TW504393B - Device and method for treating a wall of a blood vessel - Google Patents

Abstract

A method and device for injecting fluid into a treatment area of a vessel wall is provided herein. A first version of the device includes an inflatable balloon mounted on a catheter and a plurality of dispensers extending outwardly and moving with the balloon. At least one fluid passageway connects each injector in fluid communication with a fluid source. During use of the device, the balloon is first positioned in a vessel proximate the treatment area. Next, the balloon is inflated to embed the dispensers into the vessel wall. Subsequently, the fluid from the fluid source is introduced into the fluid passageway and through the dispensers into the treatment area. A second version of the device includes a plurality of flexible tubes mounted between a multi-lumen catheter and a grommet. A push-pull wire is connected to the grommet and passed through a lumen of the multi-lumen catheter. The dispensers are mounted on each of the flexible tubes. During use, the device is first positioned in a vessel. The push-pull wire is then partially withdrawn forcing the grommet to advance towards the multi-lumen catheter. The advancing grommet forces the flexible tubes to bow outwardly, embedding the dispensers into the vessel wall.

Description

The invention relates generally to medical devices that can be used to treat a patient's blood vessels. More special. The present invention relates to a medical device inserted into a blood vessel of a cardiovascular system of a patient, which can be used to inject a fluid directly into a blood vessel wall. In addition, the invention relates to other methods for treating blood vessels. BACKGROUND OF THE INVENTION Narrow and / or disease is a common problem in patients' blood vessels. Angioplasty is an operation used to treat narrowing of blood vessels in the human body. During angioplasty, a medical cannula with an inflatable balloon attached to the cannula handle is advanced in the blood vessel until the balloon is adjacent to the stenosis. Then, inflate the balloon. This causes the narrowed area to press into the arterial wall, causing the body's blood vessels to dilate. However, vascular shaping operations are not always successful when dealing with stenosis in blood vessels. In addition, angioplasty procedures may stimulate blood vessels, thereby causing subsequent restenosis of the blood vessels. As a result, many other devices have been proposed for use with angioplasty. For example, one such device utilizes a balloon ' to place multiple slits on the vessel wall. The drug is then released from the gap to the endothelium. Unfortunately, it has also been proven that the device is not completely satisfactory. Especially with this device, most if not all of the fluid does not penetrate the vessel wall, it is washed away and enters the bloodstream. Due to the toxic nature of certain fluids, this operation will endanger the health of the patient. In addition, because the fluid is washed away, the treatment of blood vessels is relatively ineffective. In view of the above, the object of the present invention is to provide a method that can be used to re-treat stenosis, suppress the occurrence of stenosis, and / or suppress trauma caused by intravascular manipulation. -4- This paper size applies the Chinese National Standard (CNS) A4 specification (21 〇X 297 male I)

Binding

Device and method for restenosis. Another object of the present invention is to provide a device for treating a blood vessel, which has a mechanical device penetrating the wall of the blood vessel, and is separated from a mechanical device for injecting a fluid to the blood vessel wall. Another object of the present invention is to provide a device that can selectively change the force and depth used to penetrate the vessel wall. Another object of the present invention is to provide an apparatus for treating blood vessels that is easy to use, and is relatively simple and inexpensive to manufacture. Another object of the invention is to provide a device and method for treating blood vessels that minimizes the risk to the patient. SUMMARY OF THE INVENTION The present invention is directed to devices and methods that meet these needs. The device is designed to inject fluid from a fluid source into the treatment area of the vessel wall. The device includes an extension and one or more dispensers. As provided below, the extension selectively and precisely controls the movement of the dispenser, while the fluid source selectively provides a pressurized supply of fluid to the dispenser. Therefore, the mechanism that causes the dispenser to penetrate the vessel wall is separated from the mechanism that releases fluid to the vessel wall. Importantly, the present invention can be used to safely reprocess stenosis, suppress restenosis, and / or suppress stenosis in blood vessels while reducing the risk to the patient. In addition, the invention is location specific and allows the clinician to accurately deliver fluid only to the correct area of the blood vessel. This is important because many fluids can have adverse effects on other areas of the body. For example, some fluids can cause blindness. In the first version of the present invention, the protruding portion includes a balloon which can be expanded from the first shape which is shrunk to the second shape which is expanded. The dispenser projects radially from the balloon and moves between the first and second shapes as the balloon moves. The dispenser preferably penetrates the endothelial layer of the blood vessel in the treatment area, and selectively releases fluid when the ball is in the second shape (504) A.7 B7 5. Invention description (3) With this shape, it is possible to precisely control the depth to which the dispenser penetrates into the vessel wall and the force used to penetrate the vessel wall. This allows the present invention to deliver fluid to the appropriate area of the vessel wall, while minimizing damage to the vessel wall. In addition, balloons can be used to dilate blood vessels simultaneously. At least one fluid path is connected to the fluid source, and the fluid communicates with the dispenser. For example, the fluid pathway may include an elastic tubular cuff that substantially surrounds and surrounds at least a portion of the outer surface of the balloon. The fluid source includes a fluid pump that is in fluid communication with the fluid pathway to selectively pressurize the fluid from the fluid source to the dispenser. Each dispenser may be essentially a tubular protrusion with an attachment end and a cannula section for invading the vessel wall. -The attachment end includes a base plate that sits directly on the tubular cuff. In certain embodiments provided herein, the open edge of the dispenser is the sleeve section. In other embodiments, each dispenser may include a porous section, or through an opening in the wall of the dispenser, representing a sleeve section. Depending on the fluid and the desired treatment, the fluid may be released substantially while the dispenser passes through the processing zone, or it may be delayed until the dispenser passes through the processing zone until the fluid is released from the dispenser. The extension of the second edition includes a multi-lumen cannula, a backing ring, multiple flexible tubes, which connect the backing ring to the cannula, and one or more dispensers protected by the elastic tube. The backing ring is movable relative to the cannula to allow the flexible tube to approach the vessel wall again. The invention also expands the processing area and delivers the fluid from the fluid source to -6- This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm)

