JP2003506142A - Medical devices that release nitric oxide - Google Patents

Abstract

  (57) [Summary] The present invention provides a medical device that integrates a compound that releases nitric oxide for the purpose of altering angiogenic activity in the tissue surrounding the implant device. More specifically, an angioplasty implant device configured to be implanted in the myocardium of the heart is provided. The nitric oxide releasing compound can be attached to the device by placing it in a polymer matrix coating or directly to the surface of the device after reaction with the organosilane.

Description

Detailed Description of the Invention

FIELD OF THE INVENTION The present invention relates to medical devices that release nitric oxide when implanted in tissue to alter the angiogenic effect. More specifically, a method of attaching a nitric oxide compound to a medical device is provided to allow for the gradual release of the nitric oxide when implanted in tissue. It Further provided is a myocardial implant having a nitric oxide releasing compound.

BACKGROUND OF THE INVENTION Tissue becomes ischemic when sufficient blood flow is blocked. Ischemia causes pain in the affected tissue area and, in the case of muscle tissue, inhibits muscle function. If untreated, ischemic tissue will infarct and permanently cease to function. Ischemia may result from blockage of the vasculature, which prevents the oxygen-containing blood stream from reaching the affected tissue regions. However, ischemic tissue may regenerate until it functions normally even when oxygen-containing blood is inhibited, which means that the ischemic tissue may remain viable for some time while in hibernation. It depends on what is possible. The ischemic tissue can be regenerated by restoring the blood flow to the ischemic region. Although ischemia can occur in various parts of the human body, it often affects the myocardial tissue of the heart. Often, the myocardium lacks oxygenated blood flow due to coronary artery disease or occlusion of the coronary arteries that normally supply blood flow to the myocardium. Ischemic tissue causes pain in the affected person.

The treatment of myocardial ischemia has been addressed by several techniques designed to restore blood supply to the affected area. The conventional approach to the treatment of ischemia has been to administer anticoagulants for the purpose of increasing blood flow by lysing or preventing the formation of thrombus in the ischemic area.

Another conventional method of increasing blood flow to the ischemic tissue of the myocardium is coronary artery bypass graft (CABG). One method of coronary artery bypass grafting (CABG) consists of implanting a piece of vein between the aorta and the coronary artery to bypass the embolized portion of the coronary artery. When blood flow is reperfused into the coronary arteries ahead of the occlusion, the oxygenated blood supply is restored to the area of ischemic tissue.

Early researchers reported promising results in myocardial revascularization by drilling into the myocardium to create multiple channels for blood flow more than 30 years ago. ing. Sen, P.M. K. et al. , "Transmyocardial
Acupuncture-A New Approach to Myoc
"ardial revascularization", Journal o
f Thoracic and Cardiovascular Surger
y, vol. 50, No. 2, August 1965, 181-
189 pages. Other researchers have also reported varying levels of success rates for various methods of restoring blood flow to muscles by perforating the heart muscle (commonly known as transmyocardial revascularization or TMR). However, many of them faced common problems such as blockage of the formed flow path. Researchers have reported various techniques for piercing muscle tissue to avoid such blockages. These techniques include perforation with wires that have hard, pointed ends, coring with hypotubes, and the like. According to these reports, in many cases of these methods, tissue trauma or rupture occurs, which is said to eventually lead to blockage of the flow channel.

[0006] Another method of forming channels that potentially prevents such blockage problems is by using laser technology. It is reported that the thermal energy of the laser was used to form the flow channel, and the open flow channel was retained in the myocardium. Miroseini
, M .; et al. , "Revascu1arization of
he Heart by Laser ", Jouna1 of Micros
urgery, vol. 2, No. 4, June 1981, 253
~ 260 pages. The laser is said to form a clean in-vivo channel without tearing or trauma, suggesting that it does not scar and is less likely to cause channel obstruction as a result of healing. US Pat. No. 5,769,843 (Abela et al.) Discloses a method of making a channel for laser-produced TMR using a catheter-based system. The Abela patent further discloses a magnetic guidance system for guiding the catheter to a desired location within the heart. Aita Patent No. 5,380,3
No. 16 and 5,389,096 disclose another method of catheter-based TMR.

