 American Cyanamid Co Stable pharmaceutical gel preparation
US5026350A (en) * 1986-10-09 1991-06-25 Hakko Electric Machine Works Co., Ltd. Set of double needles for injecting liquid medicine
US5606019A (en) 1987-10-29 1997-02-25 Protien Polymer Technologies, Inc. Synthetic protein as implantables
DE3740728A1 (en) * 1986-12-10 1988-06-23 Ajinomoto Kk adhesive
FR2627984B1 (en) 1988-03-03 1990-08-17 Sanofi Sa pulverulent composition based on alginate dental impression
US5372138A (en) 1988-03-21 1994-12-13 Boston Scientific Corporation Acousting imaging catheters and the like
US5588432A (en) 1988-03-21 1996-12-31 Boston Scientific Corporation Catheters for imaging, sensing electrical potentials, and ablating tissue
US4869717A (en) 1988-04-25 1989-09-26 Adair Edwin Lloyd Gas insufflation needle with instrument port
US5116317A (en) * 1988-06-16 1992-05-26 Optimed Technologies, Inc. Angioplasty catheter with integral fiber optic assembly
DE68922497D1 (en) 1988-08-24 1995-06-08 Marvin J Slepian Endoluminal seal with bisdegradierbaren polymeric.
US5575815A (en) 1988-08-24 1996-11-19 Endoluminal Therapeutics, Inc. Local polymeric gel therapy
US5634946A (en) * 1988-08-24 1997-06-03 Focal, Inc. Polymeric endoluminal paving process
US5843156A (en) 1988-08-24 1998-12-01 Endoluminal Therapeutics, Inc. Local polymeric gel cellular therapy
JPH0662678B2 (en) 1988-11-28 1994-08-17 電気化学工業株式会社 Hyaluronic acid immobilized proteins and a method of manufacturing the same
US5049130A (en) 1988-12-23 1991-09-17 Cardiovascular Imaging Systems, Inc. System and method for pressure filling of catheters
US5109859A (en) * 1989-10-04 1992-05-05 Beth Israel Hospital Association Ultrasound guided laser angioplasty
WO1991007154A1 (en) 1989-11-13 1991-05-30 President And Fellows Of Harvard College EXTRALUMINAL REGULATION OF THE GROWTH AND REPAIR OF TUBULAR STRUCTURES ιIN VIVO
US5811533A (en) 1990-06-11 1998-09-22 Nexstar Pharmaceuticals, Inc. High-affinity oligonucleotide ligands to vascular endothelial growth factor (VEGF)
US5573934A (en) 1992-04-20 1996-11-12 Board Of Regents, The University Of Texas System Gels for encapsulation of biological materials
FR2668698B1 (en) 1990-11-06 1997-06-06 Ethnor surgical instrument trocar.
CA2094250A1 (en) 1990-12-10 1992-06-11 Joshua Makower Device and method for interstitial laser energy delivery
US5171217A (en) 1991-02-28 1992-12-15 Indiana University Foundation Method for delivery of smooth muscle cell inhibitors
US5465147A (en) 1991-04-29 1995-11-07 Massachusetts Institute Of Technology Method and apparatus for acquiring images using a ccd detector array and no transverse scanner
US6134003A (en) 1991-04-29 2000-10-17 Massachusetts Institute Of Technology Method and apparatus for performing optical measurements using a fiber optic imaging guidewire, catheter or endoscope
DK0590015T3 (en) 1991-06-17 2000-11-06 Pharmacia & Upjohn Ab A composition for tissue processing comprising fibrin or fibrinogen and biodegradable and biocompatible polymer
US6152141A (en) 1994-07-28 2000-11-28 Heartport, Inc. Method for delivery of therapeutic agents to the heart
US5270300A (en) 1991-09-06 1993-12-14 Robert Francis Shaw Methods and compositions for the treatment and repair of defects or lesions in cartilage or bone
US6491938B2 (en) 1993-05-13 2002-12-10 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US6663881B2 (en) 1993-01-28 2003-12-16 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5981568A (en) 1993-01-28 1999-11-09 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
CA2108137A1 (en) 1992-02-10 1993-08-11 Tai Chun Cheng Composite material having a lubricous surface for catheter use
DE69333482D1 (en) 1992-02-21 2004-05-13 Boston Scient Ltd Catheter for image formation by means of ultrasound
US6231881B1 (en) 1992-02-24 2001-05-15 Anton-Lewis Usala Medium and matrix for long-term proliferation of cells
JP3063935B2 (en) 1992-05-12 2000-07-12 宇部興産株式会社 Adhesion, heat resistance and 耐Ka - polyimide siloxane composition having both Le resistance
US5336252A (en) 1992-06-22 1994-08-09 Cohen Donald M System and method for implanting cardiac electrical leads
US5365325A (en) 1992-08-10 1994-11-15 Hitachi, Ltd. Method of multi-color recording using electro-photography process and apparatus therefor wherein mixed colors generation is prevented
US5672153A (en) 1992-08-12 1997-09-30 Vidamed, Inc. Medical probe device and method
DE4235506A1 (en) 1992-10-21 1994-04-28 Bavaria Med Tech Catheter for injection of drugs
US5709854A (en) 1993-04-30 1998-01-20 Massachusetts Institute Of Technology Tissue formation by injecting a cell-polymeric solution that gels in vivo
US5437632A (en) 1993-06-02 1995-08-01 Target Therapeutics, Inc. Variable stiffness balloon catheter
US5725551A (en) * 1993-07-26 1998-03-10 Myers; Gene Method and apparatus for arteriotomy closure
WO1995012424A1 (en) 1993-11-03 1995-05-11 Astra Aktiebolag Device for mixing a pharmaceutical compositiion with another agent
US5795331A (en) 1994-01-24 1998-08-18 Micro Therapeutics, Inc. Balloon catheter for occluding aneurysms of branch vessels
FR2715855A1 (en) 1994-02-10 1995-08-11 Floch Serge Protector for syringe used with beta-radiation emitter
DE69530914T2 (en) 1994-02-17 2004-03-11 New York Blood Center, Inc. Biological bioadhesive preparations, the fibrin glue and liposome-contained process for their production and use
