NZ572463A - Angioplasty medical devices made of elastomeric material - Google Patents

Abstract

Disclosed is a medical device or parts thereof for angioplasty, which is made of elastomeric material, characterized in that said elastomeric material comprises a polyamide-based polymer obtained from the polymerization of a compound forming polyamide blocks that is selected from the group consisting of an aminocarboxylic acid of Formula (1) and a lactam of Formula (2) with a polyether diamine triblock compound of Formula (3) and a dicarboxylic acid of Formula (4), wherein the groups R1, R2 and R3 are each binding groups comprising a hydrocarbon chain therein that may be interrupted by one or more amide groups; x is an integer from 1 to 20; y is an integer from 4 to 50, z is an integer from 1 to 20 and m is 0 or 1.

Description

New Zealand Paient Spedficaiion for Paient Number 572463 Received at IPONZ on 28 February 2011 DESCRIPTION "ANGIOPLASTY MEDICAL DEVICES MADE OF ELASTOMERIC MATERIAL" The present invention generally relates to the use of a 5 material for angioplasty medical devices, particularly for angioplasty catheters and more particularly for balloons placed at a catheter distal end.

The use of catheters in angioplasty is widely known. A catheter provided with a balloon at the distal 10 end thereof is advanced, by following a guide wire, to the ostium of the narrowed artery. When the balloon has been placed at the narrowing of the artery, it is repeatedly inflated and deflated. The insufflation, with subsequent deflation, of the balloon within the artery 15 reduces the amount of narrowing of the arterial lumen and restores a suitable blood flow within the heart region, which is diseased because of the stenosis.

The chemical-physical and mechanical characteristics of the plastic material of which the 20 balloon is made determine its compliance, i.e. the adaptability of the balloon to the arterial system, and the resistance to deployment, which are primary characteristics for an optimum operation of the balloon. The compliance and resistance requirements, and the size 25 of the balloon may vary according to the type of use and Received at IPONZ on 28 February 2011 2 size of the vessel in which the catheter is delivered. The advantages offered by the various polymers are correlated to the particular mechanical applications of the balloons.

The problem addressed by the present invention is to provide angioplasty medical devices or parts thereof having improved physical characteristics as compared with those of the prior art. Particularly, the present invention aims to solve the problem of achieving 10 angioplasty catheters, more particularly parts of the same, such as outer tubes, tips and balloons, which are made of a flexible material that is also provided with a high degree of resistance.

The object of the present invention is the use of a constitutive material for angioplasty medical devices and particularly for catheters or parts thereof, such as balloons, tubes and tips, such as defined in the annexed claims; or at least to provide the public with a useful choice.

Further characteristics and the advantages of the medical devices being the object of the present invention will appear more clearly from the following detailed description of the invention.

Received at IPONZ on 28 February 2011 2a The present invention provides a medical device or parts thereof for angioplasty, which is made of elastoraeric material, characterized 5 in that said elastomeric material comprises a polyamide-based polymer obtained from the polymerization of a compound forming polyamide blocks that is selected from "the group consisting of an aminocarboxylic acid of Formula (1) and a lactam of 10 Formula (2): H3N-Rl-COOH (1) -CGNH^^ (2) with a polyether diamine triblock compound of Formula (3) : ca3 CH3 CH3 H2N-t CHCHaO^CHaCH^HsCHa-OijtCH^HO^ CH2CH-NH2 (3) and a dicarboxylic acid of Formula (4) : HOOC- (R3)m-COOH (4) wherein the groups Rl, R2 and R3 are each binding groups comprising a hydrocarbon chain therein that may be interrupted by one or more amide groups; x is an integer from 1 to 20; y is an integer from 4 to 50, z is an 25 integer from 1 to 20; m is 0 or 1.

In an embodiment, the angioplasty medical devices, and particularly, catheters or parts thereof, preferably catheters balloons, are made of a polyamide-based 3 thermoplastic elastomer.

This elastomer comprises monomers forming polyamide blocks, which are the hard portion of the material, modified with a group which is the soft part.

This elastomer is obtained by polymerizing a compound forming polyamide blocks selected from the group consisting of an aminocarboxylic acid such as of Formula (1) and a lactam such as of Formula (2): H2N-R1-C00H (1) (2) with a triblock polyetherdiamine compound of Formula (3) : CBh CEh CH3 I " I ' HaN-fCHCHiO^C^CHaCHsCHj-O^tCHaCHO^-CHaCH-NHa (3) and a dicarboxylic acid such as of Formula (4): HOOC-(R3)m-COOH (4) In said formulae, the groups Rl, R2 and R3 are each binding groups comprising a hydrocarbon chain therein, which may be interrupted by one or more amide groups. Preferably, Rl and R2 comprise independently an alchilene group having 2 to 20 carbon atoms and amide 25 bonds and R3 comprises an alkylene group having 1 to 20 4 carbon atoms. x may change from 1 to 20, preferably from 1 to 18, more preferably from 1 to 16; y may change from 4 to 50, preferably from 5 to 45, more preferably from 8 to 3 0 5 and z may change from 1 to 20, preferably from 1 to 18, more preferably from 1 to 12; m is 0 or 1.

Generally, the polymerization is carried out using 15 to 70 wt% of the compound of Formula (1) and/or (2) 10 and a mixture of compounds of Formulae (3) and (4) having a total weight ranging between 30 and 85%. This polymerization is carried out in a reactor at a temperature ranging between 150 and 300 °C, preferably between 160 and 280 °C, more preferably between 180 and 15 250 °C.