[0007] To some extent, it is generally recognized in the public literature that it is desirable to perform transmyocardial revascularization (TMR) using a laser-free catheter insertion technique, but such a technique is practical. There is no evidence of incarnation. For example, US Pat. No. 5,429,144 (Wilk) discloses a method of inserting an expandable implant into a preformed channel in the myocardium for the purpose of creating blood flow from the left ventricle to tissue. Has been done.

Further, a method of placing a stent in the myocardium and performing TMR is described in US Pat.
No. 10,836 (Hussein et al.). Huss
The ein patent discloses several embodiments of stents that are delivered via the epicardium of the heart into the myocardium and are positioned to open against the left ventricle. The purpose of this stent is to maintain an open channel in the myocardium through which blood enters the ventricles and perfuses into the myocardium.

Angiogenesis, which is the growth of new blood vessels in tissues, is a research topic whose number has increased in recent years. Such angioplasty for the new supply of oxygenated blood to certain areas of tissue has the potential to treat a variety of tissue and muscle disorders, particularly ischemia. Such studies have primarily focused on the completion of angiogenic factors such as human growth factors produced by genetic engineering techniques. It has been reported that when such a growth factor is injected into myocardial tissue, angiogenesis starts at that site, and a new dense capillary network is formed. Schumacher
et al. , "Induction of Neo-Angiogenes
is in Ischemic Myocardium by Human G
raw Factors ", Circulation, 1998; v
ol. 97, 645-650.

Assisting the initiation of naturally-occurring angiogenic machinery in tissues during coagulation and fibrin formation, such as releasing growth factors, may be a desirable method for the treatment of ischemic tissue. It is recognized that coagulation proteases and the regulatory mechanisms that act during thrombus formation may initiate the vascular proliferative response. Robert S. Schla
nt (et al.), The Heart (1994). Nitric oxide (NO) has proven to be a useful compound in promoting angiogenesis in tissues. M. Ziche, "Nitric Oxide an
d Angiogenesis ”, pp. 297-306, Angioge.
esis: Models, Modulators, and Clini
cal Applications, Maragodakis, Plen
um Press, N.M. Y. , 1998.

However, it can be difficult for a nitric oxide compound to effectively supply nitric oxide to tissues because it is rapidly volatile before nitric oxide becomes highly volatile and therapeutically effective. This is because the concentration decreases. US Pat. No. 5,676,963 (Keefer
et al. ) Discloses retaining a nitric oxide-releasing compound in a polymer matrix attached to an implantable medical device.

It would be desirable to provide a myocardial angioplasty implant device that is capable of reliably and controllably releasing a nitric oxide compound that promotes angiogenic activity within myocardial tissue when implanted. It is also desirable to provide a mechanism for attaching a compound that releases nitric oxide to the device, such that the use of a polymer matrix on the device is not required. One of the objects of the present invention is to provide a mechanism for controllably administering nitric oxide to promote angiogenic activity.

SUMMARY OF THE INVENTION The present invention provides a method for coupling a nitric oxide (NO) releasing compound to an implantable medical device. NO is believed to have an effect on angiogenic activity in tissues. NO may be useful in inhibiting angiogenesis, which is useful in preventing tumor growth. However, NO may also have the potential to increase angiogenic activity within the tissue. Tissues that would benefit from angiogenic activity include myocardial ischemic tissue of the heart. Therefore, an angioplasty implant configured to promote angiogenesis in the heart's myocardium has an N in a controlled manner when implanted.
It may be even more effective if treated to release O 2.

The angioplasty implant device has a diameter of about 1 to 1.5 mm and a length (about 7 to 9 mm) slightly shorter than the thickness of the myocardial wall of the other party to be transplanted. A flexible spiral spring body can also be included. The device can be made from any material, but preferred materials include the following materials. That is, surgical stainless steel, nickel-titanium alloy, MP35N, or either permanent or biodegradable polymers. The device is percutaneously implantable via a delivery catheter that is configured to be guided into the left ventricle of the heart to enter the endocardium and deliver the implant. In other cases, the device is surgically delivered epicardially or transthoracically while surrounding the perforation delivery device. Not only is the device configured to promote angiogenesis by eliciting an insult response to the tissue at the site of implantation, it also carries a nitric oxide-releasing compound and is also located near the tissue to be treated. Is configured to function as a storage for holding. In addition, the device can carry other angiogenic agents, such as growth factors, or cellular components that are effective in regenerating ischemic tissue.

