High Pressure Low Cost Multilayer Balloon Catheter CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No. 61/994,437 filed May 16, 2014, the content of which is incorporated by reference in its entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

Not Applicable

BACKGROUND OF THE INVENTION

Balloon catheters are employed in a variety of medical procedures including plain old balloon angioplasty (POBA) as well as for delivery of medical devices to the treatment site such as stent delivery.

Medical applications where a balloon catheter is employed intraluminally such as for POBA and stent delivery can be demanding applications due to the extremely small vessels, and the tortuous and long distances the catheter may travel to the treatment site. For this reason, trackability is an important parameter for a balloon catheter. Also, for the balloon, it is typically desirable that the balloon be thin walled and have high strength.

The art referred to and/or described above is not intended to constitute an admission that any patent, publication or other information referred to herein is "prior art" with respect to the present disclosure. In addition, this section should not be construed to mean that a search has been made or that no other pertinent information as defined in 37 C.F.R. § 1.56(a) exists.

All US patents and applications and all other published documents mentioned anywhere in this application are incorporated herein by reference in their entirety.

Without limiting the scope of the invention a brief summary of some of the claimed embodiments of the present disclosure is set forth below. Additional details of the summarized embodiments of the invention and/or additional embodiments of the present disclosure may be found in the Detailed Description of the Invention below. BRIEF SUMMARY OF THE INVENTION

In one aspect, the present disclosure relates to a multilayer shaft with an integral balloon having a total shaft length of at least 70 cm.

The integral balloon may have a burst strength of at least 30,000 psi (3.068427xl0 ⁸ Pa).

The integral balloon may have a distension per atmosphere between 6 and 14 atmospheres that is no greater than 0.9%.

The integral balloon may have a double wall thickness of 0.0254 mm to

0.127 mm.

The integral balloon may have a balloon outer diameter of 1.5 mm to 28 mm.

The shaft may have a shaft outer diameter that is 15-55% of the balloon outer diameter.

The shaft may have a shaft inner diameter that is 11 -50% of the balloon outer diameter.

The shaft may have an outer layer formed of nylon and an inner layer formed of poly(ether-block-amide).

The shaft may have an inner layer formed of poly(ether-block-amide), a middle layer formed of nylon, and an outer layer formed of poly(ether-block-amide).

The nylon may be selected from the group consisting of aromatic and aliphatic nylons. The aliphatic nylons may be selected from the group consisting of nylon 12; nylon 6; nylon 6/10; nylon 6/12; and nylon 1 1.

The poly(ether-block-amide) may have a shore D hardness of 60-74D. In a further aspect, the present disclosure relates to a tubular shaft comprising a wall that comprises: an outer layer of poly(ether-block-amide); a middle layer of nylon; an inner layer of poly(ether-block-amide); wherein a section of the wall is expandable or inflatable.

The distal end of the section of the wall may be proximal to the distal end of the tubular shaft.

The section of the wall may be a balloon. The section of the wall may have a double wall thickness of about 0.0254 mm to about 0.127 mm.

The section of the wall may have a burst strength of at least 30,000 psi (3.068427xl0 ⁸ Pa).

The section of the wall may have a distension per atmosphere between 6 and 14 atmosphere that is no greater than 0.9%.

The section of the wall may have an outer diameter of about 1.5 mm to about 28 mm.

The tubular shaft may have a length of at least 70 cm.

The remainder of the tubular shaft may have an outer diameter of 15- 55% of the outer diameter of the section of the wall.

The remainder of the tubular shaft may have an inner diameter of 1 1- 50% of the outer diameter of the section of the wall.

The inner and outer layers may be formed of poly(ether-block-amide) having a shore D of about 60-74. The outer layer may have a lower shore D than the inner layer.

The nylon of the inner layer may be selected from the group consisting of aromatic and aliphatic nylons. The aliphatic nylons may be selected from the group consisting of nylon 12; nylon 6; nylon 6/10; nylon 6/12; and nylon 1 1.

The tubular shaft may define a lumen. The lumen may be an inflation lumen. The lumen may be a single lumen.

