JP3503417B2 - Balloon catheter and method of manufacturing balloon used therein - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a balloon catheter and a method for manufacturing a balloon used therefor, and more particularly, to an intravascular stricture in a percutaneous endoluminal surgery including peripheral angioplasty, coronary angioplasty and valvular angioplasty. The present invention relates to a balloon catheter used for dilatation treatment and improving peripheral blood flow, and a method for manufacturing a balloon used therein.

[0002]

2. Description of the Related Art When a stenosis or occlusion occurs in a blood vessel such as a blood vessel, an angioplasty (PTA) is performed to expand the stenosis or occlusion of the blood vessel to improve the blood flow on the peripheral side of the blood vessel. : Percutaneous Transluminal Angioplast
y PTCA: Percutaneous Transluminal Coronary Ang
ioplasty, etc.) has many surgical cases in many medical institutions, and has become a common surgery for cases of this type.

Balloon catheters are mainly used in sets of guide catheters and guide wires to dilate stenosed areas of the coronary arteries. In angioplasty using this balloon catheter, first, a guide catheter is inserted from the femoral artery, the tip is positioned at the entrance of the coronary artery via the aorta, and then the guide wire penetrating the balloon catheter is used to narrow the coronary artery. Advance beyond the site, then advance the balloon catheter along the guidewire, inflate the balloon while it is in the stenosis to dilate the stenosis, and then deflate the balloon to remove it outside the body To do. However, balloon catheters are not limited to the treatment of arterial stenosis, but are useful for many medical applications, including insertion into blood vessels, as well as insertion into various body cavities.

Various proposals have been made for the characteristics of balloons used for balloon catheters and methods for producing them. For example, in Japanese Examined Patent Publication No. 3-63908 (a method for producing a catheter balloon of a high molecular weight biaxially oriented flexible polymer), a material made of polyethylene terephthalate homopolyether is biaxially stretched to form a balloon wall. A balloon with improved tensile strength is disclosed, but since this polyethylene terephthalate homopolyester is a material with extremely high crystallinity, the resulting balloon is stiff, which results in pinholes and winging during refolding. (Phenomenon in which the folded part spreads outward in the radial direction like a bird's wing) was a major problem.

Further, in Japanese Patent Laid-Open No. 3-57462 (balloon for medical device and its molding), a tube made of a nylon material or a polyamide material is biaxially oriented, and its extension is caused by its radial orientation (stretching ratio). The properties (expansion profile) can be controlled to desired properties from compliant (Compliant) to non-compliant (Non-Compliant), and nylon and polyamide materials are mentioned as possible materials. However, since nylon itself is a resin having high crystallinity, if the wall thickness of a balloon made from this exceeds 20 μm, winging at the time of refolding has been a problem. Further, when a balloon is molded from a nylon or polyamide material, the variation of the breaking pressure is large, that is, the standard deviation is large. Therefore, when the thickness of the balloon having a diameter of 3.0 mmφ is 20 μm or less, it is defined in the FDA guidelines. Rated burst pressure is 1
Achieving 2 atm was the limit.

Further, in Japanese Patent Laid-Open No. 6-304920 (Expandable inflatable balloon having elastic stress response and its manufacturing method), individual molecules of a polymer chain are separated by a region having an ability to unwind. Although a technique for making a balloon using a block copolymer having a region of interaction between chains has been described, the object of the present invention is to improve elastic stress response, tensile strength (increasing average breaking pressure). In particular, the main purpose is to prevent winging at the time of refolding due to thermal contraction of the balloon even when sterilized by heating at 50 to 60 ° C. All soft segments of the block copolymer material exemplified in this publication are polyethers.

Further, the publication of WO 95/23619 discloses making a balloon from a polyamide or polyester thermoplastic elastomer. These thermoplastic elastomers are characterized in that the hard segment is polyamide or polyester and the soft segment is polyether. The object of the present invention is to make balloons having high wall tensile strength, thin wall thickness, compliant to semi-compliant properties by using these thermoplastic elastomers.

