The invention relates to an extrusion product consisting of or comprising a co-extrudate of a polyether block polyamide and a polyamide. Preferred extrusion products are medical tubing, in particular balloon tubing. The invention also relates to a method for producing inventive extrusion products.
In the field of medical technology, there is a constant need for improved materials. The improvement is to be judged from the point of view of the application purpose. For example, in stent delivery systems (systems that allow deployment of a stent), tubing is used that balloons when pressurized. These materials should preferably have the best possible property window, in particular the following properties:
- They should ensure a secure adhesion of the stent to the balloon,
- They should have low balloon compliance (growth of the balloon under increasing pressure),
- They should be well weldable with common (inner shaft) hose materials,
- - They should have a low wall thickness.
Other desirable properties are for. Good flexibility, good stent retention behavior, and sufficient resistance to pressure.
Materials for corresponding balloon hoses are disclosed, inter alia, in the following publications: US 2010/0057001 A1
. US 6,132,824
. US 5,254,090
. US 5,195,969
. US 6,124,007
; WO 2007/120323 A2
. WO 1990/0139242
; EP 0 903 121 A1
. EP 0 745 395 B1
and EP 2 008 674 A1
The cited references disclose products each having at least two layers of different polymers. In particular, these products are medical balloon tubing. Although many of the listed materials have good properties in one or more of the above requirements, significant improvements in other areas mentioned above are desirable:
For example, balloon tubes made of polyamide have a low compression-normalized compliance and a low profile, but a significantly improved stent adhesion. Balloon hoses made of polyether block polyamide, such as. B. PEBAX, while ensuring a good stent liability, but on the other hand are poor with common materials to weld.
From the prior art, in particular from the above-mentioned publications, and multilayer balloon tube materials are known, for. B. those made of PET and polyamide. These have but z. B. the disadvantage that this combination shows too little adhesion, d. H. the adhesion between the balloon and a stent crimped on it becomes too low. This has a negative impact on the function of the catheter.
The object of the present invention was therefore to specify materials which provide a good property window, in particular for use as balloon tubes, in particular for stent delivery systems, in the sense of the requirements described above.
This object is achieved by an extrusion product consisting of or comprising a co-extrudate
- (i) a polyether block polyamide (B) of the general formula (I) HO- (CO-PA-CO-O-PE-O) n -H (I), where PA is a polyamide, PE is a polyether and n is a number from 1-10. and (ii) a polyamide P. Preferably n = 1.
In the context of this application, an extrusion product is to be understood as meaning a product which can be produced in an extrusion process. Common extrusion methods here are profile or tube extrusion, cable extrusion, film extrusion, z. B. Cast or blown film extrusion
Co-extrusion is understood to mean that two different materials are extruded together. In this case, it is preferred that co-extrusion does not result in complete mixing, but very particularly preferably in the region of the interfaces, a compound with sufficient adhesion of the two materials to one another is built up.
Preference is given to an inventive extrusion product, wherein PA is a polyamide of the general formula (II), (III) or (IV): H- (NH- (CH 2 ) x -CO) m -OH (II) H- (NH- (CH 2 ) y -CO-NH- (CH 2 ) z -CO) p -OH (III) H (NH- (CH 2 ) yb -NH-CO- (CH 2 ) yz -CO) pb -OH (IV), in which
each x independently of the others a number from 1-20 means
each y independently of the others means a number from 1-20,
each z independently of the others means a number of 1-20,
each yb independently of the others means a number from 1-20,
every yz independent of the others means a number from 1-20,
m is a number or a range of numbers within 60-130,
p is a number or a range of numbers within 50-100,
pb means a number or range of numbers within 50-100 and / or
PE is a polyether of general formula (IV), (V) or (VI): H- (CH 2 O) q -H (V) H - ((CH 2 O) a - (CH (CH 3 ) O) b ) r -H (VI) H - ((CH 2 ) h -O) k -H (VII), in which
q means a number or a range of numbers within 100-1000,
each a, independently of the others, means a number of 0-10,
each b, regardless of the others, means a number of 0-10,
where at least a or b ≥ 2
r is a number or range of numbers within 50-1000,
each h, independently of the others, means a number of 2-4
k means a number or a range of numbers within 30-450 and / or
the polyamide P is a polyamide of the general formula (VIII), (IX) or (X): H- (NH- (CH 2 ) c -CO) s -OH (VIII) H- (NH- (CH 2 ) d -CO-NH- (CH 2 ) e -CO) t -OH (IX) H- (NH- (CH 2) ya -NH-CO- (CH 2) zb -CO) pb -OH (X), in which
each c, independently of the others, means a number of 1-20,
s means a number or range of numbers within 60-130
each d, independently of the others, means a number from 1-20,
each e, regardless of the others, means a number of 1-20,
t means a number or range of numbers within 50-100
every ya, regardless of the others, means a number from 1-20,
each one, irrespective of the others, means a number of 1-20,
pb means a number or range of numbers within 50-100.