The tubular shaft may form a part of a balloon catheter.

The balloon catheter may include an inner shaft positioned inside the tubular shaft. A distal end region of the inner shaft may be secured to a distal end region of the tubular shaft. The inner shaft of the balloon catheter may define a guidewire lumen.

The balloon catheter may further include a manifold at a proximal end. The manifold may be secured to the tubular shaft and the inner shaft. The manifold may form the proximal end of the balloon catheter. The manifold may include a plurality of outlets. The plurality of outlets may include a first outlet in communication with the lumen defined by the tubular shaft and a second outlet in communication with the guidewire lumen. The balloon catheter may consist of the tubular shaft, the inner shaft positioned inside the tubular shaft, and the manifold.

In another aspect, the present disclosure relates to a method of forming the multilayer shaft where the method comprises: a first stretching step wherein a portion of a distal end region of a multilayer polymeric tube is stretched at a first pressure and a first temperature, and the first pressure is equal to ambient pressure; a second stretching step wherein the multilayer polymeric tube is stretched at a second pressure and the first temperature until the extruded tube is stretched to 25 to 75%, preferably, 35-65%, more preferably 45-55%, and most preferably 50% the desired final length, and the second pressure is greater than the first pressure; a third stretching step wherein the multilayer polymeric tube is stretched at a third pressure and the first temperature to form a stretched multilayer polymeric tube having a final stretched length, and the third pressure is less than the second pressure and greater than the first pressure; and a balloon forming step wherein a section of the stretched multilayer polymeric tube is formed into an integral balloon.

In a further aspect of the method, forming the integral balloon may comprise: placing the section of the stretched multilayer polymeric tube into a balloon mold; pressurizing the stretched multilayer polymeric tube to a fourth pressure at a second temperature to form the section into the integral balloon, wherein the fourth pressure is different than the first, second, and third pressures, and the second temperature is greater than the first temperature; and heat setting the integral balloon at a third temperature greater than the second temperature.

The method may further comprise a first quenching step after the third stretching step, wherein during the first quenching step the temperature is reduced to a fourth temperature less than the first temperature and pressure is reduced from the third pressure.

The method may further comprise a second quenching step after the heat setting step, wherein during the second quenching step the temperature is reduced to a fifth temperature less than the first temperature. The integral balloon may be removed from the mold after the second quenching step.

In a further aspect of the method, the multilayer polymeric tube may be formed by coextrusion. In a further aspect of the method, the multilayer polymeric tube may include a layer of poly(ether-block-amide) and a layer of nylon.

In a further aspect of the method, the multilayer polymeric tube may include a layer of poly(ether-block-amide) and a layer of nylon. The poly(ether-block- amide) may have a shore D hardness of about 60-74D. The nylon may be selected from the group consisting of aromatic and aliphatic nylons. The aliphatic nylons may be selected from the group consisting of nylon 12; nylon 6; nylon 6/10; nylon 6/12; and nylon 11.

In a further aspect, the present disclosure relates to a method of making a balloon catheter comprising: inserting an inner shaft into a lumen of the multilayer shaft; and securing a distal end region of the inner shaft to a distal end region of the multilayer shaft.

A hot jaw, a laser bonder, a means of fusion, or a means of adhesion may be used to secure the distal end region of the inner shaft to the distal end region of the multilayer shaft.

The method of making a balloon catheter may further comprise attaching a manifold to the inner shaft and the multilayer shaft. The manifold may be attached by an adhesive selected from the group consisting of: a UV cure adhesive; a two part epoxy; and a high strength adhesive.

These and other aspects of an integral balloon shaft, a balloon catheter, methods of making an integral balloon shaft, and methods of making the balloon catheter are pointed out with particularity in the claims annexed hereto and forming a part hereof. However, for further understanding reference can be made to the drawings which form a further part hereof and the accompanying descriptive matter, in which one or more embodiments are illustrated and described.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

FIG. 1 is a view of a balloon catheter.

FIG. 2 is an enlarged view of a portion of the balloon catheter of FIG. 1. FIG. 3 is a graft of the experimental results for the average balloon burst pressure.