The polymerization can be carried out according to two different methods: the first method is inserting in the reactor the components of Formula (1) and/or (2) , the component of 20 Formula (3) and the component of Formula (4) , heating and adjusting the pressure to complete polymerization. The second synthetic method provides a pre-polymerization between the components of Formula (1) and/or (2) with the component from Formula (4), and 25 subsequent addition within the reactor of the component of Formula (3) to complete polymerization.

In both cases, the polymerization may be carried out in a batch-loaded vessel or in a continuous reactor (PFR).

The aminocarboxylic acids of Formula (1) and the lactams of Formula (2) may be aliphatic, alicyclic or aromatic, for example they can be obtained from the reaction between diamines and dicarboxylic acids and salts thereof. The diamines and the dicarboxylic acids 10 can be aliphatic, alicyclic and aromatic. Preferably, the diamines and the dicarboxylic acids are aliphatic.

Examples of diamine compounds include diamines having 2 to 20 carbon atoms, such as ethylendiamine, triethylene diamine, tetramethylene diamine, hexa-, 15 hepta-, octa-, nona-, deca-, undeca-, dodeca- methylene diamine, 2,2,4-trimethyl hexamethylene diamine, 2,4,4-trimethyl hexamethylene diamine and 3-methyl hexamethylene diamine.

Examples of dicarboxylic acids include dicarboxylic 20 acids having 2 to 20 carbon atoms, such as oxalic acid, succinic acid, glutaric acid, adipic acid, azelaic acid, etc. Alternatively, the dicarboxylic acid (4) may be synthesized by dimerization of unsaturated fatty acids. Examples of these unsaturated fatty acids are: Pripol 25 1004, Pripol 1006, Pripol 1009 and Pripol 1013 sold by 6 Unichema North America, Chicago, 111., USA.

Examples of lactams include compounds having 5 to 20 carbon atoms, such as e-caprolactam, co-enantholactam, oo-undeca-lactam, 2-pyrrolidone, etc.

Examples of amino-carboxylic acids include aliphatic co-aminocarboxylic acids having 5 to 20 carbon atoms, such as 6-aminocaproic acid, 7-aminoheptanoic acid, 8-aminooctanoic acid, 10-aminocapric acid, 11-aminoundecanoic acid and 12-aminododecanoic acid. 10 The polyamide segment is preferably selected from PA 6, PA 6/6, PA 6/9, PA 6/10, PA 6/12, PA 6/36, PA 11, PA 12, PA 12/12. Furthermore, copolyamides or multipolyamides are preferably used, which are obtained from C2-C36 dicarboxylic acids and C2-Ci2 diamines as well 15 as lactam 6, lactam 12, isophtalic, terephtalic and naphthalene dicarboxylic acids.

The polyamide segments can be also obtained from monomers of C6-Ci2 lactams or monomers of C6-C12 aminocarboxylic acids. The polyamide component can also 20 be obtained from the polycondensation of the corresponding diamine salts and carboxylic acids as described above. By changing x, y and z in the polyether diamine triblock compound (Pe) of formula (3): ch3 ch3 ch3 HaN-^CHCHsOiTt-CHaCHaCHaCHj-O^-fCHaCHOiT-CHaCH-NHa (3) a material is obtained, which has different physical characteristics.

If the material is required to be highly 5 transparent, x must range between 2 and 6, preferably between 3 and 4; y must range between 6 and 12, preferably between 8 and 10; z must range between 1 and 5, preferably between 2 and 3.

On the other hand, if the material is required to 10 have high stress resistance, x must range between 2 and 10, preferably between 2 and 6; y must range between 13 and 28, preferably between 13 and 21; z must range between 1 and 9, preferably between 1 and 5.

The poly-ether diamine triblock compound of Formula 15 (3) being used can be identified as a polyether diamine triblock XYX . This group is sold by HUNTSMAN Corp., USA: with the code XTJ-533 is identified a compound in which x is approximatively equal to 12, y is approximatively equal to 11 and z is approximatively 20 equal to 11. With the code XTJ-536 is identified the material in which x is approximatively equal to 9, y is approximatively equal to 17 and z is approximatively equal to 8. With the code XTJ-542 is identified the material in which x is approximatively equal to 3, y is 25 approximatively equal to 9 and z is approximatively 8 equal to 2.

Three preferred compositions of the polyether diamine triblock compound are reported in Table 1 below: Table 1 name X Y z XYX-1 3 14 2 XYX-2 14 4 XYX-3 3 19 2 Preferably, the polyamide-based polymer is represented by the general formula (5): HO-(OC-PA-CO-HN-Pe-NH) n-H (5) wherein PA is the polyamide portion and Pe the soft 10 portion, i.e. a polyether portion, whereas n is the number of units forming the polymer.

This polymer has a molecular weight ranging between 19000 and 50000.

The polymers described above and used in the 15 present invention to obtain medical devices for angioplasty are for example sold under the name of UBESTA XPA ™ by UBE INDUSTRIES, LTD. Examples of particularly suitable commercially available polymers are UBESTA XPA 9055™, UBESTA XPA 9063™, UBESTA XPA 20 9044™, UBESTA XPA 9070™.

The hardness of the material such as measured using 9 the Shore D scale is indicated by the last two digits of the numeric code following the wording UBESTA XPA. Different materials will be thus used for different uses, according to the desired hardness and flexibility, 5 by mixing them together either with the addition of polyamide or not.

The polyamide-based polymer of the present invention may be used as such for manufacturing medical devices for angioplasty, particularly for catheter 10 balloons, or a mechanical mixture of the same also including polyamide in the mixture may be used. In the latter case, the polyamide-based polymer is comprised in the mixture from 10 to 90wt%, preferably 75 to 25%, more preferably 60 to 40wt%, the remaining part of the 15 mixture being polyamide.