It is preferred that at least one
- - x is a number of 5, 10, 11 or 17 and / or
- - y is a number of 5, 10, 11 or 17 and / or
- - z is a number of 5, 10, 11 or 17 and / or
- - yb is a number of 4, 6, 12 or 16 and / or
- - For example, a number of 2, 4, 10 or 14 means.
It is further preferred that at least one a and / or at least one b is a number from 1-20, preferably 1-10.
It is also preferred that at least one
- C is a number of 5, 10, 11 or 17
- D is a number of 5, 10, 11 or 17
- - e is a number of 5, 10, 11 or 17
- - ya is a number of 4, 6, 12 or 16 and / or
- - For example, a number of 2, 4, 10 or 14 means.
More preferred is an inventive extrusion product, wherein the polyether block polyamide (B) is selected from the group consisting of PEBAX SA01 MED 33 series, especially PEBAX ® 7233 SA 01 MED, PEBAX ® 7033 SA 01 MED, PEBAX ® 6333 SA 01 MED, PEBAX ® 5533 SA 01 MED, PEBAX ® 4233 SA 01 MED and / or the polyamide P is selected from the group consisting of polyamides of the formula VIII, in particular polyamide 12, preferably selected from the group consisting of Grilamid L25, Rilsan AESNO or Vestamid L, or polyamide 11, preferably selected from the group consisting of Rilsan BESNO, or from polyamide 6, preferably selected from the group consisting of Grilon F34, Grilon F40, Grilon F47 or Ultramid B or from co-polyamides according to formula IX, preferably selected from Group consisting of Grilon CA6, Grilon CF6, Grilon CF7, Grilon CR8, Grilon CR9, or polyamides of formula X, preferably selected from the group consisting of polyamide 66 or polyamide 612 and polyamide 46.
Particularly preferred polyether block polyamide B to be used is PEBAX 7033 SA 01 Med: meaning the variables and the formulas I, II and VII:
n = 1, x = 11, m = 90-135, s = h and k = 33-50
Particularly preferred as polyamide P is Grilamid L25 with meaning of the variables according to formula VIII c = 11 and s = 90-130.
The extrusion product according to the invention is preferably tubular.
Tubular in this context means that it is an elongate product having a preferably round outer diameter and a diameter to length ratio of at least 1: 5, preferably at least 1:10. The underlying diameter is the largest diameter that arises in a cross section perpendicular to the extrusion direction of the extrusion material, wherein the diameter value is based on the largest numerical value. Further, a tubular product according to this invention has an elongated, preferably continuous cavity which extends parallel to the length of the extrusion product in its interior. Preferably, a hose according to the invention is multi-layered.
Very preferred in this context is an extrusion product, wherein the layer thickness ratio of the outer layer to the inner layer is 1:10 to 10: 1. Preferred layer thickness ratios (s.o.) in this context are 5: 1 to 1:10, more preferably 1: 1 to 1:10 and most preferably 1: 5.
Further preferred is an inventive extrusion product, wherein the polyether block polyamide (B) forms the outer layer of the hose and the polyamide (P) forms the inner layer of the hose.
In the context of this application, layer thickness is to be understood as meaning the following:
The layer thickness is measured from the beginning of the corresponding material layers of a clear boundary surface (eg - material / air) to the next clear boundary surface (eg material / deviating material). If there are no distinct interfaces but mixing zones, the center of the mixing zone is chosen as one of the two material boundaries for the determination of the layer thickness of the respective material. For the purposes of the present invention, the layer thickness analysis is to be determined regularly perpendicular to the main extrusion direction. In the case of a tubular extrusion, this means that of Center of the hose is a radial section outwards, on the course of the layer thickness determination is performed.
The extrusion products according to the invention have - with increasing preference (see above) - a particularly good property window with regard to the properties of pressure-standardized compliance, profile, bursting pressure, stent retention force, weldability and with regard to trackability DIN EN ISO 25539-2 ) on.
Pressure-standardized compliance (also pressure-standardized balloon compliance) in the context of this application is to be understood as meaning the following:
The pressure standardized balloon compliance [% / atm] is calculated by:
D RBP is the balloon diameter at rated burst pressure (preferably = 16 atm), D NP is the balloon diameter at nominal pressure (preferably 9 atm) and Δ (RBP - NP) is the pressure difference between rated burst pressure and nominal pressure.
For the purposes of this application, the term "rated burst pressure" is to be understood as meaning the following:
Based on in vitro tests at 37 ° C ± 2 ° C, 99.9% (confidence interval 95%) of the balloons do not burst at a pressure less than or equal to the "Rated Burst Pressure" (FDA Guidance No. 1545, 2010).