FIG. 4 is a graft of the experimental results for the average double wall thickness. DETAILED DESCRIPTION OF THE INVENTION

While the subject matter of the present disclosure may be embodied in many different forms, there are described in detail herein specific preferred

embodiments of the present disclosure. This description is an exemplification of the principles of the present disclosure and is not intended to limit the present disclosure to the particular embodiments illustrated.

For the purposes of this disclosure, like reference numerals in the figures shall refer to like features unless otherwise indicated.

As used in this disclosure, the terms "connect"; "engage"; "secure"; "attach" do not include "indirect" connection, engagement, securement or attachment. Thus, for example Element B "connecting" Elements A and C, directly connects A and C with no other element between A and B or between B and C.

As used in this disclosure, an "end" is the last part or extremity of an element, while an "end region" of an element is a region adjacent to, and includes, the "end."

As used in this disclosure, a "section" extends from a first longitudinal position to a second longitudinal position of the tubular shaft or wall, and extends around the entire circumference of the tubular shaft or wall.

Integral Balloon Shaft

The integral balloon shaft 22 of the present disclosure is a tubular shaft 22 with an integral balloon 24 (e.g. FIG. 2). As used in this disclosure, "integral" means one-piece construction. In one aspect, the balloon shaft 22 has a length of at least 70 cm and defines a single lumen that is an inflation lumen. The integral balloon shaft 22 has one or more of the following attributes: a balloon 24 with: a burst strength of at least 30,000 psi (2.068427xl0 ⁸ Pa); a burst pressure of at least 280 psi

(1.930532xl0 ⁶ Pa); a double wall thickness of about 0.001 inches to about 0.005 inches (about 0.0254 mm to about 0.127 mm); a distension per atmosphere between 6 and 14 atmosphere that is no greater than 0.9%; a balloon outer diameter of about 1.5 to about 28 mm; and a shaft 22 with a shaft outer diameter (OD) that is 15-55% of the balloon outer diameter (OD); and a shaft inner diameter (ID) that is 1 1-50% of the balloon outer diameter (OD). The balloon shaft 22 may be formed from an extruded multilayer polymeric tube so that the balloon shaft 22 has at least two polymeric layers forming a wall of the balloon shaft 22. Thus, as used herein, a "multilayer shaft" has no gaps between adjacent layers forming the balloon shaft 22.

Suitable polymers for the polymeric layers include, but are not limited to: poly(ether-block-amides) and nylons. In one aspect, the balloon shaft 22 has two polymeric layers, an outer polymeric layer and an inner polymeric layer. In a further aspect of a balloon shaft 22 with two polymeric layers, nylon forms the outer polymeric layer and poly(ether-block-amide) forms the inner polymeric layer.

For example, the balloon shaft 22 may have three polymeric layers, an outer polymeric layer, a middle polymeric layer, and an inner polymeric layer. The outer polymeric layer may have a lower shore D hardness than the inner polymeric layer. At least one of the polymeric layers may comprise nylon. An outer shaft with three polymeric layers, a poly(ether-block-amide) may form the outer and inner layers and a nylon forms the middle layer.

The poly(ether-block-amides) may have a shore D hardness of about 60- 74D. Poly(ether-block-amide) copolymers are available from Arkema, North America under the tradename of Pebax®. Arkema's headquarters are located in Philadelphia, Pa. Specific grades of Pebax® useful herein include, but are not limited to 6333, 7033, and 7233.

Suitable nylons include aromatic and aliphatic nylons. Examples of aliphatic nylons include nylon 12, nylon 6, nylon 6/10, nylon 6/12 and nylon 1 1. Nylon 12 is available from a variety of polymer manufacturers. For example, nylon 12 is available from Degussa-Huls AG, North America under the tradename Vestamid® L2101F. Degussa's national headquarters are located in Dusseldorf, Germany.

Examples of aromatic nylons include the Grivory family of polymers (commercially available from EMS (Sumter, S.C.)), nylon MXD-6 polymers (commercially available from Mitsubishi Gas Chemical (Tokyo, Japan)), and the Trogamid family of polymers (commercially available from Degussa AG (Germany). The nylon may have a shore D hardness of 40-88.