US5464395A (en) 1994-04-05 1995-11-07 Faxon; David P. Catheter for delivering therapeutic and/or diagnostic agents to the tissue surrounding a bodily passageway
CA2187802A1 (en) 1994-04-13 1995-10-26 Manfred W. Baetscher .alpha.(1,3) galactosyltransferase negative swine
US5580856A (en) 1994-07-15 1996-12-03 Prestrelski; Steven J. Formulation of a reconstituted protein, and method and kit for the production thereof
US5516532A (en) * 1994-08-05 1996-05-14 Children's Medical Center Corporation Injectable non-immunogenic cartilage and bone preparation
EP1009317A4 (en) 1997-08-28 2001-01-24 Boston Scient Corp System for implanting a cross-linked polysaccharide fiber and methods of forming and inserting the fiber
US6099864A (en) 1994-12-02 2000-08-08 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration In situ activation of microcapsules
CA2208554A1 (en) 1994-12-28 1996-07-04 Omrix Biopharmaceuticals S.A. Device for applying one or several fluids
US5919570A (en) 1995-02-01 1999-07-06 Schneider Inc. Slippery, tenaciously adhering hydrogel coatings containing a polyurethane-urea polymer hydrogel commingled with a poly(N-vinylpyrrolidone) polymer hydrogel, coated polymer and metal substrate materials, and coated medical devices
US5551427A (en) 1995-02-13 1996-09-03 Altman; Peter A. Implantable device for the effective elimination of cardiac arrhythmogenic sites
US5869127A (en) 1995-02-22 1999-02-09 Boston Scientific Corporation Method of providing a substrate with a bio-active/biocompatible coating
US5580714A (en) 1995-03-08 1996-12-03 Celox Laboratories, Inc. Cryopreservation solution
US5906934A (en) * 1995-03-14 1999-05-25 Morphogen Pharmaceuticals, Inc. Mesenchymal stem cells for cartilage repair
US5554389A (en) 1995-04-07 1996-09-10 Purdue Research Foundation Urinary bladder submucosa derived tissue graft
US5669883A (en) 1995-04-12 1997-09-23 Symbiosis Corporation Veress needle and cannula assembly
US6102904A (en) 1995-07-10 2000-08-15 Interventional Technologies, Inc. Device for injecting fluid into a wall of a blood vessel
US5693029A (en) 1995-07-10 1997-12-02 World Medical Manufacturing Corporation Pro-cell intra-cavity therapeutic agent delivery device
US6143211A (en) 1995-07-21 2000-11-07 Brown University Foundation Process for preparing microparticles through phase inversion phenomena
WO1997012629A1 (en) 1995-10-05 1997-04-10 Genentech, Inc. Improved angiogenesis using hepatocyte growth factor
US6726677B1 (en) 1995-10-13 2004-04-27 Transvascular, Inc. Stabilized tissue penetrating catheters
CA2379971A1 (en) 1999-10-05 2001-04-12 Transkaryotic Therapies, Inc. Hybrid matrices and hybrid matrix mixtures
US6482231B1 (en) 1995-11-20 2002-11-19 Giovanni Abatangelo Biological material for the repair of connective tissue defects comprising mesenchymal stem cells and hyaluronic acid derivative
EP0871512A1 (en) 1995-12-22 1998-10-21 Beth Israel Deaconess Medical Center Localized intravascular delivery of growth factors for promotion of angiogenesis
US6447504B1 (en) 1998-07-02 2002-09-10 Biosense, Inc. System for treatment of heart tissue using viability map
US6632436B2 (en) 1996-01-25 2003-10-14 Genitrix Llc Vaccine compositions and method of modulating immune responses
WO1997045532A1 (en) 1996-05-28 1997-12-04 Brown University Research Foundation Hyaluronan based biodegradable scaffolds for tissue repair
US5655548A (en) 1996-09-16 1997-08-12 Circulation, Inc. Method for treatment of ischemic heart disease by providing transvenous myocardial perfusion
US5957941A (en) 1996-09-27 1999-09-28 Boston Scientific Corporation Catheter system and drive assembly thereof
US5827313A (en) 1996-09-27 1998-10-27 Boston Scientific Corporation Device for controlled longitudinal movement of an operative element within a catheter sheath and method
US5980887A (en) 1996-11-08 1999-11-09 St. Elizabeth's Medical Center Of Boston Methods for enhancing angiogenesis with endothelial progenitor cells
EP0842640A1 (en) 1996-11-13 1998-05-20 Sulzer Osypka GmbH Heart catheter with electrode positioned on a distensible element
US6120520A (en) 1997-05-27 2000-09-19 Angiotrax, Inc. Apparatus and methods for stimulating revascularization and/or tissue growth
US6102926A (en) 1996-12-02 2000-08-15 Angiotrax, Inc. Apparatus for percutaneously performing myocardial revascularization having means for sensing tissue parameters and methods of use
US6432119B1 (en) 1999-03-17 2002-08-13 Angiotrax, Inc. Apparatus and methods for performing percutaneous myocardial revascularization and stimulating angiogenesis using autologous materials
US5730732A (en) 1996-12-04 1998-03-24 Ethicon, Inc. Non-magnetic stainless steel surgical needle
GB9700624D0 (en) 1997-01-14 1997-03-05 Danbiosyst Uk Drug delivery composition
US5935160A (en) 1997-01-24 1999-08-10 Cardiac Pacemakers, Inc. Left ventricular access lead for heart failure pacing
JP3134287B2 (en) 1997-01-30 2001-02-13 株式会社ニッショー Intracardiac suture surgery for catheter assembly
JP4116683B2 (en) 1997-02-28 2008-07-09 ツェー・エス・エル・ベーリング・ゲー・エム・ベー・ハー Sustained-release topical delivery formulation
US5968064A (en) 1997-02-28 1999-10-19 Lumend, Inc. Catheter system for treating a vascular occlusion
US6443949B2 (en) 1997-03-13 2002-09-03 Biocardia, Inc. Method of drug delivery to interstitial regions of the myocardium