The polyamide used in these mixtures is selected from the group consisting of: PA 6, PA 6/6, PA 6/9, PA 6/10, PA 6/12, PA 6/36, PA 11, PA 12 and PA 12/12. Preferably, it is polyamide 12.

The resulting compound will have mechanical characteristics mediated between those of its basic components.

The medical devices for angioplasty, particularly catheters and more particularly catheter balloons 25 obtained with the inventive material exhibit improved physical characteristics as compared with the medical devices, particularly catheter balloons that are obtained with materials known in the art, such as pebax, which is manufactured by Arkema, and grilamid FE7303, 5 manufactured by EMS. These improved characteristics are illustrated herein below also by means of comparative examples.

The balloons obtained with the elastomeric material described in the present invention, in fact, have an 10 optimum characteristic of high flexibility and elasticity. In fact, considering that by flexibility of a material is meant the capacity of this material to return to its original shape after its initial shape has been temporarily changed by a deformation, it is 15 understood that a balloon made of a very flexible material will easily withstand the mechanical stress caused by the repeated action of inflation and deflation which is required during an angioplasty operation.

Furthermore, it has been surprisingly found that 20 the balloon made of elastomeric material being the object of the present invention has an optimum compliance characteristic, which is meant as a percentage increase in the balloon diameter following pressure increase, in addition to an optimum 25 characteristic of adaptability to the arteries and 11 resistance to deployment.

This combination of the characteristics of good flexibility on the one side, and optimum compliance and resistance on the other side characterizes the balloons 5 of the present invention and is further a combination of basic features for a balloon which is delivered in a patient's arterial system during the angioplasty treatment.

The compliance test is carried out by measuring the 10 diameter increase (in mm) of the balloon being tested as compared with the pressure increase (in bars) to burst pressure.

With this experiment it has also been possible to ascertain that a lower average thickness can be 15 maintained in the balloon wall as compared with normal thicknesses of prior art balloons, by maintaining high burst pressure values. Consequently, with the same balloon diameter, a lower wall thickness, i.e. a lower amount of material, can be used as compared with prior 20 art, while still maintaining high burst pressure levels (RBP) . As a consequence, this characteristic of the inventive material results in the great advantage that balloons can be used, which are provided with a smaller profile which requires smaller delivery devices, thereby 25 the delivery of the catheter and delivery device in the 12 arterial system is less traumatic for the patient.

This characteristic is particularly advantageous also with coronary medical balloons, which require high flexibility, compliance and low thickness, mainly with 5 coronary total occlusion (CTO) . In this case, in fact, the artery is almost completely blocked by one or more stenosis, and catheters must be used, which are provided with a high RBP rate (Rate Burst Pressure) , low thickness of the balloon wall and high tensile at break 10 rate, i.e. which are capable of being delivered within the small cavity between the stenosis and withstanding high inflating pressures.

The sum of these characteristics has been surprisingly found using the elastomeric material of 15 this invention, either taken as such or mixed with polyamide.

Due to the good flexibility, the balloon according to the present invention also has a good manoeuvrability. In fact, the elastomeric material also 20 has a good capacity of following the trace and a good adaptation to the vessel path. Accordingly, this characteristic also improves the capacity of advancing the catheter, the balloon being placed at the distal end thereof, along the vessel system to reach the stenosis 25 lesion. When the narrowing of the artery has been WO 2007/132485 PCT/IT2006/000355 13 obtained, the good flexibility of the balloon also provides the non-insufflated balloon with improved capacity to be placed at the stenosis obstruction. The improved adaptability of the material facilitates the 5 passage of the non-insufflated balloon through the narrowed arterial region. This facilitated passage of the balloon through the venous pathway and through the stenosis lesion finally ensures a lower risk of causing further damages both to the venous system involved and 10 stenosis lesion.

The good characteristics of flexibility and elasticity of the balloon of the present invention then allow to obtain balloons, which are advantageously characterized by an improved "return-behaviour" to the 15 original diameter size, after each subsequent insufflation. This allows one to use the same balloon for a greater number and longer duration of insufflations. The flexibility is measured by means of a bounce flexibility test of balloon tubes. The test has 20 been carried out according to the standards as reported by the International Organization for Standardization and described in the standard ISO 14630: 1997. A balloon tube having 0.9 mm outer diameter is positioned by fixing the same to a support equipment, such that 0.15 25 mm operating length is obtained. The tip of a feeler 14 that is connected to a dynamometer is just leant against the surface of said balloon-tube. This feeler is lowered to contact the tube and the force is measured, which is required to obtain a certain lowering amount for the 5 feeler. The lowering speed of the feeler is 20 mm/min.

The good behaviour of the balloon with respect to wear further derives from high flexibility. In fact, during normal use of the angioplasty balloons, the breaking pressure of the balloon is reduced throughout 10 subsequent repeated insufflations. On the other hand, the good flexibility of the balloon made of elastomeric material of the present invention improves the capacity of maintaining the value of breaking pressure as determined for the new balloon. This characteristic also 15 allows using the balloon according to the present invention for a greater number of insufflations and a longer duration of the same.

A further advantage of the balloons obtained with an elastomeric material of the present invention is the 20 good behaviour of the balloon in the tensile test.

A test has been carried out on the balloons of the present invention aiming at evaluating the force required to cause the balloon to break by means of tensile stress. This test has been also carried out 25 according to the standards as reported by the International Organization for Standardization and described in the standard ISO 14630: 1997. To carry out the test, the balloons are attached at the one end thereof to a fixed clamp, and at the other end to a 5 mobile cross-piece which moves at a speed of 50 mm/min, the balloon being elongated to break. The elongation of the balloon is calculated along with the respective yield load until a peak load is reached, which is the breaking point of the balloon and then the corresponding 10 breaking load.