A section 24 of the balloon shaft 22 is inflatable or expandable (e.g. FIGS. 1-2). Since the section 24 of the balloon shaft 22 is inflatable or expandable, the section 24 can be described as a balloon, the inflatable section 24 of the balloon shaft 22 is referred to herein as a balloon 24. Since the balloon 24 is a part of the balloon shaft 22, the balloon 24 is not bonded or welded to the balloon shaft 22. Therefore since the balloon 24 is not a separate component secured to the balloon shaft 22, the balloon 24 and balloon shaft 22 can be described as: a single component; a one-piece construction; or integral. Further, since the balloon 24 is a part of the balloon shaft 22 at least one of the polymeric layers of the balloon 24 is the same as the polymeric layers of the balloon shaft 22. Typically, all layers of the balloon 24 are the same as the layers of the balloon shaft 22.

The balloon 24 can have any suitable longitudinal length and diameter. As noted above, one characteristic of the integral balloon 24 is a burst strength of at least 30,000 psi (2.068427xl0 ⁸ Pa). Burst strength, a measure of the strength of the balloon, is calculated using the following formula:

Strength (psi) = PxD/2t

where P = internal pressure when the balloon bursts, the burst pressure (psi) (1 psi = 6894.75729 Pa); D is the exterior diameter of the balloon (cm); and t is the wall thickness of the portion of the balloon with the larger exterior diameter (cm).

Examples of a balloon shaft 22 with an integral balloon 24 are provided in Table 1. Reference to Examples A-E will be made hereinafter.

Table 1

The trilayer balloon shafts 22 of Examples A and C-E have an outer layer of poly(ether-block-amide); a middle layer of nylon; and an inner layer of poly(ether-block-amide). The bilayer balloon shaft 22 of Example B has an outer layer of nylon and an inner layer of poly(ether-block-amide).

In one aspect, the integral balloon shaft 22 is formed from a multilayer polymeric tube (hereinafter extruded tube). Each layer of the extruded tube extends from one end of the extruded tube to the other end of the extruded tube. Any suitable means can be used to form the multilayer polymeric tube. In one aspect, the multilayi polymeric tube is formed by coextrusion.

Some exemplary inner and outer diameters for an extruded tube are provided in Table 2. A portion of the end section is formed into the balloon 24.

Table 2

Aspects of the balloon of Examples A-E are provided in Table 3 where 2x wall is a measurement of the double wall thickness; D is the diameter of the balloon; burst pressure is the pressure at which the balloon bursts; and distension (Dist.) is a measure of percent balloon expansion per atmosphere between 6 and 14 atm. The measurement of the double wall thickness (2x wall) can be obtained by measuring the thickness of a deflated flattened balloon. Distension of the balloon is measured between 6 and 14 atmospheres by inflating the balloon initially to 6 atmospheres and measuring the expansion of the balloon as the balloon is further inflated to 14 atmospheres. As noted above, the balloon has a distension per atmosphere between 6 and 14 atmospheres that is no greater than 0.9%. Thus, when the balloon is inflated from 6-7 atmospheres, 7-8 atmospheres, 8-9 atmospheres, 9-10, atmospheres, 10-11 atmospheres, 11-12 atmospheres, 12-13 atmospheres, or 13-14 atmospheres, the balloon expands/distends no more than 0.9%.

Table 3

Balloon Properties

Ex. Avg. 2x wall Min. 2x wall D at Burst Dist. Burst

6 atm Pressure Strength

Aspects of the integral balloon shaft 22 of Examples A-E are provided

Table 4.

