JP2007500060A - Therapeutic drug delivery system - Google Patents

Abstract

The therapeutic drug delivery system includes a perfusion molded foam, such as a non-perforated perfusion molded foam, in a fluid connection with a container for storing a first drug. The size and dimensions of the perfusion molded foam are determined to be suitable for placement within the patient. The second agent is placed in the perfusion molded foam portion. The second agent may be supplied separately to the perfusion molded foam, pre-existing in the perfusion molded foam, or present as a coating or other residual element on the perfusion molded foam It may be. The perfusion molded foam expands to a predetermined maximum diameter and is pressed against the target site within the patient. In a corresponding method, when the first drug is delivered from the first drug container through the perfusion molded foam, the first drug reacts with the second drug to produce a therapeutic drug. Pressure may be applied to the therapeutic agent. The therapeutic agent is released from a portion of the perfusion molded foam at the target site. The perfusion molded foam functions to maintain the pressure and concentration of the therapeutic agent at a predetermined value for the desired residence time at the target site.

Description

The present invention relates to the delivery of therapeutic agents, and more particularly to an apparatus and / or system for delivering a multi-part treatment method to a target site within a patient.

RELATED APPLICATION This application claims priority and benefit of all applications in common with co-pending US patent application Ser. No. 10 / 444,213 filed on May 22, 2003. The disclosure of that application is incorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION Radially stretchable devices are used in a wide variety of applications, including multiple biological applications. For a radially extensible device in the form of an inflatable balloon, to treat a bodily route occluded by a disease and to hold a medical device delivered by a catheter in such a bodily route in place Applications have been proposed. Such stretchable devices can be made of an elastomeric material such as latex.

  Some elastomeric balloons are made to deliver a drug-containing liquid or gas to a target site. Unfortunately, there are some limitations on the range of drugs that can be delivered by such balloons. The only therapeutic drugs currently available with elastomeric balloons are either premixed or those that do not require mixing but can be stored for a pre-determined shelf life. In other words, currently available therapeutic drugs can be manufactured by the manufacturer, stored in the manufacturer's storage facility, shipped to the clinical user, stored for a period of time, and finally used when needed Must be such a drug. Such a delivery process can take days to months. Drugs that can withstand such processes are more expensive due to the need to add preservatives and temperature safeguards, or specific drug properties are advantageous to be able to withstand such processes Can be a more undesirable drug because it cannot be.

  In addition, therapeutic drugs that have limited time in the form of fluid (eg, minutes to hours) are also excluded from use with existing catheter balloon systems. The reason is that a change to a non-fluid (or highly viscous) form or a transition to a less useful form occurs long before it is shipped to a clinical user and introduced into a catheter balloon. It is in. Such drugs create the possibility that doctors, nurses, or clinical technicians will accidentally administer expired drugs. Such misadministration can be ineffective or harmful.

  US Pat. No. 6,500,174 describes a medical balloon catheter assembly that includes a balloon having a permeable region and a non-permeable region. The permeable region is formed of a porous material that is formed by a balloon sufficient to allow a pressurized volume of fluid to ablate the tissue in contact with the permeable region. It is a material that can pass from inside the chamber to the permeable region. The assembly includes an ablation element disposed within the balloon chamber that generates the necessary ablation current to flow through the pressurized fluid to tissue outside the chamber. Thus, the structure disclosed in that patent is similar to that previously described for other elastomeric balloons made for liquid or gas delivery, from inside the balloon chamber to the outside of the balloon chamber through the permeable region. It is only sufficient to allow the passage of fluid. However, even with this ablation assembly, the user cannot combine multiple fluids using a drug delivery device to obtain a mixture of therapeutic agents. Furthermore, no conditions are presented regarding maintaining the pressure in the fluid to increase the tissue absorption of the fluid after the fluid has passed through the permeable region.

  US Pat. No. 6,491,938 describes a method for inhibiting stenosis or restenosis after vascular trauma, comprising administering an effective amount of a cytoskeletal inhibitor. The patent describes a device suitable for local delivery of at least two therapeutic agents, a unit dose first therapeutic agent and a unit dose second therapeutic agent, and a description of their use. Describes the kit that contains it. The first and second agents in unit dosage form may be introduced through separate lumens of the catheter or may be mixed and then introduced into a single lumen of the catheter. However, no discussion or structure is disclosed regarding holding at least two different components in separate storage devices for combination to make a therapeutic agent or other desired agent. The '938 only discusses the administration of a plurality of different drugs to body tissue, similar to implementation with other known elastomeric balloons made for liquid or gas delivery. Such known balloons simply receive multiple drugs from one or more catheters for delivery through the balloon. In addition, the '938 patent describes a method for improving local penetration of therapeutic agents or drugs into the target tissue and reducing the systemic dose required to obtain effective drug administration or therapeutic results. There is no disclosure or discussion of the ability of the balloon structure to maintain fluid pressure outside the balloon when administering fluid to the tissue.

SUMMARY OF THE INVENTION There is a need in the art for a therapeutic drug delivery system for combining multiple components to produce a therapeutic drug and delivering the drug to a target site within a patient. The present invention aims to provide a further solution to solve this problem.

  In one exemplary embodiment of the present invention, the therapeutic drug delivery system is a non-perforated perfusate molded foam in fluid contact with a first drug source and is sized and dimensioned for placement within a patient. A perfusion molded foam having The second agent is placed on the portion of the perfusion molded foam. When the first drug is delivered from the first drug source via the perfusion molded foam with the perfusion molded foam pressed against the target site, the first drug reacts with the second drug for therapeutic use. A drug is produced and the therapeutic drug is released from a portion of the perfusion molded foam at the target site for the desired residence time.

  In various aspects of the invention, the perfusion molded foam is coupled to a first drug source. In order to change the permeability of the therapeutic agent to the target site, the fluid pressure and residence time of the therapeutic agent delivery system can be controlled. The second agent may be disposed on at least one of the surface and the interior of the perfusion molded foam.

  In a further aspect of the invention, the structure of the perfusion molded foam is a structure suitable for pressurization at about 6 atmospheres. The physical state of the therapeutic agent may include at least one of a gas, a liquid, a powder, a gel, a microparticle, and a nanoparticle. The consistency of the first drug and the second drug may be substantially the same. The therapeutic agent may be released to the target site under pressure and the fluid pressure may be maintained for a desired residence time outside the perfusion molded foam.

  In one exemplary embodiment of the present invention, a therapeutic drug delivery system includes a first drug source, a second drug source, and a non-perforated perfusion molded foam. The non-perforated perfusion molded foam is disposed within the patient and is in fluid contact with the first drug source and the second drug source. When the first agent and the second agent are introduced into the perfusion molded foam, the first agent reacts with the second agent to produce a therapeutic agent for release to the target site within the patient. The

  In various aspects of the invention, the perfusion molded foam is coupled to a first drug source. In order to bring the therapeutic agent concentration to a value when the therapeutic agent is administered to the target site, the drug delivery structure may apply fluid pressure to the target site in a controlled manner over the desired residence time. Good. Fluid pressure and residence time are controllable to change the permeability of the therapeutic agent to the target site. The perfusion molded foam may be suitable for pressurization at about 6 atmospheres. The physical state of the therapeutic agent may include at least one of a gas, a liquid, a powder, a gel, a microparticle, and a nanoparticle. The therapeutic agent may be released to the target site under pressure and the fluid pressure may be maintained for a desired residence time outside the perfusion molded foam.

  In another aspect of the invention, the therapeutic drug delivery system includes a therapeutic drug delivery structure. A microporous film is disposed around at least a portion of the therapeutic drug delivery structure. The first drug source contains the first drug and is in fluid contact with the therapeutic drug delivery structure. The second drug source contains the second drug and is in fluid contact with the therapeutic drug delivery structure. The therapeutic drug delivery structure is suitable for applying pressure to the target site for a desired residence time, which is the period during which the therapeutic drug is administered to the target site within the patient.