Outfit

B7 V. Description of the invention (4) The method of the treatment zone. The method includes advancing the protrusion in the blood vessel, expanding the protrusion in the blood vessel, and selectively releasing fluid from the dispenser to the treatment zone. The expansion of the protruding portion causes the open end of each dispenser to penetrate the treatment area. In addition, the expansion of the protruding portion may also cause the simultaneous expansion of the blood vessel. The present invention is also a method for treating a living blood vessel wall. The method includes providing a fluid 'Advance the protruding portion in the blood vessel, move the protruding portion to the second shape, so that the sleeve of the dispenser contacts at least a part of the vessel wall, and selectively The step of releasing fluid into the vessel wall and enclosing at least a part of the vessel wall. The fluid can be forced from each dispenser into the vessel wall at a rate sufficient to cause local swelling in the vessel wall. This allows the blood vessel to be dispersed The fluid in the wall distributes the mud in the wall of the blood vessel. In this specific embodiment, the dispensers are preferably spaced appropriately in order to create a number of locally spaced swellings which subsequently cause the fluid to actually spread in the blood Around the wall. The type of fluid can be changed to meet the specific needs of the patient. More specifically, the fluid can be designed to re-treat stenosis or disease, and to suppress restenosis by minimizing the effects of previous intravascular procedures, And / or stenosis in blood vessels thereof. For example, to suppress restenosis, the fluid may contain an anti-proliferative agent that inhibits the proliferation of smooth muscle cells that grow in blood vessels under certain pathological conditions. Selective killing may be used Fluids of rapidly dividing cells to inhibit the proliferation of smooth tissue growth. Suitable fluids may include anti-proliferative agents such as methamphetamine, dehydrocortisone, adriomycin, mitomycin, proteins Synthetic inhibitors, toxin fragments, such as Pseudomonas, exotoxin. This paper applies Chinese National Standard (CNS) A4 specifications (210X 297 mm). 504393 A7 B7 5. Description of the invention (5) (PE) or castor Protein A (RA) toxins, as well as radioactive isotopes such as 111 indium, 90 yttrium, 67 gallium, 99mTc (chromium 99), 2Q5 thorium and 32P (phosphorus 32) radiopharmaceuticals. This device is uniquely provided and suitable for safety To deliver dangerous fluids into the vessel wall while minimizing the amount of fluid being washed out into the bloodstream or, for example, the device can be used to deliver fluids that stimulate collateral vessels. This develops a narrow stenosis in the original blood vessel In the event, preventive treatment is provided to the patient by creating new collateral vessels. For this purpose, fluids including angiogenic factor inhibitors can be used. In order to reduce the amount of fluid that is washed out into the bloodstream, part of the fluid It can precipitate at the blood vessel pΗ 値 near the blood vessel. Usually p 血管 of the blood vessel is about 7. Therefore, a fluid having a fluid pρ which is lower than about 6 or higher than about 8 can be used. The fluid is dispersed in the vessel wall After the inside, the ρ 流体 of the fluid is close to 7, and some of the fluid precipitates. In this embodiment, the fluid may contain a precipitant, an active component attached to or contained in the precipitant, and carried Precipitant and carrier component of active component. The precipitant precipitates on the vessel wall, and the carrier component is washed away into the bloodstream. Because the active component is attached or contained within the precipitant, the active component of the fluid remains in the vessel wall. This reduces the amount of active components of the fluid that are washed away into the bloodstream. With regard to this particular embodiment, the active component of the fluid may include, for example, an anti-proliferative agent as outlined above. Alternatively, the precipitant and active ingredient may include, for example, radionuclide or radiopharmaceutical precipitates, such as gold colloids, i.e. 198Au and 199Au, and / or inorganic precipitates. In addition, the active component of the fluid can be designed to have a slow, timed release. This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 504393 A7 B7 V. Description of the invention G) Formulation to release the active ingredient to the vessel wall over an extended period of time. Stated otherwise, the active component can be slowly biodegraded over a period of time, gradually releasing the active component of the fluid into the vessel wall. Biodegradable polymers can be used to provide formulations with controlled release active ingredients. Alternatively, the fluid may include a binder that protects the active components of the fluid. The adhesive binds, attaches or crosslinks to at least a portion of the vessel wall. The adhesive may include a ligand that binds to a portion of the blood vessel wall, such as collagen or smooth muscle cells of the blood vessel wall. This ensures that huge amounts of active components of the fluid remain in the blood vessel wall and reduces the amount of active components of the fluid that are washed away into the bloodstream. Examples of ligands that bind to vascular wall components include PDGF receptors, attachment molecules, including but not limited to certain molecules of the integrin family, and receptors on activated platelets, such as thrombin receptors. Alternatively, collagen-bound tridentite can be used. In another embodiment, the adhesive may have a direct affinity to the vessel wall or some of its components to form ions, covalent bonds, or Van der Waals attractive forces. In another embodiment, a gene therapy fluid can be used on the vessel wall. For example, the fluid may include a retrovirus, an adenovirus vector, or an adeno-associated vector (AAV), which carries appropriate DNA baggage for proper genetic transformation. The present invention allows the use of fluids that genetically change the designated treatment location of blood vessels without affecting the rest of the body. In addition, the dispenser can be extended for this device. This feature allows the device to deliver fluid, from the blood vessel through the vessel wall, and into the organ or a specific -9- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm).