Due to its high flexibility, a further advantage of the material described herein is an improved manoeuvrability of all the catheter, when applied to various catheter portions, such as inner tube, outer 15 tube, tip. In fact, the catheter portions made of elastomeric material according to the present invention provide the catheter with a good capacity of following the trace and a good adaptation to the vessel pathway.

Another advantage of using the material described 20 herein applied to angioplasty balloons is the characteristic of high viscosity of this material and the capacity of maintaining a high viscosity level also over time. This advantage is particularly seen in the material's good fluidity behaviour during the extrusion 25 process to form the tube, from which the balloon is then 16 obtained. Accordingly, the elastomeric material described in the present invention does not require the polyamide formulation to be added with plasticizers as adjuvants.

A further advantage of the elastomeric material described herein is the low water absorption in aqueous solutions. In fact, polymer substances are known to absorb water and thus tend to swell. The polymers of the present invention, on the contrary, due to low water 10 absorption do not tend to swell and thus exhibit very low weight and volume increase in aqueous solutions, their shape, volume and size remaining unchanged.

This characteristic is also very advantageous mainly during the step of extruding the tube from which 15 the balloon is obtained. In fact, before extrusion, all the materials must be put in an oven to lose the residual humidity of the grains. A polymer material that exhibits a low water absorption thus requires, firstly, a shorter pre-drying time. Furthermore, during the 20 extrusion step, the tube protruding from the die is passed through calibration and cooling tanks containing water. The greater the amount of water that the polymer tube tends to absorb, the greater the risk that micro-cavities are formed within the tube wall and 25 consequently micro-cavities within the balloon wall. 17 These micro-cavities are sudden variations in the thickness of the balloon wall and thus are likely to be breakage weak points in the balloon.

Furthermore, it should be noted that the 5 elastomeric material as described in the present invention has a high chemical resistance to hydrolysis in aqueous milieu. This chemical stability to hydrolytic degradation contributes to increase the shelf life of the balloon obtained with said material, since it 10 ensures that the particular mechanical characteristics of the balloon are maintained over time.

The production of tubes for processing the elastomeric material being the object of the present invention can be carried out by means of one of a number 15 of extrusion or pultrusion techniques, which are well known to those skilled in the art, at temperatures ranging between 150° and 350°C.

Particularly, the tubes intended for manufacturing the balloons described herein have been made by 20 extruding the elastomeric material being the object of the present invention by means of single-screw extruders, at temperatures ranging between 200°C and 250°C.

Other extrusion temperatures can be used when the Received at IPONZ on 28 February 2011 18 plant characteristics and ratios of the individual components of the elastomeric material being the object of the present invention are changed.

The term "comprising" as used in this specification and claims means "consisting at least in part of". When interpreting statements in this specification and claims which includes the "comprising", other features besides the features prefaced by this term in each statement can also be present. Related terms such as "comprise" and "comprised" are to be interpreted in similar manner.

In this specification where reference has been made to patent specifications, other external documents, or other sources of information, this is generally for the purpose of providing a context for discussing the features of the invention. Unless specifically stated otherwise, reference to such external documents is not to be construed as an admission that such documents, or such sources of information, in any jurisdiction, are prior art, or form part of the common general knowledge in the art.

In the description in this specification reference may be made to subject matter that is not within the scope of the claims of the current application. That subject matter should be readily identifiable by a person skilled in the art and may assist in putting into practice the invention as defined in the claims of this application.

Received at IPONZ on 28 February 2011 18a The invention is further described by means of the 5 following examples, which are referred only to the balloons, by way of non-limiting illustrations thereof, from which the characteristics and advantages of the present invention will appear even more clearly.

To carry out the tests, different material mixtures 10 have been arranged.

The following example demonstrate with comparative tests that the medical devices for angioplasty of the invention, preferably catheters or parts thereof, have the above-mentioned improved characteristics as compared 15 with the devices made of known materials, such as grilamid FE73 03.

EXAMPLE 1 The first tested mixture consists of 40wt% Polyamide 12 and 60wt% UBESTA XPA 9063™.

Several physical characteristics of mixture 1 are reported in Table 2: 19 Table 2 Characterist ic Method Unit mixture of 40% PA12 -60% UBESTA XPA 9063 Mel ting Point ISO 11357 °C 164 (UBESTA XPA 9063) -178 (PA12) Glass transition temperature ISO 11357 °C -56 MVR ASTM 123 8 (215°C, 2.16 Kg) ml/min 7.3 tensile strength ASTM D638 Mpa 38.34 Tensile Elongation ASTM D638 % 450 Flexural elastic modulus ASTM D790 Mpa 713 Hardness ASTM D2240 Shore D 67.5 Heat distortion temperature under 0.46 Mpa load ASTM D648 °C 106 Table 3, reported herein below, shows the data 5 obtained from a flexural test that is carried on extruded tubes, from which the balloons are subsequently obtained, which are made of elastomeric material WO 2007/132485 PCT/IT2006/000355 according to the present invention. The tubes used have 0.70 mm outer diameter and 0.40 mm inner diameter. This test confirms the characteristic of high flexibility of the material described above. In Table 3 there are 5 reported the load values (expressed in Newtons), which are obtained at preset lowering amounts for the feeler (1 to 8 mm).