[0008]

Therefore, in view of the above-mentioned situation, the present invention intends to solve the problems by carrying out a comparative examination with respect to a conventional balloon material and a manufacturing method, and a novel balloon for a balloon catheter. It is an object of the present invention to find a material, provide a balloon catheter that can solve various conventional problems and can adapt to the demands of medical sites, and a method for manufacturing a balloon used therein. Specifically, the first object of the present invention is to reduce the variation (standard deviation) of the bursting pressure of the balloon so that even a thin balloon can achieve the rated bursting pressure defined in the FDA guidelines, that is, the guaranteed withstand pressure. It is to raise it. A second object of the present invention is the non-compliant which is most required in the medical field regarding the stretchability of the balloon.
It is to realize a balloon having characteristics in the range from to semi-compliant accurately and easily. A third object of the present invention is to maintain flexibility of the balloon and prevent pinholes and winging during refolding.

[0009]

In order to solve the above problems, the present invention is a balloon catheter having a balloon at the distal end of a catheter shaft, wherein the balloon has a tensile strength of 300 kg / cm ² or more. (ASTM D638
Method), elongation of 600% or less (ASTM D638
Law by), using the soft segment in a thermoplastic elastomer having the physical properties of Shore hardness (D scale) range of more than 50D is a material composed of polyester, VA
Rune parison from room temperature to
Axial at a temperature within 80% of the heat distortion temperature
Depending on the process of stretching more than 2 times and pressurized gas or liquid
A plurality of steps in the radial direction, including a step of stretching,
Stretching is within a range of 1.2 to 2.5 per stage
Configured a balloon catheter that lies in the. And whether the balloon is non-compliant
To have properties in the semi-compliant range.
It

The present invention is a method for manufacturing a balloon provided at the distal end of a catheter shaft, which has a tensile strength of 300 kg / cm ² or more (according to the ASTM D638 method) and an elongation of 600% or less (ASTM D638 method). ), The Shore hardness (D scale) is a thermoplastic elastomer having physical properties in the range of 50 D or more, and the soft segment is made of polyester, and the balloon parison is heated from room temperature to a heat distortion temperature of the thermoplastic elastomer. At a temperature in the range of 80%, it comprises a step of stretching at least twice in the axial direction, and a step of stretching in a radial direction with a pressurized gas or liquid in a plurality of steps, and the stretching in the radial direction is one step. The present invention provides a method for manufacturing a balloon, characterized in that the stretching ratio (outer diameter after stretching / outer diameter before stretching) is about 1.2 to 2.5. It is intended to. And said
Balloons are non-compliant to semi-compliant
Try to have the characteristics of Ant's range.

Here, when the outer diameter of the balloon when expanded is 3.5 mmφ or less and the wall thickness is 20 μm or less, the rated breaking pressure is preferably 12 atm or more and 18 atm or less. Further, it is preferable that the hard segment of the thermoplastic elastomer is one kind selected from polyester, polyamide and polyurethane.

[0012] Here, in the extensibility of the balloon when it is expanded, when the expansion pressure is increased from about 6 atm to about 12 atm, the case where the diameter of the balloon is increased by 2 to 7% is a non-compliant. , Semi-Compliant (Semi-Complian
t), compliant with a 16-40% increase (C
ompliant) is generally defined.

The rated burst pressure defined in the FDA guidelines is statistically 9% with a reliability of at least 95%.
It guarantees that 9.9% of the balloon will not burst at or below the minimum burst pressure and is defined by the formula: Minimum breaking pressure = X−K × SD Here, K is a coefficient and is shown in the table depending on the probability P, the reliability C, and the number n of balloons to be tested. In the present invention, P = 0.999 (99. 9%), C = 0.95
(95%) and n = 50, so K = 3.
It becomes 766. X is the average burst pressure of the balloon, SD
Is the standard deviation. Then, the rated breaking pressure is expressed by the following equation using the minimum breaking pressure obtained by the above equation. Rated burst pressure = Minimum burst pressure-SD

[0014]

DETAILED DESCRIPTION OF THE INVENTION In accordance with the present invention, ASTM D638
Tensile strength of 300kg / cm ² or more, elongation of 6
A balloon is molded using a thermoplastic elastomer having a physical property of 00% or less and a Shore hardness (D scale) of 50D or more. Generally, a thermoplastic elastomer is composed of a hard segment having high crystallinity and a soft segment having low crystallinity. When a balloon of a balloon catheter is made by using this, a hard segment having a crystallinity or a surrounding The binding force of the molecule with the hard segment greatly contributes to the wall tensile strength. In addition, the structure in the soft segment, such as the polar group and the length of the aliphatic group, greatly affects the compliance and other physical properties. Therefore, the structure and physical properties of the soft segment are as important as those of the hard segment.