US6416510B1 (en) 1997-03-13 2002-07-09 Biocardia, Inc. Drug delivery catheters that attach to tissue and methods for their use
US5984908A (en) 1997-04-10 1999-11-16 Chase Medical Inc Venous return catheter having integral support member
US6110459A (en) 1997-05-28 2000-08-29 Mickle; Donald A. G. Transplants for myocardial scars and methods and cellular preparations
US6068599A (en) 1997-07-14 2000-05-30 Matsushita Electric Industrial Co., Ltd. Blood vessel puncturing device using ultrasound
DE19734220C2 (en) 1997-08-07 2000-01-13 Pulsion Verwaltungs Gmbh & Co Catheter system with an insertion wire
US6050949A (en) * 1997-09-22 2000-04-18 Scimed Life Systems, Inc. Catheher system having connectable distal and proximal portions
US6890546B2 (en) 1998-09-24 2005-05-10 Abbott Laboratories Medical devices containing rapamycin analogs
US6440947B1 (en) 1997-10-07 2002-08-27 The Regents Of The University Of California Method for treating occlusive peripheral vascular disease and coronary disease
US6146373A (en) 1997-10-17 2000-11-14 Micro Therapeutics, Inc. Catheter system and method for injection of a liquid embolic composition and a solidification agent
US6458095B1 (en) 1997-10-22 2002-10-01 3M Innovative Properties Company Dispenser for an adhesive tissue sealant having a housing with multiple cavities
US6151525A (en) 1997-11-07 2000-11-21 Medtronic, Inc. Method and system for myocardial identifier repair
EP0914835B1 (en) 1997-11-10 2005-08-24 Alomone Labs Ltd. Biocompatible polymeric coatings
US6221425B1 (en) 1998-01-30 2001-04-24 Advanced Cardiovascular Systems, Inc. Lubricious hydrophilic coating for an intracorporeal medical device
WO1999038495A3 (en) * 1998-01-30 1999-09-30 Robert N Jennings Jr Controlled release delivery of peptide or protein
US6309370B1 (en) 1998-02-05 2001-10-30 Biosense, Inc. Intracardiac drug delivery
EP0938871A3 (en) 1998-02-27 2001-03-07 ECLIPSE SURGICAL TECHNOLOGIES, Inc. Surgical apparatus
JP4448614B2 (en) 1998-03-31 2010-04-14 メドトロニック バスキュラー インコーポレイテッドMedtronic Vascular,Inc. Tissue penetrating catheter system with a built-in image transducers
US5979449A (en) 1998-04-09 1999-11-09 Steer; Eugene Lyle Oral appliance device and method for use thereof for appetite suppression
EP1071445A2 (en) 1998-04-17 2001-01-31 Angiogenix, Incorporated Therapeutic angiogenic factors and methods for their use
US6183444B1 (en) * 1998-05-16 2001-02-06 Microheart, Inc. Drug delivery module
US6613070B2 (en) 1998-08-04 2003-09-02 Baxter International Inc. System and method for sealing vascular penetrations with hemostatic gels
US6632457B1 (en) 1998-08-14 2003-10-14 Incept Llc Composite hydrogel drug delivery systems
WO2000010622A1 (en) 1998-08-20 2000-03-02 Cook Incorporated Coated implantable medical device
DK1107791T3 (en) 1998-09-04 2007-09-03 Scios Inc Hydrogel for the controlled release delivery of growth factors
US6630457B1 (en) 1998-09-18 2003-10-07 Orthogene Llc Functionalized derivatives of hyaluronic acid, formation of hydrogels in situ using same, and methods for making and using same
US6162202A (en) 1998-10-26 2000-12-19 Sicurelli; Robert Flexible syringe needle
EP1129683A4 (en) 1998-11-10 2002-06-19 Denki Kagaku Kogyo Kk Hyaluronic acid gel, process for the preparation thereof and medical materials containing the same
US6761887B1 (en) 1998-11-16 2004-07-13 Osiris Therapeutics, Inc. Alginate layer system for chondrogenic differentiation of human mesenchymal stem cells
ES2228165T3 (en) 1998-12-09 2005-04-01 Cook Incorporated hollow, curved, SUPERELASTICA needle for medical use.
US6328229B1 (en) 1998-12-18 2001-12-11 Cohesion Technologies, Inc. Low volume mixing spray head for mixing and dispensing of two reactive fluid components
US6338717B1 (en) * 1998-12-22 2002-01-15 Asahi Kogaku Kogyo Kabushiki Kaisha Tip of ultrasonic endoscope
WO2000041732A1 (en) 1999-01-19 2000-07-20 The Children's Hospital Of Philadelphia Hydrogel compositions for controlled delivery of virus vectors and methods of use thereof
US7615373B2 (en) 1999-02-25 2009-11-10 Virginia Commonwealth University Intellectual Property Foundation Electroprocessed collagen and tissue engineering
US6777231B1 (en) 1999-03-10 2004-08-17 The Regents Of The University Of California Adipose-derived stem cells and lattices
US6296602B1 (en) 1999-03-17 2001-10-02 Transfusion Technologies Corporation Method for collecting platelets and other blood components from whole blood
JP3678602B2 (en) 1999-03-17 2005-08-03 住友ベークライト株式会社 Syringe fixed injection device
US6312725B1 (en) 1999-04-16 2001-11-06 Cohesion Technologies, Inc. Rapid gelling biocompatible polymer composition
US6192271B1 (en) 1999-04-20 2001-02-20 Michael Hayman Radiotherapy stent
US6159443A (en) 1999-04-29 2000-12-12 Vanderbilt University X-ray guided drug delivery
CA2361129A1 (en) 1999-05-21 2000-11-30 Ed Olsen Interface needle and method for creating a blunt interface between delivered liquids
US6283947B1 (en) 1999-07-13 2001-09-04 Advanced Cardiovascular Systems, Inc. Local drug delivery injection catheter
US7815590B2 (en) 1999-08-05 2010-10-19 Broncus Technologies, Inc. Devices for maintaining patency of surgically created channels in tissue
US7288096B2 (en) 2003-01-17 2007-10-30 Origin Medsystems, Inc. Apparatus for placement of cardiac defibrillator and pacer