The balloon diameter is measured by means of a 2-axis measuring laser and averaged in each case from three individual measurements proximally, in the middle and distal (measured in the cylindrical area of the balloon).
For the purposes of this application, profile is to be understood as meaning:
- - Maximum balloon diameter in the folded state
The profile is measured as follows:
Inserting the folded balloon into a hole gauge with smaller openings; Resolution 0.001 inches, noting the smallest possible opening through which the balloon can be easily guided. On stent systems, the measurement is alternatively performed with a measuring laser.
For the purposes of this application, bursting pressure is to be understood as meaning the following:
Balloon burst pressure at inflation with aqueous solution at body temperature 37 ° C.
Burst pressure is measured as follows:
Fill the balloon with aqueous solution, increase the pressure in 1-atm steps until it bursts.
For the purposes of this application, the term stent holding force (dislocation force) is to be understood as meaning:
Strength at which, for the first time, slippage between the stent and the balloon occurs in the installed state without preloading, measured on air.
The stent holding force is measured as follows:
Stent withdrawal on universal tensile testing machine, adhesive connection between stent and pulling device; Increase the force until the stent slides (after ASTM F2394-07 standard Guide for Measuring Securement of Balloon Expandable Vascular Stent Mounted to Delivery System (Tape test method)). If in doubt, try the stent PRO-Kinetic Energy (BIOTRONIK AG, Switzerland).
The weldability is measured as follows:
Tensile strength of the welded joint, measured on a universal tensile testing machine.
Under Trackability DIN EN ISO 25539-2 ) is to be understood in the sense of this application as follows:
Ability of the stent or introducer system to be advanced by the operator without undesired bending or buckling or to be brought into the appropriate position.
Trackability DIN EN ISO 25539-2 ) is measured as follows:
The stent or delivery system is pushed through an anatomical vascular model including introducer. The force required for the feed is recorded.
The characteristics of the invention mentioned here are characterized by the following features:
- - The secure liability z. B. a stent to be used is ensured by an appropriate coefficient of friction of the material in direct contact with the stent. The stent holding force in comparison to the material polyamide 12 (Grilamid L25) can thereby be increased by ≥ 10%, preferably ≥ 20%.
- The pressure normalized balloon compliance is ≤ 2.0% / atm, preferably ≤ 1.8% / atm, especially ≤ 1.5% / atm.
- - The tangential bursting stress is ≥ 250 MPa, preferably ≥ 270 MPa, in particular ≥ 290 MPa.
- The folded balloon profile is low, achievable by a low DWS (double balloon wall thickness) for a given nominal balloon diameter (D NP ), where preferably especially
The tangential bursting stress σ t
is given by:
burst pressure, D Bursting balloon
diameter is about to burst and DWS is double the balloon wall thickness.
The double balloon wall thickness DWS is the average of three measurements, proximal, in the middle and distal of the cylindrical area of the balloon, measured without pressure on the balloon. A probe (eg Millimar incremental probe 1512, Mahr AG Switzerland) is used to determine the DWS.
Against these backgrounds, it is preferred that an inventive extrusion product is selected from the group consisting of medical tubing and balloon tubing.
In such extrusion products, the advantages described above can be exploited particularly well, especially if the preferred variants are used. This is especially true if the tube is formed of two layers, the outer layer of PEBAX 7033 SA 01 MED and the inner layer of Grilamid L25 nat. is executed. The properties of the extrusion product according to the invention can be exploited particularly well in an arrangement comprising an extrusion product according to the invention and welded thereto by a hose made of a polymer M which is materially different from the polyether block polyamide (B) and the polyamide P.
The advantage in this arrangement is the good weldability of the polyamide to be used according to the invention with the further polymer M, so that a system is produced which can withstand high pressures and considerable tensile loads.
Particularly preferred according to the invention in this context is that the arrangement according to the invention is a stent application system, since in this way the advantageous property window described above can be used particularly well for a medical application.
Part of the invention is also a process for producing an extrusion product according to the invention comprising the step of co-extruding a polyether block polyamide (B) and a polyamide (P), each as defined above.
By coextrusion, a good connection of the two co-extruded layers can be ensured and, surprisingly, the properties window described above can be achieved.
The invention will now be described by way of examples and the 1 explained in more detail:
The 1 represents:
An inventive extrusion product, which is designed as a balloon tube and is welded with hoses made of PA12 or PEBAX 7033 in the region of the inner tube.
The reference symbols mean:
LIST OF REFERENCE NUMBERS
- Outer layer of the balloon tube (here from PEBAX 7033 SA 01 MED)
- Inner layer of the balloon tube (here from Grilamid L25 PA12)
- Inner tube (here a catheter made of the polymers PA12 or PEBAX 7033)
- Weld between 2 and 3.