In the first method, the NO releasing compound can be reacted with an organosilane to attach the NO releasing compound to the structure of the implantable device. Chemical formulas of organic silane shows two types of functional groups _{(R n X (4-n} )). The X group is responsible for reaction with the substrate of the selected medical device. R is a non-hydrolyzable organic radical having a functional group s, which allows the binder to bond with the NO releasing compound.

In another aspect of the invention, the NO-releasing compound can be integrated with the metallic medical device material in the following steps. A coating of primer with excess isocyanate groups is applied to the metal surface. A coating capable of releasing NO when activated is then created by exposing its surface to a nitric oxide releasing compound.

In another aspect of the invention, NO is integrated with the surface of a medical device by first applying silane to the surface. Next, a bonding polymer having an excess of functional groups (hereinafter referred to as a graft polymer), for example, isocyanate is formed around the surface thereof.
The surface is then exposed to a NO-releasing compound that can function as a medical device coating that can release nitric oxide upon activation.

In another aspect of the invention, the NO-releasing compound is retained within the hydrophilic polyurethane matrix. More specifically, the matrix comprises a hydrophilic polyurethane matrix. In another case, the polyurethane matrix is attached to the device,
After curing, the NO-releasing compound can be infiltrated into the matrix by immersing it in an aqueous NO solution. In another embodiment of the method of the present invention, the hydrophilic polymer is attached to the surface of the device and aged and then exposed to an aqueous solution of an additive containing NO.
This aqueous medium is removed by evaporation.

[0019] One object of the present invention is to provide an angioplasty myocardial implant device in which a nitric oxide releasing compound is integrated.

Another object of this invention is a myocardial angioplasty implant that releases nitric oxide in a controllable and therapeutically effective amount for a period of time to promote angiogenesis in surrounding tissue. It is to provide a device.

[0021] Another object of the present invention is to provide a method that does not require a separate matrix to hold the material to the device, but which directly binds nitric oxide to the surface of the device.

Another object of the present invention is to provide a medical device having a coating consisting of a polymer matrix containing a NO releasing compound.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention is a variety of myocardial implants that incorporate nitric oxide (NO) -releasing compounds to aid in initiating angiogenic activity in the myocardial tissue in which the device is implanted. An optimized myocardial implant is provided. Angioplasty implants and methods for implanting same are described in pending US patent application Ser. Nos. 09 / 073,119, 09/16
4,163, 09 / 164,884, 09 / 164,173, 09/52
1,332, 09 / 299,795, 60 / 134,331, 60/13
4,106, which is incorporated herein by reference in its entirety. Examples of suitable angioplasty implant devices are described below with reference to the drawings.

FIG. 1 shows an embodiment of a cylindrical implant device. The gradient coil system 40 is formed from a filament 42, such as a strand of flat wire, having a rectangular cross section. As shown in FIG. 2, the coil is formed such that the cross-sectional long axis 47 of the rectangular wire is oriented at an acute angle to the longitudinal axis 50 of the coil 40. This orientation creates a protruding edge 44 on each winding 46 of the coil, which cuts into the tissue like a nail and acts as an anchoring mechanism for the device.

FIG. 3 shows a segment of a rolled ribbon implant embodiment. Implant 60 is formed by a filament of rectangular cross-section filament wrapped around a ribbed mandrel. In this embodiment, the long axis 47 of the rectangular cross-section ribbon
Are oriented substantially perpendicular to the longitudinal axis 50 of the implant as shown in FIG. In this configuration, the long axis 4 of the rectangular ribbon coil 42 is
7 does not extend radially along the acute axis of the longitudinal axis 50 of the implant 40. It is believed that the larger the coil surface area extending away from the longitudinal axis of the implant, the more stable the implant and the less likely it will be to move once implanted within the myocardium. The implant is preferably formed from 316 stainless steel wire having a rectangular cross section. The preferred dimensions for filaments of rectangular cross section have a minor axis width of 0.0762 mm (0.003 mm).
Inches to 0.127 millimeters (0.005 inches), long axis 0.3
81 millimeters (0.015 inches) to 0.4572 millimeters (0.0
18 inches).