Table 3 Cross-beam displacement Samp le 1 mm 2 mm 3 mm 4 mm mm 6 mm 7 mm 8 mm Load (N) 1 0.015 0.021 0.024 0.028 0.031 0.032 0.034 0 . 035 2 0.014 0.018 0.020 0.021 0.023 0.025 0.028 0.026 3 0.017 0.021 0 . 024 0 . 028 0.029 0.030 0.032 0.032 4 0.019 0.023 0.028 0.032 0.029 0.035 0.036 0.036 0.016 0.023 0.028 0.029 0.030 0.033 0.034 0.033 Aver age 0.016 0.021 0.025 0.028 0.029 0.031 0.033 0.032 The table shows a maximum load point of 0.036 N at 7-8 mm feeler travel. This result is particularly significant as it points out the optimal flexural characteristic of the inventive material.

To better appreciate the high flexibility of the tube made of elastomeric material according to the present invention, a comparative test has been carried out with equally sized tubes made of prior art grilamid® FE73 03. The results are reported in Table 4: 21 Table 4 Displacemen t mixture 1 grilamid FE7303 of crossbeam average values average values 1 mm 0.016 0.026 2 mm 0.021 0.031 s 3 mm 0.025 0.035 4 mm 0.028 0.038 aS mm 0.029 0.042 0 i-3 6 mm 0.031 0.044 7 mm 0.033 0.044 8 mm 0. 032 0042 Maximum load 0.033 0.044 Tubes having the same size have been used for the 5 comparative test. The wall thickness is 0.15 mm. The various materials have the same degree of hardness. As may be seen in Table 4, the material from mixture 1 of the invention has a maximum load, at the same travel of the feeler, which is lower than the known material, and 10 consequently an improved flexibility as compared with grilamid.

A tube made of material from mixture 1 has 67.5 Shore D hardness, 713 Mpa flexural elastic modulus, 38.34 Mpa tensile strength at break and about 450% 15 elongation at break. With grilamid FE7303, the comparative tests have demonstrated Shore D values, flexural elastic modulus and tensile strength at break 22 comparable with those of mixture 1, whereas the elongation at break is about 300%. Consequently, the inventive mixture 1 has an improved capacity of elongation as compared with the known product.

In the compliance and flexibility tests, 31 balloon samples have been tested having 1.25 mm outer diameter at 6 bar rated pressure, with 0.02 double average wall thickness.

The compliance test is carried out by measuring the 10 diameter increase (in mm) of the balloon being tested as compared with the pressure increase (in bars) to burst pressure.

The most significant data obtained from this test are reported in Table 5. The reported data relate to the 15 average burst pressure recorded, the standard deviation of the measurements performed and the RBP (Rated Burst Pressure) calculated.

Table 5 Balloon diameter 1.25 Double average wall thickness 0.020 Average burst pressure (bar) 23 . 04 Standard deviation 0.85 Calculated RBP (bar) 18.68 The following Table 6 shows the results obtained 23 from comparative measurement tests of "average burst pressure" and "calculated burst pressure" with the same balloon diameter and double average wall thickness, between the mixture 1 of the invention and grilamid 5 FE7303.

Table 6 mixture 1 Grilamid FE73 03 Balloon diamete r Double average wall thicknes s (mm) Average burst pressure (bar) Burst pressure calculate d (RBP) Double average wall thicknes s (mm) Average burst pressure (bar) Burst pressure calculate d (RBP) 1.50 0.020 21.55 16.65 0.024 18.23 14 .27 2.00 0.030 24 .94 21.11 0.034 22.80 19 .57 2.50 0.032 19.15 16 .54 0.038 19.95 14 . 03 3 .00 0.038 22.88 .90 0.042 22.96 18.50 As may be seen in Table 6, with the same balloon 10 diameter, the inventive material allows having a lower wall thickness while maintaining good burst pressure levels, as compared with the known product. This entails great advantages in terms of applications, which have been explained above.

A further advantage of the balloons obtained with the elastomeric material from mixture 1 is the optimum behaviour during the tensile test. To better appreciate this aspect, comparative tests have been carried out using balloons obtained with mixture 1 and balloons 24 obtained from grilamid FE7303. The data obtained are reported in Table 7.

Table 7 Load (N) % Elongation Mixture 1 9.1 50 Grilamid FE7303 2.6 As may be seen from the data reported in Table 7, the balloons obtained with the elastomeric material of mixture 1 are considerably more resistant and have a percentage elongation at break equal to about twice 10 those obtained with prior art materials.

The load expressed in Newton represents the tensile stress to be applied to break the balloon.

The mixture 1 is particularly advantageous for the extrusion of coronary medical balloons, which require 15 high flexibility and compliance, mainly with coronary total occlusion (CTO) . At the same time, a high RBP value (Rate Burst Pressure) is required, while maintaining a low thickness of the balloon wall and a high tensile at break value. The sum of these 20 characteristics has been surprisingly found using the elastomeric material of this invention, either taken as such or mixed with polyamide.

WO 2007/132485 PCT/IT2006/000355 EXAMPLE 2 The second mixture consists of 60wt% Polyamide 12 and 40wt% UBESTA XPA 9063™.

Several physical characteristics of mixture 2 are 5 reported in Table 8: Table 8 Characterist ic Method Unit mixture of 60% PA12 -40% UBESTA XPA 9063 Melting Point ISO 11357 °C 164 (UBESTA XPA 9063) -178 (PA12) Glass transition temperature ISO 11357 °C -56 MVR ASTM 1238 (215°C, 2.16 Kg) ml (min) 3.5 Tensile strength ASTM D638 Mpa 46.17 Tensile Elongation ASTM D638 % 350 Flexural elastic modulus ASTM D790 Mpa 1066 Hardness ASTM D2240 Shore D 70.5 Heat distortion temperature under 0.46 Mpa load ASTM D648 °C 120 26 Table 9, reported herein below, shows the data obtained from a flexural test that is carried on extruded tubes made of elastomeric material according to the present invention from which the balloons are 5 subsequently obtained. The tubes used have 0.90 mm outer diameter and 0.50 mm inner diameter. This test confirms the characteristic of high flexibility of the material described above. In Table 8 there are reported the load values (expressed in Newtons), which are obtained at 10 preset lowering amount values for the feeler (1 to 8 mm) .