Table 4

As noted above, the shaft 22 may have a shaft outer diameter (OD) that is 15-55% of the balloon outer diameter (OD); and a shaft inner diameter (ID) that is 11-50% of the balloon outer diameter (OD). As can be seen in Table 4, the comparative outer diameter and inner diameter measurements depend in part on the size of the balloon. Thus, for example, a 3 mm balloon may have a shaft outer diameter (OD) that is 40-55% of the balloon outer diameter (OD); a 3mm balloon may have a shaft inner diameter (ID) that is 35 to 50% of the balloon outer diameter; a 7 mm balloon may have a shaft outer diameter (OD) that is 20-35% of the balloon outer diameter (OD); a 7 mm balloon may have a shaft inner diameter (ID) that is 17-35% of the balloon outer diameter (OD); a 12 mm balloon may have a shaft outer diameter (OD) that is 15-30% of the balloon outer diameter (OD); and a 12 mm balloon may have a shaft inner diameter that is 1 1-17% of the balloon outer diameter (OD).

The shaft ID % strain is calculated by the following formula: ID stretched tube - ID extruded tube

ID extruded tube FIGS. 3-4 graphically compare an integral balloon shaft 22 with a 6 x 40 mm balloon 24 (Example 1), to a commercially available 2 layer balloon tacked or bonded onto a shaft (Comparative Example A). As can be seen, the burst pressures of the integral balloon 24 are comparable to the burst pressures of the tacked balloon of Comparative Example A; and the double wall thicknesses of the integral balloon 24 is slightly greater than the double wall thickness of the tacked balloon of Comparative Example A.

Balloon Catheter

In a further aspect, the integral balloon shaft 22 forms a part of a balloon catheter 20 that can be employed in any of a variety of medical procedures including, but not limited to angioplasty (PTCA) procedures; for delivery medical devices such as stents or valves; genitourinary procedures; biliary procedures; neurological procedures; peripheral vascular procedures; renal procedures; etc. The balloon catheter 20 is particularly useful for procedures that require high pressure to treat, such as a blockage of a major artery, at an AV Fistula vein or graft where resistant lesions occur as a result of hemodialysis, or where heavy calcification and arterial elasticity present extreme challenges to clinicians.

In addition to an integral balloon shaft 22, the balloon catheter 20 includes an inner shaft 26 positioned inside the balloon shaft 22 (e.g. FIG. 2). The inner shaft 26 has a length greater than the length of the balloon shaft 22, and an outer diameter less than the inner diameter of the balloon shaft 22. In one aspect, the inner shaft 26 is tubular and defines a guidewire lumen for passage of a guidewire 32 therethrough (e.g. FIGS. 1-2).

The inner shaft 26 comprises a polymer. The inner shaft can have a single polymeric layer or a plurality of polymeric layers. Any suitable polymer can be used for the inner shaft 26. Examples of suitable polymers for the inner shaft include, but are not limited to: high density polypropylene (e.g. Marlex®); poly(ether-block- amides) (e.g. Pebax®); polyamides (e.g. Grilamid®); and combinations thereof.

Further, the inner shaft can have a reinforcement layer, as is known in the art.

A distal end region of the inner shaft 26 and a distal end region of the balloon shaft 22 can be secured to one another to form a distal tip 28 of the balloon catheter 20 (e.g. FIG. 2). Any suitable means can be used to secure the shafts 22, 26 to one another. The distal tip can be a tapered bumper tip. In one aspect, the guidewire lumen extends through the distal tip (e.g. FIGS. 1-2). In a further aspect, the distal tip 28 has a length of about 4 mm to about 5 mm. Thus, the distal end of the balloon 24 is proximal to the distal end of the balloon shaft 22, and is proximal to the distal end of the balloon catheter 20.

In a further aspect, a balloon catheter 20 as described herein includes a manifold/handle 30 (herein after manifold) at the proximal end (e.g. FIG. 1). In one aspect, the manifold is secured to both the balloon shaft 22 and the inner shaft 26. The manifold 30 has a plurality of outlets 31. In one aspect, the manifold has two outlets with one outlet in communication with the inflation lumen of the balloon shaft 22, and another outlet in communication with the guidewire lumen of the inner shaft 26.

Thus, in one aspect, the balloon catheter 20 has three components: the balloon shaft 22 with integral balloon 24; an inner shaft 26; and a manifold 30.

The balloon catheter 20 may include one or more areas, bands, coatings, members, etc. that is (are) detectable by imaging modalities such as X-Ray, MRI, ultrasound, etc. In some embodiments at least a portion of the balloon catheter 20 is at least partially radiopaque.