504393

Organization area. * This is important to acknowledge that the device according to the present invention uses a mechanical device that separates the mechanical device that releases fluid into the blood and the wall, causing the dispenser to penetrate the vessel wall. In addition, the device changes the amount of force used to penetrate the vessel wall and simultaneously expands the vessel wall. Also, a unique fluid is provided in this article, which minimizes the amount of fluid that is washed out into the bloodstream, while maximizing the amount of fluid left in the vessel wall. In addition, the present invention is particularly suitable for injecting a radioisotope directly into a blood vessel wall.

The brief description of the assembly will be the most thorough understanding of the novel features of the present invention and the invention itself, such as its structure and operation, from the pictures in the appendix, together with the accompanying description, where: Figure 1 is a perspective view of a patient , Placing a device having the characteristics of the present invention in its artery;

Fig. 2 is a perspective view of a device having the characteristics of the present invention; Fig. 3A is a cross-section of the device of Fig. 2 taken on line 3-3 in a patient's artery; Fig. 3B is an artery and multiple placed in the patient's artery FIG. 4A is a perspective view of a first specific embodiment of a distributor having features of the present invention; FIG. 4B is a perspective view of a second specific embodiment of a distributor having features of the present invention Figure 4C is the third specific embodiment of the distributor with the characteristics of the present invention -10- This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 public love) 504393

V. Side view of the description of the invention; Figure 4D is a side view of a fourth specific embodiment of the dispenser having the features of the present invention; Figure 4E is a side view of the fifth specific embodiment of the dispenser having the features of the present invention 5A is a perspective view of a specific embodiment of a plurality of distributors having the features of the present invention; FIG. 5B is a perspective view of another specific embodiment of a plurality of distributors having the features of the present invention; Perspective view of another specific embodiment of the characteristic device; FIG. 7 is a cross-section taken on line 7-7 of FIG. 6; FIG. 8 is a perspective view of another specific embodiment of the device having the characteristics of the present invention; 9 is the cross-section of the device of FIG. 8 and is shown in a shrunken shape, as seen along the line 9-9 in FIG. 8; FIG. 10 is the cross-section of the device of FIG. 8 and is shown in an expanded shape As seen along line 9-9 in Figure 8; Figure 11 is a cross-section of the device of Figure 8 placed in a patient's blood vessel; Figure 12A is a portion of the blood vessel and device before the dispenser penetrates the vessel wall Longitudinal section; FIG. 12B is a view of the A longitudinal section of a blood vessel and a part of the device; Figure 12C is a cross-section of the axis of the blood vessel and the device, explaining the dispenser through the blood vessel wall; • 11-504393 A7 B7 V. Description of the invention (9) Figure 12D explains that the fluid has been injected After entering the blood vessel wall, a longitudinal section of the blood vessel wall; FIG. 12E is a cross-sectional view explaining the axis of the fluid dispenser injected into the blood vessel wall; FIG. 12F is a longitudinal section of a part of the blood vessel and the device, explaining the distribution of fluid into the blood vessel wall; Figure 12G is a cross-section of the axis of the blood vessel and the device, explaining the distribution of fluid into the blood vessel wall; Figure 13 A is a longitudinal section of the blood vessel and the device, explaining the distribution of radioactive isotope-containing fluid into the blood vessel wall; After the isotope fluid is distributed to the vessel wall, a longitudinal section of a part of the blood vessel and the device; Figure 14A is a longitudinal section of the blood vessel and the device, explaining the distribution of the fluid containing the sediment into the vessel wall; Then, a longitudinal section of a part of the blood vessel and the device; FIG. 15A is a longitudinal section of a part of the blood vessel and the device, explaining the injection of a fluid with an adhesive into the blood vessel wall; 15B is a longitudinal section of a part of a blood vessel and a device, explaining the combination of a granule with a wall of a blood vessel; FIG. 16A is a longitudinal section of a blood vessel, explaining a cell gene of a blood vessel and a part of a device having features of the present invention; 16B is a longitudinal section of a blood vessel, explaining that a fluid containing a viral gene is injected into a blood vessel wall by the device; and FIG. 16C is a longitudinal section of a part of a blood vessel, explaining that the viral gene has been in cells-12 National Standard (CNS) A4 (210 X 297 mm)