  In various aspects of the invention, the therapeutic drug delivery structure may be a stent. The microporous film may be formed of PTFE. The microporous film may contain a second drug. A non-perforated perfusion molded foam delivers the first drug from the first drug source to the therapeutic drug delivery structure, which causes the first drug and the second drug to interact to produce the therapeutic drug. And the perfusion molded foam may be placed with the drug delivery structure at a location in the body such that the therapeutic drug is released from a portion of the therapeutic drug delivery structure to provide a local therapeutic effect. The residence time may be controllable to vary the amount of therapeutic agent administered to the target site. The therapeutic agent delivery system may be able to apply pressure, including the fluid pressure of the therapeutic agent, to the target site in a controlled manner over its residence time, thereby administering the therapeutic agent to the target site. In doing so, the concentration of the therapeutic agent may be set to a certain value.

  In another aspect of the invention, the therapeutic drug delivery system includes a therapeutic drug delivery structure fully encapsulated within the microporous film. The first drug source contains the first drug and is in fluid contact with the therapeutic drug delivery structure. The second drug source contains the second drug and is in fluid contact with the therapeutic drug delivery structure. The first agent and the second agent may be combined to produce a therapeutic agent.

  In another aspect of the invention, a method of administering a therapeutic agent includes placing a therapeutic agent delivery structure within a patient. A first drug is introduced into the therapeutic drug delivery structure and reacts with a second drug disposed on the portion of the therapeutic drug delivery structure to produce a therapeutic drug. The therapeutic agent is released from multiple locations along the therapeutic agent delivery structure at a controlled rate to a target site within the patient.

  In aspects of the invention, the therapeutic drug delivery structure may be a non-perforated perfusion molded foam. The second drug may be disposed on at least one of the surface and the interior of the therapeutic drug delivery structure. Placing the therapeutic drug delivery structure may include inserting the perfusion molded foam into a body part of the patient that is proximal to the target site requiring treatment. Placing the therapeutic drug delivery structure may include inserting a catheter containing the perfusion molded foam into a body part of the patient proximal to the target site requiring treatment.

  In a further aspect of the invention, the second agent may be placed in a film placed on at least a portion of the perfusion molded foam. The second agent may enter the perfusion molded foam. The second drug may be introduced into the patient by allowing the second drug to enter the perfusion molded foam and pass through at least a portion of the perfusion molded foam. As the first drug and the second drug pass through the plurality of locations and into the patient's body, the first drug reacts with the second drug by polymerizing with the second drug, thereby A therapeutic amount of drug may be produced.

  In aspects of the present invention, a therapeutic drug delivery structure includes a stent disposed within a patient and a perfusion molded foam disposed within at least a portion of the stent for delivering at least one component of the therapeutic drug. And may be formed. The perfusion molded foam is suitable for at least one of deploying a stent and delivering a therapeutic agent in the form of at least one of a bioactive agent and a chemical agent to the stent and the patient's body. Also good. The film may include a second drug and may be disposed on at least a portion of the stent. Placing the therapeutic drug delivery structure may include inserting a perfusion molded foam and a stent into a body part of the patient that is proximal to the target site. Introducing the first drug may include allowing the first drug to enter the therapeutic drug delivery structure. The method may further include allowing a second agent to enter the perfusion molded foam and enter the patient body through the perfusion molded foam and the stent.

  In a further aspect of the invention, the step of reacting the first agent and the second agent comprises the first agent and the second agent when the first agent and the second agent pass through the plurality of locations and into the patient body. The step of polymerizing the second agent with the second agent to produce a therapeutic amount of the drug. The method may further include leaving at least a first portion of the drug delivery structure in the patient and removing a second portion of the drug delivery structure. Introducing the first agent may include allowing the first agent to enter the drug delivery device in a manner that releases the therapeutic agent into the patient's body.

  The step of the first drug reacting with the second drug is such that one of the first and second drugs acts as a catalyst for the other of the first and second drugs, thereby treating the therapeutic drug. May be included. The step of reacting the first agent with the second agent may occur as at least one of an emulsion process, a water soluble process, a lipophilic process, and a water insoluble process. The method may further include removing the therapeutic drug delivery structure from the patient body.

  In a further aspect of the invention, removal of the therapeutic drug delivery structure may occur immediately after the therapeutic drug is released into the patient. The therapeutic drug delivery structure may be used to apply fluid pressure of the therapeutic drug to the target site. The therapeutic drug delivery structure provides a therapeutic drug in a controlled manner while maintaining the therapeutic drug concentration at any one of constant, variable, and intermittent when the therapeutic drug is administered to the target site. May be released. Controlled mode means controlling the perfusion rate of at least one of the first and second agents, controlling the fluid pressure of at least one of the first and second agents, and / or treating Altering the consistency of the therapeutic drug to control the flow rate through the medicinal drug delivery device may be included.

  In a further aspect of the present invention, the method of the present invention may include the step of releasing the therapeutic agent over a predetermined residence time. The residence time may be controllable so that the tissue penetration of the therapeutic agent can be changed by changing the fluid pressure and residence time of the therapeutic agent. The therapeutic agent may be released to the target site under pressure and the fluid pressure may be maintained for a desired residence time outside the therapeutic agent delivery structure.

  The invention will be better understood with reference to the following description and attached drawings.

Detailed description
An illustrative embodiment of the present invention is an apparatus for combining two or more components within a delivery device or immediately prior to introduction into the delivery device, thereby providing the resulting therapeutic agent to a target site within a patient. , Systems, and methods. The components can be mixed with any combination of other nanoparticle slurries, solids, semisolids, gels, liquids, or gases to produce the desired therapeutic agent, nanoparticle slurries, solids, semisolids. It may be a solid, gel, liquid, or gas. There may be two or more ingredients necessary for the combination to produce the desired therapeutic agent. Mixing two or more components immediately prior to delivery to a patient allows the use of specific components and / or drugs that have a relatively short usable life and cannot be used otherwise. However, it should be noted that the present invention is not limited to the use of only short-lived components, drugs, or drugs. The present invention is useful for any therapeutic agent that requires some mixed preparation just before or simultaneously with topical administration to tissue.

  1 to 9, like parts are given like reference numerals. These figures are in accordance with the present invention an apparatus, system for generating a therapeutic element generated with at least two components that are mixed just prior to entering a patient's body and delivering it to a target site within the patient's body And an example of a method aspect. In the following, the invention will be described with reference to the exemplary embodiments shown in these figures, but it should be understood that the invention can be implemented in numerous other ways. Those skilled in the art will further appreciate various ways of changing each parameter of the disclosed aspects, such as the size, shape, or type of an element or material, in a manner consistent with the spirit and scope of the present invention. It is.

  FIGS. 1 and 2 show a radially stretchable device 10 having a molded foam useful for local tissue perfusion, such as a body 12 that is typically composed of an inelastically stretched fluoropolymer material. The extendable device provided by the present invention is suitable for a wide range of applications, such as various medical treatment applications. Examples of biological applications include the treatment of transplanted vascular grafts, stents, prostheses, or other types of medical implants, and blood vessels, urinary tract, intestine, nasal cavity, nerve sheath, bone cavity, urine There is use as a catheter balloon to treat the route of any body cavity, space, or hollow organ, such as a tube. Other examples include selective devices for removing obstructions such as emboli and blood clots in blood vessels, expansion devices for restoring the patency of blocked body passages, and means for closing or filling the passage or space. For use as a centering mechanism for transvascular devices and catheters. The extendable device 10 may also be used as a sheath covering a conventional balloon for the purpose of controlling the extension of a conventional catheter balloon.