The implant device of the present invention is surgically delivered to the envisioned tissue site. Figure 4A
4C illustrates an example of a surgical delivery device used to deliver an implant to tissue, such as the tissue of the myocardium of the heart. The delivery device illustrated in FIG. 4A includes an obturator 80 that includes a spindle 82 that can be grasped and manipulated.
The tip 81 of the main shaft 82 is shown in detail in FIG. 4B and includes a small diameter device support portion 84 having a sharp tip 86 suitable for piercing tissue. Axis segment 8
The diameter of 4, for example, is configured to fit closely inside the device. The proximal end of segment 84 terminates in a shoulder 88 formed at the junction of the adjacent slightly widened portions 90 proximal of the shaft. The tip of the device support segment 84 includes a radially projecting pin 92 sized to project and fit between adjacent coils of the device coil. The pin 92 threadably engages the coil and the obturator 80 can be simply twisted off the obturator and removed from the implanted coil after insertion of the assembly into tissue. Alternatively, the obturator may be constructed without a protruding pin 92 to allow the device to be slid onto and removed from the obturator without screwing. Implant device 2
When attached to obturator 80, the proximal end of the device abuts shoulder 88 and extends tail 28, if present, along obturator segment 90, as shown in FIG. 4C. .

In use, the envisaged tissue site is first reached by a surgical method, eg an incision. Next, the obturator with the implant device loaded into the segment 84 is penetrated into the tissue to deliver the implant. A sharp tip can pierce the tissue and push the obturator and implant inwardly into the tissue. In the example of myocardial delivery, the obturator reaches the epicardial surface of the heart and penetrates it to deliver the implant. Shoulder 88 prevents proximal migration of the implant along segment 84 during delivery. Desirably, the tip of the obturator is projected to the epicardium and slightly beyond this to install the implant device. The obturator is then unscrewed and removed to separate it from the implant device. If the obturator is configured without pins 92, the obturator can be removed directly from the device and tissue. The puncture hole coagulates at the epicardium by simply applying a light sealing pressure to the epicardial puncture.

The implant device can otherwise be delivered percutaneously from the endocardium to the myocardium. As shown in FIGS. 5A-5D, the delivery catheter 136 is
It can be pre-introduced into the left ventricle and advanced into the left ventricle 122 around the guidewire 134 anchored to the tissue by the barbed tip 135. To reach the left ventricle of the heart percutaneously, a guide catheter (not shown) is advanced through the patient's blood vessel and introduced into the left ventricle 122 of the heart 120. The guide wire 134 having a barb at the tip is inserted from the inside of the guide catheter to the ventricle to insert the myocardium 124.
Perforate and anchor in the tissue. After anchoring the guidewire, the steerable delivery catheter 136 is advanced over and around the guidewire and positioned within the ventricle just adjacent the endocardium 126 to facilitate delivery of the implant device 40.
To facilitate delivery of multiple devices, the guidewire lumen of delivery catheter 136 is eccentrically positioned with respect to the catheter. Therefore, as the catheter rotates about the guide wire, the center of the catheter will rotate along a circular path as shown in FIGS. The supply area can be addressed. The outer diameter of the delivery catheter is desirably less than 2.54 millimeters (0.100 inches). In addition, the delivery catheter extends over the entire length of the catheter and is tipped at the tip.
Steering ability can be provided by having the tip of the catheter bend by pulling a wire from the proximal end using a wire. This maneuverability provides a large area of delivery in a single catheter procedure. A description of the construction of a delivery catheter for reaching multiple sites within the left ventricle is set forth in US patent application Ser. No. 09 / 073,118 dated May 5, 1998, the entire disclosure of which is incorporated herein by reference. Included in the calligraphy.