In a further aspect, at least a portion of the balloon catheter 20 is configured to include one or more mechanisms for the delivery of a therapeutic agent. Often the agent will be in the form of a coating or other layer (or layers) of material placed on a surface of the balloon catheter 20. The surface with a coating or layer can be the outer surface, the inner surface, or both the inner and outer surfaces. In one aspect, the balloon 24 has a coating of therapeutic agent.

A therapeutic agent may be a drug or other pharmaceutical product such as non-genetic agents, genetic agents, cellular material, etc. Some examples of suitable non-genetic therapeutic agents include but are not limited to: anti-thrombogenic agents such as heparin, heparin derivatives, vascular cell growth promoters, growth factor inhibitors, Paclitaxel, etc. Where an agent includes a genetic therapeutic agent, such a genetic agent may include but is not limited to: DNA, RNA and their respective derivatives and/or components; hedgehog proteins, etc. Where a therapeutic agent includes cellular material, the cellular material may include but is not limited to: cells of human origin and/or non-human origin as well as their respective components and/or derivatives thereof. Where the therapeutic agent includes a polymer agent, the polymer agent may be a polystyrene-polyisobutylene-polystyrene triblock copolymer (SIBS), polyethylene oxide, silicone rubber and/or any other suitable substrate.

Method

As discussed above, a balloon shaft 22 with an integral balloon 24 is formed from an extruded tube. In summary, to form the balloon shaft 22 with an integral balloon 24, the extruded tube is formed into a stretched extruded tube before a section of the extruded tube is formed into a balloon 24.

To stretch the extruded tube, the extruded tube can be placed into a stretching machine with two clamps, for example, one movable clamp and one stationary clamp. The movable clamp is attached to the distal end region of the extruded tube and the stationary clamp is attached to the proximal end region of the extruded tube. A gas pressure source is in communication with the lumen of the extruded tube. The stationary clamp may have rubber pads which fix the extruded tube in position, but allows gas flow to pressurize the extruded tube.

The extruded tube is subjected to a multistage stretching process having three stretching steps or stages. In the first stretching step, a selected portion of the distal end region of the extruded tube is stretched at a first pressure and a first temperature, where the first pressure is equal to ambient pressure. In the second stretching step, the extruded tube is stretched at a second pressure and the first temperature until the extruded tube is stretched to 25 to 75%, preferably, 35-65%, more preferably 45-55%, and most preferably 50% the desired final length, where the second pressure is greater than the first pressure. In the third stretching step, the extruded tube is stretched at a third pressure and the first temperature until the extruded tube is stretched to the final stretched length, where the third temperature is less than the second pressure and greater than the first pressure.

The first stretching step typically reduces the dimensions of the distal end region of the extruded tube, and the third stretching step advantageously optimizes the material modulus, the inner diameter, and the outer diameter of the stretched extruded tube. After the third stretching step, the stretched extruded tube is quenched at a second temperature less than ambient temperature, and the pressure is reduced from the third pressure. Then a portion of the stretched extruded tube is placed into a balloon mold for formation of the integral balloon 24. The balloon mold may have three sections, a distal end section, a body section, and a proximal end section. While in the mold, the stretched tube is pressurized to a fourth pressure at an elevated third temperature to form the balloon 24, where the third temperature is greater than the first temperature; the balloon 24 is heat set at a fourth temperature greater than the third temperature; and then quenched at a reduced fourth temperature for removal of the balloon shaft 22 with an integral balloon 24 from the mold, where the fourth temperature is less than ambient temperature.

This manufacturing method is a simplified manufacturing process that achieves the same superior balloon properties as commercially available balloons. This method is described in greater detail with reference to Examples A-E.

Stretching the Extruded Tube

Example A

The extruded tube is placed into the two clamps of the stretching machine. An initial distance of 516 mm separates the two clamps.

For the first stretching step, a distal region of the extruded tube next to the movable clamp is contact heated to a first temperature, and the extruded tube is stretched to form a distal neck with transition. In one aspect, the first temperature is 80° C; the first pressure is ambient pressure; and the distal region is approximately 127 mm (5 inches).