  The body 12 of the radially extendable device 10 can be deployed by applying an extension force from the small first diameter state shown in FIG. 1 to the large second diameter state shown in FIG. The radially extensible device 10 of the embodiments shown herein can have a number of different perfusion molded foams. As shown, the extensible part 10 is a catheter or other structure capable of supplying fluid (in the form of a nanoparticle slurry, semi-solid, solid, gel, liquid, or gas) under pressure to a perfusion molded foam. This is a stretchable perfusable foam that can be connected to

  The body 12 of the radially extendable device 10 is preferably characterized by a non-perforated monolithic structure or the like. That is, the main body 12 is a single unitary object made of a substantially uniform material. The embodiment of the body 12 is made using an extrusion extension process as detailed in US patent application Ser. No. 10/131396, filed Apr. 22, 2002 and incorporated herein by reference. Other methods include plasma-treated PTFE and additional wet-stretched PTFE as described in US patent application Ser. No. 09 / 678,765 filed Oct. 3, 2000 and incorporated herein by reference. There is a way to do it. This treatment yields a body 12 characterized by a seamless structure of inelastically stretched fluoropolymer. The fluoropolymer has a predefined size and shape in the state of a large second diameter. The body 12 can be reliably and predictably extended to a pre-defined and fixed maximum diameter and a pre-defined shape regardless of the extension force used to extend the device. Alternatively, it should be noted that each of the fabrication methods described above relates to fabricating an elastomeric perfusion molded foam suitable for exemplary purposes as an example of a therapeutic delivery device. The radially extendable device 10 can be made of many other different materials, as would be understood by one skilled in the art. Other materials that can be used in the present invention include materials having sufficient porosity properties to allow fluids to pass through, as will be described in detail below.

  For example, a suitable fluoropolymer material is polytetrafluoroethylene (“PTFE”), or copolymers of tetrafluoroethylene and other monomers may be used. Such monomers include ethylene, chlorotrifluoroethylene, perfluoroalkoxytetrafluoroethylene, or propylene fluoride such as hexafluoropropylene. The most frequently used is PTFE. Thus, the radially extensible device 10 can be made of a variety of fluoropolymer materials, and a variety of fluoropolymer materials can be used in the fabrication methods of the present invention, but the description herein specifically refers to PTFE. .

  Thus, the present invention is not limited to only using the elastomeric extensible perfusion molded foam used in exemplary embodiments of the present disclosure, but utilizes a number of different fluid delivery device technologies and materials. And this will be understood by those skilled in the art.

  In FIG. 2, the body 12 of the radially extendable device 10 preferably has a generally tubular shape when extended, but other cross sections such as square, oval, elliptical, polygonal, etc. may be used. The cross section of the body 12 is preferably continuous and uniform along the length of the body. However, in other embodiments, the cross-section may vary in size and / or shape along the length of the body. FIG. 1 shows the body 12 in a relaxed and small first diameter state. The body 12 has a central lumen 13 extending along the longitudinal axis 14 between the first end 16 and the second end 18.

  Shown is a deployment mechanism in the form of an elongated hollow tube 20 disposed within the central lumen 13 to provide a radial deployment or extension force to the body 12. The radial deployment force causes the body 12 to radially expand from the first state to the large second diameter state shown in FIG. The first end 16 and the second end 18 are connected to the outer surface of the hollow tube 20 in a sealed state. The first end 16 and the second end 18 may be thermally bonded, glued together, or between the wall of the body 12 and the tube 20 and the first end 16 and the second end 18. It may be attached by other suitable means to prevent fluid from leaking from the second end 18.

  The hollow tube 20 includes a longitudinally extending lumen 22 and a number of side holes 24 that provide fluid contact between the outer surface of the tube 20 and the lumen 22. The tube 20 may be coupled to one or more fluid supply sources (discussed below) to selectively supply fluid to the lumen 13 of the body 12 via the lumen 22 and side holes 24. The pressure from the fluid imparts a radial extension force on the body 12, thereby causing the body 12 to develop radially into a large second diameter state. Since the body 12 is composed of an inelastic material, the connection between the tube 20 and the fluid supply source can be released or the fluid pressure in the lumen 13 of the body 12 can be substantially reduced by other methods Generally, the body 12 will not return to a small first diameter state. However, the main body 12 is crushed by its own weight, and the diameter is reduced. The body 12 may be fully contracted to the initial small diameter condition, for example, by applying a negative pressure from a vacuum source or the like.

  The radially extendable device 10 is not limited to use with a deployment mechanism that utilizes a fluid deployment force, such as a hollow tube 20, as would be understood by one skilled in the art. Other known deployment mechanisms may be used to radially deploy the radially extendable device 10 such as, for example, mechanically operated extension elements such as mechanically actuated parts, or nitinol, etc. Machine elements composed of temperature-activatable materials.

  FIG. 3 is a schematic diagram showing the fine structure of the wall of an ePTFE perfusion molding foam 110 formed by an extrusion extension process, such as the main body 12. For illustration purposes, the microstructure of the perfusion molded foam 110 is shown exaggerated. Therefore, although the dimensions of the microstructure are enlarged, the general features of the microstructure shown in the figure are representative of the many microstructures present in the perfusion molded foam 110.

  The microstructure of the ePTFE perfusion molded foam 110 features nodes 130 interconnected by fibrils 132. The node 130 is oriented generally perpendicular to the longitudinal axis 114 of the perfusion mold 110. This microstructure of nodes 130 interconnected by fibrils 132 provides a microporous structure with microfibril voids. A microfibril void is a void that defines a through-hole or channel 134 that extends completely from the inner wall 136 to the outer wall 138 of the perfusion molded foam 110. The through-holes 134 are voids between nodes that are oriented generally perpendicular (relative to the longitudinal axis 114) and traverse from the inner wall 136 to the outer wall 138. The size and geometry of the through-hole 134 may be altered by an extrusion elongation process detailed on U.S. Patent Application No. 09/411797 filed October 1, 1999 and incorporated herein by reference. And thereby a non-permeable, semi-permeable or permeable microstructure can be obtained.

  The size and geometry of the through-hole 134 can be varied to form a variety of different orientations. For example, by twisting or rotating the ePTFE perfusion mold 110 during the extrusion and / or stretching process, the micrometer has an angle with respect to an axis perpendicular to the longitudinal axis 114 of the perfusion mold 110. The channel can be oriented. The stretchable device 10 is obtained by subjecting it to an extrusion process followed by stretching the polymer and sintering the polymer to fix the stretched structure of the through-holes 134.

  Due to the microporous structure of the through-holes 134 of the material forming the extensible device 10, the wall of the extensible device 10 is permeable without the need to drill the extensible device 10. The microporous structure of the device improves the controllability and uniformity of the distribution of fluid passing through the wall of the extensible device 10 compared to a perforated device in which fluid flows out only from the perforation. Thus, as described herein, the non-perforated structure of the extensible device 10 contributes to the effective distribution of fluid by the extensible device 10.

  In one embodiment, the ePTFE perfusion molded foam 110 and the resulting extensible device 10 have a uniform micronode structure over the entire cross section and length of the ePTFE perfusion molded foam. With this uniform fine node structure, the stretchable device 10 extends to the second diameter in a reliable and predictable manner, thereby improving the stretch characteristics of the stretchable device. The fine node structure may be characterized by nodes that are smaller in size and mass (eg, 25-30 μm) than nodes in conventional ePTFE grafts. Furthermore, the space between nodes (referred to as “internode distance”) and the space between fibers (referred to as “interfibril distance”) may also be small (for example, 1 μm to 5 μm) compared to a conventional ePTFE graft. Further, in a preferred embodiment, the internode distance and the interfibril distance may be uniform over the entire length and the entire cross section of the ePTFE perfusion molded foam. This uniform node structure may be created by forming a billet with a uniform lubricant level over the entire cross section and length. When this tubular extrudate is stretched at a high stretch rate, such as a rate greater than 1 inch / second, a fine node structure is obtained. Preferably, the extrudate elongation rate is about 10 inches / second or more. The node structure may be made non-uniform by changing the placement and amount of lubricant and the elongation process.