B7 B7 V. Description of the invention (10) ~ Attacks cell genes internally and replaces cell genes. DESCRIPTION OF THE INVENTION Referring initially to FIG. 1, there is shown a device 10 according to the present invention placed in a blood vessel of the upper body of a patient 12 for injecting a fluid 13 into the wall of a living blood vessel iJ. However, the device 10 may be used in arteries and blood vessels throughout the patient 12. Importantly, as provided in detail below, the device 10 'provided herein allows the fluid 13 to be injected substantially symmetrically directly into the blood vessel 11 to the periphery of the blood vessel 11. Referring to FIG. 2, the first version of the device 10 has the features of the present invention and includes a multi-lumen cannula 14, a protrusion 15 thereon, a tubular sleeve 18, and a plurality of dispensers 2 0 as in FIG. 2. As explained in 3A, the protruding portion 15 may be an inflatable balloon 16. Balloon 16 is at least swelled and deflated between the first, actually shrunken shape, and the second, 'expanded shape. When in the first shape, balloon 16 is actually deflated. When in the second shape, the balloon 16 can be inflated to any extent from partial inflation to full inflation, depending on the size of the blood vessel 11. The balloon 16 and the tubular cuff 18 can be made from many materials, including polyethylene terephthalate (PET). In addition, FIG. 2 indicates that the tubular cuff 18 surrounds a solid portion of the balloon 16 and a plurality of dispensers 20 are positioned on the tubular cuff 18. Among them, the illustrated distributor 20 is only representative. Provided by FIG. 3A between the balloon 16, the tubular cuff 18, and the dispenser 20, a more complete identification of structural cooperation, where the distal end 22 of the tubular cuff 18 will be seen directly attached to the outer surface 25 of the balloon 16 on. Figure 3A also shows the tubular sleeve-13- This paper size applies to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 504393 A7 ____B7 X; Description of the invention Υπ) ^ ~-The sleeve 18 actually surrounds and surrounds the balloon 16, The proximal end 24 of the tubular cuff 18 extends from the proximal end of the balloon and passes over the balloon 16 covering the sleeve 14. The tubular cuff 18 cooperates with the outer surface 25 of the balloon 16 to define a portion of the fluid path 26. The proximal end 24 may be connected to the outer cavity 27 (not shown in Fig. 38) of the cannula 14 to complete the fluid pathway 26. Figure 3A further shows the distal end 28 of the balloon 16, fixed on the cannula 14, and the proximal end of the balloon 16 is attached to the cannula 14, creating an inflation chamber 3 2 inside the balloon. The steam valve 3 4 of the balloon allows > the waste body to approach the expansion Xuan 3 2. For the purpose of the present invention 'a balloon lumen (not shown) may be fluidly connected to the balloon valve 3 4 and the sleeve 14. Fig. 3A also shows a cannula 14 formed with an inner lumen 36, which has dimensions to receive a guide wire 38 passing therethrough. The blood vessel 11 includes a plurality of layers. To facilitate the current discussion, some layers are explained in Fig. 3B, namely the endothelial layer 35a, the basement membrane layer 35b, the sheet layer 35c, the middle layer 35d, and the outer membrane layer 35e. The base film layer 35b, the sheet layer 35c, and the middle layer 35d should be regarded as an inner layer. It is important for the present device 10 to precisely control the depth of the distributor 20 by controlling the length of each distributor '20. Therefore, the device 10 is capable of delivering a fluid 13 to a desired target layer of the blood vessel 11. For example, as explained in Fig. 3B, the dispenser 20 penetrates the endothelial layer 35a, the basement membrane layer 35b, and the sheet layer 35c to accurately deliver the fluid 13 to the middle layer 35d, which is the target layer in this example. Alternatively, for example, the shorter dispenser 20 can be used to deliver the fluid 13 to the sheet 35c. In addition, for the present invention, the device 10 can be used to simultaneously dilate the blood vessels 11. Referring now to FIG. 4A, each dispenser 20 includes a base plate 40 and a tubular protrusion 42 having an attachment end 44 and a sleeve section 46. In addition, see the tube-shaped protrusions -14- This paper size applies to China National Standard (CNS) A4 (210X297 mm)

Hold

504393 A7 _____B7 ΐ, description of the invention (12) " ^ ^ 42 The attachment end 44 is fixed and becomes an essential part of the base plate 40. Preferably, the dispenser 20 is made of nickel, and a tubular protrusion 42 is formed by punching a hole in the base plate 40. In the specific embodiment illustrated in FIG. 4A, the nesting section 46 is defined by an opening opposite to the base plate 40. The tubular protrusion 42 defines a fluid channel 48 that extends via the dispenser 20. Each dispenser 20 shown in Fig. 4A is practically ring-shaped. FIG. 4B shows another specific embodiment of the dispenser 20. The tubular protrusion 42 shown in Fig. 4B is actually conical. Similarly, the dispenser 20 in Figure 4] B is preferably made of nickel and is formed with a fluid passage 48 extending through the syringe 20. 4C and 4E illustrate another specific embodiment of an additional dispenser 20. In the specific embodiment explained in Figs. 4C to 4E, the tubular protrusion 42 is actually conical. However, in Fig. 4C, the sleeve section 46 is defined by an opening extending through the side of the tubular protrusion 42. Slightly similar, in Fig. 4D, the sleeve section 46 is defined by a pair of openings extending through the sides of each tubular protrusion 42. This feature prevents the insertion of the socket segment 46 during the insertion of the blood vessel 11. In FIG. 4E, the tubular protrusion 42 is made of a porous material. Accordingly, the porous material defines the nesting section 46 of each dispenser 20. Basically, in this specific embodiment, the fluid 13 is forced through the porous tubular protrusion 42. FIG. 5A shows a plurality of dispensers 20 formed on the same base plate 50. Fig. 5A shows in particular the extended base plate 50, from which the dispenser 20 has been formed. In various important respects, the dispenser 20 shown in Fig. 5A is structurally the same as the dispenser 20 discussed above with reference to Fig. 4A. The only difference is that they are collectively on the same base plate 50. -15- The standard of this paper is SSC Standard (CNS) Α4 (210 X 297)