DE60008001D1 (en) 1999-09-21 2004-03-04 Inst Cardiologie De Montreal M Local administration of 17-beta estradiol for improving the vascular endothelial function after vascular injury
US20040229856A1 (en) 1999-09-21 2004-11-18 Baskaran Chandrasekar Local delivery of 17-beta estradiol for preventing vascular intimal hyperplasia and for improving vascular endothelium function after vascular injury
WO2001024775A9 (en) 1999-10-01 2002-12-05 Essentia Biosystems Inc Gel-forming compositions
US6916488B1 (en) 1999-11-05 2005-07-12 Biocure, Inc. Amphiphilic polymeric vesicles
US6360129B1 (en) * 1999-12-13 2002-03-19 Cardiac Pacemakers, Inc. Mannitol/hydrogel cap for tissue-insertable connections
US6547806B1 (en) 2000-02-04 2003-04-15 Ni Ding Vascular sealing device and method of use
EP1258484B1 (en) 2000-02-18 2009-01-14 Kyowa Hakko Kirin Co., Ltd. Novel isoxazole and thiazole compounds and use thereof as drugs
WO2002072166A1 (en) 2001-03-13 2002-09-19 Biocure, Inc. Compositions for drug delivery
US6464862B2 (en) 2000-03-13 2002-10-15 Baramy Engineering Pty Ltd. Gross pollutant trap
US6458098B1 (en) 2000-03-17 2002-10-01 Nozomu Kanesaka Vascular therapy device
US6683192B2 (en) 2000-03-30 2004-01-27 Curis, Inc. Small organic molecule regulators of cell proliferation
US6478776B1 (en) 2000-04-05 2002-11-12 Biocardia, Inc. Implant delivery catheter system and methods for its use
EP1351696A4 (en) 2000-06-26 2004-04-14 Rxkinetix Inc Composition for delivery of hematopoietic growth factor
JP3618736B2 (en) 2000-07-12 2005-02-09 ザ ボード オブ リージェンツ,ザ ユニバーシティ オブ テキサス システム Treatment method using a thrombin-derived peptides
US20020081732A1 (en) * 2000-10-18 2002-06-27 Bowlin Gary L. Electroprocessing in drug delivery and cell encapsulation
US6478775B1 (en) * 2000-10-02 2002-11-12 Genyx Medical Inc. Device for delivering non-biodegradable bulking composition to a urological site
US6808483B1 (en) 2000-10-03 2004-10-26 Paul A. Spence Implantable heart assist devices and methods
CA2429168C (en) 2000-11-15 2010-06-08 Bio Syntech Canada Inc. Method for restoring a damaged or degenerated intervertebral disc
US6846319B2 (en) 2000-12-14 2005-01-25 Core Medical, Inc. Devices for sealing openings through tissue and apparatus and methods for delivering them
RU2345719C2 (en) 2001-01-16 2009-02-10 Васкулар Терапиез, Ллс. Method of prevention or treatment of reduction of access for vessel hemodialysis and device for its realisation and other vascular grafts
US6602241B2 (en) 2001-01-17 2003-08-05 Transvascular, Inc. Methods and apparatus for acute or chronic delivery of substances or apparatus to extravascular treatment sites
US6612977B2 (en) * 2001-01-23 2003-09-02 American Medical Systems Inc. Sling delivery system and method of use
US6620927B2 (en) 2001-02-22 2003-09-16 Anika Therapeutics, Inc. Thiol-modified hyaluronan
US6565530B2 (en) 2001-02-28 2003-05-20 Scimed Life Systems, Inc. Immobilizing objects in the body
US6777000B2 (en) 2001-02-28 2004-08-17 Carrington Laboratories, Inc. In-situ gel formation of pectin
ES2257539T3 (en) 2001-02-28 2006-08-01 Rex Medical, L.P. Apparatus for supplying fluid for ablative treatment of injuries.
WO2002072191A2 (en) 2001-03-12 2002-09-19 Chachques Juan C Method of providing a dynamic cellular cardiac support
US7029838B2 (en) 2001-03-30 2006-04-18 Arizona Board Of Regents On Behalf Of The University Of Arizona Prevascularized contructs for implantation to provide blood perfusion
US7396582B2 (en) * 2001-04-06 2008-07-08 Advanced Cardiovascular Systems, Inc. Medical device chemically modified by plasma polymerization
US20020188170A1 (en) 2001-04-27 2002-12-12 Santamore William P. Prevention of myocardial infarction induced ventricular expansion and remodeling
US6628988B2 (en) 2001-04-27 2003-09-30 Cardiac Pacemakers, Inc. Apparatus and method for reversal of myocardial remodeling with electrical stimulation
US6887857B2 (en) 2001-04-27 2005-05-03 Scimed Life Systems, Inc. Microparticle protection of therapeutic agents
US6660034B1 (en) 2001-04-30 2003-12-09 Advanced Cardiovascular Systems, Inc. Stent for increasing blood flow to ischemic tissues and a method of using the same
EP1423175B1 (en) 2001-08-08 2013-10-02 Brown University Research Foundation Methods for micronization of hydrophobic drugs
US6663596B2 (en) 2001-08-13 2003-12-16 Scimed Life Systems, Inc. Delivering material to a patient
JP2003062089A (en) 2001-08-24 2003-03-04 Sumitomo Bakelite Co Ltd Connector for medical application
EP1436346A1 (en) 2001-09-11 2004-07-14 Consorzio per gli studi universitari Method for the preparation of silk fibroin hydrogels
US6790455B2 (en) 2001-09-14 2004-09-14 The Research Foundation At State University Of New York Cell delivery system comprising a fibrous matrix and cells
US7112587B2 (en) 2001-09-21 2006-09-26 Reddy Us Therapeutics, Inc. Methods and compositions of novel triazine compounds
EP1438060B1 (en) 2001-09-28 2015-11-11 Esperion Therapeutics Inc. Prevention and treatment of restenosis by local administration of drug
WO2003064637A9 (en) 2001-11-06 2004-02-19 Medtronic Inc Method and system for myocardial infarction repair
KR101054023B1 (en) * 2001-11-07 2011-08-04 아이드게노시셰 테크시셰 호흐쉘 취리히 Synthetic matrix for controlling cellular proliferation and tissue regeneration
US7035092B2 (en) 2001-11-08 2006-04-25 Apple Computer, Inc. Computer controlled display device