  As will be described in detail below, when the body 12 of the radially extendable device 10 is inflated by the fluid, the fluid may pass through the body 12 in a leaching manner and be administered to a target site within the patient. The fluid may be under fluid pressure when contacting the target site. The fluid may further comprise one or more drugs having therapeutic properties for healing the target site where the abnormality has occurred. Examples of therapeutic drugs and therapeutic agents are shown in Table 1 below.

  Surgical adhesives, adhesion-preventing gels and / or films, and tissue-absorbing biological coatings may also be used with the present invention, with or without the therapeutic drugs and agents in Table 1. it can. Adhesive type polymers can include one-part and two-part adhesives for use with or without therapeutic drugs and agents. Examples of adhesion-type polymers are derived from 2-octyl cyanoacrylate, patient's own plasma mixed with human-derived collagen and thrombin suspension to produce a natural biological sealant, patient's blood preparation There are fibrin glue and polymer hydrogel. As shown in Table 1, tissue-absorbing therapeutic agents include fish oil omega-3 fatty acids, vegetable oils containing fish oil omega-3 fatty acids, other oils or substances suitable for enhancing tissue absorption, adhesion, and lipophilic permeation. , And combinations thereof may be incorporated into the fluid. Combined with therapeutic drugs to enhance drug tissue adhesion and improve penetration of therapeutic drugs in and out of cells, while reducing traumatic tissue adhesion formation at and around the target treatment site Or you may use the gel, solution, or compound which forms an adhesion prevention film, without using together. At selected sites that are prone to adhesion formation, such as stented blood vessels and dilated urethra, such therapeutic delivery methods that prevent adhesions have the advantage of reduced tissue adhesion formation.

  The internode distance and interfibril distance may be varied to provide control over a relatively wide range so that fluid can pass through the through holes or channels 134. The size of the through-hole or channel 134 can be selected, for example, by manufacturing processes such as those detailed in US patent application Ser. No. 09/411797, which is already incorporated herein by reference. The inter-node distance of the wall microstructure in the microporous region, and thus the width of the through-hole or channel 134, may be from about 1 μm to about 150 μm. If the distance between the nodes is this level, the flow rate of the fluid passing through the wall of the body 12 is about 0.01 ml / min to about 100 ml / min.

  The internode distance may vary from place to place along the microporous structure so that the size of the channel 134 varies from place to place or region. Thereby, the flow rate can be changed for each region in the same microporous structure at substantially the same fluid pressure.

  Realizing this different flow rate with the radially extensible device 10 helps to change the fluid pressure during the expansion of the extensible device 10 and also changes the residence time of the extensible device 10 at the target site requiring therapeutic treatment. Is also possible. Yet another factor can include the relative consistency of each solution to be mixed, and the solution consistency of the resulting therapeutic agent. The higher the viscosity, the greater the resistance to flow, and thus the longer the residence time required to administer a sufficient amount of drug.

  Residence time is a measurement of the length of time that the extensible device 10 is placed in a patient and administers one or more therapeutic agents to a location within the patient, such as a target site. A target site is a place that requires therapeutic treatment. If the size and shape of the through-hole or channel 134 can be changed, the residence time can be changed. If it is desirable to increase the residence time, the size and shape of the through hole 134 may be changed so that less fluid passes through. Similarly, if the amount of therapeutic fluid to be administered is the same and it is desirable to reduce the residence time, the through-hole 134 may be varied to allow fluid to pass at a higher flow rate. Furthermore, as shown in one exemplary embodiment of the invention and later in the specification, the application of pressure of fluid absorbed by the tissue of the body lumen also affects the residence time.

  The microporous structure of the through-hole 134 is such that the fluid pressure of the fluid passing therethrough can vary over a substantial range and the flow rate of the fluid passing through the through-hole 134 is substantially equal. For example, in a given embodiment, the flow rate of fluid through the through-hole 134 is maintained substantially constant over a predetermined fluid pressure range. Or you may make it the change rate of the flow volume of a fluid become smaller than the change rate of the given fluid pressure. For example, in one embodiment involving pressurization of fluid external to the extensible device 10, the pressure inside the extensible device 10 may be up to about 6 atmospheres, or may be about 6 atmospheres. . Other ranges that have been confirmed to be usable with the extendable device 10 include pressures in the range of 2-4 atmospheres. One of the consequences of having a relatively low fluid pressure inside the flexible extensible device 10 is that the extensible device 10 matches the shape of the body lumen or body cavity where the extensible device 10 functions. The body tissue is not easily damaged by the overexpansion of the extendable device 10.

  By changing the flow of fluid to the extensible device 10, the pressure inside the extensible device 10 may be provided at a constant, variable, or intermittent value. As will be described in more detail below, changes in fluid pressure inside the extensible device 10 can affect changes in fluid pressure outside the extensible device 10.

  A therapeutic drug delivery system 200 in accordance with the teachings of the present invention is shown in FIG. The expandable device 10 is in fluid contact with the first storage container 212 via a tubular joint 214. The expandable device 10 is also in fluid contact with the second storage container 216 via the second tubular joint 218. Various amounts of one or more ingredients supplied in fluid form from the first storage container 212 and the second storage container 216 are mixed in the expandable device 10 and then from the expandable device 10. It may be drained and placed into the patient's body. Further, the connection to the extensible device 10 may be removable so that the connection to the storage container can be easily switched.

  There may be a plurality of other storage containers, and the storage container 222 having the tubular joint 224 and the storage container 226 having the tubular joint 228 are representative thereof. The number of storage vessels 212, 216, 222, and 226 (and corresponding tubular fittings 214, 218, 224, and 228) depends on the number of components that need to be held separately until the desired mixing process occurs. Each storage vessel 212, 216, 222, and 226 may hold a separate component until mixing occurs. Thus, the number of storage containers can vary. In addition, the type of storage container can vary. Any of the storage containers 212, 216, 222, and 226 may be suitable for holding solids, liquids, or gases. More specifically, the first storage vessel 212 may be designed for liquid holding and the second storage vessel 216 may be designed for gas holding, or vice versa, or one may be solid. Hold one of the liquid or gas and the other hold the other. Although the design of a container capable of holding a solid, liquid, and / or gas need not be single, such design is considered functional for the present invention.

  Alternatively, different designs may be used depending on the physical state of the components being stored. The solids held by the storage containers 212, 216, 222, and 226 may be in the form of a powder so that they can be easily transferred to the extensible device 10 for mixing with a liquid or gas. Further, the storage containers 212, 216, 222, and 226 may be heated or cooled, if necessary, to keep the stored components at a desired temperature.

  In the remainder of this description, the exemplary embodiment uses a first storage container 212 and a second storage container 216. However, when the applicant refers to the first storage container 212 and the second storage container 216, the storage containers 212, 216, 222, and 226, as well as additional unnumbered containers, are referred to as a plurality of containers. It is intended to mean a container and this should be understood. Thus, in this description and illustration of two containers, the use of any number of storage containers required for a particular embodiment, from one to multiple, is also contemplated.

  A controller 220 may be provided along the first tubular joint 214 and the second tubular joint 218 to vary or control the amount of component fluid that passes through the expandable device 10. The controller 220 can take many different forms. The controller 220 primarily restricts and / or diverts flow from the first storage vessel 212 and the second storage vessel 216 and any additional vessels. The controller 220 may include a simple valve that can regulate the flow rate, or may be more sophisticated as will be appreciated by those skilled in the art. This exemplary controller may also provide sufficient pumping action to pressurize fluid supplied from the first storage container 212 and the second storage container 216 to the extendable device 10. Alternatively, the storage containers 212 and 216 themselves may be directly pressurized. One example of a controller is a pressure injector that is conventionally used to expand an angioplasty balloon catheter along with a pressure gauge. One or more pressurized injection devices connected to the manifold inject a plurality of treatment elements into the device.