For the compliance, see Japanese Patent Laid-Open No. 3-574.
As disclosed in Japanese Patent Laid-Open No. 62-62, in the case of a balloon made of only a highly crystalline portion such as nylon, it is greatly affected by the radial stretch ratio during blow molding. Especially when a balloon is made from a material such as nylon, it is possible to adjust the wide range from compliant to non-compliant with the stretch ratio in the radial direction, but it is possible to adjust to a wide range when adjusting to one extensibility. It means that precise fine adjustment is difficult. In particular, since the introduction of a stent to be left in a blood vessel in order to prevent restenosis, the stretchability of the balloon has become important mainly in the range from semi-compliant to non-compliant.

[0016] WO 90/01302 discloses a balloon using a polyurethane elastomer for the purpose of improving tensile strength and imparting a desired elongation to a balloon for PTCA. Further, JP-A-6-304920 discloses that a balloon is made by using a block copolymer material in order to improve elastic stress response and tensile strength, and both of them are examples of polyurethane type of Dow Chemical Company. "Pellethane" (having a Shore hardness of 75D or more) is mentioned as an elastomer.

This polyurethane elastomer "Pellet
"hane" is a material whose soft segment is composed of polyether, and in the balloon formed by this, even if a high hardness "Pellethane" is used, when a high pressure of 12 atm or more is applied. The elongation characteristics are compliant, and the elongation in the axial direction also occurs. Further, in the case of "Pellethane", if a temperature of 60 ° C. or higher is applied after the balloon is molded, it has a big problem that it is easily contracted.

In the specification of WO 95/23619, a soft segment is a polyether and a hard segment is a polyamide or a polyester in order to make a high wall tensile strength, a thin wall thickness and a compliant to semi-compliant balloon. A balloon molded from a thermoplastic elastomer consisting of is disclosed. According to the description, the structural formula of the polyamide-based thermoplastic elastomer is as follows.

[0019]

[Chemical 1]

The soft segment of the polyether herein is a polyether composed of C ₂ -C ₁₀ diols, more particularly polyethers having 2 to 10 linear saturated aliphatic carbon atoms between the ether bonds, preferably Is an ether segment having 4 to 6 carbons between ether bonds,
Most preferably it is described as a poly (tetramethylene ether) segment. These ether segments provide compliant to semi-compliant elongation properties, which can be very difficult and consistent with non-compliance performance when molded to give balloons near-non-compliant elongation properties. It is difficult to produce elongation characteristics close to that of a client accurately and with good reproducibility.

All of these block copolymers or thermoplastic elastomers disclosed in WO 90/01302, JP-A-6-304920 and WO 95/23619 have a soft segment composed of a polyether.

On the other hand, in the present invention, it has been discovered that among thermoplastic elastomers, the use of a thermoplastic elastomer having a soft segment of polyester has various advantages over the prior art.

A first advantage of the present invention is that when a balloon is formed by using a thermoplastic elastomer whose soft segment is made of polyester, it is possible to make the variation of the breaking pressure of the balloon very small. When the variation of the burst pressure is reduced, the standard deviation (SD) becomes smaller,
Even with the same average breaking pressure, the rated breaking pressure can be increased.

Table 1 shows that a tube of outer diameter / inner diameter = 0.96 mm / 0.43 mm produced by Teijin Nubelin "P4165" was blow-molded to have an outer diameter of 3.0 mmφ and a wall thickness of 19 μ.
It is data of the breaking pressure (n = 30) of the balloon after making a balloon of m and annealing it at about 95 ° C. According to this, the standard deviation is 5.65 psi (0.41 atm).