Table 9 Cross -beam displacement Sample 1 mm 2 mm 3 mm 4 mm mm 6 mm 7 mm 8 mm 1 0 . 009 0 .020 0.032 0.044 0. 053 0.056 0 .057 0 .057 2 0 . 014 0 .027 0. 038 0.050 0.057 0.060 0 .062 0 . 062 S 3 0 . 015 0 .028 0.039 0.050 0.060 0.061 0 .062 0 . 063 4 0 . 015 0 .028 0.043 0.051 0.062 0.067 0 .073 0 . 070 nj 0 0 .012 0 . 030 0.038 0.052 0.061 0.065 0 .067 0 . 067 i-l Averag e 0 .013 0 .027 0.038 0.049 0.059 0.062 0 .064 0 .064 The table shows a maximum load point of 0.073 N at a feeler travel of 77 mm. This result is particularly significant as it points out the optimal flexural characteristics of the inventive material.

To better appreciate the high flexibility of the 27 tube made of elastomeric material according to the present invention, a comparative test has been carried out with equally sized tubes made of a material widely used in the art. The results are reported in Table 10: Table 10 Displacemen t mixture 2 Grilamid FE7303 of crossbeam average values average values 1 mm 0.013 0.009 2 mm 0.027 0.025 's 3 mm 0.038 0.041 4 mm 0.049 0.052 n3 mm 0.059 0.062 0 J 6 mm 0.062 0.066 7 mm 0.064 0.069 8 mm 0.064 0.068 Maximum load 0.064 0.069 Tubes having the same size have been used for the comparative test. The wall thickness is 0.20 mm. The 10 various materials have the same degree of hardness.

A tube made of material of mixture 2 has 70.5 Shore D hardness, 1066 Mpa flexural elastic module, 46.17 Mpa tensile strength at break and about 350% elongation at break.

In the compliance and flexibility tests, 31 balloon samples have been tested having 3 mm outer diameter at 7 bar rated pressure, with 0.0383 double average wall 28 thickness.

The compliance test is carried out by measuring the diameter increase (in mm) of the balloon being tested as compared with the pressure increase (in bars) to burst 5 pressure.

The most significant data obtained from this test are reported in Table 11. The reported data relate to the average burst pressure recorded, the standard deviation of the measurements performed and the RBP 10 (Rated Burst Pressure) calculated.

Table 11 Balloon diameter (mm) 3 Average wall thickness (mm) 0.038 Average burst pressure (bar) 22.88 Standard deviation 0.38 Calculated RBP (bar) .91 Comparative tensile at break tests have been 15 carried out also for mixture 2. The data obtained are reported in Table 12.

Table 12 Load (N) % Elongation Mixture 2 23 125 Grilamid FE7303 21 45 29 Balloons obtained with mixture 2 have a greater break resistance and a percentage elongation at break which are more than twice those obtained with prior art materials.

EXAMPLE 3 To better appreciate the characteristics of flexibility of the balloons made of elastomeric material of the present invention as compared with those of the prior art, comparative bounce flexibility tests have been carried out such as widely described above. 10 balloons have been used to carry out this test: balloons made of a material as from mixture 1 (40% Pal2, 60% UBESTA XPA 9063™); 5 balloons made of a material widely used in the prior art.

The test has been carried out by mounting the balloons at the distal end of 10 catheters having the same technical characteristics. The catheters differ from each other only by the distal balloon. The results are reported in Table 13: Table 13 Cross-beam displacement Sample 1 mm 2 mm 3 mm 4 mm mm 6 mm 7 mm 8 mm Maximum value ' 1 0.012 0,017 0,020 0,024 0.025 0^027 0,028 0.02 9 0.029 ■*- 2 ;0.018 ;0.021 ;0.023 ;0.026 ;0.029 ;0.031 ;0.030 ;0,028 ;0.031 ;3 ;0. 004 ;0.008 ;0.010 ;0.012 ;0.013 ;0.018 ;0.017 ;0.016 ;0.018 ;S ;4 ;0.016 ;0.019 ;0.021 ;0.026 ;0.027 ;0.029 ;0.027 ;0.026 ;0.029 ;'■■•••■'"''S v; ;0.007 ;0.008 ;0.011 ;0.015 ;0,,O24 ;o.oas: ;0,024 ;0.024 ;0.025 ;T) ;(0 ;6 , ;0*005 OL Q08 OiQia 0.015 ;0.020 0.023 0.025 0.025 0.025 O j 7 0. 004 0.008 0. 011 0.014 0. 018 0. 020 0. 021 0. 023 0.023 8 0.011 0 . 012 0.017 0.021 0.023 0.025 0.028 0.027 0.028 9 0.004 0 . 007: 0.011 0.016 0:,BSQ 0,026 0.025 0. 023 0 026 0.026 0^32 6;. 035 0. 042 0,046 0.048 0. 047 Q<-075 0 048 Legenda: Table 14 Sample Balloon diameter (mm) Balloon length (mm) material 1 1.25 mixture 1 (40% 3?A12/60% UBESTA XPA 9063™) ' 2 1.25 grilamid FE73 03 3 1.50 mixture 1 (40% PA12/60% UBESTA XPA 9063™) 4 1.50 grilamid FE7303 r, :! ;;j: B j' , 2.00 mixture 1 <40% PA12/-60% UBESTA XPA 9063™) , • grilamid PE7303 7 2.25 mixture 1 (40% PA12/60% UBESTA XPA 9063™) 8 2.25 grilamid FE73 03 V9 ' ' 2.50 mixture 1 (40% PA12/60% UBESTA XPA 9063™)■ 2.50 grilamid FE7303 The test has been carried out with pairs of balloons having the same diameter, the same length but 5 different constitutive materials.