Similarly 'FIG. 5B shows a plurality of dispensers 20 formed on the same base plate 50. FIG. In various important respects, the dispenser 20 shown in Fig. 5B is structurally the same as the dispenser 20 discussed above with reference to Fig. 4] 8. Furthermore, the only difference is that they are collectively on the same base plate 50. Referring back to FIG. 3A, the dispensers 20 are on the tubular cuffs 18 such that the fluid channels 48 and holes 52 in the tubular cuffs 18 of each individual dispenser 20 are paired A to do this in a particular dispenser 2 Fluid transfer is established between 0 and the infusion chamber 26. In fact, it may be best to place the dispenser 20 on the tubular sleeve 8 in the construction of the device 10. This can be done in any way known in the art, such as by gluing and The dispenser 20 pierces the tubular cuff 18. When the balloon 16 is inflated, the dispenser 20 of the present invention extends between about 0.005 inches to about 0.02 inches from the tubular cuff 18. However, those skilled in the art will recognize that these distances are only representative. In other specific embodiments of the invention shown in FIG. 6, the basic components of the device 10 include a multi-lumen cannula 14 for receiving a guide wire 38, a balloon i6, a plurality of dispensers 20, and a plurality of The tubular channel 6 4 on the outer surface 2 5 of the balloon 6. Each tubular channel 64 has a smaller diameter than the balloon 6 and its position is substantially parallel to the longitudinal axis 65 of the balloon 16. . Figure 6 further shows that on the surface of each tubular sleeve 64 is a dispenser 20. The dispenser 20 is positioned on the surface of the tubular sleeve 64 so that when the balloon 16 is inflated, the dispenser 20 moves outward with radiation. Note, however, that the display of the dispenser 20 is for illustrative purposes only, and it is understood that any of the dispensers 20 or combinations of dispensers 2 discussed in relation to the previous specific embodiments may be used. ^ 04393 A7 B7 V. Description of the Invention (14) Referring now to FIG. 7, the cross section of the device 10 shows the tubular passage 64 in more detail. More specifically, the distal end 66 of the tubular passage 64 is sealed, creating a portion of the fluid pathway 26 that connects the dispenser 20 to a fluid source 60. 6 and 7, it is understood that the proximal end 68 of the tubular channel 64 is in fluid communication with the outer lumen 27 of the cannula, which is in fluid communication with the fluid pump 58 and the fluid source 60. Returning again to FIG. 7, the dispenser 20 is shown on the outer surface of the tubular passage 64. As shown in more detail in FIG. 7, the base 40 of each of the dispensers 20 on the tubular passage 64 covers the corresponding hole 70. From this section, it is understood that any number of tubular channels 64 can be placed on the outer surface of the balloon 16. It is further understood that any number of dispensers can be placed on a single tubular channel 64. Figure 8 shows a second version of the extension 15 which includes a multi-lumen cannula 80 and a iliac ring 82. Both the multi-lumen cannula 80 and the cushion ring 8 · 2 are arranged on about the same longitudinal axis, and the cushion ring 82 is located at a distance from the multi-lumen sleeve 80 in a separated form. Using some type of device, move the ring of constriction along the longitudinal axis 8 2. For example, referring to FIG. 8, it is shown that the push-pull wire 84 is connected to the backing ring 82. The push-pull wire 84 is extended through one lumen of the multi-lumen cannula 80, allowing the push-pull wire 84 to be moved in line with the longitudinal axis in a transformed manner. The push-pull wire moves in the transformation, causing the pad ring 82 to undergo a similar transformation displacement. In many cases, it will be desirable to use a combination of the device of the present invention and a guide wire 38. In such cases, a push-pull wire 84 can be formed having two cavities in which the guide wire 38 passes. In the second edition, a plurality of hollow, elastic tubes were attached between the backing ring 82 and the multi-lumen cannula 80. Each flexible tube 86 includes a distal end 88, an inlet end 90, and a central region 92. The proximal end 90 of each tube 86 is connected to multi = 504393 A7 B7 15 V. Description of the invention (Sleeve 80 connected. The distal end 88 of each tube 86 is connected to the backing ring 82. Preferably, the tubes 86 are radial Distributed around the multi-lumen cannula 80 and the backing ring 82, distributed in the manner shown in Figure 8. Now referring to Figures 9-11, it can be seen that each flexible tube 86 has a lumen The shape of 94. The lumen of the flexible tube 86 passes through a flexible sleeve 80 'to allow the fluid 13 to pass through a multi-lumen sleeve 80 and into the flexible tube 86. Each tube of the elastic tube 86 The lumens 94 are respectively passed through a multi-lumen cannula 80 ′ to allow different fluids 13 to pass through each flexible tube 86. Alternatively, the lumen 94 of each flexible tube 86 may be attached to one or Multiple on the common lumen within the multi-lumen cannula 80. Figures 9 and 10 also show multiple dispensers 20 attached to the central area 90 of each tube 86. Each flexible tube 86 is Shape with multiple holes%, which is consistent with individual dispenser 20. Functionally, each hole connects the channel and lumen 94 of the individual dispenser 20 respectively The fluid pump 58 is allowed to withdraw fluid 13 from the fluid source 60, inject it into the lumen 94, and eject it through the dispenser 20. ... Figures 9 and 10 also show that the present invention is the first shrinkable shape ( (Shown in Figure $) and a second expanded shape (shown in Figure 10). It can be seen in more detail that the distance between the cushion ring 82 and the multi-lumen cannula 80 is the first separation distance 98. The device 10 shown in FIG. 9 also has the first full width indicated by 100. In comparison, the distance between the cushion ring 82 shown in FIG. 10 and the multi-lumen cannula 80 is the first Two separation distances 102 are shorter than the first separation distance 98 of Fig. 9. The device 10 shown in Fig. 10 also has a second full width 104, which is larger than the first separation distance shown in Fig. 9 A full width of 10 is larger.