  The component fluid in the first storage container 212 may be different from the component fluid in the second storage container 216. The component fluid contained in each of the first storage container 212 and the second storage container 216 may include any desired number of therapeutic agents or other liquids or gases. The therapeutic drug delivery system 200 includes a chemical, physical, polymeric, emulsifiable, water-soluble, parent, or mixed fluid contained in each of the first storage container 212 and the second storage container 216 when mixed. Useful when producing oily, water-insoluble, or other reactions or processes. Generally produced by this reaction has a relatively short lifetime or changes in properties relatively quickly (eg within a few minutes or hours), thus compromising the effectiveness or usefulness of such mixtures. It is a fluid that is difficult to store and ship to clinical users without mixing. The fluid obtained in this way may also have a limited time during which an increased therapeutic benefit can be maintained. Thus, to maximize the benefits of the mixture, each component of the mixture (ie, the component fluid stored in each of the storage containers 212 and 216) must be mixed immediately prior to introduction into the patient. Note, however, that it is not a requirement that the mixture has a relatively short usable life or that the mixture has other properties that require the mixture to be prepared immediately before use. Mixtures that have a usable lifetime of, for example, days, weeks, or years may be mixed in the therapeutic drug delivery system of the present invention. However, a more general application of the therapeutic drug delivery system of the present invention is likely to target mixtures with a short usable life. Furthermore, the mixing of two or more components is not simply a combination of two different therapeutic agents that can be administered separately and do not require mixing. By mixing the components according to the method of the present invention, a therapeutic agent or a therapeutic agent that is enhanced or improved as a result of mixing is produced.

  In another configuration, the first tubular joint 214 and the second tubular joint 218 may be connected to the extendable device 10 without interposing the controller 220 therebetween. The amount of fluid required for mixing is determined by the degree of dilution (or absence of dilution) for the individual fluids.

  Other aspects of the invention include differences in the source and location of two or more components to produce a therapeutic drug or agent. As mentioned above, each component may be in a separate storage container. Or, one of the components is present in or on the stretchable device 10 and mixed with other components as the other components flow into or through the wall of the stretchable device 10 Also good. For example, the source of one component may be a storage container and another second component is present in a coating or film on the extensible device or PTFE forming the extensible device 10 Or it may exist as a part of other materials. As the component in the storage container passes through the wall of the extensible device 10, it mixes with the second component on the extensible device 10, thereby producing a therapeutic drug or drug immediately prior to delivery to the patient. Is done. The components on the extensible device 10 may further be in the form of an adhesive or the like.

  More specifically, in one embodiment of the invention, each component that is mixed to produce a therapeutic drug or agent may include a two-part adhesive. When each component of the two-component adhesive is mixed, an adhesive solution is generated. The adhesive fluid is then delivered to the patient through the extendable device 10 or 210 where it is administered simultaneously with the expansion of the perfusion molded foam and cures in place. Immediately before the adhesive liquid cures, the extensible device 10 or 210 is contracted by applying a negative pressure to the adhesive liquid with the same pressure controller.

  The adhesive may also be used to apply one or more components to the surface of the extensible device. When the additional ingredients are delivered via the therapeutic drug delivery system, they are combined and mixed with the adhesive and one or more ingredients disposed with the adhesive so that the desired therapeutic drug is obtained. can get.

  Change the various properties of the ingredients, whether the storage containers 212 and 216 contain multiple ingredients or a single ingredient, and whether the ingredients are in solid, liquid, or gaseous form May be. For example, the components may be diluted or strengthened, heated or cooled, mixed or layered, and the like. In addition, the components may vary in their supply, for example, a constant, variable, or intermittent flow rate may be provided to and via the extendable device 10. In addition, the ingredients may vary in terms of their state, for example, solid powders, semi-solids, nanoparticles, gels, liquids, gases, highly viscous liquids, coatings mixed with polymers such as PTFE and cured, etc. It may be.

  In a further embodiment of the invention, one or more components may be combined to form a polymer body with or without a therapeutic agent. For example, ingredients that, when combined, produce a polymeric material may be placed in each of the storage containers 212 and 216. Delivery of the first component and the second component to the stretchable device 10 causes the components to mix and then be released to a target site within the patient. This mixture cures at the target site to form a polymer structure. Such structures can also be used to stop internal bleeding, cover a series of sutures to form a smooth surface, adhere body tissues, and apply a protective coating to diseased or damaged tissues. Good.

  It should be noted that the resulting drug may be in physical form including gas, liquid, powder, gel, microparticle, nanoparticle, whether therapeutic or non-therapeutic.

  FIG. 5A shows the expandable device 10 inserted into a representative partial cross-section of a body lumen 230 having an inner wall 232. The body lumen 230 may be, for example, a blood vessel, a capillary, or other closed structure into which the stretchable device 10 can be inserted. Hereinafter, the use of the extendable device 10 will be described in detail.

  In use, the extensible device 10 is inserted into a patient and manipulated to reach a target site within the body lumen 230, for example as shown in FIG. As will be appreciated by those skilled in the art, the pressure within the expandable device 10 may span a number of different pressure ranges. For example, the pressure may be up to about 6 atmospheres in one exemplary embodiment, may be from about 2 to about 4 atmospheres in another example, or may be in any other desired pressure range. . The expandable device 10 may expand under pressure from an ingressing fluid or drug, thereby pressing against the inner wall 232 of the body lumen 230 at the site where the expandable device 10 has been inserted. It should be noted that the blood vessel shown as a representative example of the body lumen 230 is an example of a suitable target site for introducing a therapeutic agent by the stretchable device 10 according to the present invention. Only.

  The extensible device 10 is provided in a number of different size ranges. This size is such that the expandable device 10 in the fully expanded state is larger than 100% of the internal diameter of the body lumen or body cavity in which the expandable device 10 is placed. In other words, the expandable device 10 expands to fully occupy the body lumen or space within the body cavity, thereby applying pressure from the expandable device 10 to the body lumen or tissue of the body cavity. If the extendable device 10 is too small, it will not reach the wall of the body lumen even when fully inflated, and therefore no contact will occur. If the expandable device 10 is too large, damage to the body lumen or body cavity occurs when the device 10 is fully expanded. In some cases this may be desirable (eg, when it is desirable to force a healing repair of a blood vessel). In other cases, however, it is undesirable for the extendable device 10 to be too large for a body lumen or body cavity. Therefore, the user needs to select a size suitable for the intended work. For example, when the extensible device 10 needs to apply a non-damaging pressure to a body lumen or body cavity, the device expands to expand to about 101% to 150% of the inner diameter of the body lumen or body cavity. A possible device 10 may be selected. As will be appreciated by those skilled in the art, other based on the pressure applied by the expandable device 10, the strength of the body lumen or body cavity, and whether the desired result is undamaged or damaging It is also possible to use a size range of.

  In one exemplary embodiment shown in FIG. 5C, the semi-enclosed space 234 may be formed by the pressure applied by the expandable device 10 to the inner wall 232. The semi-enclosed space 234 can be defined as the area between the expandable device 10 and the inner wall 232 when the expandable device 10 is pressed against the inner wall 232 of the body lumen 230. One side of the semi-enclosed space 234 touches the extendable device 10, the opposite side touches the inner wall 232 of the body lumen, and the third side can stretch when pressurized fluid occupies the space It contacts a small orifice 236 formed around the edge where the device 10 terminates.