US6973349B2 (en) 2001-12-05 2005-12-06 Cardiac Pacemakers, Inc. Method and apparatus for minimizing post-infarct ventricular remodeling
US7169127B2 (en) * 2002-02-21 2007-01-30 Boston Scientific Scimed, Inc. Pressure apron direct injection catheter
JP4229621B2 (en) 2002-03-05 2009-02-25 修 加藤 Chemical liquid injection catheter
WO2003079985A3 (en) 2002-03-18 2007-01-11 Univ Carnegie Mellon Method and apparatus for preparing biomimetic scaffold
US7131997B2 (en) 2002-03-29 2006-11-07 Scimed Life Systems, Inc. Tissue treatment
JP4638735B2 (en) 2002-06-24 2011-02-23 タフツ ユニバーシティー Silk biomaterials and methods of use thereof
US7008411B1 (en) 2002-09-30 2006-03-07 Advanced Cardiovascular Systems, Inc. Method and apparatus for treating vulnerable plaque
US7438692B2 (en) 2002-10-18 2008-10-21 Mark Tsonton Localization mechanism for an MRI compatible biopsy device
US20040106896A1 (en) 2002-11-29 2004-06-03 The Regents Of The University Of California System and method for forming a non-ablative cardiac conduction block
JP2006516134A (en) 2002-12-24 2006-06-22 アン−ゴ−ゲン・インコーポレイテッド The encapsulated cell therapy
CA2511521C (en) 2002-12-30 2012-02-07 Angiotech International Ag Drug delivery from rapid gelling polymer composition
US7250041B2 (en) 2003-03-12 2007-07-31 Abbott Cardiovascular Systems Inc. Retrograde pressure regulated infusion
US20050015048A1 (en) * 2003-03-12 2005-01-20 Chiu Jessica G. Infusion treatment agents, catheters, filter devices, and occlusion devices, and use thereof
WO2004082491A1 (en) 2003-03-18 2004-09-30 Robert Ganz Method and device for delivering a substance to tissue layers
US7641643B2 (en) 2003-04-15 2010-01-05 Abbott Cardiovascular Systems Inc. Methods and compositions to treat myocardial conditions
CN100393367C (en) 2003-05-05 2008-06-11 宾-古里安尼格夫大学研究及发展部 Injectable cross-linked polymeric preparations and uses thereof
US7129210B2 (en) 2003-07-23 2006-10-31 Covalent Medical, Inc. Tissue adhesive sealant
WO2005018697A3 (en) 2003-08-13 2005-12-15 Kiem Dang Active agent delivery systems, including a single layer of a miscible polymer blend, medical devices, and methods
US7998112B2 (en) * 2003-09-30 2011-08-16 Abbott Cardiovascular Systems Inc. Deflectable catheter assembly and method of making same
CN1913929A (en) 2003-12-10 2007-02-14 细胞生物工程公司 Methods and composition for soft tissue feature reconstruction
US7273469B1 (en) 2003-12-31 2007-09-25 Advanced Cardiovascular Systems, Inc. Modified needle catheter for directional orientation delivery
US7976847B2 (en) 2004-01-13 2011-07-12 Vasogenix Pharmaceuticals, Inc. Controlled release CGRP delivery composition for cardiovascular and renal indications
US20050186240A1 (en) 2004-02-23 2005-08-25 Ringeisen Timothy A. Gel suitable for implantation and delivery system
CN104174071A (en) 2004-04-28 2014-12-03 安希奥设备国际有限责任公司 Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use
US20060293612A1 (en) * 2004-06-24 2006-12-28 Boston Scientific Scimed, Inc. Apparatus and method for treating occluded vasculature
JP2006014570A (en) 2004-06-29 2006-01-12 Muscle Corp Power regeneration method and converter device using the same
US20060084607A1 (en) 2004-07-06 2006-04-20 Lisa Spirio Purified amphiphilic peptide compositions and uses thereof
GB0419653D0 (en) * 2004-09-04 2004-10-06 Psimedica Ltd Needle assembly
WO2006039704A3 (en) 2004-09-30 2007-11-15 Dennis C Argentieri Pharmaceutical composition and method for treating a joint capsule arthropathy
US20060149392A1 (en) 2004-12-07 2006-07-06 Kuo-Huang Hsieh Biomaterials for guided tissue regeneration and drug delivery
US8303972B2 (en) 2005-04-19 2012-11-06 Advanced Cardiovascular Systems, Inc. Hydrogel bioscaffoldings and biomedical device coatings
US8187621B2 (en) 2005-04-19 2012-05-29 Advanced Cardiovascular Systems, Inc. Methods and compositions for treating post-myocardial infarction damage
US8828433B2 (en) 2005-04-19 2014-09-09 Advanced Cardiovascular Systems, Inc. Hydrogel bioscaffoldings and biomedical device coatings
JP4762785B2 (en) 2005-06-02 2011-08-31 西川ゴム工業株式会社 Gelatin sponge
ES2401706T3 (en) 2005-07-27 2013-04-23 Eli Lilly And Company A method of treating cancer cells to create a modified cancer cell causing an immunogenic response
WO2007048831A3 (en) 2005-10-27 2007-06-28 Coloplast As Biodegradable scaffold with ecm material
US7732190B2 (en) * 2006-07-31 2010-06-08 Advanced Cardiovascular Systems, Inc. Modified two-component gelation systems, methods of use and methods of manufacture
US8741326B2 (en) 2006-11-17 2014-06-03 Abbott Cardiovascular Systems Inc. Modified two-component gelation systems, methods of use and methods of manufacture
US9005672B2 (en) 2006-11-17 2015-04-14 Abbott Cardiovascular Systems Inc. Methods of modifying myocardial infarction expansion
US8192760B2 (en) 2006-12-04 2012-06-05 Abbott Cardiovascular Systems Inc. Methods and compositions for treating tissue using silk proteins

Patent Citations (102)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6183432B2 (en) *
US6183330B2 (en) *
US6179809B2 (en) *
US3804097A (en) * 1972-12-14 1974-04-16 P Rudie Method of irrigating and treating an abcess
US5128326A (en) * 1984-12-06 1992-07-07 Biomatrix, Inc. Drug delivery systems based on hyaluronans derivatives thereof and their salts and methods of producing same
US4794931A (en) * 1986-02-28 1989-01-03 Cardiovascular Imaging Systems, Inc. Catheter apparatus, system and method for intravascular two-dimensional ultrasonography