6A and 6B show side views of a delivery device 140 suitable for a cylindrical implant device 40. The delivery device 140 illustrated in FIG. 6A can be used with a conventional guide catheter or the steerable catheter 136 described above. The delivery device 140 includes an outer push tube 156 and an independently slidable elongated inner shaft 142 having a sharp closure head 146 at the front end. The plugging head 146 is formed at the tip of the inner shaft 142 by any convenient means and is configured to have a sharp piercing tip 148. Included in the material forming the embolization head 146 is a contrasting material such as gold or platinum to allow visualization of the distal region of the device under a fluorescent microscope. Thermally bonded to the proximal end 150 of the plugging head 146 is a flexible crimp.
kle) tube 152, for example polyethylene terephthalate (PET)
) And other materials. Base end 1 of wrinkled tube 152 by heat bonding
Mounted on 54 is a push tube 156, which is formed from closely-spaced springs, in which a PET shrink tubing is formed around the outer surface to form the air gap created by the coil. I'm trying to fill it. The wrinkled tube 152 collapses under compressive load to form a random pattern of folds 158, which increases the overall diameter of the wrinkled tube 152 to mount a hollow or generally cylindrical implant thereon. It comes into engagement and frictional contact with the inner surface of device 40.

When tensioned as shown in FIG. 6B, the wrinkled tube stretches and returns to its unbroken, small diameter state. The shape of the wrinkled tube is such that the inner shaft 142 having an obturator 146 connected to the distal end 155 of the wrinkled tube is relatively positioned with respect to the push tube 156 connected to the proximal end 154 of the wrinkled tube. It is operated by moving to. Inner shaft and push
The tubes are slidable relative to each other and may be operable from the proximal end of the device by extending a suitable handle and core wire.

To deliver implant device 40 to a tissue site, the device must first be loaded around the wrinkled tube. The push tube is moved in the distal direction and the core wire is moved in the proximal direction to compress the wrinkled tube 152, effectively increasing the diameter of the wrinkled tube. The wrinkled tube having an increased diameter engages the inner chamber 6 (hereinafter lumen 6) of the implant device 40,
It is held in place for delivery to tissue as illustrated in Figure 6A. After advancing within the guide catheter to the intended location, the tip of the delivery device is advanced distally from the guide catheter, with the pointed tip 148 penetrating the tissue 124 and the implant device 40 implanted. . After delivery into the tissue, the wrinkled tube is tensioned to retract the folds engaging the lumen of the implant device 40, as illustrated in FIG. 6B. After reducing the profile of the wrinkled tube 152, the implant device 40 is simply slipped off the wrinkled tube surrounding the embolic head 146 and remains in place in the tissue 124.
The delivery device is then removed from the tissue. In the following, methods of integrating NO compounds with these devices will be described.

In one aspect of the invention, the NO-releasing compound is attached directly to the device surface,
In such a case, no coating of the polymer matrix first applied to the device to retain the compound is required. The NO releasing compound reacts with the organosilane in solution. The reaction product is an adduct of a silane-NO releasing compound. This adduct can be coated on medical devices such as myocardial implants by hydrolyzing the X groups. After hydrolysis, reactive silanol groups are formed which react with the device surface to form covalent bonds. In other cases, the organosilane is first applied to the device surface and then reacted with the NO-releasing compound. In other cases, film-forming materials may be added to the coating formulation.

Embodiment 1 The following embodiment illustrates the method. Nucleophilic complex oxides of nitrogen, such as ((CH ₃ ) ₂ CHNH [N (
O) NO] Na). _{((CH 3)} 2) CHNH can react with silane (e.g., 3-isocyanate propyl triethoxysilane as an example) containing isocyanate functional groups. The method of the present invention provides sufficient free OH (oxidation) to attach the molecules.
Provided is a primer for a medical device material having no surface. The resulting adduct (?) Still contains nitric oxide-releasing functional groups (N ₂ O ₂ ), which further enhances the ability to attach the surface of the medical device to the substrate of the medical device. Prepare The surface at this time may be metal, ceramic, or plastic.