  For further explanation, FIG. 5A shows the expandable device 10 in a state of being expanded by a fluid flowing in the direction of arrow A and pressed against the inner wall 232 of the body lumen 230. In the state of this figure, there is no semi-enclosed space 234 because the fluid expanding the expandable device 10 has not yet passed through the wall of the expandable device. When a sufficient amount of fluid has passed through the wall of the extensible device, the fluid is kept under pressure and pressed against the inner wall 232 and the outer wall of the extensible device 10, thereby creating a semi-enclosed space 234. FIG. 5B shows some more fluid gathering outside the extensible device 10 and beginning to form a semi-enclosed space 234 (however, as the figure shows, the space is not yet complete). Pressurized fluid is further supplied to the exterior of the expandable device 10 to expand the space, thereby forming a semi-enclosed space 234 as shown in FIG. 5C. When the semi-enclosed space 234 is fully sized, it reaches the end of the expandable device 10 and a small orifice 236 is formed. Further supply of pressurized fluid to the expandable device 10 maintains pressure outside the expandable device 10, maintains a semi-closed space 234, and keeps the small orifice 236 open. The small orifice 236 closes when the fluid pressure outside the expandable device is substantially reduced.

  The semi-closed space 234 guides the pressurized fluid discharged from the through hole 134 of the extendable device 10 in the direction of arrow B in the figure. With this configuration, the therapeutic agent and / or drug concentrated in the fluid is in full contact with the target site on the inner wall 232. In this way, at least a portion of the therapeutic agent and / or drug permeates into the local cell space and tissue of the inner wall 232 of the permeation region 238. In addition, a portion of the fluid forms a small orifice 236 around the edge of the extensible device 10 and then leaks through the small orifice 236 in the direction of arrow C. Thus, a portion of the pressure from within the expandable device 10 is transferred to the semi-enclosed space 234 so that fluid is pressed against the inner wall 232 of the body lumen 230. As the fluid exits the semi-enclosed space 234, the drug and / or drug contained in the fluid is diluted and substantially washed away. This process is called kinetic isolation pressure (KIP) action.

  The KIP action helps create a semi-enclosed space 234 between the extensible device 10 and the inner wall 232 of the body lumen 230, and thus more evenly distributes or distributes the therapeutic drug or agent to the permeable region 238 of the inner wall 232 Help contact. This semi-enclosed space 234 is continuously filled with fluid that flows through the wall of the extensible device 10 into the semi-enclosed space 234. Due to this continuous fluid movement and the high pressure in the semi-enclosed space 234, contact between the actual structure of the extensible device 10 and the inner wall 232 or the permeable region 238 is not prolonged. . Thus, a fluid that contains at least one therapeutic agent or drug at a concentration and is continuously stirred contacts the inner wall 232. At certain locations on the tissue of the inner wall 232, fluid movement constantly agitates the therapeutic agent or drug, thereby continuously providing a fresh fluid supply and uniform or substantially homogeneous fluid contact. There is no opportunity for some areas of therapeutic drugs or drugs to stagnate.

  By continuously stirring and re-feeding the fluid containing at least one therapeutic drug or drug, the concentration of the therapeutic drug or drug in the tissue portion is regulated and substantially uniform. Furthermore, the fluid is pressurized so that the therapeutic drug or agent can be delivered or contacted undamaged. In addition, any structure that interferes with drug contact, such as stent struts or areas where the balloon is pressed against the inner wall 232, can cause fluid and therefore therapeutic drug or drug storage, There is no such structure. The uniform contact of the therapeutic agent or drug with a substantially uniform concentration increases the efficiency of tissue penetration, and the concentration of the therapeutic drug or agent that penetrates the inner wall 232 of the body lumen 230 is also more uniform. Become.

  The delivery of a therapeutic agent or drug needs to achieve a sufficient concentration at the target site to be effective. Conventional methods require that the dose or volume of the drug or drug be substantially greater than that of the present invention in order to obtain a therapeutic effect at the target site. In conventional methods, it was necessary to include a sufficient amount of drug or drug to be able to penetrate tissue and at the same time work around structures such as stent struts while being washed away from the target site. Or, in the conventional method, a drug is administered to a patient in a substantially larger amount by using a systemic administration method instead of a targeting method. However, the present invention uses at least a pressurized fluid containing a higher concentration of the therapeutic drug and / or agent to more efficiently and evenly distribute the therapeutic drug and / or drug to the tissue at the target site. An undamaged method of improving the penetration of one therapeutic drug and / or drug into tissue is provided.

  6A, 6B, and 6C illustrate an exemplary embodiment of an additional medical device that can be used with the stretchable device 10. FIG. FIG. 6A is a perspective view of stent 240 fully encapsulated in coating 242. FIG. FIG. 6B is a perspective view of a stent 244 having a partial coating 246. FIG. 6C is a perspective view of a stent 248 with no coating or with a coating on individual wires of the stent 248. FIG. As will be appreciated by those skilled in the art, coatings 242 and 246 may be made of PTFE or other suitable material. Further, coating 242 may include one or more therapeutic agents, or one or more components for producing a therapeutic agent as described herein. As will be appreciated by those skilled in the art, the expandable device 10 can be positioned within any of the stents 240, 246, or 248 to extend the stents 240, 246, and 248 against the lumen wall within the patient. May be.

  In another configuration, the expandable device 10 may extend within an already extended stent (eg, the stents 240, 246, and 248 of FIGS. 6A, 6B, and 6C). In such a configuration, the stent 240, 246, or 248 has already extended the body lumen or body cavity to as much as 110% of its original inner diameter. The expandable device 10 is then expanded and brought into contact with and pressed against the stent 240, 246, or 248. Because additional structure is provided by the stent 240, 246, or 248 and the body tissue has already been stretched, the force that pushes back the expandable device 10 is greater and slightly compresses the expandable device 10. Further, the pressure in the expandable device 10 can be increased up to about 6 atmospheres, compared to 3-4 atmospheres in configurations that do not use the stents 240, 246, or 248.

  As described above, the size and dimensions of the extensible device 10 are determined so that the extensible device 10 can extend to a diameter sufficient for the size of the body lumen specific to the application so that a semi-enclosed space can be formed. Is done. In other words, if the extendable device 10 is too small, the small orifice 236 becomes too large to maintain the fluid pressure. If the extendable device 10 is too large, the body lumen may be ruptured by the application of substantial pressure when the expandable device 10 is extended. Similar to that described above, the pressurized fluid flowing out by forming a small orifice 236 while applying slight pressure to both the body lumen wall and the expandable device 10 is a semi-enclosed space. There is no small orifice 236 unless it is within. The distance between the body lumen and the expandable device 10 (ie, the height of the orifice) may be from about 1/1000 inch to about 1 mm.

  Further, in configurations where the stent 240, 246, or 248 is used with the expandable device 10, a relatively high pressure is obtained within the expandable device 10 as described above (eg, up to about 6 atmospheres). This high pressure further enhances the penetration of the therapeutic agent into the body lumen or tissue of the body cavity.

  The therapeutic agent administered over time to the target site on the inner wall 232 penetrates the tissue on the inner wall 232. As described herein, fluid containing a therapeutic agent that has not penetrated the inner wall 232 exits the semi-enclosed space 234 and is washed away. With the KIP action, the fluid delivered to the target site can be substantially diluted because the target site can be brought into contact with the fluid flow over time. Thus, the fluid that delivers the drug is substantially diluted so that the therapeutic drug that has not penetrated the body tissue can exit to other parts of the patient's body without adverse effects It is.

  If a particular therapeutic agent (or other fluid) does not require the benefit of using KIP action, the fluid will pass through the expandable device 10 and contact the body lumen without being pressurized. May be. Such non-pressurized delivery may occur by fluid leaching from the porous wall of the extensible device 10 and delivered to a target site in the body lumen. The ability to combine two or more components immediately prior to entry into or within the extensible device 10 increases the number of therapeutic and other drugs that can be administered to the target site. As mentioned above, a mixture in which two or more components can be mixed and then administered directly to the target site within a few seconds or minutes, so that other methods do not provide a sufficient useful life Can also be used.