As may be seen in the comparative test, the balloons made of a material according to the present invention are considerably more flexible than those made of prior art material.

As may be seen from the analysis of data, very high 31 hardness values are obtained with these 2 mixtures of examples 1 and 2 (67.5 Shore D for mixture 1 with 40% PA 12 and 60% UBESTA XPA 9063 ™ and 70.5 Shore D for mixture 2 with 70% PA12 and 30% UBESTA XPA 9063™) .

Nevertheless, very high flexural values have been however obtained. This detail has emerged also from the comparative test reported in the example 3 by comparing different balloons. To those skilled in the art the reported values will clearly appear as significant in 10 order to define the good compliance characteristic of the balloons according to the present invention. Particularly, the burst pressure data as stated above are significant in combination with the characteristic of good flexibility of the balloons. In fact, it can be 15 deduced that the balloons being the object of the present invention have a compliance characteristic which is usually found in much less flexible materials. Furthermore, the novel balloons as described herein have the significant advantage of a greater burst pressure 20 and hence a higher RBP, in addition to a less percentage diameter increase between the rated pressure and said RBP, as compared with those prior art balloons having comparable hardness characteristics.

Furthermore, the low value of standard deviation 25 calculated on the tested balloon samples demonstrates 32 the high uniformity of behaviour and characteristics of the balloons obtained with the novel material according to the present invention. Moreover, this data is an index of high reproducibility of the advantageous 5 characteristics specific of the balloons being the object of the invention described herein.

The good compliance characteristics of the balloon obtained with the elastomeric material described in the present invention allow applying said balloons in the 10 coronary therapy, because the risk of breaking the vessel due to a too high expansion of the balloon is low.

Those skilled in the art will readily understand that the elastomeric material being the object of the 15 present invention can be also used for manufacturing medical devices for angioplasty, particularly catheters or parts thereof, such as tubes, balloons, connections, tips, etc.

Advantageously, it has been found that the 20 elastomeric material being the object of the present invention can be also used in tubes and/or multi-layer balloons, i.e. consisting of layers made of different materials, with different mechanical characteristics. Particularly, tubes and balloons for catheters are known 25 to be used, which consist of several layers of different

Claims (50)

WO 2007/132485 PCT/IT2006/000355 33 materials (see for example patent WO 03/072177). The advantage of using multi-layer tubes and balloons is that different materials can be used for the inner and outer walls, these materials being selected based on 5 their mechanical characteristics. 34 CLAIHS

1. A medical device or parts thereof for angioplasty, which is made of elastomeric material, characterized 5 in that said elastomeric material comprises a polyamide-based polymer obtained from the polymerization of a compound forming polyamide blocks that is selected from "the group consisting of ail aminocarboxylic acid of Formula (1) and a lactam of 10 Formula (2): H3N-Rl-COOH (1) 2-CONH^^ (2) with a polyether diamine triblock compound of Formula (3) : 15 CH3 ch3 ch3 I I I HzN-f-CHCHaO-j^CHaCHaCHsCHa-O^tCHaCHOiT-CHzCH-NHa (3 ) and a dicarboxylic acid of Formula (4) : 20 HOOC- {R3) m-COOH (4) wherein the groups Rl, R2 and R3 are each binding groups comprising a hydrocarbon chain therein that may be interrupted by one or more amide groups; x is an integer from 1 to 20; y is an integer from 4 to 50, 2 is an 25 integer from 1 to 20; m is 0 or 1.

2. The medical device according to claim 1, wherein Rl and R2 independently comprise an alkylene group having 2 to 20 carbon atoms and amide bonds, R3 comprises an alkylene group having 1 to 20 carbon atoms, x is an integer from 1 to 18, y is an integer from 4 to 50, and z is an integer from 1 to 20.

3. The medical device according to claim 2 wherein x is an integer from 1 to 16.

4. The medical device according to claim 2 wherein y is an integer from 5 to 45.

5. The medical device according to claim 2 wherein y is an integer from 8 to 30.

6. The medical device according to claim 2 wherein z is an integer from 1 to 18.

7. The medical device according to claim 2 wherein z is an integer from 1 to 12.

8. The medical device according to any one of claims 1 to 7, wherein x, y and z are 3, 14, 2 or they are 5, 14, 4, respectively, or they are 3, 19, 2, respectively.

9. The medical device according to any one of claims 1 to 8, wherein said aminocarboxylic acid of Formula (1) and said lactam of Formula (2} are independently aliphatic, alicyclic or aromatic.

10. The medical device according to any one claim 1 to 9, wherein said aminocarboxylic acid of Formula (1) and said lactam of Formula (2) are independently obtained from the .reaction between diamines and aliphatic, alicyclic or aromatic acids, or salts thereof. 36

11.The medical device according to claim 10, wherein said diamine compounds include diamines having 2 to 20 carbon atoms.

12.The medical device according to claim 11 wherein said diamine compounds are selected from the group comprising ethylendiamine, triethylene diamine, tetramethylene diamine, hexa-, hepta-, octa-' nona-, deca-, undeca-, dodeca- methylene diamine, , 2,2,4-trimethyl hexamethylene diamine, 2,4,4- trimethyl hexamethylene diamine and 3-methyl hexamethylene diamine.