US5000185A (en) * 1986-02-28 1991-03-19 Cardiovascular Imaging Systems, Inc. Method for intravascular two-dimensional ultrasonography and recanalization
US5092848A (en) * 1988-10-13 1992-03-03 Deciutiis Vincent L Intravenous catheter with built-in cutting tip and method for making the same
US5092130A (en) * 1988-11-09 1992-03-03 Mitsubishi Denki Kabushiki Kaisha Multi-stage cold accumulation type refrigerator and cooling device including the same
US5328955A (en) * 1988-11-21 1994-07-12 Collagen Corporation Collagen-polymer conjugates
US5100185A (en) * 1989-03-14 1992-03-31 Kiekert Gmbh & Co. Motor-vehicle door latch
US5024234A (en) * 1989-10-17 1991-06-18 Cardiovascular Imaging Systems, Inc. Ultrasonic imaging catheter with guidewire channel
US5485486A (en) * 1989-11-07 1996-01-16 Qualcomm Incorporated Method and apparatus for controlling transmission power in a CDMA cellular mobile telephone system
US6409716B1 (en) * 1989-12-15 2002-06-25 Scimed Life Systems, Inc. Drug delivery
US5202745A (en) * 1990-11-07 1993-04-13 Hewlett-Packard Company Polarization independent optical coherence-domain reflectometry
US5203338A (en) * 1990-12-17 1993-04-20 Cardiovascular Imaging Systems, Inc. Vascular catheter having low-profile distal end
US5321501A (en) * 1991-04-29 1994-06-14 Massachusetts Institute Of Technology Method and apparatus for optical imaging with means for controlling the longitudinal range of the sample
US5291267A (en) * 1992-01-22 1994-03-01 Hewlett-Packard Company Optical low-coherence reflectometry using optical amplification
US5540912A (en) * 1992-03-30 1996-07-30 Alza Corporation Viscous suspensions of controlled-release drug particles
US5306250A (en) * 1992-04-02 1994-04-26 Indiana University Foundation Method and apparatus for intravascular drug delivery
US6689608B1 (en) * 1993-02-01 2004-02-10 Massachusetts Institute Of Technology Porous biodegradable polymeric materials for cell transplantation
US6060053A (en) * 1993-04-30 2000-05-09 Children's Medical Center Corp. Injectable chondrocyte-carrier suspension for treatment of vesicoureteral reflux and incontinence
US6206893B1 (en) * 1993-11-08 2001-03-27 Perclose, Inc. Device and method for suturing of internal puncture sites
US5499630A (en) * 1993-11-22 1996-03-19 Kabushiki Kaisha Toshiba Catheter type ultrasound probe
US5380292A (en) * 1993-12-22 1995-01-10 Wilson-Cook Medical, Inc. Gastrointestinal needle mechanism
US6334872B1 (en) * 1994-02-18 2002-01-01 Organogenesis Inc. Method for treating diseased or damaged organs
US5419777A (en) * 1994-03-10 1995-05-30 Bavaria Medizin Technologie Gmbh Catheter for injecting a fluid or medicine
US6391052B2 (en) * 1994-04-29 2002-05-21 Scimed Life Systems, Inc. Stent with collagen
US6056744A (en) * 1994-06-24 2000-05-02 Conway Stuart Medical, Inc. Sphincter treatment apparatus
US5621610A (en) * 1994-06-30 1997-04-15 Compaq Computer Corporation Collapsible computer keyboard structure with associated collapsible pointing stick
US6346515B1 (en) * 1994-07-19 2002-02-12 Colbar R & D Ltd. Collegan-based matrix
US5879713A (en) * 1994-10-12 1999-03-09 Focal, Inc. Targeted delivery via biodegradable polymers
US6051071A (en) * 1994-12-05 2000-04-18 Societe Nationale D'etude Et De Construction De Moteurs D'aviation Device for extracting gas from an oven for chemical vapor deposition or infiltration in an installation for fabricating composite material parts
US6251104B1 (en) * 1995-05-10 2001-06-26 Eclipse Surgical Technologies, Inc. Guiding catheter system for ablating heart tissue
US5919449A (en) * 1995-05-30 1999-07-06 Diacrin, Inc. Porcine cardiomyocytes and their use in treatment of insufficient cardiac function
US5900433A (en) * 1995-06-23 1999-05-04 Cormedics Corp. Vascular treatment method and apparatus
US6190353B1 (en) * 1995-10-13 2001-02-20 Transvascular, Inc. Methods and apparatus for bypassing arterial obstructions and/or performing other transvascular procedures
US5642234A (en) * 1995-10-30 1997-06-24 Lumatec Industries, Inc. Illuminated magnifying lens assembly
US6051648A (en) * 1995-12-18 2000-04-18 Cohesion Technologies, Inc. Crosslinked polymer compositions and methods for their use
US20020042473A1 (en) * 1995-12-18 2002-04-11 Trollsas Olof Mikael Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use
US20020013408A1 (en) * 1995-12-18 2002-01-31 Rhee Woonza M. Cross-linked polymer compositions and methods for their use
US6759431B2 (en) * 1996-05-24 2004-07-06 Angiotech Pharmaceuticals, Inc. Compositions and methods for treating or preventing diseases of body passageways
US5785689A (en) * 1996-07-18 1998-07-28 Act Medical, Inc. Endoscopic catheter sheath position control
US5740808A (en) * 1996-10-28 1998-04-21 Ep Technologies, Inc Systems and methods for guilding diagnostic or therapeutic devices in interior tissue regions
US5722403A (en) * 1996-10-28 1998-03-03 Ep Technologies, Inc. Systems and methods using a porous electrode for ablating and visualizing interior tissue regions
US6071305A (en) * 1996-11-25 2000-06-06 Alza Corporation Directional drug delivery stent and method of use
US6395023B1 (en) * 1997-02-07 2002-05-28 Endovasc Ltd., Inc. Prosthesis with biodegradable surface coating and method for making same
US6093177A (en) * 1997-03-07 2000-07-25 Cardiogenesis Corporation Catheter with flexible intermediate section