Also, we have conducted similar experiments on several lots, but the standard deviation is still 5.48-5.69 ps.
i (0.398 to 0.412 atm), and balloons of the same diameter made of polyethylene (standard deviation 1.4 atm), polyethylene terephthalate balloon (standard deviation 1.1 atm), nylon balloon (nylon 12). , The standard deviation was 1.0 atm). In addition, PeBax, a thermoplastic polyamide-based elastomer whose soft segment is polyether
(Atochem Co., Ltd.) has a standard deviation of 0.9 atm, Hytrel (trademark of DuPont), which is also a polyester elastomer, has a standard deviation of 1.02 atm, and Pellethane (Trademark of Dow Chemical Co., Ltd.), which is a polyurethane elastomer, has a standard deviation. Is 0.98 atm,
The present invention was found to be greatly improved.

[0026]

[Table 1]

We have found that the soft segment further reduces the standard deviation of the burst pressure of a thermoplastic elastomer balloon composed of polyester by employing the following molding method.

In this molding method, the outer diameter of the original tube is first stretched in the radial direction so as to fall within the range between the outer diameter of the original tube and the final balloon diameter, and then the radial extension is performed again to reach the final diameter. To do so. This stretching step is not limited to two steps, and may be performed multiple times such as three times and four times. This number is especially important when molding a balloon having a large diameter. In this process, of course, axial stretching is also necessary, but it may be performed simultaneously with or before and after radial stretching.

Table 2 shows that a tube having an outer diameter of 1.8 mm was formed from a tube having an outer diameter / inner diameter of 0.96 mm / 0.43 mm produced by Teijin Nubelin "F4165", and then a final drawing was conducted by two steps. Diameter 3.0 mmφ, wall thickness 1
The data of breaking pressure (n = 30) after forming into a balloon of 9 μm and then annealing at around 95 ° C. are shown.
According to this, the standard deviation is 3.53 psi (0.24a
It is understood that it is possible to further reduce the standard deviation.

[0030]

[Table 2]

The Teijin Nuberane series is composed of an aromatic polyester for the hard segment and an aliphatic polyester for the soft segment. The Toyobo Perprene S series has a similar structure. Using this, a similar experiment (the same experiment as in Table 2) was carried out, but the standard deviation of the breaking pressure was 0.23 atm, and a result similar to that of Nubelin P4165 was obtained. The structure of Perprene S series is as follows.

[0032]

[Chemical 2]

A second advantage of the present invention is that when a balloon is molded from a thermoplastic elastomer whose soft segment is made of polyester, its elongation characteristics are particularly within the range of non-compliant and semi-compliant, and the stretching ratio in the radial direction. Therefore, it is easy to adjust. Figure 1 shows polyethylene, PET, and Teijin Nubelin P4165.
The measurement result of the elongation property of is shown. In the graph of FIG. 1, the draw ratio in the radial direction is shown in parentheses after the material.

A balloon made of Teijin Nubelin P4165 was folded and heat set at 70-80 ° C for 5-10 minutes. About manufactured balloon 12a
Although tm was added and expansion and contraction were repeated, the winging at the time of refolding as seen in polyethylene terephthalate was not seen. This is because the crystallinity of the thermoplastic elastomer in which the soft segment of the present invention is composed of polyester is not as high as that of polyethylene terephthalate, and therefore the balloon itself becomes soft. Further, the wall tensile strength was not as strong as that of polyethylene terephthalate, and a wall thickness of 10 μm or more was inevitably required, so no pinhole was observed.

According to the present invention, the outer diameter when expanded is 3.5 mm.
Even if the thickness is φ or less and the wall thickness is 10 to 20 μm, a balloon having a rated breaking pressure of 12 to 18 atm can be manufactured with good reproducibility within the range of non-compliant and semi-compliant.