In another embodiment of coupling a NO compound to a medical device, the NO-releasing compound is retained within a hydrophilic polyurethane matrix integrated into the device. This matrix contains other moieties that can react with polyols, amines or isocyanates (
It can be formed by adding a polyethylene oxide in the presence of a carrier organic solvent from an isocyanate-terminated adduct that has been reacted with a moiety). The NO-releasing adduct is soluble in the carrier organic solvent and is added to the coating mixture. in this way,
Primers are used to ensure that there is a surface to which the polyurethane matrix will react and bind.

In a method similar to that disclosed above, the polyurethane matrix has a moiety that is capable of reacting with a polyol, amine, or isocyanate.
In the presence of a medium, it is formed from an isocyanate-terminated adduct (prepolymer) reacted with) and polyethylene oxide. After curing the hydrophilic polyurethane on the device surface, the device is placed in an aqueous solution of NO-releasing adduct. This hydrophilic substance absorbs the aqueous solution of the adduct containing NO. The aqueous medium of the aqueous solution is removed by evaporation, which can be assisted by evacuation. In this method, a primer is used to ensure that there is a surface to which the polyurethane matrix can be attached.

Hydrophilic polymers or hydrogels can also be attached to the surface. In the case of NO-releasing adducts that are soluble in the carrier organic solvent, this adduct is added to the coating mixture. In the case of NO-releasing compounds that are soluble in aqueous media, this hydrophilic substrate absorbs the aqueous solution of the NO-containing adduct after the hydrophilic or hydrogel is attached to the catheter. The aqueous medium is then removed by evaporation, which can be assisted by evacuation. In this method, a primer is used to ensure that there is a surface on which the polyurethane matrix can react to obtain a bond.

In light of the above, the present invention provides an angioplasty implant useful in tissues such as ischemic myocardial tissue, wherein the angioplasty implant is a particularly effective combination of a device and a NO-releasing compound attached to the device. Will be understood. In addition, the method does not require the device to be first coated with a polymer matrix to retain the NO,
An effective method of coupling NO-releasing compounds directly to the device is provided.

However, the foregoing description of the invention is merely intended to illustrate this and other modifications, embodiments and equivalents will be apparent to those skilled in the art without departing from the spirit of the invention. What should happen should be understood.

[Brief description of drawings]

[Figure 1]   FIG. 1 is a side view of an embodiment of a tissue implant device.

[Fig. 2]   2 is a partial cross-sectional view of the tissue implant device shown in FIG.

FIG. 3 is a partial cross-sectional view of a variation of the tissue implant device shown in FIG.

FIG. 4A is a side view of a tissue implant device delivery system. FIG. 4B is a detailed side view of the tip of the tissue implant device delivery system. FIG. 4C is a detailed side view of the distal end of the tissue implant device delivery system mounting the implant.

5A-5D are schematic views of an implant device delivered to the myocardium by a percutaneously loaded delivery catheter.

FIG. 6A is a side view of a delivery device for delivering an implant device to a tissue site. FIG. 6B is a side view of the delivery device after releasing the implant device into the tissue site.

[Procedure for Amendment] Submission for translation of Article 34 Amendment of Patent Cooperation Treaty

[Submission date] October 1, 2001 (2001.10.1)

[Procedure Amendment 1]

[Document name to be amended] Statement

[Name of item to be amended] Claims

[Correction method] Change

[Contents of correction]

[Claims]

[Procedure Amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0026

[Correction method] Change

[Contents of correction]