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504393 A7 ------------- B7___ V. Description of the invention ^ ~ " --------- The first shrinking shape shown in Figure 9 and Figure 1〇 The difference between the second expanded shapes shown in the figure is achieved by moving the ring η along the longitudinal transformation. In more detail, because the push-pull wire 82 is moved toward the multi-lumen cannula 80, each elastic tube 86 is bent away from the longitudinal axis. In this way, a push-pull wire 84 can be used to change the ring 82, causing the elastic tube to be bent one side = seen, and straightened, as seen in FIG. In some cases, it is desirable to make the flexible tube 86 using a resilient material that prefers the tube 86 to be a curved or straightened shape. Referring to Figures 12a-12f ', a velocity that is sufficient to produce local swelling 106 in the wall of the blood vessel 丨 may force the fluid 13 from each dispenser 20 into the wall of the blood vessel 11. This valley fluid 13 is dispersed in the wall of the blood vessel 11 and distributed around the blood vessel η. Preferably, as explained in Figures 12a and 12f, partitioning the dispenser 20 produces a plurality of partitioned local swellings 106 which subsequently spread the fluid 3 around the wall of the blood vessel 11. The speed required to produce local swelling 106 depends on the viscosity of the fluid 13 used. Usually, between about 400 microliters and 700 microliters of fluid 1 3, dispersed between about 5 and 45 seconds, is sufficient to produce the desired local swelling. However, it should be acknowledged that the content and time frame provided in this article is only representative. The time structure and content required to cause the desired local swelling will vary depending on many factors, such as the viscosity of the fluid i3. The creation of a plurality of spaced apart local swellings 106, followed by the required interval to spread the fluid 13 along the treatment zone 54, will also vary depending on the fluid 13 used. Xian believes that the dispenser 20 should be separated by a circumferential distance of about 1 mm to 6 mm, separated by about 70 degrees to 140 degrees. In addition, the dispenser 20 should be separated by about 0.5 -19. This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 504393 A7 ---------------- --- 67 _ V. Description of the invention (17) " ~ ----- Longitudinal distance between mm and 3 mm 丨 丨 〇. The composition of the fluid 13 to be injected into the blood vessel η depends on the treatment to be performed and the physical characteristics of the patient 12. More specifically, it can be designed to re-treat a stenosis or disease, to suppress restenosis by minimizing the effects of previous intravascular procedures, and / or to suppress the flow of stenosis in the vascular crest. For example, to inhibit restenosis, fluid 13 may contain an anti-proliferative agent that inhibits the proliferation of smooth muscle cells that grow in blood vessels under certain pathological conditions. These fluids, which selectively kill rapidly dividing cells, can be used to inhibit the proliferation of smooth tissue. Appropriate fluids may contain anti-formicin, dechlorocortisone, adriamycin, mitogen, synthesis inhibitors, such as Pseudomonas, exotoxin (ρΕ) or ricin A ( (RA) Toxin fragments such as toxins, as well as radioactive isotopes 112, such as diindium, 9 ° yttrium, 67 gallium, cardiac Tc (chromium 99), radioactive drugs such as thorium and 32P (phosphorus 32). Ham believes that this device is uniquely provided and is suitable for safely delivering dangerous fluid 13 into the vessel wall 11 while minimizing the amount of fluid 13 that is washed out into the bloodstream. … Or, for example, the device can be used to deliver fluids 13 that stimulate collateral vessels. This feature allows for patient preventative treatment by creating new collateral vessels in the event that the original blood vessel develops a stenosis. For this purpose, fluids including angiogenic factor inhibitors are available. Figures 13a and 13b explain a fluid 13 containing a radioactive isotope 112, which reduces and inhibits the growth of tissues and / or cells of the blood vessel 11. Because the radioisotope 1 12 is directly injected into the blood vessel 11 and symmetrically injected around the blood vessel i J ', a relatively low half-life with a relatively short half-life can be used -20-This paper size applies to Chinese national standards (CNS) A4 specification (210X297 mm) Binding and binding ... * ......... Γ ... 504393 A7 __ B7 V. Description of the invention (18) Radioactive isotope 112 of energy. These relatively low-energy radioisotopes 112 should cause minimal harm to the patient 12. The device 10 is uniquely provided herein and is suitable for safely delivering only the radioisotope 112 into the treatment zone 54 of the vessel wall 11 while minimizing the amount of radioisotope 112 being washed out into the bloodstream. In addition, the radioisotope 112 can be encapsulated in a suitable carrier, such as a microlipid modified with amine · mannose, which can be quickly absorbed by the smooth muscle cells of the sheet 35c. The precise dose of radiation delivered to the blood vessel 11 can be varied to suit the needs of the patient. It is currently believed that tissue-absorbed doses between about 8 and 40 Gray will be used to suppress restenosis. The precise content of the fluid 13 and the type of fluid 13 injected into the blood vessel 11 can be changed, which is why the fluid 13 is washed out into the blood stream and / or the active life of the fluid 13. Referring to Figs. 14a and 14b, in order to minimize the content of the fluid 13 being washed out into the blood stream, a portion of the fluid 13 can be precipitated at about the blood vessel pH 値. Usually the pH of blood vessels is about 7. Therefore, a fluid 1 3 having a p 低 lower than about 6 or higher than about 8 may be used. After the fluid 13 is dispersed in the wall of the blood vessel 11, the ρ 该 of the fluid is close to 7, and a part of the fluid 13 is precipitated. With regard to this specific embodiment, the fluid 13 may contain a precipitant 114, an active component 115 attached or incorporated with the precipitant 114, and a carrier component 117 carrying the precipitant 114 and the active component 115. Active component 115 is part of fluid 1 3 designed to treat patient 12. In this example, the precipitating agent 114 can form a precipitate in the wall of the blood vessel 11 while the carrier component 117 is washed off into the blood stream. Because the active ingredient 115 is attached or incorporated into the precipitant 114, this ensures that the flow-21-this paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 504393 A7 _____ _ B7 V. Description of the invention ( 19) The huge active component 115 of the body 13 remains in the blood vessel wall 11 and reduces the content of the active component 115 of the fluid 13 which is washed out into the blood stream. In this particular embodiment, the active component 115 of the fluid 13 may, for example, include an anti-proliferative formulation as outlined above. Alternatively, the sinking agent 114 and the active ingredient 115 may be radionuclides or radiopharmaceutical precipitants, such as gold colloids, that is, 198Au and 199An, and / or inorganic precipitates, such as organic-metal precipitates.