13.The medical device according to any one of claims 1 to 12, wherein said dicarboxylic acid (4) include dicarboxylic acids having 2 to 20 carbon atoms.

14.The medical device of claim 13 wherein the dicarboxylic acid is searched from the group comprising oxalic acid, succinic acid, glutaric acid, adipic acid and azelaic acid.

15.The medical device according to any one of claims 1 to 14, wherein said dicarboxylic acid (4) is synthesized by dimerization of unsaturated fatty acids.

16.The medical device according to any one of claims 1 to 15, wherein said lactams (2) include compounds having 5 to 2 0 carbon atoms.

17.The medical device of claim 16 wherein the lactams are selected from the group comprising €- caprolactam, w-enantholactam, co-undeca-lactam and 2-pyrrolidone. 37

18.The medical device according to any one of claims 1 to 17, wherein said amino-carboxylic acids (!) include aliphatic to-aminocarboxylic acids having 5 to 20 carbon atoms.

19.The medical device according to claim 18 wherein the amino-carboxylic acids are selected from the group comprising 6-am.inocaproic acid, 1~ aminoheptanoic acid, 8-aminooctanoic acid, 10- aminocapric acid, 11-aminoundecanoic acid and. 12- aminododecanoic acid.

20.The medical device according to any one of claims 1 to 19, wherein the polyamide segment is selected from PA 6, PA 6/6, PA 6/9, PA 6/10, PA 6/12, PA 6/36, PA 11, PA 12 and PA 12/12, or is obtained from C2-C36 dicarboxylic acids and C2-C12 diamines, from monomers of C6-Ci2 lactams or monomers of Cs-Ci2 aminocarboxylic I acids.

21.The medical device according to any one of claim 1 to 20, wherein^ said polyamide-based polymer is represented by Formula {5). HO-(OC-PA-CO-HN-Pe-NH)n-H (5) wherein PA is the polyamide portion and Pe is a - polyether portion, whereas n is the number of units forming the polymer. j

22.The medical device according to claim 21, wherein the molecular weight of said polyamide-based polymer ranges between 19000 and 50000. 38

23.The medical device according to any one of claims 1 to 22, wherein said polymerization is carried out using 15 to 70wt% of said compound of Formula (1) and/or (2) and a mixture of said compounds of Formula (3) and (4), with total weight ranging from 30 to 85%.

24.The medical device according to claim 23, wherein said polymerization is carried out by mixing said compounds of Formula (1) and/or (2), said compound of Formula (3) and said compound of' Formula (4) , by heating at a temperature ranging between 150 and 300°C.

25.The medical device according to claim 24 wherein the temperature ranges between 160 and 180°C.

2 6.The medical device according to claim 25 wherein the temperature ranges between 180 and 250°C.

27.The medical device according to any one of claims 23 to 26, wherein said polymerization is carried out by pre- polymerizing said compounds of formula (1) and/or (2) with said compound of Formula (4) and subsequently adding said compound of Formula (3) to the pre- polymer thus obtained, until the polymerization is completed.

28.The medical device according to any one of claims 1 to 27, wherein said elastomeric material further comprises polyamide.

29.The medical device according to claim 28, wherein said polyamide is selected from: PA 6, PA 6/6, PA 6/9, PA 6/10, PA 6/12, PA 6/36, PA 11, PA 12 and PA 12/12. 39

30.The medical device according to claim 29 wherein said polyamide is polyamide 12.

31.The medical device according to any one of claims 28 to 30, wherein said polyamide-based elastomer according to any one of claims 1 to 27 is comprised in said elastomeric material in amounts from 10 to 90%.

32.The medical device according to claim 31 wherein said polyamide-based elastomer is comprised in amounts from 75 to 25% by weight.

33.The medical device according to claim 31 wherein said polyamide-based elastomer is comprised in amounts from 60 to 40% by weight.

34. The medical device according to any one of claims 1 to 33, wherein said device is an angioplasty catheter or part thereof.

35.The medical device according to claim 34 wherein said part thereof is a tube, tip or balloon.

36. The medical device according to any one of claims 1 to 33, wherein said elastomeric material is in multi-layer form.

37.The medical device according to any one of claims 1 to 33, wherein said device is a balloon for angioplasty catheters.

38.The medical device according to claim 37, wherein said balloon has a diameter of 1.50 mm, a double average wall thickness lower than 0.023 ram.

39.The medical device according to claim 37 or 38, ; wherein said balloon has a maximum flexural load lower than 0.04.0 N. 40

40.The medical device of claim 39 wherein said balloon has a maximum flexural load lower than 0.036 N.

41. The medical device of any one of claims 36 to 40, wherein said balloon has, at. 2 mm diameter, an average burst pressure higher than 23 bar, and a calculated RBP higher than 20 bar.

42.The medical device according to claim 41 wherein said balloon has an average burst pressure higher than 24 bar.

43.The medical device according to claim 41 wherein said balloon has an average burst pressure higher than 20.5 bar.

44.The medical device according to any one of claims 36 to 43, wherein said balloon has a tensile strength at break higher than 5 N.

45.The medical device of claim 44 wherein said .balloon has a tensile strength at break higher than 7 N.

46.The medical device of claim 44 wherein said balloon has a tensile strength at break equal to or higher than 9 N.

47.The medical device according to any one of claims 36 to 46, wherein said balloon has a percentage elongation at break higher than 30%.

48.The medical device according to claim 47 wherein said balloon has a percentage elongation at break higher than 4 0%.

49.The medical device according to claim 47 wherein said balloon has a percentage elongation at break equal to or higher than 50%. Received at IPONZ on 28 February 2011 41

50.A medical device according to claim 1, substantially as herein described with reference to any example thereof. 28226/3087673_lJDOC