  In the remaining figures and examples, KIP action may be utilized to deliver pressurized fluid to a target site within a body lumen, or if desired, a non-pressurized fluid delivery process may be utilized. May be.

  FIG. 7 illustrates one exemplary method of administering a therapeutic drug according to the present invention. The method includes placing a drug delivery structure, such as extendable device 10, at a target site, such as body lumen 230, within a patient (stage 300). A first drug or drug-containing component is introduced into the drug delivery structure and reacted with a second drug or drug-containing component disposed within the delivery structure to produce a therapeutic drug (step 302). The therapeutic drug is then released from a plurality of locations along the drug delivery structure at a controlled rate to a target site within the patient (step 304). If the size of the stretchable device 10 is sufficient and the pressure provided to the stretchable device is appropriate, the therapeutic drug is released by the KIP action, resulting in better tissue penetration with shorter residence times.

  FIG. 8 illustrates one exemplary embodiment of forming a polymer body within a patient. The method includes placing a delivery structure, such as extendable device 10, at a target site in a patient (step 320). A first component is introduced into the delivery structure and reacted with a second component disposed within the delivery structure to produce a compound (stage 322). The compound is released from a plurality of locations along the delivery structure at a predetermined controlled rate and is administered to the target site to form a polymer body (step 324). If the size of the stretchable device 10 is sufficient and the pressure provided to the stretchable device is appropriate, the therapeutic drug is released by the KIP action, resulting in better tissue penetration with shorter residence times.

  FIG. 9 illustrates one exemplary embodiment of administering therapeutic gas to a target site within a patient. A gas delivery structure, such as extendable device 10, is placed at the target site (step 330). The gas delivery structure receives a first gas, and the first gas reacts with a second gas disposed within the delivery structure to generate a therapeutic gas (stage 332). The therapeutic gas is released from a plurality of locations along the gas delivery structure at a predetermined controlled rate and administered to the target site (step 334). If the size of the stretchable device 10 is sufficient and the pressure provided to the stretchable device is appropriate, the therapeutic drug is released by the KIP action, resulting in better tissue penetration with shorter residence times.

  In each of the embodiments shown in FIGS. 7, 8, and 9, these methods are described as having a second gas or component disposed within the delivery structure. It should be noted that the gas or component may be present in the delivery structure in a number of different ways. For example, the second gas or component may be supplied to the delivery structure immediately before or simultaneously with the introduction of the first gas or component to the delivery structure. Alternatively, the second gas or component may be sealed within the delivery structure until use by a clinical user. Alternatively, the component or gas may be present inside the delivery device structure, for example incorporated into PTFE material or other delivery device material, or applied as a coating on the wall of the delivery device structure. Good.

  In view of the foregoing description, many modifications and alternative embodiments of the invention will be apparent to those skilled in the art. Accordingly, the description herein is to be construed as illustrative only, and its purpose is to teach those skilled in the art the best mode of carrying out the invention. The details of construction may vary widely without substantially departing from the spirit of the invention, and all modifications falling within the scope of the invention disclosed are reserved for their exclusive use.

1 is a cross-sectional side view of a radially extensible device in accordance with the teachings of the present invention. FIG. The device is shown in a small first diameter state. FIG. 2 is a side sectional view of the radially extendable device of FIG. The device is shown in a large second diameter state. 1 is a schematic diagram illustrating the microstructure of a portion of the wall of a stretched fluoropolymer perfusion molded foam used during the manufacturing process of the present invention to obtain a radially stretchable device of the present invention. 1 is a diagram illustrating a therapeutic drug delivery system according to one aspect of the present invention. FIG. 1 is a cross-sectional view illustrating an extendable device disposed on an inner wall of a body lumen according to one aspect of the present invention. 1 is a perspective view showing a stent for use with the present invention. FIG. 2 is a flowchart illustrating an example method of administering a therapeutic drug according to one aspect of the present invention. 2 is a flow chart illustrating an example of a method for forming a polymer body according to one aspect of the present invention. It is the flowchart which showed the example of the aspect which administers therapeutic gas to the target site | part in a patient's body.

Claims (65)