In addition, the active component 115 of the fluid 13 can be designed as a slow, time-release formulation so that the active component 115 is released into the vessel wall 11 for an extended period of time. In other words, the active component 1-5 can be slowly biodegraded over a period of time, and the active component released into the fluid i 3 into the vessel wall 11 over an extended period of time. Biodegradable polymers can be used to provide controlled release formulations of the active ingredient 115. Or, referring to Figures 15A and 15B, the fluid 13 may include a binder 116, an active component 115, and a carrier component 117. The adhesive 116 protects the active component 115 of the fluid. The adhesive 116 is suitable for bonding, attaching or cross-linking to at least a portion of the wall of the blood vessel 11. For example, the adhesive can pick up a ligand that binds to a portion of a blood vessel wall, such as collagen or smooth muscle cell components of the blood vessel wall. Because the adhesive 16 protects the active component 115, this ensures that the huge active component 115 of the fluid 3 remains in the vessel wall 11 and reduces the active component 115 of the fluid 3, which is washed out into the bloodstream. Content. Examples of ligands that bind to arterial wall components include PDGF receptors, attachment molecules, including but not limited to certain knives for integrin release, and receptors on activated platelets, such as thrombin receptors . Other types of ligands are from aArlington Heights, -22- The paper size is suitable for the country's standard (CNS) A4 specifications (21GX 297 public reply 5 504393 A7 B7 V. Description of the invention (20)-

Amersham, Illinois, sold under the name Ceretec®. Alternatively, for example, tridentate rotation combined with collagen can be used. In another embodiment, the ' granule may have a direct affinity for forming ions, covalent bonds, or van der Waals attraction to the vessel wall or some of its components. Alternatively, as explained in Figs. 16a-16c, gene therapy can be performed on blood vessels 1 1 using fluids 3. In this specific embodiment, the fluid 3 may include a suitable viral vector 118, which is suitable for infecting the cell 120, and a cell gene 122 may be replaced, regulated, inhibited or promoted in the cell 120. For example, the fluid 1 3 may include a retrovirus, an adenoviral vector, or an adeno-associated vector (AAV) 'which carries appropriate DNA baggage for proper genetic transformation. Alternatively, for example, gene therapy can be performed using naked DNA or polycation-agglutinated oxidants. The present invention allows the use of a fluid 13 which genetically alters the processing position 54 of the blood vessel 11 without affecting the rest of the body. The present invention can utilize other fluids, including antibodies, such as monoclonal antibodies at the receptor site, toxic agents such as saponin: y :, genetic material such as DNA, and cells such as endothelial cells. Substances, and / or drugs such as heparin. The examples provided herein are only examples of fluids 13 that can be used in the present invention. Those skilled in the art will recognize that other fluids 1 3 can be developed as improvements in medical technology. In addition, those skilled in the art will recognize that the present invention can be used for applications other than restenosis suppression. For example, the present invention can be delivered from a blood vessel 1 i to a specific organ using an extended dispenser 20. Operation It is best to refer to Figs. 1-3 at first to imagine the operation example of the extended part 丨 5 balloon 丨 6 version. First, the guide wire 38 is placed on the blood vessel of the patient 12 u I_ -23. This paper size applies the Chinese National Standard (CNS) A4 specification (2ΐ〇χ ^^ ϋ --- one-