US6358247B1 (en) * 1997-03-13 2002-03-19 Peter A. Altman Cardiac drug delivery system
US6086582A (en) * 1997-03-13 2000-07-11 Altman; Peter A. Cardiac drug delivery system
US6207180B1 (en) * 1997-04-03 2001-03-27 Thomas B. Ottoboni Intravesical drug delivery
US6183330B1 (en) * 1997-05-01 2001-02-06 Phillips Plastics Corporation Display device and method therefor
US6682730B2 (en) * 1997-05-28 2004-01-27 Genzyme Corporation Transplants for myocardial scars
US6022540A (en) * 1997-09-04 2000-02-08 Osiris Therapeutics, Inc. Ligands that modulate differentiation of mesenchymal stem cells
US6179809B1 (en) * 1997-09-24 2001-01-30 Eclipse Surgical Technologies, Inc. Drug delivery catheter with tip alignment
US6916648B2 (en) * 1997-10-17 2005-07-12 Genentech, Inc. Secreted and transmembrane polypeptides and nucleic acids encoding the same
US6749617B1 (en) * 1997-11-04 2004-06-15 Scimed Life Systems, Inc. Catheter and implants for the delivery of therapeutic agents to tissues
US6045565A (en) * 1997-11-04 2000-04-04 Scimed Life Systems, Inc. Percutaneous myocardial revascularization growth factor mediums and method
US6183432B1 (en) * 1997-11-13 2001-02-06 Lumend, Inc. Guidewire and catheter with rotating and reciprocating symmetrical or asymmetrical distal tip
US6197324B1 (en) * 1997-12-18 2001-03-06 C. R. Bard, Inc. System and methods for local delivery of an agent
US6371992B1 (en) * 1997-12-19 2002-04-16 The Regents Of The University Of California Acellular matrix grafts: preparation and use
US6221049B1 (en) * 1998-01-13 2001-04-24 Lumend, Inc. Methods and apparatus for crossing vascular occlusions
US6235000B1 (en) * 1998-01-13 2001-05-22 Lumend, Inc. Apparatus for crossing total occlusion in blood vessels
US6231546B1 (en) * 1998-01-13 2001-05-15 Lumend, Inc. Methods and apparatus for crossing total occlusions in blood vessels
US6201608B1 (en) * 1998-03-13 2001-03-13 Optical Biopsy Technologies, Inc. Method and apparatus for measuring optical reflectivity and imaging through a scattering medium
US6175669B1 (en) * 1998-03-30 2001-01-16 The Regents Of The Universtiy Of California Optical coherence domain reflectometry guidewire
US6206914B1 (en) * 1998-04-30 2001-03-27 Medtronic, Inc. Implantable system with drug-eluting cells for on-demand local drug delivery
US6379379B1 (en) * 1998-05-05 2002-04-30 Scimed Life Systems, Inc. Stent with smooth ends
US6346099B1 (en) * 1998-08-11 2002-02-12 Biocardia, Inc. Catheter drug delivery system and method for use
US6177407B1 (en) * 1998-08-13 2001-01-23 University Of Southern California Methods to increase blood flow to ischemic tissue
US6191144B1 (en) * 1998-08-17 2001-02-20 Warner-Lambert Company Method of using angiotensin converting enzyme inhibitor to stimulate angiogenesis
US6217527B1 (en) * 1998-09-30 2001-04-17 Lumend, Inc. Methods and apparatus for crossing vascular occlusions
US6058329A (en) * 1998-10-13 2000-05-02 Cardiac Pacemakers, Inc. Optimization of pacing parameters based on measurement of acoustic noise
US6737072B1 (en) * 1998-12-03 2004-05-18 Michael Nerlich Matrix for tissue engineering formed of a hyaluronic acid ester and hydrolyzed collagen
US6193763B1 (en) * 1998-12-17 2001-02-27 Robert A. Mackin Apparatus and method for contemporaneous treatment and fluoroscopic mapping of body tissue
US6210392B1 (en) * 1999-01-15 2001-04-03 Interventional Technologies, Inc. Method for treating a wall of a blood vessel
US6371935B1 (en) * 1999-01-22 2002-04-16 Cardeon Corporation Aortic catheter with flow divider and methods for preventing cerebral embolization
US6217554B1 (en) * 1999-02-12 2001-04-17 Pharmaspec Corporation Methods and apparatus for delivering substances into extravascular tissue
US6858229B1 (en) * 1999-04-26 2005-02-22 California Institute Of Technology In situ forming hydrogels
US20030040712A1 (en) * 1999-07-13 2003-02-27 Pinaki Ray Substance delivery apparatus and a method of delivering a therapeutic substance to an anatomical passageway
US6358258B1 (en) * 1999-09-14 2002-03-19 Abbott Laboratories Device and method for performing end-to-side anastomosis
US6385476B1 (en) * 1999-09-21 2002-05-07 Biosense, Inc. Method and apparatus for intracardially surveying a condition of a chamber of a heart
US6368285B1 (en) * 1999-09-21 2002-04-09 Biosense, Inc. Method and apparatus for mapping a chamber of a heart
US6748258B1 (en) * 1999-11-05 2004-06-08 Scimed Life Systems, Inc. Method and devices for heart treatment
US6992172B1 (en) * 1999-11-12 2006-01-31 Fibrogen, Inc. Recombinant gelatins
US6241710B1 (en) * 1999-12-20 2001-06-05 Tricardia Llc Hypodermic needle with weeping tip and method of use
US6706034B1 (en) * 1999-12-30 2004-03-16 Advanced Cardiovascular Systems, Inc. Process for agent retention in biological tissues
US6415510B2 (en) * 2000-02-08 2002-07-09 Airbus Deutschland Gmbh Method of fabricating leading edge nose structures of aerodynamic surfaces
US6346098B1 (en) * 2000-03-07 2002-02-12 The Board Of Trustees Of The Leland Stanford Junior University Methods and kits for locally administering an active agent to an interstitial space of a host
US20020076441A1 (en) * 2000-04-27 2002-06-20 Macromed, Inc. Bioactive agent delivering system comprised of microparticles within a biodegradable to improve release profiles