A therapeutic drug delivery system comprising:
A non-perforated perfusion molded foam in fluid contact with a first drug source, the perfusion molded foam having a size and dimensions suitable for placement within a patient; and a portion of the perfusion molded foam A second drug;
Here, when the first drug is delivered from the first drug supply source through the perfusion molded foam with the perfusion molded foam pressed against the target site, the first drug reacts with the second drug. A therapeutic agent delivery system wherein a therapeutic agent is generated and the therapeutic agent is released from a portion of the perfusion molded foam at a target site for a desired residence time.   The therapeutic drug delivery system of claim 1, wherein the perfusion molded foam is coupled to a first drug source.   The therapeutic drug delivery system of claim 1, wherein fluid pressure and residence time of the therapeutic drug delivery system are controllable to change the permeability of the therapeutic drug to the target site.   The therapeutic drug delivery system of claim 1, wherein the second drug is disposed on at least one of a surface and an interior of the perfusion molded foam.   2. The therapeutic drug delivery system according to claim 1, wherein the structure of the perfusion molded foam is a structure suitable for pressurization at about 6 atmospheres.   2. The therapeutic drug delivery system of claim 1, wherein the physical state of the therapeutic drug comprises at least one of a gas, a liquid, a powder, a gel, a microparticle, and a nanoparticle.   2. The therapeutic drug delivery system of claim 1, wherein the first drug and the second drug have substantially the same consistency.   The therapeutic drug delivery system of claim 1, wherein the therapeutic drug is released under pressure to a target site and fluid pressure is maintained for a desired residence time outside the perfusion molded foam. A therapeutic drug delivery system comprising:
First drug source;
A second drug source; and a non-perforated perfusate molded foam disposed within the patient and in fluid contact with the first drug source and the second drug source;
Here, when the first drug and the second drug are introduced into the perfusion molded foam, the first drug and the second drug react to be released to the target site in the patient. A therapeutic drug delivery system in which a drug is produced.   10. The therapeutic drug delivery system of claim 9, wherein the perfusion molded foam is coupled to a first drug source.   The drug delivery structure can apply fluid pressure to the target site in a controlled manner over a desired residence time to bring the therapeutic agent concentration to a value when administering the therapeutic agent to the target site. Item 10. The therapeutic drug delivery system according to Item 9.   12. The therapeutic drug delivery system of claim 11, wherein fluid pressure and residence time are controllable to change the permeability of the therapeutic drug to the target site.   10. The therapeutic drug delivery system of claim 9, wherein the perfusion molded foam is suitable for pressurization at about 6 atmospheres.   10. The therapeutic drug delivery system of claim 9, wherein the physical state of the therapeutic drug includes at least one of a gas, liquid, powder, gel, microparticle, and nanoparticle.   10. The therapeutic agent delivery system of claim 9, wherein the therapeutic agent is released to the target site under pressure and fluid pressure is maintained for a desired residence time outside the perfusion molded foam. A therapeutic drug delivery system comprising:
Therapeutic drug delivery structure;
A microporous film disposed around at least a portion of the therapeutic drug delivery structure;
A first drug source containing a first drug and in fluid contact with the therapeutic drug delivery structure; and containing a second drug and in fluid contact with the therapeutic drug delivery structure; A second drug source;
Here, the therapeutic drug delivery structure is a structure suitable for applying pressure to the target site over a desired residence time, which is the period during which the therapeutic drug is administered to the target site within the patient. system.   17. The therapeutic drug delivery system of claim 16, wherein the therapeutic drug delivery structure comprises a stent.   The therapeutic drug delivery system of claim 16, wherein the microporous film is formed of PTFE.   17. The therapeutic drug delivery system of claim 16, wherein the microporous film contains a second drug.   A non-perforated perfusate molded foam disposed with a drug delivery structure at a location within the body, wherein the perfusion molded foam delivers a first drug from a first drug source to a therapeutic drug delivery structure. Perfusion molding in which one drug and a second drug interact to produce a therapeutic drug and the therapeutic drug is released from a portion of the therapeutic drug delivery structure to provide a local therapeutic effect 21. The therapeutic drug delivery system of claim 19, further comprising a foam.   21. The therapeutic drug delivery system of claim 20, wherein the residence time is controllable to vary the amount of therapeutic drug administered to the target site.   A pressure, including the fluid pressure of the therapeutic agent, can be applied to the target site in a controlled manner over the residence time, thereby providing a certain level of therapeutic agent concentration when the therapeutic agent is administered to the target site. 21. The therapeutic drug delivery system of claim 20, which can be made.   21. The therapeutic drug delivery system of claim 20, wherein the perfusion molded foam is suitable for pressurization at about 6 atmospheres.   21. The therapeutic drug delivery system of claim 20, wherein the physical state of the therapeutic drug comprises at least one of a gas, liquid, powder, gel, microparticle, and nanoparticle.   17. The therapeutic drug delivery system of claim 16, wherein the therapeutic drug is released under pressure to a target site and fluid pressure is maintained for a desired residence time outside the therapeutic drug delivery structure. A therapeutic drug delivery system comprising:
A therapeutic drug delivery structure fully encapsulated within the microporous film;
A first drug source containing the first drug and in fluid contact with the therapeutic drug delivery structure; and a second drug containing the second drug and in fluid contact with the therapeutic drug delivery structure supply source;
Here, a therapeutic drug delivery system in which a first drug and a second drug combine to produce a therapeutic drug.   27. The therapeutic drug delivery system of claim 26, wherein the therapeutic drug delivery structure comprises a stent.   27. The therapeutic drug delivery system of claim 26, wherein the microporous film is formed of PTFE.   27. The therapeutic drug delivery system of claim 26, wherein the microporous film contains a second drug.   A non-perforated perfusate molded foam disposed with a drug delivery structure at a location within the body, wherein the perfusion molded foam delivers a first drug from a first drug source to a therapeutic drug delivery structure. Perfusion molding in which one drug and a second drug interact to produce a therapeutic drug and the therapeutic drug is released from a portion of the therapeutic drug delivery structure to provide a local therapeutic effect 34. The therapeutic drug delivery system of claim 33 further comprising a foam.   32. The therapeutic drug delivery system of claim 30, wherein the residence time is controllable to vary the amount of therapeutic drug administered to the target site.   A pressure, including the fluid pressure of the therapeutic agent, can be applied to the target site in a controlled manner over the residence time, thereby providing a certain level of therapeutic agent concentration when the therapeutic agent is administered to the target site. 32. The therapeutic drug delivery system of claim 30, wherein   32. The therapeutic drug delivery system of claim 30, wherein the perfusion molded foam is suitable for pressurization at about 6 atmospheres.   32. The therapeutic drug delivery system of claim 30, wherein the physical state of the therapeutic drug comprises at least one of a gas, a liquid, a powder, a gel, a microparticle, and a nanoparticle.   27. The therapeutic drug delivery system of claim 26, wherein the therapeutic drug is released to the target site under pressure and fluid pressure is maintained for a desired residence time outside the therapeutic drug delivery structure. A method of administering a therapeutic agent comprising the following steps:
Placing a therapeutic drug delivery structure within a patient;
Introducing a first agent into the therapeutic agent delivery structure to react with a second agent disposed on a portion of the therapeutic agent delivery structure to produce a therapeutic agent; and treating the therapeutic agent with the treatment Releasing from a plurality of locations along the drug delivery structure to a target site within the patient at a controlled rate.   38. The method of claim 36, wherein the therapeutic drug delivery structure comprises a non-perforated perfusion molded foam.   38. The method of claim 36, wherein the second agent is disposed on at least one of the surface and the interior of the therapeutic drug delivery structure.   38. The method of claim 36, wherein positioning the therapeutic drug delivery structure comprises inserting a perfusion molded foam into a body part of the patient that is proximal to the target site requiring treatment.   38. The method of claim 36, wherein positioning the therapeutic drug delivery structure comprises inserting a catheter comprising a perfusion molded foam into a body part of a patient that is proximal to a target site requiring treatment.   40. The method of claim 36, wherein the second agent is disposed in a film disposed over at least a portion of the perfusion molded foam.   38. The method of claim 36, wherein the second agent is advanced into the perfusion molded foam.   38. The method of claim 36, further comprising introducing the second agent into the patient by entering the second agent into the perfusion mold and passing through at least a portion of the perfusion mold.   When the first drug reacts with the second drug, the first drug and the second drug pass as the first drug and the second drug pass through the plurality of locations and into the patient's body. 40. The method of claim 36, comprising producing a therapeutic amount of the drug by polymerizing.   38. The therapeutic agent delivery structure includes a stent disposed within the patient and a perfusion molded foam disposed within at least a portion of the stent for delivering at least one component of the therapeutic agent. the method of.   Perfusion molded foam suitable for at least one of deploying a stent and delivering a therapeutic agent in the form of at least one of a bioactive agent and a chemical agent to the stent and patient body 46. The method of claim 45, wherein the method is a molded foam.   46. The method of claim 45, wherein a film comprising a second agent is disposed on at least a portion of the stent.   46. The method of claim 45, wherein positioning the therapeutic drug delivery structure comprises inserting a perfusion molded foam and a stent into a body part of the patient that is proximal to the target site.   46. The method of claim 45, wherein introducing the first drug comprises advancing the first drug into the therapeutic drug delivery structure. 46. The method of claim 45, further comprising the step of entering a second agent into the perfusion molded foam and through the perfusion molded foam and stent into the patient body.   When the first drug reacts with the second drug, the first drug and the second drug pass as the first drug and the second drug pass through the plurality of locations and into the patient's body. 46. The method of claim 45, comprising producing a therapeutic amount of the drug by polymerizing.   46. The method of claim 45, further comprising leaving at least a first portion of the drug delivery structure in the patient and removing a second portion of the drug delivery structure.   38. The method of claim 36, wherein introducing the first agent comprises advancing the first agent into the drug delivery device in a manner that releases the therapeutic agent into the patient body.   The stage in which the first drug reacts with the second drug causes one of the first and second drugs to act as a catalyst for the other of the first and second drugs, thereby 40. The method of claim 36, comprising generating.   38. The method of claim 36, wherein the step of reacting the first agent with the second agent occurs as at least one of an emulsion process, a water soluble process, a lipophilic process, and a water insoluble process.   38. The method of claim 36, further comprising removing the therapeutic drug delivery structure from the patient body.   57. The method of claim 56, wherein removing the therapeutic agent delivery structure occurs immediately after releasing the therapeutic agent into the patient.   57. The method of claim 56, further comprising applying a fluid pressure of the therapeutic agent to the target site using the therapeutic agent delivery structure.   When administering a therapeutic agent to a target site, the therapeutic agent delivery structure maintains the therapeutic agent concentration at any one of constant, variable, and intermittent, while controlling the therapeutic agent in a controlled manner. 57. The method of claim 56, further comprising the step of releasing.   60. The method of claim 59, wherein the controlled manner comprises controlling the perfusion rate of at least one of the first and second agents.   60. The method of claim 59, wherein the controlled manner comprises controlling the fluid pressure of at least one of the first and second agents.   60. The method of claim 59, wherein the controlled manner comprises changing the consistency of the therapeutic drug to control the flow rate through the therapeutic drug delivery device.   38. The method of claim 36, further comprising releasing the therapeutic agent over a predetermined residence time.   64. The method of claim 63, wherein the residence time is controllable such that the tissue penetration of the therapeutic agent can be altered by changing the fluid pressure and residence time of the therapeutic agent.   38. The method of claim 36, wherein the therapeutic agent is released to the target site under pressure and fluid pressure is maintained for a desired residence time outside the therapeutic agent delivery structure.

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