For the second stretching step, the extruded tube is stretched to a distance of about 716 mm in an 80° C hot bath, at a velocity of 50 mm/sec, and an inflation pressure of 280 psi (1.930532xl0 ⁶ Pa).

When the extruded tube reaches a length of about 716 mm, the third stretching step begins. In the third stretching step, the pressure is reduced to 180 psi (1.241056xl0 ⁶ Pa) and the extruded tube is stretched to a final length.

After the third stretching step, the stretched extruded tube is quenched in a 1 1° C bath, the pressure is reduced from 180 psi (1.241056xl0 ⁶ Pa), and the stretched extruded tube is released from the two clamps that are separated at least by 990 mm. Examples B-D

The extruded tube is placed into the two clamps of the stretching machine. An initial distance of about 366 mm separates the two clamps.

For the first step, a distal region of the extruded tube next to the movable clamp is contact heated to a first temperature, and the extruded tube is stretched to form a distal neck with transition. In one aspect, the distal region has a length of about 25 mm; the first temperature is 80° C; the pressure is ambient pressure; and the extruded tube is stretched a distance of about 416 mm.

For the second stretching step, the extruded tube is stretched in an 80° C hot bath at a velocity of 50 mm/sec to a distance of about 716 mm at an inflation pressure of 357 psi (2.461428xl0 ⁶ Pa).

When the extruded tube reaches a length of about 716 mm, the third stretching step begins. In the third stretching step, the pressure is reduced to 290 psi (1.9994796xl0 ⁶ Pa) and stretched to about 990 mm.

Then the stretched extruded tube is quenched in a 11° C bath, the pressure is reduced from 290 psi (1.9994796xl0 ⁶ Pa), and the stretched extruded tube released from the two clamps that separated at least by 990 mm.

Example E

The extruded tube is placed into the two clamps of the stretching machine. An initial distance of about 336 mm separates the two clamps.

For the first step, a distal region of the extruded tube next to the movable clamp is contact heated to a first temperature, and the extruded tube is stretched to form a distal neck with transition. In one aspect, the distal region has a length of about 25 mm; the first temperature is 80° C; the pressure is ambient pressure; and the extruded tube is stretched a distance of about 386 mm.

For the second stretching step, the extruded tube is stretched in an 80° C hot bath at a velocity of 50 mm/sec to a distance of about 716 mm at an inflation pressure of 275 psi (1.896058xl0 ⁶ Pa).

When the extruded tube reaches a length of about 716 mm, the third stretching step begins. In the third stretching step, the pressure is reduced to 190 psi (1.310039xl0 ⁶ Pa), and the extruded tube is stretched to about 990 mm. Then the stretched tube is quenched in an 1 1° C bath, the pressure is reduced from 190 psi (1.310039xl0 ⁶ Pa), and the stretched tube released from the two clamps that are separated by 990 mm.

Aspects of the stretched tube used to form the integral balloon shaft of

Examples A-E are provided in Table 5 :

Table 5

Forming the Integral Balloon

In one aspect, a balloon mold with a 50.8 mm (2 inches) distal end section, a 40 mm body section, and a 101.6 mm (4 inches) proximal end section is used to form a 40 mm balloon. The transition between the smaller outer diameter distal end region and larger outer diameter proximal end region of the stretched tube is placed in the proximal mold section. The stretched tube and mold are placed into a mold holder and then onto the molding machine arm. The stretched tube is pressurized at a fourth pressure and placed in bath at a third temperature until the balloon is formed.

Depending on the diameter of the balloon to be formed, the fourth pressure may be less than or greater than the third pressure.

Next, the mold is transferred to a heat set station set at a fourth temperature for 60-90 seconds. In one aspect, the fourth temperature is greater than the first temperature.