US6548081B2 (en) * 2000-07-28 2003-04-15 Anika Therapeutics, Inc. Bioabsorbable composites of derivatized hyaluronic acid and other biodegradable, biocompatible polymers
US6554801B1 (en) * 2000-10-26 2003-04-29 Advanced Cardiovascular Systems, Inc. Directional needle injection drug delivery device and method of use
US20020090725A1 (en) * 2000-11-17 2002-07-11 Simpson David G. Electroprocessed collagen
US20020072706A1 (en) * 2000-12-11 2002-06-13 Thomas Hiblar Transluminal drug delivery catheter
US6692466B1 (en) * 2000-12-21 2004-02-17 Advanced Cardiovascular Systems, Inc. Drug delivery catheter with retractable needle
US6599267B1 (en) * 2000-12-22 2003-07-29 Advanced Cardiovascular Systems, Inc. Transluminal injection device for intravascular drug delivery
US20030078671A1 (en) * 2001-04-27 2003-04-24 Lesniak Jeanne M. Prevention of myocardial infarction induced ventricular expansion and remodeling
US6702744B2 (en) * 2001-06-20 2004-03-09 Advanced Cardiovascular Systems, Inc. Agents that stimulate therapeutic angiogenesis and techniques and devices that enable their delivery
US20030023202A1 (en) * 2001-07-26 2003-01-30 Nielson David H. Apparatus for delivering aerosolized fibrin endoscopically to a wound
US20030050597A1 (en) * 2001-09-12 2003-03-13 3M Innovative Properties Company Apparatus and methods for dispensing an adhesive tissue sealant
US7393339B2 (en) * 2003-02-21 2008-07-01 C. R. Bard, Inc. Multi-lumen catheter with separate distal tips
US20050042254A1 (en) * 2003-07-16 2005-02-24 Toby Freyman Aligned scaffolds for improved myocardial regeneration

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090012536A1 (en) * 2006-08-03 2009-01-08 Rassman William R Hair harvesting device and method with localized subsurface dermal fluid insertion
US8366723B2 (en) * 2006-08-03 2013-02-05 Rassman Licensing, Llc Hair harvesting device and method with localized subsurface dermal fluid insertion
US20090240208A1 (en) * 2008-03-19 2009-09-24 Warsaw Orthopedic, Inc. Microparticle delivery syringe and needle for placing particle suspensions and removing vehicle fluid
US20140128810A1 (en) * 2011-03-23 2014-05-08 Nanbu Plastics Co., Ltd. Percutaneous medication device and needle formation used for the device
US20140257190A1 (en) * 2011-10-18 2014-09-11 Tsinghua University Disposable Array-Type Micro Injection Needle Head And Pre-Filling Injector Thereof
US20150374915A1 (en) * 2014-06-30 2015-12-31 Elwha Llc Active Lubrication of Penetrating Devices
US9919112B2 (en) 2014-06-30 2018-03-20 Elwha Llc Active lubrication of penetrating devices
US9919111B2 (en) 2014-06-30 2018-03-20 Elwha Llc Active lubrication of penetrating devices
US20160073937A1 (en) * 2014-09-11 2016-03-17 Becton, Dickinson And Company Blood sampling system for improving draw success and reducing hemolysis

Also Published As

Publication number Publication date Type
US9687630B2 (en) 2017-06-27 grant
US20110077618A1 (en) 2011-03-31 application
US20130338633A1 (en) 2013-12-19 application
WO2009058525A1 (en) 2009-05-07 application

Similar Documents

Publication Publication Date Title
Bell et al. Changes in fine structure during silk protein production in the ampullate gland of the spider Araneus sericatus
Zisch et al. Biopolymeric delivery matrices for angiogenic growth factors
Venugopal et al. Biomaterial strategies for alleviation of myocardial infarction
Zhong et al. Biomaterials for the central nervous system
US6969373B2 (en) Syringe system
Patel et al. Angiogenesis with biomaterial-based drug-and cell-delivery systems
Leung et al. Biomedical applications of nanofibers
US6716190B1 (en) Device and methods for the delivery and injection of therapeutic and diagnostic agents to a target site within a body
US20030059463A1 (en) Medical device
US20030203003A1 (en) Drug releasing biodegradable fiber implant
US5797870A (en) Pericardial delivery of therapeutic and diagnostic agents
US20060265043A1 (en) Method and apparatus for treating vulnerable plaque
EP0537559B1 (en) Polymeric compositions useful as controlled release implants
Martens et al. Percutaneous cell delivery into the heart using hydrogels polymerizing in situ
US20060106364A1 (en) Injection of fibrin sealant in the absence of corticosteroids in spinal applications
US20040005295A1 (en) System and method for treating cardiac arrhythmias with fibroblast cells
US5702716A (en) Polymeric compositions useful as controlled release implants
US5840059A (en) Therapeutic and diagnostic agent delivery
Nelson et al. Intra-myocardial biomaterial injection therapy in the treatment of heart failure: Materials, outcomes and challenges
US20060093644A1 (en) Methods of administering microparticles combined with autologous body components
US20060173440A1 (en) Microcatheter Devices and Methods for Targeted Substance Delivery
US6547767B1 (en) Syringe assembly for a catheter
US20020182186A1 (en) Materials and methods for inducing angiogenesis and the repair of mammalian tissue
US20030032938A1 (en) Method of treating the heart
US6494862B1 (en) Substance delivery apparatus and a method of delivering a therapeutic substance to an anatomical passageway

Legal Events

Date Code Title Description
AS Assignment

Owner name: ABBOTT CARDIOVASCULAR SYSTEMS INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BASU, SHUBHAYU;CHAN, GREG W.;REEL/FRAME:020492/0474

Effective date: 20080204