Example 1 - Preparation of a Co Extradate According to the Invention
By means of a co-extrusion process, a co-extrudate of the polyamide Grilamid L25 as the inner layer 2 and PEBAX 7033 as the outer layer 1 was co-extruded. The co-extrudate is a balloon tube. The layer thickness of the inner layer was 0.14 mm, that is about 90% of the total layer thickness, that of the outer layer 0.02 mm, that is about 10% of the total layer thickness.
The inner layer of this co-extradate was perfectly welded with an inner tube 3 (inner shaft with low friction) made of PA12 or PEBAX 7033. The welding process used was a thermal method, such. B. laser welding.
Example 2 - Properties of the Co-Extradate from Example 1:
The co-extrudate was subjected to the property tests described above and compared with balloon tubes made of polyamide Grilamid L25, PEBAX 7033 SA01 or polyester. Table 1: Comparison of preferred properties
Performance / Material Polyamide Grilamid L25 Pebax 7033 SA01 polyester Combination 90% PA inside 10% Pebax exterior
compliance ++ ⌀ ++ ++
Balloon DWS (Double Wall Thickness) + ⌀ ? +
Burst pressure + ⌀ ++ +
Stent retention force ⌀ + ? +
Weldability to PA12 or PEBAX 7033 + + - +
Trackability / Flexibility + ++ ⌀ +
Legend: Very good ++, Good +, Fair (+), Average ⌀, Bad -, Unknown?
It has been found that all properties tested to an at least satisfactory extent by the co-extrudate according to the invention, but with respect to the compliance to an outstanding Be fulfilled. Thus, the very good stent holding power of the PEBAX can be combined with the compliance and the profile of PA12. It was unpredictable that after co-extrusion and because of the combination of materials, these properties are retained. At the same time, the co-extrudate is perfectly weldable with a low-friction inner shaft 3 made of PA12 or PEBAX 7033.
Overall, the polyamide used inside the balloon ensures good mechanical properties (in particular compliance). The material used on the outside ensures good stent holding power. The combination of the two materials allows a low profile and achieves excellent trackability in the benchmark test.
The exterior material (PEBAX) can develop a particularly strong adhesion to the stent thereon. This is aided by a soft surface of the inserted balloon in that, as the hardness decreases, there is an increased contact area between the balloon surface and the stent thereon, as the balloon surface conforms perfectly to the stent structure. Accordingly, there is also a larger area for developing adhesion forces. The process of adapting the tubing surface to the stent is further enhanced by the contact force exerted by the stent on the tubing. Such a connection provides measurable higher stent holding forces than z. B. of PA12 balloon surfaces are known.
An example of said invention (see Example 1) is summarized in the following table: TABLE 2
Catheter with CoEx Pebax 7033 / PA12 (3.25 mm nominal diameter / 18mm nominal length) Catheter with Pebax 7033 balloon (3.0mm nominal diameter / 18mm nominal length) Catheter with PA12 balloon (3.0 mm nominal diameter / 18 mm nominal length)
# MW staff # MW Staff w number means tert Staff w
Stent holding force [N] 5 6.6 0.4 73 6.6 1.2 26 5.4 1.4
Compliance [%] (9-16 atm) 5 07.11% 0.7 data sheet 14% N / A data sheet 02.10% N / A
Pressure standardized balloon compliance [% / atm] NP = 9 atm RBP = 16 atm 5 1.7 0.1 data sheet 2.0 N / A data sheet 1.3 N / A
tangential bursting stress [MPa] 5 301 7 73 284 N / A 26 278 N / A
Burst pressure [bar] 5 24.7 0.4 73 26.5 (min 21- max 30) 1.5 26 27.7 (min 25- max 30) 1.6
DWS / D NP [-] 5 0010 0.0001 data sheet 0013 N / A data sheet 0012 N / A
where #: number of samples, MW: mean, rod: standard deviation, NA: not applicable, NP: nominal pressure, RBP: Rated burst pressure, nominal diameter: diameter at nominal pressure, nominal length: length at nominal pressure.
Similar property windows show other combinations according to the invention.
QUOTES INCLUDE IN THE DESCRIPTION
This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.
Cited patent literature
- US 2010/0057001 A1 
- US 6132824 
- US 5254090 
- US 5195969 
- US 6124007 
- WO 2007/120323 A2 
- WO 1990/0139242 
- EP 0903121 A1 
- EP 0745395 B1 
- EP 2008674 A1 
Cited non-patent literature
- DIN EN ISO 25539-2 
- ASTM F2394-07 Standard 
- DIN EN ISO 25539-2 
- DIN EN ISO 25539-2