Then the mold is transferred to a quench bath at a fifth temperature to cool the shaft and mold to allow for removal of the balloon shaft 22 with the integral balloon 24 from the mold. In one aspect the fifth temperature, less than the first temperature

Example A To form a 3 x 40 mm balloon, the stretched tube in the balloon mold is pressurized with nitrogen gas at 500 psi (3.4473786xl0 ⁶ Pa) and placed in a 95° C bath until the balloon is formed. Next, the mold is transferred to a heat set station set for 125° C for one (1) minute before the mold is transferred to a 10° C quench bath to cool the shaft and mold to allow for removal of the balloon shaft 22 with the integral balloon 24 from the mold.

Examples B-D

To form a 7 x 40 mm balloon, the stretched tube in the balloon mold is pressurized with nitrogen gas at 265 psi (1.82711 lxlO ⁶ Pa) and placed in a 95° C bath until the balloon is formed. Next, the mold is transferred to a heat set station set for 125° C for one (1) minute before the mold is transferred to a 10° C quench bath to cool the shaft and mold to allow for removal of the balloon shaft 22 with the integral balloon 24 from the mold.

Example E

To form a 12 x 40 mm balloon, the stretched tube in the balloon mold is pressurized with nitrogen gas at 300 psi (2.068427xl0 ⁶ Pa) and placed in a 95° C bath until the balloon is formed. Next, the mold is transferred to a heat set station set for

125° C for one (1) minute before the mold is transferred to a 10° C quench bath to cool the shaft and mold to allow for removal of the balloon shaft 22 with the integral balloon 24 from the mold.

Aspects of forming the integral balloon of Examples A-E are provided in Table 6.

Table 6

Forming a Balloon Catheter with the Integral Balloon Shaft

As noted above, a balloon shaft 22 with integral balloon 24 can form a part of a balloon catheter 20. In one aspect, a method of forming a balloon catheter 20 includes: inserting a polymeric tube into the lumen of a shaft 22 with the integral balloon 24, where the shaft 22 is considered to be an outer shaft and the polymeric tube is considered to be an inner shaft 26; securing the outer shaft 22 and inner shaft 26 to one another to form a shaft assembly; and attaching a manifold 30 to a proximal end of the shaft assembly to form the balloon catheter 20.

Any suitable means can be used to secure the outer shaft 22 and inner shaft 26. For example, a hot jaw, a laser bonder, a means of fusion, or a means of adhesion can be used to fuse the outer shaft 22 and inner shaft 26. In one aspect, securing the outer shaft 22 and inner shaft 26 to one another forms a distal tip 28, such as a tapered bumper tip. In a further aspect, about 4-5 mm of the outer shaft 22 distal to the balloon 24 is fused to the inner shaft 26.

Any suitable means can be used to attach the manifold 30 to the shaft assembly. For example, a UV cure adhesive; a two part epoxy; a high strength adhesive; or any other means of adhesion can be used to attach the manifold. As used herein a "high strength adhesive" is an adhesive capable of withstanding internal pressure of 500 psi (3.447379xl0 ⁶ Pa) and higher.

The above disclosure is intended to be illustrative and not exhaustive. This description will suggest many variations and alternatives to one of ordinary skill in this art. The various elements shown in the individual figures and described above may be combined or modified for combination as desired. All these alternatives and variations are intended to be included within the scope of the claims where the term "comprising" means "including, but not limited to".

Further, the particular features presented in the dependent claims can be combined with each other in other manners within the scope of the disclosure such that the disclosure should be recognized as also specifically directed to other embodiments having any other possible combination of the features of the dependent claims. For instance, for purposes of claim publication, any dependent claim which follows should be taken as alternatively written in a multiple dependent form from all prior claims which possess all antecedents referenced in such dependent claim if such multiple dependent format is an accepted format within the jurisdiction (e.g. each claim depending directly from claim 1 should be alternatively taken as depending from all previous claims). In jurisdictions where multiple dependent claim formats are restricted, the following dependent claims should each be also taken as alternatively written in each singly dependent claim format which creates a dependency from a prior antecedent-possessing claim other than the specific claim listed in such dependent claim below.

This completes the description of the disclosure. Those skilled in the art may recognize other equivalents to the specific embodiment described herein which equivalents are intended to be encompassed by the claims attached hereto.