[0036]

EFFECTS OF THE INVENTION According to the balloon catheter of the present invention and the method of manufacturing a balloon used for the balloon catheter of the present invention, the variation (standard deviation) of the balloon breaking pressure can be suppressed to a small value, and thus even a thin wall balloon can be FDA.
The rated burst pressure defined in the guideline can be increased. Further, regarding the stretchability of the balloon, which is important when the stent is expanded, it is possible to easily manufacture the balloon having the characteristics most required in the medical field in the range of non-compliant to semi-compliant. Further, the formed balloon is soft and does not generate pinholes or winging at the time of refolding, and thus has high reliability and excellent operability.

[Brief description of drawings]

FIG. 1 is a graph showing a relationship between pressure and balloon diameter elongation of a thermoplastic elastomer balloon according to the present invention, a conventional PET balloon and a conventional polyenelene balloon.

─────────────────────────────────────────────────── ─── Continuation of the front page (56) Reference JP-A-9-56806 (JP, A) JP-A-5-220215 (JP, A) JP-A-10-506562 (JP, A) JP-A-9- 509860 (JP, A) (58) Fields surveyed (Int.Cl. ⁷ , DB name) A61L 29/00-29/18 A61M 25/00

Claims (12)

(57) [Claims] 1. A balloon catheter having a balloon at the distal end of a catheter shaft, wherein the balloon has a tensile strength of 300 kg / cm ² or more and an elongation of 600.
% Or less, the Shore hardness of which is 50D or more, the thermoplastic elastomer having a physical range of the soft segment is made of polyester material , the balloon parison,
From room temperature to 80% of the heat distortion temperature of the thermoplastic elastomer
At a temperature within the temperature range of 2 times or more in the axial direction
And multiple steps in the radial direction with pressurized gas or liquid,
The step of stretching in the radial direction includes one step.
A balloon catheter having a stretch ratio of 1.2 to 2.5 . 2. The balloon is non-compliant
Claim 1 with properties ranging from to semi-compliant
The balloon catheter described. 3. The balloon has an outer diameter of 3.5 when expanded.
When the diameter is less than mmφ and the wall thickness is less than 20 μm, the rated breaking pressure is
It is 12 atm or more and 18 atm or less.
The balloon catheter described. 4. A hard segment of the thermoplastic elastomer.
Of polyester, polyamide, polyurethane
It is 1 sort (s) chosen from the inside.
Balloon catheter. 5. A hard seg of the thermoplastic elastomer.
Of polyester, polyamide, polyurethane
One selected from the above (excluding polyurethane)
The balloon catheter according to any one of claims 1 to 3. 6. A hard segment of the thermoplastic elastomer.
Mention is aromatic polyester, soft segment is fat
The aliphatic polyester according to any one of claims 1 to 3.
Balloon catheter. 7. A bar provided at the distal end of the catheter shaft.
A method for manufacturing a rune, having a tensile strength of 300 kg / c
m ² or more, elongation of 600% or less, Shore hardness of 50 D or less
A thermoplastic elastomer with physical properties in the above range
Uses a material whose segment consists of polyester
The balloon parison from room temperature to the thermoplastic elastomer
At a temperature in the range of 80% of the heat distortion temperature of the mer, the axis
Direction more than 2 times, and pressurized gas or liquid
By a plurality of steps in the radial direction by stretching,
The stretching ratio in one direction is 1.2 to 2.5
The method for producing a balloon is characterized in that 8. Non-compliant to semi-compliant plastic
The balloon of claim 7 having properties in the range of iantes.
Production method. 9. The balloon has an outer diameter of 3.5 when expanded.
When the diameter is less than mmφ and the wall thickness is less than 20 μm, the rated breaking pressure is
It is 12 atm or more and 18 atm or less.
A method for producing a balloon as described. 10. A hard core of the thermoplastic elastomer.
The pigment is polyester, polyamide, polyurethane
It is 1 sort (s) selected from the inside, In any one of Claims 7-9.
Manufacturing method of balloon. 11. A hard core of the thermoplastic elastomer.
The pigment is polyester, polyamide, polyurethane
With one selected from (excluding polyurethane)
A method for manufacturing a balloon according to any one of claims 7 to 9. 12. The hard elastomer of the thermoplastic elastomer.
Aromatic is polyester and soft segment is
It is an aliphatic type polyester, It is any one of Claims 7-9.
Manufacturing method of balloon.