The implant device of the present invention is surgically delivered to the envisioned tissue site. Figure 4A
4C illustrates an example of a surgical delivery apparatus used to deliver an implant to tissue, such as tissue of the heart's myocardium. The delivery device illustrated in FIG. 4A includes an obturator 80 that includes a spindle 82 that can be gripped and manipulated. The tip 81 of the main shaft 82 is shown in detail in FIG. 4B and includes a small diameter device support portion 84 having a sharp tip 86 suitable for piercing tissue. Axis segment 84
The diameter of is designed to fit closely inside the device, for example. The proximal end of the segment 84 terminates in a shoulder 88 formed on the connection which is a proximally adjacent slightly widened portion 90 of the shaft. The tip of the device support segment 84 includes a radially projecting pin 92 that is sized to project and fit between adjacent coils of the device coil. The pin 92 threadably engages the coil and the obturator 80 can be simply twisted off the obturator and removed from the implanted coil after insertion of the assembly into tissue. Alternatively, the obturator can be constructed without a protruding pin 92 to allow the device to be slid into and out of the obturator without screwing in and out. As shown in FIG. 4C, when the implant device 40 is mounted to the obturator 80, the proximal end of the device abuts the shoulder 88 and, if present, the tail 28 along the obturator segment 90. Extend.

[Procedure 3]

[Document name to be amended] Statement

[Correction target item name] 0033

[Correction method] Change

[Contents of correction]

[0033] Example 1   The following embodiments illustrate the method. Nitrous compounds in nucleophilic complexes
It is like in a nucleophilic residue of a primary amine, which is ((CH _Three )_TwoCHNH [N (O) NO] Na). ((CH_Three)_Two) CHNH is isocyanate
Silanes containing nate functional groups (eg 3-isocyanatopropyltriene as an example)
(Toxysilane). The method of the present invention has sufficient capacity to attach molecules.
Provides a primer for medical device materials that does not have OH (oxidation) on the surface
It The obtained adduct has a functional group (N_TwoO_Two) Still included
This further provides the ability to bond the surface of the medical device to the substrate of the medical device.
The surface may be metal, ceramic or plastic.

─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Silag Bee Shah             United States New Hampshire             03060 Nashua Number 11 New             Castle Drive 28 F term (reference) 4C060 MM25                 4C081 AB12 AC03 BA12 CE02                 4C167 AA74 BB06 BB26 CC19 DD10                       FF05 GG02 GG16 GG42 GG45

Claims (13)

[Claims] 1. A body configured to be implanted in myocardial tissue, a nitric oxide-releasing compound integrated with the body, which is therapeutically effective to promote angiogenesis in the tissue. Nitric oxide-releasing compound that releases nitric oxide from the device to surrounding tissue over a period of time. 2. The angioplasty implant of claim 1, wherein the body comprises a flexible coil. 3. The angioplasty implant of claim 1, wherein the nitric oxide releasing compound is directly bound to the surface of the device. 4. The angioplasty implant of claim 3, wherein the nitric oxide releasing compound reacts with the organosilane to become covalently integrated with the surface of the device. 5. The angioplasty implant of claim 1, wherein the nitric oxide releasing compound is integrated with the surface of the body by coating a polymer matrix. 6. A method of promoting angiogenesis within the myocardium of a heart, comprising providing at least one angioplasty implant comprising a body incorporating a nitric oxide releasing compound, said at least one Implanting a body into the myocardium for controlled release of nitric oxide from the body to surrounding tissue. 7. The method for promoting angioplasty in the myocardium of the heart of claim 6, wherein the angioplasty implant is surgically implanted into the myocardium from the epicardium of the heart. 8. The method of claim 6, wherein the angioplasty implant is implanted percutaneously from the endocardium into the myocardium. 9. The blood vessel in the myocardium of the heart of claim 6, wherein the nitric oxide releasing compound is directly bound to the body of the device by a covalent bond formed by the presence of an organosilane. How to promote formation. 10. A method of binding a nitric oxide releasing compound to a medical device, wherein the nitric oxide releasing compound is bound to a surface of the device by reacting the nitric oxide releasing compound with an organosilane. A method comprising the steps of: 11. The method of claim 10, wherein the organosilane and the nitric oxide releasing compound react with each other on the surface of the device to promote binding of the nitric oxide releasing compound to the device. The method described. 12. The method of claim 10, wherein the organosilane is first applied to the surface of the device and dried, and then the nitric oxide releasing compound is applied to the device and dried. . 13. The method of claim 10, wherein a primer coating that provides free hydroxyl groups to the surface of the device is first applied to the device prior to depositing the nitric oxide releasing compound and the organosilane. the method of.