Hold

A7 η ---- ~-_Β7 V. Description of the invention ^) · ^. This is done to establish a mechanical pathway through the blood vessel 11 to the treatment zone 54 of the fluid to be released 13. Next 'on the guide wire 38, the balloon 16 attached to the sleeve 14 is moved to the processing area 54. While moving in the blood vessel 11, the balloon 16 is in its first shape. Once the balloon 16 is in the proper position near the processing area 54, the expander 56 'is activated to expand the balloon 16 into its second shape. As shown in Figure 2, the expander 56 is connected to the proximal (extracorporeal) end of the device 10. Referring back to FIG. 3, it will be known that when the balloon 16 is inflated, the expanded balloon 16 drives the tubular cuff 18 and causes the tubular cuff 18 to expand as well. As a result, the dispenser 20 on the tubular cuff 18 moves rapidly from the cannula 18 and is buried in the processing area 54. In addition, the balloon 16 can be used to simultaneously expand the blood vessel ι1σ. As for the dispenser 20 embedded in the treatment area 54, the fluid fpu 58 shown in FIG. 2 is moved, and the fluid 3 is drawn from the fluid source 60 to the fluid passage 2 6 in. Importantly, this aspiration action also causes any fluid 1 3 that has been aspirated into the fluid passage 26 to be expelled through the fluid channel 4 8 ′ of the dispenser 20 into the tissue of the treatment area 54. . Alternatively, the fluid pump 38 can be moved before the dispenser 20 is buried in the blood vessel wall, and the valve 62 can be blocked from using the valve 62 until the dispenser 20 is buried in the processing area 54. Then the shutter 62 is opened when the dispenser 20 penetrates into the processing area 54 so that the injection and the embedding of the dispenser 20 into the processing area 54 actually occur simultaneously. Alternatively, the injection of the fluid 3 can be delayed by waiting for the valve 62 to open, with a delay of at least about 1 second to about 20 seconds. In addition, one or more fluids may be released in the vessel wall 11 at different time intervals. The fluid 1 3 has been dispersed from the fluid source 60 to the processing area 5 4 of the building 1 This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 male ---------_ 504393 A7 __B7 5. Description of the invention (22) 'By inverting the expander 56, the balloon 16 can be deflated into the first shape. This action will cause the balloon 16 to collapse and retract the dispenser 20 from the processing area 54. The entire device 10 can then be withdrawn from the patient 12 via the guide wire 38. The specific embodiment shown in Figures 6 and 7 utilizes a plurality of individual tubular channels 64. With regard to this specific embodiment, it is possible to Between each of the tubular channels 64, the flow body is maintained in communication with or separated from it. For example, each of the tubular channels 64 can be fluidly connected together in an outer lumen 27 of the cannula 14, Establish fluid communication between each of the tubular channels 64 to provide fluid 1 to each of the tubular channels 64 from the same fluid pump 58. Alternatively, each tubular channel 64 may be provided Correspond and separate the outer lumen 2 7 and establish itself with the corresponding and independent fluid pump 5 8 The physical relationship maintains fluid separation between each of the tubular channels 64. As a result, it is possible to use a plurality of tubular channels 64, which are respectively connected to separate fluid pumps 58 while injecting various fluids 13 simultaneously. Although, as shown and discussed in detail herein, the injection of fluid 13 into the special device 10 within the processing zone 54 is fully capable of winning the goal and providing the aforementioned benefits', it should be understood that the presently preferred specific embodiments of the present invention are for explanation only. It is not intended to limit the details shown in this article, and the details of the structure or design that are different from those defined in the scope of the patent application in the appendix. -25- This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 public love)

Claims (1)

504393 AB c D 6. Application scope 1. A device for treating a blood vessel wall, the device comprising: a fluid source containing a fluid; an extension portion that moves between a collapsed shape and an expanded shape; a dispenser, It moves between the collapsed shape and the expanded shape with the extension; and a fluid path connected to a fluid source, which communicates with the dispenser by fluid. 2. The device according to item 1 of the scope of patent application, wherein the fluid inhibits the proliferation of smooth tissue growing in the blood vessels. 3. The device according to item 1 of the patent application, wherein the fluid comprises a radioactive isotope. 4. The device according to item 1 of the scope of patent application, wherein the fluid stimulates the development of collateral vessels. 5. The device according to item 1 of the patent application, wherein the fluid comprises 99mTc (Cr 99). 6. The device according to item 1 of the scope of patent application, wherein the fluid includes 32P (phosphorus 32). The device according to item 1 of the scope of patent application, wherein the fluid is available for gene therapy. 8-The device according to item 1 of the patent application, wherein the fluid comprises a gold colloid. 9. The device according to item 1 of the scope of patent application, wherein at least a part of the fluid forms a sediment under the blood vessel pΗ 値 of the blood vessel. 1 〇. The device according to item 1 of the scope of the patent application, wherein the fluid has a fluid ρη 値 different from the pH of the blood vessel, and at least a part of the fluid is about -26- This paper size applies Chinese National Standard (CNS) a4 Specification (21〇x 297mm) A8 B8 C8 'Scope of patent application A precipitate forms under the pΗ 値 of the blood vessel, so that when the fluid approaches the pΗ 値 of the blood vessel, the fluid will settle in the vessel wall. 1 1 The device according to item i of the patent application, wherein the fluid comprises a radiopharmaceutical sink. 1 2. A device according to item 1 of the patent application, wherein the fluid comprises an inorganic precipitate. 13. Apparatus according to item i of the patent application, wherein the fluid has a fluid pΗ 値 below about pp6. 14. The device according to item 1 of the patent application, wherein the fluid has a fluid pH higher than about ρΗ8. 15. A device according to item 1 of the patent application, wherein the fluid includes an adhesive that binds to at least a portion of a blood vessel wall. 16. A device according to item 15 of the patent application, wherein the fluid includes a ligand that binds to at least a portion of a blood vessel wall. 17. A device according to item 15 of the patent application, wherein the fluid comprises a ligand that binds to a collagen protein. 1 8. The device according to item 15 of the patent application, wherein the fluid has an active component protected by an adhesive. [19] The device according to item 18 of the scope of patent application, wherein the fluid has an active component that inhibits the proliferation of smooth tissue that grows in the vessel wall. 20. Apparatus according to item 18 of the scope of application, wherein the fluid has an active component comprising a radioisotope. 2 1 · The device according to item 1 of the scope of patent application, wherein the fluid source forces the fluid at a rate sufficient to produce local swelling in the blood vessel wall from the dispenser -27- the paper scale applies the Chinese National Standard (CNS) A4 specification ( 210X 297 mm) 504393 ABCD 々 The scope of patent application enters the vessel wall. 2 2. The device according to item 1 of the scope of patent application, which comprises a plurality of spaced-apart distributors which are separated by a certain distance so that the fluid is actually dispersed around the vessel wall. 2 3. The device of claim 22, wherein the fluid source forces the fluid into the vessel wall from a plurality of spaced-apart dispensers at a rate sufficient to produce at least one local swelling in the vessel wall. -28- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)